{"id":"colchicine","rwe":[{"pmid":"41905101","year":"2026","title":"Multi-target pyrazolopyrimidine-coumarin derivatives as potent CA IX/XII and tubulin polymerization inhibitors: Design, synthesis, and biological evaluation.","finding":"","journal":"European journal of medicinal chemistry","studyType":"Clinical Study"},{"pmid":"41904738","year":"2026","title":"Incidence and management of pyrexia syndrome in patients treated with dabrafenib and trametinib: a retrospective study.","finding":"","journal":"Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer","studyType":"Clinical Study"},{"pmid":"41897198","year":"2026","title":"Effect of Colchicine Use and Usual Care Alone on the Rate of Progression to Chronic Kidney Disease and Mortality in Patients with Heat-Related Injury.","finding":"","journal":"Healthcare (Basel, Switzerland)","studyType":"Clinical Study"},{"pmid":"41897084","year":"2026","title":"Association Between Vitamin D, Vitamin B12 and Folate Levels and Persistent Subclinical Inflammation in Pediatric Familial Mediterranean Fever.","finding":"","journal":"Children (Basel, Switzerland)","studyType":"Clinical Study"},{"pmid":"41891111","year":"2026","title":"In-silico studies on effective phytochemicals of Crocus sativus, Ocimum tenuiflorum and its modifications targeting NIPAH virus.","finding":"","journal":"In silico pharmacology","studyType":"Clinical Study"}],"_fda":{"id":"62a7d89d-9856-446f-aaa2-962825fef0a6","risks":["Risk Summary Available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Error! Hyperlink reference not valid. ). Colchicine crosses the human placenta. Although animal reproductive and developmental studies were not conducted with colchicine tablets, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.","Risk Summary Colchicine is present in human milk (see Error! Hyperlink reference not valid. ) . Adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. There are no data on the effects of colchicine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for colchicine tablets and any potential adverse effects on the breastfed child from colchicine tablets or from the underlying maternal condition."],"set_id":"0f69b9c6-8c00-45e2-b950-34dc5ae62352","openfda":{"nui":["N0000193949","M0000713"],"upc":["0371205687304"],"unii":["SML2Y3J35T"],"route":["ORAL"],"rxcui":["197541"],"spl_id":["62a7d89d-9856-446f-aaa2-962825fef0a6"],"brand_name":["colchicine"],"spl_set_id":["0f69b9c6-8c00-45e2-b950-34dc5ae62352"],"package_ndc":["71205-687-05","71205-687-10","71205-687-21","71205-687-30","71205-687-60","71205-687-90"],"product_ndc":["71205-687"],"generic_name":["COLCHICINE"],"product_type":["HUMAN PRESCRIPTION DRUG"],"pharm_class_cs":["Alkaloids [CS]"],"substance_name":["COLCHICINE"],"pharm_class_epc":["Alkaloid [EPC]"],"manufacturer_name":["Proficient Rx LP"],"application_number":["ANDA209876"],"original_packager_product_ndc":["43598-372"]},"version":"4","pregnancy":["8.1 Pregnancy Risk Summary Available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Error! Hyperlink reference not valid. ). Colchicine crosses the human placenta. Although animal reproductive and developmental studies were not conducted with colchicine tablets, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behcet’s disease, or familial Mediterranean fever (FMF) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications."],"overdosage":["10 OVERDOSAGE The exact dose of colchicine that produces significant toxicity is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder toxicities such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe reactions such as myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg. The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen. Life-threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion. Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchicine is not effectively removed by dialysis [see Error! Hyperlink reference not valid. ] ."],"description":["11 DESCRIPTION Colchicine is an alkaloid chemically described as (S)N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo [alpha] heptalen-7-yl) acetamide with a molecular formula of C 22 H 25 NO 6 and a molecular weight of 399.4. The structural formula of colchicine is given below. Colchicine, USP occurs as a white to pale yellow powder that is very soluble in water, freely soluble in alcohol and chloroform, slightly soluble in ether, practically insoluble in cyclohexane. Colchicine Tablets, USP are supplied for oral administration as purple color, film-coated, capsule shaped tablets debossed with ‘ 372’ on one side and score line on the other side of the tablet. Each tablet contains 0.6 mg of the active ingredient colchicine USP. Inactive ingredients: FD&C BLUE #2, FD&C RED #40, hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polydextrose, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin. Colchicine Structural Formula logo"],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Colchicine Tablets USP, 0.6 mg are purple colored, film-coated, capsule shaped tablets debossed with ‘ 372’ on one side and score line on the other side of the tablet. Bottles of 5 NDC 71205-687-05 Bottles of 10 NDC 71205-687-10 Bottles of 21 NDC 71205-687-21 Bottles of 30 NDC 71205-687-30 Bottles of 60 NDC 71205-687-60 Bottles of 90 NDC 71205-687-90 logo 16.2 Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light. DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER."],"spl_medguide":["Medication Guide Colchicine Tablets, USP (KOL-chi-seen) for oral use Read the Medication Guide that comes with colchicine tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about colchicine tablets when you start taking it and at regular checkups. What is the most important information that I should know about colchicine tablets? Colchicine tablets can cause serious side effects or death if levels of colchicine are too high in your body. • Taking certain medicines with colchicine tablets can cause your level of colchicine to be too high, especially if you have kidney or liver problems. • Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of colchicine tablets may need to be changed. • Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. • Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine tablets and cause serious side effects or death. • Talk to your healthcare provider or pharmacist before taking any new medicine. • Especially tell your healthcare provider if you take: • atazanavir sulfate (Reyataz) • cyclosporine (Neoral, Gengraf, Sandimmune) • fosamprenavir (Lexiva) with ritonavir • indinavir (Crixivan) • ketoconazole (Nizoral) • nefazodone (Serzone) • ritonavir (Norvir) • telithromycin (Ketek) • clarithromycin (Biaxin) • darunavir (Prezista) • fosamprenavir (Lexiva) • itraconazole (Sporanox) • lopinavir/ritonavir (Kaletra) • nelfinavir mesylate (Viracept) • saquinavir mesylate (Invirase) • tipranavir (Aptivus) Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can interact with colchicine tablets. • Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. • Keep colchicine tablets out of the reach of children. What are colchicine tablets? Colchicine tablets are a prescription medicine used to: • prevent and treat gout flares in adults • treat familial Mediterranean fever (FMF) in adults and children age 4 or older Colchicine tablets are not a pain medicine, and it should not be taken to treat pain related to other conditions unless specifically prescribed for those conditions. Who should not take colchicine tablets? Do not take colchicine tablets if you have liver or kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these patients even when taken as directed. See “What is the most important information that I should know about colchicine tablets?” What should I tell my healthcare provider before starting colchicine tablets? See “What is the most important information that I should know about colchicine tablets?” Before you take colchicine tablets, tell your healthcare provider about all your medical conditions, including if you: • have liver or kidney problems. • are pregnant or plan to become pregnant. It is not known if colchicine tablets will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. • are a male with a female partner who can become pregnant. Receiving treatment with colchicine tablets may be related to infertility in some men that is reversible when treatment is stopped. • are breastfeeding or plan to breastfeed. Colchicine passes into your breast milk. You and your healthcare provider should decide if you will take colchicine tablets while breastfeeding. If you take colchicine tablets and breastfeed, you should talk to your child’s healthcare provider about how to watch for side effects in your child. Tell your healthcare provider about all the medicines you take, including ones that you may only be taking for a short time, such as antibiotics. See “What is the most important information that I should know about colchicine tablets?” Do not start a new medicine without talking to your healthcare provider. Using colchicine tablets with certain other medicines, such as cholesterol-lowering medications and digoxin, can affect each other, causing serious side effects. Your healthcare provider may need to change your dose of colchicine tablets. Talk to your healthcare provider about whether the medications you are taking might interact with colchicine tablets and what side effects to look for. How should I take colchicine tablets? • Take colchicine tablets exactly as your healthcare provider tells you to take it. If you are not sure about your dosing , call your healthcare provider. • Colchicine tablets can be taken with or without food. • If you take too many colchicine tablets, go to the nearest hospital emergency room right away. • Do not stop taking colchicine tablets even if you start to feel better, unless your healthcare provider tells you. • Your healthcare provider may do blood tests while you take colchicine tablets. • If you take colchicine tablets daily and you miss a dose, then take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time. o If you have a gout flare while taking colchicine tablets daily, report this to your healthcare provider. What should I avoid while taking colchicine tablets? Avoid eating grapefruit or drinking grapefruit juice while taking colchicine tablets. It can increase your chances of getting serious side effects. What are the possible side effects of colchicine tablets? Colchicine tablets can cause serious side effects or even cause death. See “What is the most important information that I should know about colchicine tablets?” Get medical help right away if you have: • Muscle weakness or pain • Numbness or tingling in your fingers or toes • Unusual bleeding or bruising • Increased infections • Feel weak or tired • Pale or gray color to your lips, tongue or palms of your hands • Severe diarrhea or vomiting Gout Flares: The most common side effect of colchicine tablets in people who have gout flares is diarrhea. FMF: The most common side effects of colchicine tablets in people who have FMF are abdominal pain, diarrhea, nausea and vomiting. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of colchicine tablets. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store colchicine tablets? • Store colchicine tablets at room temperature between 20° to 25°C (68° to 77°F). • Keep colchicine tablets in a tightly closed container. • Keep colchicine tablets out of the light. Keep colchicine tablets and all medicines out of the reach of children. General Information about colchicine tablets Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use colchicine tablets for a condition for which it was not prescribed. Do not give colchicine tablets to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about colchicine tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about colchicine tablets that is written for healthcare professionals. What are the ingredients in colchicine tablets? Active Ingredient: colchicine. Inactive Ingredients: FD&C BLUE #2, FD&C RED #40, hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polydextrose, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin. All other trademarks are the property of their respective owners. For more information, call Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784. Rx Only Distributor: Dr. Reddy’s Laboratories Inc., Princeton, NJ 08540 Made in India Repackaged and Relabeled by: Proficient Rx LP Thousand Oaks, CA 91320 This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 03/2021"],"geriatric_use":["8.5 Geriatric Use Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] ."],"pediatric_use":["8.4 Pediatric Use The safety and efficacy of colchicine in children of all ages with FMF has been evaluated in uncontrolled studies. There does not appear to be an adverse effect on growth in children with FMF treated long-term with colchicine. Safety and effectiveness of colchicine in pediatric patients with gout has not been established."],"effective_time":"20250701","clinical_studies":["14 CLINICAL STUDIES The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate-lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares. The efficacy of a low-dosage regimen of oral colchicine (colchicine tablets total dose 1.8 mg over one hour) for treatment of gout flares was assessed in a multicenter, randomized, double-blind, placebo-controlled, parallel group, one week, dose-comparison study. Patients meeting American College of Rheumatology criteria for gout were randomly assigned to three groups: high-dose colchicine (1.2 mg, then 0.6 mg hourly x 6 hours [4.8 mg total]); low-dose colchicine (1.2 mg, then 0.6 mg in one hour [1.8 mg total] followed by five placebo doses hourly); or placebo (two capsules, then one capsule hourly x six hours). Patients took the first dose within 12 hours of the onset of the flare and recorded pain intensity (11-point Likert scale) and adverse events over 72 hours. The efficacy of colchicine was measured based on response to treatment in the target joint, using patient self-assessment of pain at 24 hours following the time of first dose as recorded in the diary. A responder was one who achieved at least a 50% reduction in pain score at the 24-hour postdose assessment relative to the pretreatment score and did not use rescue medication prior to the actual time of 24-hour postdose assessment. Rates of response were similar for the recommended low-dose treatment group (38%) and the nonrecommended high-dose group (33%) but were higher as compared to the placebo group (16%) as shown in Table 8. Table 8. Number (%) of Responders Based on Target Joint Pain Score at 24 Hours Post First Dose Colchicine Tablets Dose Responders n (%) Low-Dose High-Dose (n = 74) (n = 52) Placebo n (%) (n = 58) % Differences in Proportion Low-Dose High-Dose vs Placebo vs Placebo (95% Cl) (95% Cl) 28 (38%) 17 (33%) 9 (16%) 22 (8, 37) 17 (1, 33) Figure 1 shows the percentage of patients achieving varying degrees of improvement in pain from baseline at 24 hours. Figure 1: Pain Relief on Low and High Doses of Colchicine Tablets and Placebo (Cumulative) The evidence for the efficacy of colchicine in patients with FMF is derived from the published literature. Three randomized, placebo-controlled studies were identified. The three placebo-controlled studies randomized a total of 48 adult patients diagnosed with FMF and reported similar efficacy endpoints as well as inclusion and exclusion criteria. One of the studies randomized 15 patients with FMF to a six month crossover study during which five patients discontinued due to study noncompliance. The ten patients completing the study experienced five attacks over the course of 90 days while treated with colchicine compared to 59 attacks over the course of 90 days while treated with placebo. Similarly, the second study randomized 22 patients with FMF to a four month crossover study during which nine patients discontinued due to lack of efficacy while receiving placebo or study noncompliance. The 13 patients completing the study experienced 18 attacks over the course of 60 days while treated with colchicine compared to 68 attacks over the course of 60 days while treated with placebo. The third study was discontinued after an interim analysis of six of the 11 patients enrolled had completed the study; results could not be confirmed. Open-label experience with colchicine in adults and children with FMF is consistent with the randomized, controlled trial experience and was utilized to support information on the safety profile of colchicine and for dosing recommendations. Figure 1: Pain Relief on Low and High Doses of Colchicine Tablets and Placebo (Cumulative)"],"pharmacokinetics":["12.3 Pharmacokinetics Absorption In healthy adults, colchicine tablets are absorbed when given orally, reaching a mean C max of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) in one to two hours (range 0.5 to 3 hours) after a single dose administered under fasting conditions. Following oral administration of colchicine tablets given as 1.8 mg colchicine over one hour to healthy, young adults under fasting conditions, colchicine appears to be readily absorbed, reaching mean maximum plasma concentrations of 6.2 ng/mL at a median 1.81 hours (range: 1.0 to 2.5 hours). Following administration of the nonrecommended high-dose regimen (4.8 mg over six hours), mean maximal plasma concentrations were 6.8 ng/mL, at a median 4.47 hours (range: 3.1 to 7.5 hours). After ten days on a regimen of 0.6 mg twice daily, peak concentrations are 3.1 to 3.6 ng/mL (range 1.6 to 6.0 ng/mL), occurring 1.3 to 1.4 hours postdose (range 0.5 to 3.0 hours). Mean pharmacokinetic parameter values in healthy adults are shown in Table 5. Table 5. Mean (% CV) Pharmacokinetic Parameters in Healthy Adults Given Colchicine Tablets C max (Colchicine ng/mL) T max T max mean (range) CL = Dose/AUC 0-t (calculated from mean values) Vd = CL/Ke (calculated from mean values) (h) Vd/F (L) CL/F (L/hr) t 1/2 (h) Colchicine Tablets 0.6 mg Single Dose (N = 13) 2.5 (28.7) 1.5 (1.0 - 3.0) 341.5 (54.4) 54.1 (31.0) -- Colchicine Tablets 0.6 mg Twice Daily x 10 Days (N = 13) 3.6 (23.7) 1.3 (0.5 - 3.0) 1150 (18.7) 30.3 (19.0) 26.6 (16.3) In some subjects, secondary colchicine peaks are seen, occurring between three and 36 hours postdose and ranging from 39 to 155% of the height of the initial peak. These observations are attributed to intestinal secretion and reabsorption and/or biliary recirculation. Absolute bioavailability is reported to be approximately 45%. Administration of colchicine tablets with food has no effect on the rate of colchicine absorption but does decrease the extent of colchicine by approximately 15%. This is without clinical significance. Distribution The mean apparent volume of distribution in healthy young volunteers is approximately 5 to 8 L/kg. Colchicine binding to serum protein is low, 39 ± 5%, primarily to albumin regardless of concentration. Colchicine crosses the placenta (plasma levels in the fetus are reported to be approximately 15% of the maternal concentration). Colchicine also distributes into breast milk at concentrations similar to those found in the maternal serum [see Use in Specific Populations (8.1 , 8.2) ] . Metabolism Colchicine is demethylated to two primary metabolites, 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively) and one minor metabolite, 10-O-demethylcolchicine (also known as colchicine). In vitro studies using human liver microsomes have shown that CYP3A4 is involved in the metabolism of colchicine to 2- and 3-DMC. Plasma levels of these metabolites are minimal (less than 5% of parent drug). Elimination/Excretion In healthy volunteers (n = 12), 40 to 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination. Following multiple oral doses (0.6 mg twice daily), the mean elimination half-lives in young healthy volunteers (mean age 25 to 28 years of age) is 26.6 to 31.2 hours. Colchicine is a substrate of P-gp. Extracorporeal Elimination Colchicine is not removed by hemodialysis. Special Populations There is no difference between men and women in the pharmacokinetic disposition of colchicine. Pediatric Patients Pharmacokinetics of colchicine was not evaluated in pediatric patients. Elderly A published report described the pharmacokinetics of 1 mg oral colchicine tablet in four elderly women compared to six young healthy males. The mean age of the four elderly women was 83 years (range 75 to 93), mean weight was 47 kg (38 to 61 kg) and mean creatinine clearance was 46 mL/min (range 25 to 75 mL/min). Mean peak plasma levels and AUC of colchicine were two times higher in elderly subjects compared to young healthy males. A pharmacokinetic study using a single oral dose of one 0.6 mg colchicine tablet was conducted in young healthy subjects (n = 20) between the ages of 18 and 30 years and elderly subjects (n = 18) between the ages of 60 and 70 years. Elderly subjects in this study had a median age of 62 years and a mean (± SD) age of 62.83 ± 2.83 years. A statistically significant difference in creatinine clearance (mean ± SD) was found between the two age groups (132.56 ± 23.16 mL/min for young vs 87.02 ± 17.92 mL/min for elderly subjects, respectively). The following pharmacokinetic parameter values (mean ± SD) were observed for colchicine in the young and elderly subjects, respectively: AUC 0-inf (ng/hr/mL) 22.39 ± 6.95 and 25.01 ± 6.92; C max (ng/mL) 2.61 ± 0.71 and 2.56 ± 0.97; T max (hr) 1.38 ± 0.42 and 1.25 ± 0.43; apparent elimination half-life (hr) 24.92 ± 5.34 and 30.06 ± 10.78; and clearance (mL/min) 0.0321 ± 0.0091 and 0.0292 ± 0.0071. Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Renal Impairment Pharmacokinetics of colchicine in patients with mild and moderate renal impairment is not known. A published report described the disposition of colchicine (1 mg) in young adult men and women with FMF who had normal renal function or end-stage renal disease requiring dialysis. Patients with end-stage renal disease had 75% lower colchicine clearance (0.17 vs 0.73 L/hr/kg) and prolonged plasma elimination half-life (18.8 vs 4.4 hours) as compared to subjects with FMF and normal renal function [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Hepatic Impairment Published reports on the pharmacokinetics of IV colchicine in patients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis and normal renal function suggest wide interpatient variability. In some subjects with mild to moderate cirrhosis, the clearance of colchicine is significantly reduced and plasma half-life prolonged compared to healthy subjects. In subjects with primary biliary cirrhosis, no consistent trends were noted [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . No pharmacokinetic data are available for patients with severe hepatic impairment (Child-Pugh C). Drug Interactions In Vitro Drug Interactions In vitro studies in human liver microsomes have shown that colchicine is not an inhibitor or inducer of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 activity. In Vivo Drug Interactions The effects of coadministration of other drugs with colchicine tablets on C max , AUC and C min are summarized in Table 6 (effect of other drugs on colchicine) and Table 7 (effect of colchicine on other drugs). For information regarding clinical recommendations, see Table 1 in Dose Modification for Coadministration of Interacting Drugs [see Error! Hyperlink reference not valid. ] . Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug Coadministered Drug Dose of Coadministered Drug (mg) Dose of Colchicine Tablets (mg) N % Change in Colchicine Concentrations from Baseline (Range: Min – Max) C max AUC 0-t Cyclosporine 100 mg single dose 0.6 mg single dose 23 270.0 (62.0 to 606.9) 259.0 (75.8 to 511.9) Clarithromycin 250 mg twice daily, 7 days 0.6 mg single dose 23 227.2 (65.7 to 591.1) 281.5 (88.7 to 851.6) Ketoconazole 200 mg twice daily, 5 days 0.6 mg single dose 24 101.7 (19.6 to 219.0) 212.2 (76.7 to 419.6) Ritonavir 100 mg twice daily, 5 days 0.6 mg single dose 18 184.4 (79.2 to 447.4) 296.0 (53.8 to 924.4) Verapamil 240 mg daily, 5 days 0.6 mg single dose 24 40.1 (-47.1 to 149.5) 103.3 (-9.8 to 217.2) Diltiazem 240 mg daily, 7 days 0.6 mg single dose 20 44.2 (-46.0 to 318.3) 93.4 (-30.2 to 338.6) Azithromycin 500 mg x 1 day, then 250 mg x 4 days 0.6 mg single dose 21 21.6 (-41.7 to 222.0) 57.1 (-24.3 to 241.1) Grapefruit juice 240 mL twice daily, 4 days 0.6 mg single dose 21 -2.55 (-53.4 to 55.0) -2.36 (-46.4 to 62.2) Estrogen-containing oral contraceptives: In healthy female volunteers given ethinyl estradiol and norethindrone (Ortho-Novum ® 1/35) coadministered with colchicine tablets (0.6 mg twice daily × 14 days), hormone concentrations are not affected. In healthy volunteers given theophylline coadministered with colchicine tablets (0.6 mg twice daily × 14 days), theophylline concentrations were not affected. Table 7. Drug Interactions: Pharmacokinetic Parameters for Coadministration of Drug in the Presence of Colchicine Tablets Coadministered Drug Dose of Coadministered Drug (mg) Dose of Colchicine Tablets (mg) N % Change in Coadministered Drug Concentrations from Baseline (Range: Min – Max) C max AUC 0-t Theophylline 300 mg (elixir) single dose 0.6 mg twice daily x 14 days 27 1.6 (-30.4 to 23.1) 1.6 (-28.5 to 27.1) Ethinyl Estradiol (Ortho-Novum ® 1/35) 21-day cycle (active treatment) + 7-day placebo 0.6 mg twice daily x 14 days 27 Conducted in healthy adult females -6.7 (-40.3 to 44.7) -3.0 AUC Ʈ (-25.3 to 24.9) Norethindrone (Ortho-Novum ® 1/35) 0.94 (-37.3 to 59.4) -1.6 (-32.0 to 33.7)"],"adverse_reactions":["6 ADVERSE REACTIONS Prophylaxis of Gout Flares: The most commonly reported adverse reaction in clinical trials of colchicine for the prophylaxis of gout was diarrhea. Treatment of Gout Flares: The most common adverse reactions reported in the clinical trial with colchicine tablets for treatment of gout flares were diarrhea (23%) and pharyngolaryngeal pain (3%). FMF: Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating colchicine tablets, usually presenting within 24 hours, and occurring in up to 20% of patients given therapeutic doses. Typical symptoms include cramping, nausea, diarrhea, abdominal pain and vomiting. These events should be viewed as dose-limiting if severe, as they can herald the onset of more significant toxicity. • Prophylaxis of Gout Flares: The most commonly reported adverse reaction in clinical trials for the prophylaxis of gout was diarrhea. • Treatment of Gout Flares: The most common adverse reactions reported in the clinical trial for gout were diarrhea (23%) and pharyngolaryngeal pain (3%). • FMF: Most common adverse reactions (up to 20%) are abdominal pain, diarrhea, nausea and vomiting. These effects are usually mild, transient and reversible upon lowering the dose ( Error! Hyperlink reference not valid. ). To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc., at 1-888- 375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience in Gout Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice. In a randomized, double-blind, placebo-controlled trial in patients with a gout flare, gastrointestinal adverse reactions occurred in 26% of patients using the recommended dose (1.8 mg over one hour) of colchicine tablets compared to 77% of patients taking a nonrecommended high dose (4.8 mg over six hours) of colchicine and 20% of patients taking placebo. Diarrhea was the most commonly reported drug-related gastrointestinal adverse event. As shown in Table 3, diarrhea is associated with colchicine tablets treatment. Diarrhea was more likely to occur in patients taking the high-dose regimen than the low-dose regimen. Severe diarrhea occurred in 19% and vomiting occurred in 17% of patients taking the nonrecommended high-dose colchicine regimen but did not occur in the recommended low-dose colchicine tablets regimen. Table 3. Number (%) of Patients with at Least One Drug-Related Treatment-Emergent Adverse Event with an Incidence of ≥ 2% of Patients in Any Treatment Group MedDRA System Organ Class MedDRA Preferred Term Colchicine Tablets Dose Placebo (N = 59) n (%) High (N= 52) n (%) Low (N = 74) n (%) Number of Patients with at Least One Drug-Related TEAE 40 (77) 27 (37) 16 (27) Gastrointestinal Disorders 40 (77) 19 (26) 12 (20) Diarrhea 40 (77) 17 (23) 8 (14) Nausea 9 (17) 3 (4) 3 (5) Vomiting 9 (17) 0 0 Abdominal Discomfort 0 0 2 (3) General Disorders and Administration Site Conditions 4 (8) 1 (1) 1 (2) Fatigue 2 (4) 1 (1) 1 (2) Metabolic and Nutrition Disorders 0 3 (4) 2 (3) Gout 0 3 (4) 1 (2) Nervous System Disorders 1 (2) 1 (1.4) 2 (3) Headache 1 (2) 1 (1) 2 (3) Respiratory Thoracic Mediastinal Disorders 1 (2) 2 (3) 0 Pharyngolaryngeal Pain 1 (2) 2 (3) 0 6.2 Postmarketing Experience Serious toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems. These most often occur with excessive accumulation or overdosage [see Error! Hyperlink reference not valid. ] . The following adverse reactions have been identified with colchicine. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of colchicine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Neurological: sensory motor neuropathy Dermatological: alopecia, maculopapular rash, purpura, rash Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia Hepatobiliary: elevated AST, elevated ALT Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis Reproductive: azoospermia, oligospermia"],"contraindications":["4 CONTRAINDICATIONS Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir). In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses. Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors ( Error! Hyperlink reference not valid. ). In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses ( Error! Hyperlink reference not valid. )."],"drug_interactions":["7 DRUG INTERACTIONS Colchicine is a substrate of the efflux transporter P-glycoprotein (P-gp). Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine. If colchicine tablets are administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely. Fatal drug interactions have been reported. Physicians should ensure that patients are suitable candidates for treatment with colchicine tablets and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction. Signs and symptoms of colchicine tablets toxicity should be evaluated promptly and, if toxicity is suspected, colchicine tablets should be discontinued immediately. Table 4 provides recommendations as a result of other potentially significant drug interactions. Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors. Table 4. Other Potentially Significant Drug Interactions Concomitant Drug Class or Food Noted or Anticipated Outcome Clinical Comment HMG-CoA Reductase Inhibitors: atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality) Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy. Other Lipid-Lowering Drugs: fibrates, gemfibrozil Digitalis Glycosides: digoxin P-gp substrate; rhabdomyolysis has been reported Coadministration of P-gp and/or CYP3A4 inhibitors (e.g., clarithromycin or cyclosporine) have been demonstrated to alter the concentration of colchicine. The potential for drug-drug interactions must be considered prior to and during therapy. See FPI for a complete list of reported and potential interactions ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ).","Drug Interactions In Vitro Drug Interactions In vitro studies in human liver microsomes have shown that colchicine is not an inhibitor or inducer of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 activity. In Vivo Drug Interactions The effects of coadministration of other drugs with colchicine tablets on C max , AUC and C min are summarized in Table 6 (effect of other drugs on colchicine) and Table 7 (effect of colchicine on other drugs). For information regarding clinical recommendations, see Table 1 in Dose Modification for Coadministration of Interacting Drugs [see Error! Hyperlink reference not valid. ] . Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug Coadministered Drug Dose of Coadministered Drug (mg) Dose of Colchicine Tablets (mg) N % Change in Colchicine Concentrations from Baseline (Range: Min – Max) C max AUC 0-t Cyclosporine 100 mg single dose 0.6 mg single dose 23 270.0 (62.0 to 606.9) 259.0 (75.8 to 511.9) Clarithromycin 250 mg twice daily, 7 days 0.6 mg single dose 23 227.2 (65.7 to 591.1) 281.5 (88.7 to 851.6) Ketoconazole 200 mg twice daily, 5 days 0.6 mg single dose 24 101.7 (19.6 to 219.0) 212.2 (76.7 to 419.6) Ritonavir 100 mg twice daily, 5 days 0.6 mg single dose 18 184.4 (79.2 to 447.4) 296.0 (53.8 to 924.4) Verapamil 240 mg daily, 5 days 0.6 mg single dose 24 40.1 (-47.1 to 149.5) 103.3 (-9.8 to 217.2) Diltiazem 240 mg daily, 7 days 0.6 mg single dose 20 44.2 (-46.0 to 318.3) 93.4 (-30.2 to 338.6) Azithromycin 500 mg x 1 day, then 250 mg x 4 days 0.6 mg single dose 21 21.6 (-41.7 to 222.0) 57.1 (-24.3 to 241.1) Grapefruit juice 240 mL twice daily, 4 days 0.6 mg single dose 21 -2.55 (-53.4 to 55.0) -2.36 (-46.4 to 62.2) Estrogen-containing oral contraceptives: In healthy female volunteers given ethinyl estradiol and norethindrone (Ortho-Novum ® 1/35) coadministered with colchicine tablets (0.6 mg twice daily × 14 days), hormone concentrations are not affected. In healthy volunteers given theophylline coadministered with colchicine tablets (0.6 mg twice daily × 14 days), theophylline concentrations were not affected. Table 7. Drug Interactions: Pharmacokinetic Parameters for Coadministration of Drug in the Presence of Colchicine Tablets Coadministered Drug Dose of Coadministered Drug (mg) Dose of Colchicine Tablets (mg) N % Change in Coadministered Drug Concentrations from Baseline (Range: Min – Max) C max AUC 0-t Theophylline 300 mg (elixir) single dose 0.6 mg twice daily x 14 days 27 1.6 (-30.4 to 23.1) 1.6 (-28.5 to 27.1) Ethinyl Estradiol (Ortho-Novum ® 1/35) 21-day cycle (active treatment) + 7-day placebo 0.6 mg twice daily x 14 days 27 Conducted in healthy adult females -6.7 (-40.3 to 44.7) -3.0 AUC Ʈ (-25.3 to 24.9) Norethindrone (Ortho-Novum ® 1/35) 0.94 (-37.3 to 59.4) -1.6 (-32.0 to 33.7)"],"spl_medguide_table":["Taking certain medicines with colchicine tablets can cause your level of colchicine to be too high, especially if you have kidney or liver problems. Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of colchicine tablets may need to be changed. Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine tablets and cause serious side effects or death. Talk to your healthcare provider or pharmacist before taking any new medicine. Especially tell your healthcare provider if you take: atazanavir sulfate (Reyataz)cyclosporine (Neoral, Gengraf, Sandimmune)fosamprenavir (Lexiva) with ritonavirindinavir (Crixivan)ketoconazole (Nizoral)nefazodone (Serzone)ritonavir (Norvir)telithromycin (Ketek)clarithromycin (Biaxin)darunavir (Prezista)fosamprenavir (Lexiva)itraconazole (Sporanox)lopinavir/ritonavir (Kaletra)nelfinavir mesylate (Viracept)saquinavir mesylate (Invirase)tipranavir (Aptivus)Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. Keep colchicine tablets out of the reach of children.prevent and treat gout flares in adultstreat familial Mediterranean fever (FMF) in adults and children age 4 or older Colchicine tablets are not a pain medicine, and it should not be taken to treat pain related to other conditions unless specifically prescribed for those conditions.have liver or kidney problems. are pregnant or plan to become pregnant. It is not known if colchicine tablets will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. are a male with a female partner who can become pregnant. Receiving treatment with colchicine tablets may be related to infertility in some men that is reversible when treatment is stopped. are breastfeeding or plan to breastfeed. Colchicine passes into your breast milk. You and your healthcare provider should decide if you will take colchicine tablets while breastfeeding. If you take colchicine tablets and breastfeed, you should talk to your child’s healthcare provider about how to watch for side effects in your child. Tell your healthcare provider about all the medicines you take, including ones that you may only be taking for a short time, such as antibiotics. See “What is the most important information that I should know about colchicine tablets?” Do not start a new medicine without talking to your healthcare provider. Using colchicine tablets with certain other medicines, such as cholesterol-lowering medications and digoxin, can affect each other, causing serious side effects. Your healthcare provider may need to change your dose of colchicine tablets. Talk to your healthcare provider about whether the medications you are taking might interact with colchicine tablets and what side effects to look for. Take colchicine tablets exactly as your healthcare provider tells you to take it. If you are not sure about your dosing, call your healthcare provider. Colchicine tablets can be taken with or without food. If you take too many colchicine tablets, go to the nearest hospital emergency room right away. Do not stop taking colchicine tablets even if you start to feel better, unless your healthcare provider tells you. Your healthcare provider may do blood tests while you take colchicine tablets. If you take colchicine tablets daily and you miss a dose, then take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time. If you have a gout flare while taking colchicine tablets daily, report this to your healthcare provider.Muscle weakness or pain Numbness or tingling in your fingers or toes Unusual bleeding or bruising Increased infections Feel weak or tired Pale or gray color to your lips, tongue or palms of your hands Severe diarrhea or vomiting Gout Flares: The most common side effect of colchicine tablets in people who have gout flares is diarrhea. FMF: The most common side effects of colchicine tablets in people who have FMF are abdominal pain, diarrhea, nausea and vomiting. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of colchicine tablets. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Store colchicine tablets at room temperature between 20° to 25°C (68° to 77°F). Keep colchicine tablets in a tightly closed container. Keep colchicine tablets out of the light. Keep colchicine tablets and all medicines out of the reach of children.
Colchicine Tablets, USP(KOL-chi-seen)for oral use
Read the Medication Guide that comes with colchicine tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about colchicine tablets when you start taking it and at regular checkups.
What is the most important information that I should know about colchicine tablets? Colchicine tablets can cause serious side effects or death if levels of colchicine are too high in your body.
••••••
••••••••
••••••••
Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can interact with colchicine tablets.
••
What are colchicine tablets? Colchicine tablets are a prescription medicine used to:
••
Who should not take colchicine tablets? Do not take colchicine tablets if you have liver or kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these patients even when taken as directed. See “What is the most important information that I should know about colchicine tablets?”
What should I tell my healthcare provider before starting colchicine tablets? See “What is the most important information that I should know about colchicine tablets?” Before you take colchicine tablets, tell your healthcare provider about all your medical conditions, including if you:
••••
How should I take colchicine tablets?
••••••o
What should I avoid while taking colchicine tablets? Avoid eating grapefruit or drinking grapefruit juice while taking colchicine tablets. It can increase your chances of getting serious side effects.
What are the possible side effects of colchicine tablets? Colchicine tablets can cause serious side effects or even cause death. See “What is the most important information that I should know about colchicine tablets?” Get medical help right away if you have:
•••••••
How should I store colchicine tablets?
•••
General Information about colchicine tablets Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use colchicine tablets for a condition for which it was not prescribed. Do not give colchicine tablets to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about colchicine tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about colchicine tablets that is written for healthcare professionals.
What are the ingredients in colchicine tablets? Active Ingredient: colchicine. Inactive Ingredients: FD&C BLUE #2, FD&C RED #40, hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polydextrose, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin. All other trademarks are the property of their respective owners. For more information, call Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784.
Rx Only Distributor: Dr. Reddy’s Laboratories Inc., Princeton, NJ 08540 Made in IndiaRepackaged and Relabeled by: Proficient Rx LP Thousand Oaks, CA 91320
"],"mechanism_of_action":["12.1 Mechanism of Action The mechanism by which colchicine tablets exert its beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β. Additionally, colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules and consequently prevents the activation, degranulation and migration of neutrophils thought to mediate some gout symptoms."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism by which colchicine tablets exert its beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β. Additionally, colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules and consequently prevents the activation, degranulation and migration of neutrophils thought to mediate some gout symptoms. 12.3 Pharmacokinetics Absorption In healthy adults, colchicine tablets are absorbed when given orally, reaching a mean C max of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) in one to two hours (range 0.5 to 3 hours) after a single dose administered under fasting conditions. Following oral administration of colchicine tablets given as 1.8 mg colchicine over one hour to healthy, young adults under fasting conditions, colchicine appears to be readily absorbed, reaching mean maximum plasma concentrations of 6.2 ng/mL at a median 1.81 hours (range: 1.0 to 2.5 hours). Following administration of the nonrecommended high-dose regimen (4.8 mg over six hours), mean maximal plasma concentrations were 6.8 ng/mL, at a median 4.47 hours (range: 3.1 to 7.5 hours). After ten days on a regimen of 0.6 mg twice daily, peak concentrations are 3.1 to 3.6 ng/mL (range 1.6 to 6.0 ng/mL), occurring 1.3 to 1.4 hours postdose (range 0.5 to 3.0 hours). Mean pharmacokinetic parameter values in healthy adults are shown in Table 5. Table 5. Mean (% CV) Pharmacokinetic Parameters in Healthy Adults Given Colchicine Tablets C max (Colchicine ng/mL) T max T max mean (range) CL = Dose/AUC 0-t (calculated from mean values) Vd = CL/Ke (calculated from mean values) (h) Vd/F (L) CL/F (L/hr) t 1/2 (h) Colchicine Tablets 0.6 mg Single Dose (N = 13) 2.5 (28.7) 1.5 (1.0 - 3.0) 341.5 (54.4) 54.1 (31.0) -- Colchicine Tablets 0.6 mg Twice Daily x 10 Days (N = 13) 3.6 (23.7) 1.3 (0.5 - 3.0) 1150 (18.7) 30.3 (19.0) 26.6 (16.3) In some subjects, secondary colchicine peaks are seen, occurring between three and 36 hours postdose and ranging from 39 to 155% of the height of the initial peak. These observations are attributed to intestinal secretion and reabsorption and/or biliary recirculation. Absolute bioavailability is reported to be approximately 45%. Administration of colchicine tablets with food has no effect on the rate of colchicine absorption but does decrease the extent of colchicine by approximately 15%. This is without clinical significance. Distribution The mean apparent volume of distribution in healthy young volunteers is approximately 5 to 8 L/kg. Colchicine binding to serum protein is low, 39 ± 5%, primarily to albumin regardless of concentration. Colchicine crosses the placenta (plasma levels in the fetus are reported to be approximately 15% of the maternal concentration). Colchicine also distributes into breast milk at concentrations similar to those found in the maternal serum [see Use in Specific Populations (8.1 , 8.2) ] . Metabolism Colchicine is demethylated to two primary metabolites, 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively) and one minor metabolite, 10-O-demethylcolchicine (also known as colchicine). In vitro studies using human liver microsomes have shown that CYP3A4 is involved in the metabolism of colchicine to 2- and 3-DMC. Plasma levels of these metabolites are minimal (less than 5% of parent drug). Elimination/Excretion In healthy volunteers (n = 12), 40 to 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination. Following multiple oral doses (0.6 mg twice daily), the mean elimination half-lives in young healthy volunteers (mean age 25 to 28 years of age) is 26.6 to 31.2 hours. Colchicine is a substrate of P-gp. Extracorporeal Elimination Colchicine is not removed by hemodialysis. Special Populations There is no difference between men and women in the pharmacokinetic disposition of colchicine. Pediatric Patients Pharmacokinetics of colchicine was not evaluated in pediatric patients. Elderly A published report described the pharmacokinetics of 1 mg oral colchicine tablet in four elderly women compared to six young healthy males. The mean age of the four elderly women was 83 years (range 75 to 93), mean weight was 47 kg (38 to 61 kg) and mean creatinine clearance was 46 mL/min (range 25 to 75 mL/min). Mean peak plasma levels and AUC of colchicine were two times higher in elderly subjects compared to young healthy males. A pharmacokinetic study using a single oral dose of one 0.6 mg colchicine tablet was conducted in young healthy subjects (n = 20) between the ages of 18 and 30 years and elderly subjects (n = 18) between the ages of 60 and 70 years. Elderly subjects in this study had a median age of 62 years and a mean (± SD) age of 62.83 ± 2.83 years. A statistically significant difference in creatinine clearance (mean ± SD) was found between the two age groups (132.56 ± 23.16 mL/min for young vs 87.02 ± 17.92 mL/min for elderly subjects, respectively). The following pharmacokinetic parameter values (mean ± SD) were observed for colchicine in the young and elderly subjects, respectively: AUC 0-inf (ng/hr/mL) 22.39 ± 6.95 and 25.01 ± 6.92; C max (ng/mL) 2.61 ± 0.71 and 2.56 ± 0.97; T max (hr) 1.38 ± 0.42 and 1.25 ± 0.43; apparent elimination half-life (hr) 24.92 ± 5.34 and 30.06 ± 10.78; and clearance (mL/min) 0.0321 ± 0.0091 and 0.0292 ± 0.0071. Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Renal Impairment Pharmacokinetics of colchicine in patients with mild and moderate renal impairment is not known. A published report described the disposition of colchicine (1 mg) in young adult men and women with FMF who had normal renal function or end-stage renal disease requiring dialysis. Patients with end-stage renal disease had 75% lower colchicine clearance (0.17 vs 0.73 L/hr/kg) and prolonged plasma elimination half-life (18.8 vs 4.4 hours) as compared to subjects with FMF and normal renal function [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Hepatic Impairment Published reports on the pharmacokinetics of IV colchicine in patients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis and normal renal function suggest wide interpatient variability. In some subjects with mild to moderate cirrhosis, the clearance of colchicine is significantly reduced and plasma half-life prolonged compared to healthy subjects. In subjects with primary biliary cirrhosis, no consistent trends were noted [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . No pharmacokinetic data are available for patients with severe hepatic impairment (Child-Pugh C). Drug Interactions In Vitro Drug Interactions In vitro studies in human liver microsomes have shown that colchicine is not an inhibitor or inducer of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 activity. In Vivo Drug Interactions The effects of coadministration of other drugs with colchicine tablets on C max , AUC and C min are summarized in Table 6 (effect of other drugs on colchicine) and Table 7 (effect of colchicine on other drugs). For information regarding clinical recommendations, see Table 1 in Dose Modification for Coadministration of Interacting Drugs [see Error! Hyperlink reference not valid. ] . Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug Coadministered Drug Dose of Coadministered Drug (mg) Dose of Colchicine Tablets (mg) N % Change in Colchicine Concentrations from Baseline (Range: Min – Max) C max AUC 0-t Cyclosporine 100 mg single dose 0.6 mg single dose 23 270.0 (62.0 to 606.9) 259.0 (75.8 to 511.9) Clarithromycin 250 mg twice daily, 7 days 0.6 mg single dose 23 227.2 (65.7 to 591.1) 281.5 (88.7 to 851.6) Ketoconazole 200 mg twice daily, 5 days 0.6 mg single dose 24 101.7 (19.6 to 219.0) 212.2 (76.7 to 419.6) Ritonavir 100 mg twice daily, 5 days 0.6 mg single dose 18 184.4 (79.2 to 447.4) 296.0 (53.8 to 924.4) Verapamil 240 mg daily, 5 days 0.6 mg single dose 24 40.1 (-47.1 to 149.5) 103.3 (-9.8 to 217.2) Diltiazem 240 mg daily, 7 days 0.6 mg single dose 20 44.2 (-46.0 to 318.3) 93.4 (-30.2 to 338.6) Azithromycin 500 mg x 1 day, then 250 mg x 4 days 0.6 mg single dose 21 21.6 (-41.7 to 222.0) 57.1 (-24.3 to 241.1) Grapefruit juice 240 mL twice daily, 4 days 0.6 mg single dose 21 -2.55 (-53.4 to 55.0) -2.36 (-46.4 to 62.2) Estrogen-containing oral contraceptives: In healthy female volunteers given ethinyl estradiol and norethindrone (Ortho-Novum ® 1/35) coadministered with colchicine tablets (0.6 mg twice daily × 14 days), hormone concentrations are not affected. In healthy volunteers given theophylline coadministered with colchicine tablets (0.6 mg twice daily × 14 days), theophylline concentrations were not affected. Table 7. Drug Interactions: Pharmacokinetic Parameters for Coadministration of Drug in the Presence of Colchicine Tablets Coadministered Drug Dose of Coadministered Drug (mg) Dose of Colchicine Tablets (mg) N % Change in Coadministered Drug Concentrations from Baseline (Range: Min – Max) C max AUC 0-t Theophylline 300 mg (elixir) single dose 0.6 mg twice daily x 14 days 27 1.6 (-30.4 to 23.1) 1.6 (-28.5 to 27.1) Ethinyl Estradiol (Ortho-Novum ® 1/35) 21-day cycle (active treatment) + 7-day placebo 0.6 mg twice daily x 14 days 27 Conducted in healthy adult females -6.7 (-40.3 to 44.7) -3.0 AUC Ʈ (-25.3 to 24.9) Norethindrone (Ortho-Novum ® 1/35) 0.94 (-37.3 to 59.4) -1.6 (-32.0 to 33.7)"],"indications_and_usage":["1 INDICATIONS AND USAGE Colchicine tablets are an alkaloid indicated for: • Prophylaxis and treatment of gout flares in adults ( 1.1 ). • Familial Mediterranean fever (FMF) in adults and children 4 years or older ( Error! Hyperlink reference not valid. ). 1.1 Gout Flares Colchicine tablets are indicated for prophylaxis and the treatment of acute gout flares. • Prophylaxis of Gout Flares: Colchicine tablets are indicated for prophylaxis of gout flares. • Treatment of Gout Flares: Colchicine tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare. 1.2 Familial Mediterranean Fever (FMF) Colchicine tablets are indicated in adults and children four years or older for treatment of familial Mediterranean fever (FMF)."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS • Fatal overdoses have been reported with colchicine in adults and children. Keep colchicine tablets out of the reach of children ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Blood dyscrasias: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia and aplastic anemia have been reported ( Error! Hyperlink reference not valid. ). • Monitor for toxicity and if present consider temporary interruption or discontinuation of colchicine ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Drug interaction P-gp and/or CYP3A4 inhibitors: Coadministration of colchicine with P-gp and/or strong CYP3A4 inhibitors has resulted in life-threatening interactions and death ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect. Consider temporary interruption or discontinuation of colchicine tablets ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). 5.1 Fatal Overdose Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Error! Hyperlink reference not valid. ] . Colchicine tablets should be kept out of the reach of children. 5.2 Blood Dyscrasias Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses. 5.3 Drug Interactions Colchicine is a P-gp and CYP3A4 substrate. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp and strong CYP3A4 inhibitors. If treatment with a P-gp or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patient’s dose of colchicine may need to be reduced or interrupted [see Error! Hyperlink reference not valid. ] . Use of colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see Error! Hyperlink reference not valid. ]. 5.4 Neuromuscular Toxicity Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, gemfibrozil, fenofibrate, fenofibric acid or benzafibrate (themselves associated with myotoxicity) or cyclosporine with colchicine tablets may potentiate the development of myopathy [see Error! Hyperlink reference not valid. ] . Once colchicine is stopped, the symptoms generally resolve within one week to several months."],"clinical_studies_table":["
Table 8. Number (%) of Responders Based on Target Joint Pain Score at 24 Hours Post First Dose
Colchicine Tablets DoseResponders n (%)Low-Dose High-Dose(n = 74) (n = 52)Placebon (%)(n = 58)% Differences in ProportionLow-Dose High-Dosevs Placebo vs Placebo(95% Cl) (95% Cl)
28 (38%) 17 (33%)9 (16%)22 (8, 37) 17 (1, 33)
"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two year studies were conducted in mice and rats to assess the carcinogenic potential of colchicine. No evidence of colchicine-related tumorigenicity was observed in mice or rats at colchicine oral doses up to 3 and 2 mg/kg/day, respectively (approximately six and eight times, respectively, the maximum recommended human dose of 2.4 mg on a mg/m 2 basis). Mutagenesis Colchicine was negative for mutagenicity in the bacterial reverse mutation assay. In a chromosomal aberration assay in cultured human white blood cells, colchicine treatment resulted in the formation of micronuclei. Since published studies demonstrated that colchicine induces aneuploidy from the process of mitotic nondisjunction without structural DNA changes, colchicine is not considered clastogenic, although micronuclei are formed. Impairment of Fertility No studies of colchicine effects on fertility were conducted with colchicine tablets. However, published nonclinical studies demonstrated that colchicine-induced disruption of microtubule formation affects meiosis and mitosis. Reproductive studies also reported abnormal sperm morphology and reduced sperm counts in males, and interference with sperm penetration, second meiotic division and normal cleavage in females when exposed to colchicine. Colchicine administered to pregnant animals resulted in fetal death and teratogenicity. These effects were dose-dependent, with the timing of exposure critical for the effects on embryofetal development. The nonclinical doses evaluated were generally higher than an equivalent human therapeutic dose, but safety margins for reproductive and developmental toxicity could not be determined."],"pharmacokinetics_table":["
Table 5. Mean (% CV) Pharmacokinetic Parameters in Healthy Adults Given Colchicine Tablets
Cmax(Colchicine ng/mL)TmaxTmax mean (range) CL = Dose/AUC0-t (calculated from mean values) Vd = CL/Ke (calculated from mean values)(h)Vd/F(L)CL/F(L/hr)t1/2(h)
Colchicine Tablets 0.6 mg Single Dose (N = 13)
2.5(28.7)1.5(1.0 - 3.0)341.5(54.4)54.1(31.0)--
Colchicine Tablets 0.6 mg Twice Daily x 10 Days (N = 13)
3.6(23.7)1.3(0.5 - 3.0)1150(18.7)30.3(19.0)26.6(16.3)
","
Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug
Coadministered DrugDose of Coadministered Drug (mg)Dose of Colchicine Tablets (mg)N% Change in Colchicine Concentrations from Baseline(Range: Min – Max)
CmaxAUC0-t
Cyclosporine100 mgsingle dose0.6 mgsingle dose23270.0(62.0 to 606.9)259.0(75.8 to 511.9)
Clarithromycin250 mg twice daily, 7 days0.6 mgsingle dose23227.2(65.7 to 591.1)281.5(88.7 to 851.6)
Ketoconazole200 mg twice daily, 5 days0.6 mgsingle dose24101.7(19.6 to 219.0)212.2(76.7 to 419.6)
Ritonavir100 mg twice daily, 5 days0.6 mgsingle dose18184.4(79.2 to 447.4)296.0(53.8 to 924.4)
Verapamil240 mg daily, 5 days0.6 mgsingle dose2440.1(-47.1 to 149.5)103.3(-9.8 to 217.2)
Diltiazem240 mg daily, 7 days0.6 mgsingle dose2044.2(-46.0 to 318.3)93.4(-30.2 to 338.6)
Azithromycin500 mg x 1 day, then250 mg x 4 days0.6 mgsingle dose2121.6(-41.7 to 222.0)57.1(-24.3 to 241.1)
Grapefruit juice240 mL twice daily, 4 days0.6 mgsingle dose21-2.55(-53.4 to 55.0)-2.36(-46.4 to 62.2)
","
Table 7. Drug Interactions: Pharmacokinetic Parameters for Coadministration of Drug in the Presence of Colchicine Tablets
Coadministered DrugDose of Coadministered Drug (mg)Dose of Colchicine Tablets (mg)N% Change in Coadministered Drug Concentrations from Baseline(Range: Min – Max)
CmaxAUC0-t
Theophylline300 mg (elixir)single dose0.6 mg twice daily x 14 days271.6(-30.4 to 23.1)1.6(-28.5 to 27.1)
Ethinyl Estradiol (Ortho-Novum® 1/35)21-day cycle (active treatment)+7-day placebo0.6 mg twice daily x 14 days27Conducted in healthy adult females-6.7(-40.3 to 44.7)-3.0AUCƮ(-25.3 to 24.9)
Norethindrone (Ortho-Novum® 1/35)0.94(-37.3 to 59.4)-1.6 (-32.0 to 33.7)
"],"adverse_reactions_table":["
Table 3. Number (%) of Patients with at Least One Drug-Related Treatment-Emergent Adverse Event with an Incidence of ≥ 2% of Patients in Any Treatment Group
MedDRA System Organ Class MedDRA Preferred TermColchicine Tablets DosePlacebo(N = 59)n (%)
High (N= 52)n (%)Low (N = 74)n (%)
Number of Patients with at Least One Drug-Related TEAE40 (77)27 (37)16 (27)
Gastrointestinal Disorders40 (77)19 (26)12 (20)
Diarrhea40 (77)17 (23)8 (14)
Nausea9 (17)3 (4)3 (5)
Vomiting9 (17)00
Abdominal Discomfort002 (3)
General Disorders and Administration Site Conditions4 (8)1 (1)1 (2)
Fatigue2 (4)1 (1)1 (2)
Metabolic and Nutrition Disorders03 (4)2 (3)
Gout03 (4)1 (2)
Nervous System Disorders1 (2)1 (1.4)2 (3)
Headache1 (2)1 (1)2 (3)
Respiratory Thoracic Mediastinal Disorders1 (2)2 (3)0
Pharyngolaryngeal Pain1 (2)2 (3)0
"],"drug_interactions_table":["
Table 4. Other Potentially Significant Drug Interactions
Concomitant Drug Class or FoodNoted or Anticipated OutcomeClinical Comment
HMG-CoA Reductase Inhibitors:atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatinPharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality)Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy.
Other Lipid-Lowering Drugs:fibrates, gemfibrozil
Digitalis Glycosides: digoxinP-gp substrate; rhabdomyolysis has been reported
","
Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug
Coadministered DrugDose of Coadministered Drug (mg)Dose of Colchicine Tablets (mg)N% Change in Colchicine Concentrations from Baseline(Range: Min – Max)
CmaxAUC0-t
Cyclosporine100 mgsingle dose0.6 mgsingle dose23270.0(62.0 to 606.9)259.0(75.8 to 511.9)
Clarithromycin250 mg twice daily, 7 days0.6 mgsingle dose23227.2(65.7 to 591.1)281.5(88.7 to 851.6)
Ketoconazole200 mg twice daily, 5 days0.6 mgsingle dose24101.7(19.6 to 219.0)212.2(76.7 to 419.6)
Ritonavir100 mg twice daily, 5 days0.6 mgsingle dose18184.4(79.2 to 447.4)296.0(53.8 to 924.4)
Verapamil240 mg daily, 5 days0.6 mgsingle dose2440.1(-47.1 to 149.5)103.3(-9.8 to 217.2)
Diltiazem240 mg daily, 7 days0.6 mgsingle dose2044.2(-46.0 to 318.3)93.4(-30.2 to 338.6)
Azithromycin500 mg x 1 day, then250 mg x 4 days0.6 mgsingle dose2121.6(-41.7 to 222.0)57.1(-24.3 to 241.1)
Grapefruit juice240 mL twice daily, 4 days0.6 mgsingle dose21-2.55(-53.4 to 55.0)-2.36(-46.4 to 62.2)
","
Table 7. Drug Interactions: Pharmacokinetic Parameters for Coadministration of Drug in the Presence of Colchicine Tablets
Coadministered DrugDose of Coadministered Drug (mg)Dose of Colchicine Tablets (mg)N% Change in Coadministered Drug Concentrations from Baseline(Range: Min – Max)
CmaxAUC0-t
Theophylline300 mg (elixir)single dose0.6 mg twice daily x 14 days271.6(-30.4 to 23.1)1.6(-28.5 to 27.1)
Ethinyl Estradiol (Ortho-Novum® 1/35)21-day cycle (active treatment)+7-day placebo0.6 mg twice daily x 14 days27Conducted in healthy adult females-6.7(-40.3 to 44.7)-3.0AUCƮ(-25.3 to 24.9)
Norethindrone (Ortho-Novum® 1/35)0.94(-37.3 to 59.4)-1.6 (-32.0 to 33.7)
"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Error! Hyperlink reference not valid. ). Dosing Instructions: Patients should be advised to take colchicine tablets as prescribed, even if they are feeling better. Patients should not alter the dose or discontinue treatment without consulting with their doctor. If a dose of colchicine tablets is missed: • For treatment of a gout flare when the patient is not being dosed for prophylaxis, take the missed dose as soon as possible. • For treatment of a gout flare during prophylaxis, take the missed dose immediately, wait 12 hours, then resume the previous dosing schedule. • For prophylaxis without treatment for a gout flare, or FMF, take the dose as soon as possible and then return to the normal dosing schedule. However, if a dose is skipped the patient should not double the next dose. Fatal Overdose: Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine. Colchicine tablets should be kept out of the reach of children. Blood Dyscrasias: Patients should be informed that bone marrow depression with agranulocytosis, aplastic anemia and thrombocytopenia may occur with colchicine tablets. Drug and Food Interactions: Patients should be advised that many drugs or other substances may interact with colchicine tablets and some interactions could be fatal. Therefore, patients should report to their healthcare provider all of the current medications they are taking and check with their healthcare provider before starting any new medications, particularly antibiotics. Patients should also be advised to report the use of nonprescription medication or herbal products. Grapefruit and grapefruit juice may also interact and should not be consumed during colchicine tablets treatment. Neuromuscular Toxicity: Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may occur with colchicine tablets alone or when it is used with certain other drugs. Patients developing any of these signs or symptoms must discontinue colchicine tablets and seek medical evaluation immediately. Infertility: Advise males of reproductive potential that colchicine tablets may rarely and transiently impair fertility [see Error! Hyperlink reference not valid. ] ."],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION The long-term use of colchicine is established for FMF and the prophylaxis of gout flares, but the safety and efficacy of repeat treatment for gout flares has not been evaluated. The dosing regimens for colchicine tablets are different for each indication and must be individualized. The recommended dosage of colchicine tablets depends on the patient’s age, renal function, hepatic function and use of coadministered drugs [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Colchicine tablets are administered orally without regard to meals. Colchicine tablets are not an analgesic medication and should not be used to treat pain from other causes. • Gout Flares: Prophylaxis of Gout Flares: 0.6 mg once or twice daily in adults and adolescents older than 16 years of age ( Error! Hyperlink reference not valid. ). Maximum dose 1.2 mg/day. Treatment of Gout Flares: 1.2 mg (two tablets) at the first sign of a gout flare followed by 0.6 mg (one tablet) one hour later ( Error! Hyperlink reference not valid. ). • FMF: Adults and children older than 12 years 1.2 - 2.4 mg; children 6 to 12 years 0.9 - 1.8 mg; children 4 to 6 years 0.3 - 1.8 mg ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). o Give total daily dose in one or two divided doses ( Error! Hyperlink reference not valid. ). o Increase or decrease the dose as indicated and as tolerated in increments of 0.3 mg/day, not to exceed the maximum recommended daily dose ( Error! Hyperlink reference not valid. ). • Colchicine tablets are administered orally without regard to meals. • See full prescribing information (FPI) for dose adjustment regarding patients with impaired renal function ( Error! Hyperlink reference not valid. ), impaired hepatic function ( Error! Hyperlink reference not valid. ), the patient’s age ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ) or use of coadministered drugs ( Error! Hyperlink reference not valid. ). 2.1 Gout Flares Prophylaxis of Gout Flares The recommended dosage of colchicine tablets for prophylaxis of gout flares for adults and adolescents older than 16 years of age is 0.6 mg once or twice daily. The maximum recommended dose for prophylaxis of gout flares is 1.2 mg/day. An increase in gout flares may occur after initiation of uric acid-lowering therapy, including pegloticase, febuxostat and allopurinol, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Colchicine tablets are recommended upon initiation of gout flare prophylaxis with uric acid-lowering therapy. Prophylactic therapy may be beneficial for at least the first six months of uric acid-lowering therapy. Treatment of Gout Flares The recommended dose of colchicine tablets for treatment of a gout flare is 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Higher doses have not been found to be more effective. The maximum recommended dose for treatment of gout flares is 1.8 mg over a 1-hour period. Colchicine tablets may be administered for treatment of a gout flare during prophylaxis at doses not to exceed 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Wait 12 hours and then resume the prophylactic dose. 2.2 FMF The recommended dosage of colchicine tablets for FMF in adults is 1.2 mg to 2.4 mg daily. Colchicine tablets should be increased as needed to control disease and as tolerated in increments of 0.3 mg/day to a maximum recommended daily dose. If intolerable side effects develop, the dose should be decreased in increments of 0.3 mg/day. The total daily colchicine tablets dose may be administered in one to two divided doses. 2.3 Recommended Pediatric Dosage Prophylaxis and Treatment of Gout Flares Colchicine tablets are not recommended for pediatric use in prophylaxis or treatment of gout flares. FMF The recommended dosage of colchicine tablets for FMF in pediatric patients 4 years of age and older is based on age. The following daily doses may be given as a single or divided dose twice daily: • Children 4 to 6 years: 0.3 mg to 1.8 mg daily • Children 6 to 12 years: 0.9 mg to 1.8 mg daily • Adolescents older than 12 years: 1.2 mg to 2.4 mg daily 2.4 Dose Modification for Coadministration of Interacting Drugs Concomitant Therapy Coadministration of colchicine tablets with drugs known to inhibit CYP3A4 and/or P-glycoprotein (P-gp) increases the risk of colchicine-induced toxic effects (Table 1) . If patients are taking or have recently completed treatment with drugs listed in Table 1 within the prior 14 days, the dose adjustments are as shown in the table below [see Error! Hyperlink reference not valid. ] . Table 1. Colchicine Tablets Dose Adjustment for Coadministration with Interacting Drugs if No Alternative Available For magnitude of effect on colchicine plasma concentrations [see Error! Hyperlink reference not valid. ] Strong CYP3A4 Inhibitors Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with strong CYP3A4 or P-gp inhibitors [see Error! Hyperlink reference not valid. ] Gout Flares Noted or Anticipated Outcome Prophylaxis of Gout Flares Treatment of Gout Flares FMF Drug Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Atazanavir Clarithromycin Darunavir/ Ritonavir When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [see Error! Hyperlink reference not valid. ] Indinavir Itraconazole Ketoconazole Lopinavir/ Ritonavir Nefazodone Nelfinavir Ritonavir Saquinavir Telithromycin Tipranavir/ Ritonavir Significant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with clarithromycin, a strong CYP3A4 inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other strong CYP3A4 inhibitors 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg - 2.4 mg Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) Moderate CYP3A4 Inhibitors Gout Flares Note or Anticipated Outcome Prophylaxis of Gout Flares Treatment of Gout Flares FMF Drug Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Amprenavir Aprepitant Diltiazem Erythromycin Fluconazole Fosamprenavir (prodrug of Amprenavir) Grapefruit juice Verapamil Significant increase in colchicine plasma concentration is anticipated. Neuromuscular toxicity has been reported with diltiazem and verapamil interactions. 0.6 mg twice a day 0.6 mg once a day 0.3 mg twice a day or 0.6 mg once a day 0.3 mg once a day 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg - 2.4 mg Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) P-gp Inhibitors Gout Flares Note or Anticipated Outcome Prophylaxis of Gout Flares Treatment of Gout Flares FMF Drug Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Cyclosporine Ranolazine Significant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with cyclosporine, a P-gp inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other P-gp inhibitors. 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 0.6 mg (1 tablet) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg - 2.4 mg Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) Table 2. Colchicine Tablets Dose Adjustment for Coadministration with Protease Inhibitors Protease Inhibitor Clinical Comment w/ Colchicine - Prophylaxis of Gout Flares w/o Colchicine – Treatment of Gout Flares w/Colchicine – Treatment of FMF Atazanavir sulfate (Reyataz) Patients with renal or hepatic impairment should not be given colchicine with Reyataz. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Darunavir (Prezista) Patients with renal or hepatic impairment should not be given colchicine with Prezista/ritonavir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Fosamprenavir (Lexiva) with Ritonavir Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Fosamprenavir (Lexiva) Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir Original dose Adjusted dose 1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg twice a day or 0.6 mg once a day 0.3 mg once a day Indinavir (Crixivan) Patients with renal or hepatic impairment should not be given colchicine with Crixivan. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Lopinavir/ Ritonavir (Kaletra) Patients with renal or hepatic impairment should not be given colchicine with Kaletra. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Nelfinavir mesylate (Viracept) Patients with renal or hepatic impairment should not be given colchicine with Viracept. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Ritonavir (Norvir) Patients with renal or hepatic impairment should not be given colchicine with Norvir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Saquinavir mesylate (Invirase) Patients with renal or hepatic impairment should not be given colchicine with Invirase/ritonavir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Tipranavir (Aptivus) Patients with renal or hepatic impairment should not be given colchicine with Aptivus/ritonavir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Treatment of gout flares with colchicine tablets is not recommended in patients receiving prophylactic dose of colchicine tablets and CYP3A4 inhibitors. 2.5 Dose Modification in Renal Impairment Colchicine dosing must be individualized according to the patient's renal function [see Error! Hyperlink reference not valid. ] . Cl cr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula: Gout Flares Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Cl cr ] 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Treatment of Gout Flares For treatment of gout flares in patients with mild (Cl cr 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. For patients with gout flares requiring repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). For these patients, the treatment course should not be repeated more than once every two weeks [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Treatment of gout flares with colchicine tablets is not recommended in patients with renal impairment who are receiving colchicine tablets for prophylaxis. FMF Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing dialysis. For these patients, the dosage should be reduced [see Error! Hyperlink reference not valid. ] . Patients with mild (Cl cr 50 to 80 mL/min) and moderate (Cl cr 30 to 50 mL/min) renal impairment should be monitored closely for adverse effects of colchicine tablets. Dose reduction may be necessary. For patients with severe renal failure (Cl cr less than 30 mL/min), start with 0.3 mg/day; any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Error! Hyperlink reference not valid. ] . For patients undergoing dialysis, the total recommended starting dose should be 0.3 mg (half tablet) per day. Dosing can be increased with close monitoring. Any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Dosing Calculation 2.6 Dose Modification in Hepatic Impairment Gout Flares Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see Error! Hyperlink reference not valid. ] . Treatment of Gout Flares For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, a treatment course should be repeated no more than once every two weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Error! Hyperlink reference not valid. ] . Treatment of gout flares with colchicine tablets is not recommended in patients with hepatic impairment who are receiving colchicine tablets for prophylaxis. FMF Patients with mild to moderate hepatic impairment should be monitored closely for adverse effects of colchicine. Dose reduction should be considered in patients with severe hepatic impairment [see Error! Hyperlink reference not valid. ] ."],"drug_abuse_and_dependence":["9 DRUG ABUSE AND DEPENDENCE Tolerance, abuse or dependence with colchicine has not been reported."],"spl_product_data_elements":["colchicine colchicine Colchicine Colchicine Fd&C Blue No. 2 Fd&C Red No. 40 Hypromellose 2208 (100 Mpa.S) Lactose Monohydrate Polyethylene Glycol, Unspecified Magnesium Stearate MICROCRYSTALLINE CELLULOSE Polydextrose STARCH, CORN Sodium Starch Glycolate Type A Corn Titanium Dioxide Triacetin Y372"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Colchicine Tablets USP, 0.6 mg — purple color, film-coated, capsule shaped tablets debossed with ‘ 372’ on one side and score line on the other side of the tablet. • Tablets: 0.6 mg colchicine ( Error! Hyperlink reference not valid. ). logo"],"clinical_pharmacology_table":["
Table 5. Mean (% CV) Pharmacokinetic Parameters in Healthy Adults Given Colchicine Tablets
Cmax(Colchicine ng/mL)TmaxTmax mean (range) CL = Dose/AUC0-t (calculated from mean values) Vd = CL/Ke (calculated from mean values)(h)Vd/F(L)CL/F(L/hr)t1/2(h)
Colchicine Tablets 0.6 mg Single Dose (N = 13)
2.5(28.7)1.5(1.0 - 3.0)341.5(54.4)54.1(31.0)--
Colchicine Tablets 0.6 mg Twice Daily x 10 Days (N = 13)
3.6(23.7)1.3(0.5 - 3.0)1150(18.7)30.3(19.0)26.6(16.3)
","
Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug
Coadministered DrugDose of Coadministered Drug (mg)Dose of Colchicine Tablets (mg)N% Change in Colchicine Concentrations from Baseline(Range: Min – Max)
CmaxAUC0-t
Cyclosporine100 mgsingle dose0.6 mgsingle dose23270.0(62.0 to 606.9)259.0(75.8 to 511.9)
Clarithromycin250 mg twice daily, 7 days0.6 mgsingle dose23227.2(65.7 to 591.1)281.5(88.7 to 851.6)
Ketoconazole200 mg twice daily, 5 days0.6 mgsingle dose24101.7(19.6 to 219.0)212.2(76.7 to 419.6)
Ritonavir100 mg twice daily, 5 days0.6 mgsingle dose18184.4(79.2 to 447.4)296.0(53.8 to 924.4)
Verapamil240 mg daily, 5 days0.6 mgsingle dose2440.1(-47.1 to 149.5)103.3(-9.8 to 217.2)
Diltiazem240 mg daily, 7 days0.6 mgsingle dose2044.2(-46.0 to 318.3)93.4(-30.2 to 338.6)
Azithromycin500 mg x 1 day, then250 mg x 4 days0.6 mgsingle dose2121.6(-41.7 to 222.0)57.1(-24.3 to 241.1)
Grapefruit juice240 mL twice daily, 4 days0.6 mgsingle dose21-2.55(-53.4 to 55.0)-2.36(-46.4 to 62.2)
","
Table 7. Drug Interactions: Pharmacokinetic Parameters for Coadministration of Drug in the Presence of Colchicine Tablets
Coadministered DrugDose of Coadministered Drug (mg)Dose of Colchicine Tablets (mg)N% Change in Coadministered Drug Concentrations from Baseline(Range: Min – Max)
CmaxAUC0-t
Theophylline300 mg (elixir)single dose0.6 mg twice daily x 14 days271.6(-30.4 to 23.1)1.6(-28.5 to 27.1)
Ethinyl Estradiol (Ortho-Novum® 1/35)21-day cycle (active treatment)+7-day placebo0.6 mg twice daily x 14 days27Conducted in healthy adult females-6.7(-40.3 to 44.7)-3.0AUCƮ(-25.3 to 24.9)
Norethindrone (Ortho-Novum® 1/35)0.94(-37.3 to 59.4)-1.6 (-32.0 to 33.7)
"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS • In the presence of mild to moderate renal or hepatic impairment, adjustment of dosing is not required for treatment of gout flare, prophylaxis of gout flare and FMF, but patients should be monitored closely ( Error! Hyperlink reference not valid. ). • In patients with severe renal impairment for prophylaxis of gout flares, the starting dose should be 0.3 mg/day for gout flares, no dose adjustment is required, but a treatment course should be repeated no more than once every two weeks. In FMF patients, start with 0.3 mg/day, and any increase in dose should be done with close monitoring ( Error! Hyperlink reference not valid. ). • In patients with severe hepatic impairment, a dose reduction may be needed in prophylaxis of gout flares and FMF patients; while a dose reduction may not be needed in gout flares, a treatment course should be repeated no more than once every two weeks ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • For patients undergoing dialysis, the total recommended dose for prophylaxis of gout flares should be 0.3 mg given twice a week with close monitoring. For treatment of gout flares, the total recommended dose should be reduced to 0.6 mg (one tablet) x 1 dose and the treatment course should not be repeated more than once every two weeks. For FMF patients, the starting dose should be 0.3 mg/day and dosing can be increased with close monitoring ( Error! Hyperlink reference not valid. ). • Females and Males of Reproductive Potential: Advise males that colchicine tablets may transiently impair fertility ( Error! Hyperlink reference not valid. ). • Geriatric Use: The recommended dose of colchicine should be based on renal function ( Error! Hyperlink reference not valid. ). 8.1 Pregnancy Risk Summary Available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Error! Hyperlink reference not valid. ). Colchicine crosses the human placenta. Although animal reproductive and developmental studies were not conducted with colchicine tablets, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behcet’s disease, or familial Mediterranean fever (FMF) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications. 8.2 Lactation Risk Summary Colchicine is present in human milk (see Error! Hyperlink reference not valid. ) . Adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. There are no data on the effects of colchicine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for colchicine tablets and any potential adverse effects on the breastfed child from colchicine tablets or from the underlying maternal condition. Data Limited published data from case reports and a small lactation study demonstrate that colchicine is present in breastmilk. A systematic review of literature reported no adverse effects in 149 breastfed children. In a prospective observational cohort study, no gastrointestinal or other symptoms were reported in 38 colchicine-exposed breastfed infants. 8.3 Females and Males of Reproductive Potential Infertility Case reports and epidemiology studies in human male subjects on colchicine therapy indicated that infertility from colchicine is rare and may be reversible. A case report indicated that azoospermia was reversed when therapy was stopped. Case reports and epidemiology studies in female subjects on colchicine therapy have not established a clear relationship between colchicine use and female infertility. However, since the progression of FMF without treatment may result in infertility, the use of colchicine needs to be weighed against the potential risks [see Error! Hyperlink reference not valid. ] . 8.4 Pediatric Use The safety and efficacy of colchicine in children of all ages with FMF has been evaluated in uncontrolled studies. There does not appear to be an adverse effect on growth in children with FMF treated long-term with colchicine. Safety and effectiveness of colchicine in pediatric patients with gout has not been established. 8.5 Geriatric Use Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . 8.6 Renal Impairment Colchicine is significantly excreted in urine in healthy subjects. Clearance of colchicine is decreased in patients with impaired renal function. Total body clearance of colchicine was reduced by 75% in patients with end-stage renal disease undergoing dialysis. Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Cl cr 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg per day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see Error! Hyperlink reference not valid. ] . Treatment of Gout Flares For treatment of gout flares in patients with mild (Cl cr 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine tablets. However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. For patients with gout flares requiring repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). For these patients, the treatment course should not be repeated more than once every two weeks [see Error! Hyperlink reference not valid. ] . FMF Although pharmacokinetics of colchicine in patients with mild (Cl cr 50 to 80 mL/min) and moderate (Cl cr 30 to 50 mL/min) renal impairment is not known, these patients should be monitored closely for adverse effects of colchicine. Dose reduction may be necessary. In patients with severe renal failure (Cl cr less than 30 mL/min) and end-stage renal disease requiring dialysis, colchicine tablets may be started at the dose of 0.3 mg/day. Any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine tablets [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . 8.7 Hepatic Impairment The clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment compared to healthy subjects [see Error! Hyperlink reference not valid. ] . Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see Error! Hyperlink reference not valid. ] . Treatment of Gout Flares For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended colchicine tablets dose is not required, but patients should be monitored closely for adverse effects of colchicine tablets. However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, the treatment course should be repeated no more than once every two weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Error! Hyperlink reference not valid. ] . FMF In patients with severe hepatic disease, dose reduction should be considered with careful monitoring [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] ."],"dosage_and_administration_table":["
Table 1. Colchicine Tablets Dose Adjustment for Coadministration with Interacting Drugs if No Alternative AvailableFor magnitude of effect on colchicine plasma concentrations [see Error! Hyperlink reference not valid.]
Strong CYP3A4 InhibitorsPatients with renal or hepatic impairment should not be given colchicine tablets in conjunction with strong CYP3A4 or P-gp inhibitors [see Error! Hyperlink reference not valid.]
Gout Flares
Noted or Anticipated OutcomeProphylaxis of Gout FlaresTreatment of Gout FlaresFMF
DrugOriginal Intended DosageAdjusted DoseOriginal Intended DosageAdjusted DoseOriginal Intended DosageAdjusted Dose
AtazanavirClarithromycinDarunavir/RitonavirWhen used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [see Error! Hyperlink reference not valid.]IndinavirItraconazoleKetoconazoleLopinavir/Ritonavir NefazodoneNelfinavirRitonavirSaquinavirTelithromycinTipranavir/Ritonavir Significant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with clarithromycin, a strong CYP3A4 inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other strong CYP3A4 inhibitors0.6 mg twice a day 0.6 mg once a day0.3 mg once a day0.3 mg once every other day1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 1.2 mg - 2.4 mgMaximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
Moderate CYP3A4 Inhibitors
Gout Flares
Note or Anticipated OutcomeProphylaxis of Gout FlaresTreatment of Gout FlaresFMF
DrugOriginal Intended DosageAdjusted DosageOriginal Intended DosageAdjusted DosageOriginal Intended DosageAdjusted Dosage
Amprenavir AprepitantDiltiazemErythromycinFluconazoleFosamprenavir (prodrug of Amprenavir)Grapefruit juiceVerapamilSignificant increase in colchicine plasma concentration is anticipated. Neuromuscular toxicity has been reported with diltiazem and verapamil interactions.0.6 mg twice a day0.6 mg once a day0.3 mg twice a day or 0.6 mg once a day0.3 mg once a day1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days.Maximum daily dose of 1.2 mg - 2.4 mgMaximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day)
P-gp Inhibitors
Gout Flares
Note or Anticipated OutcomeProphylaxis of Gout FlaresTreatment of Gout FlaresFMF
DrugOriginal Intended DosageAdjusted DosageOriginal Intended DosageAdjusted DosageOriginal Intended DosageAdjusted Dosage
CyclosporineRanolazineSignificant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with cyclosporine, a P-gp inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other P-gp inhibitors.0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.0.6 mg (1 tablet) x 1 dose. Dose to be repeated no earlier than 3 days.Maximum daily dose of 1.2 mg - 2.4 mgMaximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
","
Table 2. Colchicine Tablets Dose Adjustment for Coadministration with Protease Inhibitors
Protease InhibitorClinical Commentw/ Colchicine - Prophylaxis of Gout Flaresw/o Colchicine – Treatment of Gout Flaresw/Colchicine – Treatment of FMF
Atazanavirsulfate(Reyataz)Patients with renal or hepatic impairment should not be given colchicine with Reyataz.OriginaldoseAdjusteddose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Darunavir (Prezista)Patients with renal or hepatic impairment should not be given colchicine with Prezista/ritonavir.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Fosamprenavir (Lexiva) with RitonavirPatients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Fosamprenavir (Lexiva)Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavirOriginal doseAdjusted dose1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days.Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg twice a day or 0.6 mg once a day0.3 mg once a day
Indinavir (Crixivan)Patients with renal or hepatic impairment should not be given colchicine with Crixivan.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Lopinavir/Ritonavir(Kaletra)Patients with renal or hepatic impairment should not be given colchicine with Kaletra.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Nelfinavir mesylate (Viracept)Patients with renal or hepatic impairment should not be given colchicine with Viracept.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Ritonavir (Norvir)Patients with renal or hepatic impairment should not be given colchicine with Norvir.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Saquinavir mesylate (Invirase)Patients with renal or hepatic impairment should not be given colchicine with Invirase/ritonavir.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
Tipranavir (Aptivus)Patients with renal or hepatic impairment should not be given colchicine with Aptivus/ritonavir.Original doseAdjusted dose0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)
0.6 mg twice a day0.6 mg once a day0.3 mg once a day0.3 mg once every other day
"],"package_label_principal_display_panel":["PRINCIPAL DISPLAY PANEL – 0.6 mg Colchicine Tablets USP, 0.6 mg - 30's Count 71205-687-30"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two year studies were conducted in mice and rats to assess the carcinogenic potential of colchicine. No evidence of colchicine-related tumorigenicity was observed in mice or rats at colchicine oral doses up to 3 and 2 mg/kg/day, respectively (approximately six and eight times, respectively, the maximum recommended human dose of 2.4 mg on a mg/m 2 basis). Mutagenesis Colchicine was negative for mutagenicity in the bacterial reverse mutation assay. In a chromosomal aberration assay in cultured human white blood cells, colchicine treatment resulted in the formation of micronuclei. Since published studies demonstrated that colchicine induces aneuploidy from the process of mitotic nondisjunction without structural DNA changes, colchicine is not considered clastogenic, although micronuclei are formed. Impairment of Fertility No studies of colchicine effects on fertility were conducted with colchicine tablets. However, published nonclinical studies demonstrated that colchicine-induced disruption of microtubule formation affects meiosis and mitosis. Reproductive studies also reported abnormal sperm morphology and reduced sperm counts in males, and interference with sperm penetration, second meiotic division and normal cleavage in females when exposed to colchicine. Colchicine administered to pregnant animals resulted in fetal death and teratogenicity. These effects were dose-dependent, with the timing of exposure critical for the effects on embryofetal development. The nonclinical doses evaluated were generally higher than an equivalent human therapeutic dose, but safety margins for reproductive and developmental toxicity could not be determined."]},"tags":[{"label":"Alkaloid","category":"class"},{"label":"Small Molecule","category":"modality"},{"label":"Serine/threonine-protein kinase pim-1","category":"target"},{"label":"PIM1","category":"gene"},{"label":"TUBB","category":"gene"},{"label":"TUBB4B","category":"gene"},{"label":"M04AC01","category":"atc"},{"label":"Oral","category":"route"},{"label":"Capsule","category":"form"},{"label":"Solution","category":"form"},{"label":"Tablet","category":"form"},{"label":"Generic Available","category":"availability"},{"label":"Established","category":"status"},{"label":"Atherosclerosis","category":"indication"},{"label":"Cardiovascular disease","category":"indication"},{"label":"Chronic gouty arthritis","category":"indication"},{"label":"Familial Mediterranean fever","category":"indication"},{"label":"Gout","category":"indication"},{"label":"Gout Prevention","category":"indication"},{"label":"Scilex Pharms","category":"company"},{"label":"Approved 1960s","category":"decade"},{"label":"Antimitotic Agents","category":"pharmacology"},{"label":"Antirheumatic Agents","category":"pharmacology"},{"label":"Gout Suppressants","category":"pharmacology"},{"label":"Tubulin Modulators","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":[],"safetySignals":[{"date":"","signal":"DIARRHOEA","source":"FDA FAERS","actionTaken":"2691 reports"},{"date":"","signal":"OFF LABEL USE","source":"FDA FAERS","actionTaken":"2269 reports"},{"date":"","signal":"DRUG INEFFECTIVE","source":"FDA FAERS","actionTaken":"2214 reports"},{"date":"","signal":"NAUSEA","source":"FDA FAERS","actionTaken":"1950 reports"},{"date":"","signal":"FATIGUE","source":"FDA FAERS","actionTaken":"1749 reports"},{"date":"","signal":"DYSPNOEA","source":"FDA FAERS","actionTaken":"1466 reports"},{"date":"","signal":"ACUTE KIDNEY INJURY","source":"FDA FAERS","actionTaken":"1443 reports"},{"date":"","signal":"ARTHRALGIA","source":"FDA FAERS","actionTaken":"1432 reports"},{"date":"","signal":"HEADACHE","source":"FDA FAERS","actionTaken":"1325 reports"},{"date":"","signal":"GOUT","source":"FDA FAERS","actionTaken":"1274 reports"}],"drugInteractions":[{"url":"/drug/amprenavir","drug":"amprenavir","action":"Monitor closely","effect":"May interact with Amprenavir","source":"DrugCentral","drugSlug":"amprenavir"},{"url":"/drug/aprepitant","drug":"aprepitant","action":"Monitor closely","effect":"May interact with Aprepitant","source":"DrugCentral","drugSlug":"aprepitant"},{"url":"/drug/atazanavir","drug":"atazanavir","action":"Monitor closely","effect":"May interact with Atazanavir","source":"DrugCentral","drugSlug":"atazanavir"},{"url":"/drug/azithromycin","drug":"azithromycin","action":"Monitor closely","effect":"May interact with Azithromycin","source":"DrugCentral","drugSlug":"azithromycin"},{"url":"/drug/captopril","drug":"captopril","action":"Monitor closely","effect":"May interact with Captopril","source":"DrugCentral","drugSlug":"captopril"},{"url":"/drug/carvedilol","drug":"carvedilol","action":"Monitor closely","effect":"May interact with Carvedilol","source":"DrugCentral","drugSlug":"carvedilol"},{"url":"/drug/ciclosporin","drug":"ciclosporin","action":"Avoid combination","effect":"May interact with Cyclosporine","source":"DrugCentral","drugSlug":"ciclosporin"},{"url":"/drug/ciprofloxacin","drug":"ciprofloxacin","action":"Monitor closely","effect":"May interact with Ciprofloxacin","source":"DrugCentral","drugSlug":"ciprofloxacin"},{"url":"/drug/conivaptan","drug":"conivaptan","action":"Monitor closely","effect":"May interact with Conivaptan","source":"DrugCentral","drugSlug":"conivaptan"},{"url":"/drug/darunavir","drug":"darunavir","action":"Monitor closely","effect":"May interact with Darunavir","source":"DrugCentral","drugSlug":"darunavir"},{"url":"/drug/diltiazem","drug":"diltiazem","action":"Monitor closely","effect":"May interact with Diltiazem","source":"DrugCentral","drugSlug":"diltiazem"},{"url":"/drug/dronedarone","drug":"dronedarone","action":"Monitor closely","effect":"May interact with Dronedarone","source":"DrugCentral","drugSlug":"dronedarone"},{"url":"/drug/erythromycin","drug":"erythromycin","action":"Monitor closely","effect":"May interact with Erythromycin","source":"DrugCentral","drugSlug":"erythromycin"},{"url":"/drug/felodipine","drug":"felodipine","action":"Monitor closely","effect":"May interact with Felodipine","source":"DrugCentral","drugSlug":"felodipine"},{"url":"/drug/fluconazole","drug":"fluconazole","action":"Monitor closely","effect":"May interact with Fluconazole","source":"DrugCentral","drugSlug":"fluconazole"},{"url":"/drug/fosamprenavir","drug":"fosamprenavir","action":"Monitor closely","effect":"May interact with Fosamprenavir","source":"DrugCentral","drugSlug":"fosamprenavir"},{"url":"/drug/imatinib","drug":"imatinib","action":"Monitor closely","effect":"May interact with Imatinib","source":"DrugCentral","drugSlug":"imatinib"},{"url":"/drug/indinavir","drug":"indinavir","action":"Monitor closely","effect":"May interact with Indinavir Sulfate","source":"DrugCentral","drugSlug":"indinavir"},{"url":"/drug/itraconazole","drug":"itraconazole","action":"Monitor closely","effect":"May interact with Itraconazole","source":"DrugCentral","drugSlug":"itraconazole"},{"url":"/drug/ketoconazole","drug":"ketoconazole","action":"Monitor closely","effect":"May interact with Ketoconazole","source":"DrugCentral","drugSlug":"ketoconazole"}],"commonSideEffects":[{"effect":"Diarrhea","drugRate":"77%","severity":"serious","_validated":true},{"effect":"Pharyngolaryngeal pain","drugRate":"3%","severity":"common","_validated":true},{"effect":"Vomiting","drugRate":"19%","severity":"common","_validated":true},{"effect":"Nausea","drugRate":"17%","severity":"common","_validated":true},{"effect":"Abdominal pain","drugRate":"reported","severity":"unknown"},{"effect":"Fatigue","drugRate":"4%","severity":"mild","_validated":true},{"effect":"Gout","drugRate":"4%","severity":"mild","_validated":true},{"effect":"Headache","drugRate":"3%","severity":"mild","_validated":true},{"effect":"Abdominal Discomfort","drugRate":"3%","severity":"mild","_validated":true},{"effect":"General Disorders and Administration Site Conditions","drugRate":"2%","severity":"mild","_validated":true},{"effect":"Metabolic and Nutrition Disorders","drugRate":"2%","severity":"mild","_validated":true},{"effect":"Nervous System Disorders","drugRate":"2%","severity":"mild","_validated":true},{"effect":"Respiratory Thoracic Mediastinal Disorders","drugRate":"2%","severity":"mild","_validated":true},{"effect":"Sensory motor neuropathy","drugRate":"reported","severity":"unknown"},{"effect":"Alopecia","drugRate":"reported","severity":"unknown"},{"effect":"Maculopapular rash","drugRate":"reported","severity":"unknown"},{"effect":"Purpura","drugRate":"reported","severity":"unknown"},{"effect":"Abdominal cramping","drugRate":"reported","severity":"unknown"},{"effect":"Lactose intolerance","drugRate":"reported","severity":"unknown"},{"effect":"Leukopenia","drugRate":"reported","severity":"unknown"},{"effect":"Granulocytopenia","drugRate":"reported","severity":"unknown"},{"effect":"Thrombocytopenia","drugRate":"reported","severity":"unknown"},{"effect":"Pancytopenia","drugRate":"reported","severity":"unknown"},{"effect":"Aplastic anemia","drugRate":"reported","severity":"unknown"},{"effect":"Elevated AST","drugRate":"reported","severity":"unknown"},{"effect":"Elevated ALT","drugRate":"reported","severity":"unknown"},{"effect":"Myopathy","drugRate":"reported","severity":"unknown"},{"effect":"Elevated CPK","drugRate":"reported","severity":"unknown"},{"effect":"Myotonia","drugRate":"reported","severity":"unknown"}],"contraindications":["Acute nephropathy","Anemia due to enzyme deficiency","Aplastic anemia","Bone marrow depression","Diarrhea","Disease of blood AND/OR blood-forming organ","Disorder of muscle","Granulocytopenic disorder","Hepatic failure","Impaired renal function disorder","Leukopenia","Peptic ulcer","Renal dialysis","Rhabdomyolysis","Thrombocytopenic disorder","Uric Acid Nephropathy Gout","Uric acid renal calculus","Vomiting"],"specialPopulations":{"Pregnancy":"Available human data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Although animal reproduction and development studies indicate that colchicine causes embryofetal toxicity and altered postnatal development at exposures within or above the clinical therapeutic range.","Geriatric use":"Clinical studies with colchicine for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy.","Paediatric use":"The safety and efficacy of colchicine in children of all ages with FMF has been evaluated in uncontrolled studies. There does not appear to be an adverse effect on growth in children with FMF treated long-term with colchicine. Safety and effectiveness of colchicine in pediatric patients with gout has not been established.","Renal impairment":"In the presence of renal or hepatic impairment, patients should be monitored closely and dose adjustment should be considered as necessary.","Hepatic impairment":"In the presence of renal or hepatic impairment, patients should be monitored closely and dose adjustment should be considered as necessary."}},"trials":[],"aliases":[],"company":"Scilex Pharms","patents":[{"applNo":"N210942","source":"FDA Orange Book","status":"Active","expires":"Nov 22, 2036","useCode":"U-2814","territory":"US","drugProduct":false,"patentNumber":"12274751","drugSubstance":false},{"applNo":"N210942","source":"FDA Orange Book","status":"Active","expires":"Nov 22, 2036","useCode":"U-2814","territory":"US","drugProduct":false,"patentNumber":"12514819","drugSubstance":false},{"applNo":"N210942","source":"FDA Orange Book","status":"Active","expires":"Nov 22, 2036","useCode":"U-2814","territory":"US","drugProduct":true,"patentNumber":"10383820","drugSubstance":false},{"applNo":"N210942","source":"FDA Orange Book","status":"Active","expires":"Nov 22, 2036","useCode":"","territory":"US","drugProduct":true,"patentNumber":"10383821","drugSubstance":false},{"applNo":"N210942","source":"FDA Orange Book","status":"Active","expires":"Nov 22, 2036","useCode":"","territory":"US","drugProduct":true,"patentNumber":"9907751","drugSubstance":false},{"applNo":"N210942","source":"FDA Orange Book","status":"Active","expires":"Dec 20, 2037","useCode":"","territory":"US","drugProduct":true,"patentNumber":"10226423","drugSubstance":false},{"type":"Method of Use","number":"7619004","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-12-03"},{"type":"Method of Use","number":"7820681","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2029-02-17"},{"type":"Method of Use","number":"7915269","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2029-02-17"},{"type":"Method of Use","number":"7964647","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"8093297","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"8097655","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"8415396","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"8440722","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2029-02-17"},{"type":"Method of Use","number":"7601758","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2029-02-10"},{"type":"Method of Use","number":"7906519","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2029-02-17"},{"type":"Method of Use","number":"7935731","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-12-03"},{"type":"Method of Use","number":"8093296","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"8093298","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"8415395","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"8440721","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2029-02-17"},{"type":"Method of Use","number":"9555029","applicant":"HIKMA INTERNATIONAL PHARMACEUTICALS LLC","territory":"US","tradeName":"MITIGARE","expiryDate":"2033-08-22"},{"type":"Method of Use","number":"9789108","applicant":"HIKMA INTERNATIONAL PHARMACEUTICALS LLC","territory":"US","tradeName":"MITIGARE","expiryDate":"2033-08-22"},{"type":"Method of Use","number":"7981938","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"12364675","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"12233035","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"11026901","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"11026900","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"11026899","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"10842762","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"10265281","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"10206891","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"10130585","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2034-05-09"},{"type":"Method of Use","number":"9744144","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"11944594","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"12280025","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"9675613","applicant":"HIKMA INTERNATIONAL PHARMACEUTICALS LLC","territory":"US","tradeName":"MITIGARE","expiryDate":"2033-08-22"},{"type":"Method of Use","number":"8927607","applicant":"HIKMA INTERNATIONAL PHARMACEUTICALS LLC","territory":"US","tradeName":"MITIGARE","expiryDate":"2033-08-22"},{"type":"Method of Use","number":"7964648","applicant":"TAKEDA PHARMACEUTICALS USA INC","territory":"US","tradeName":"COLCRYS","expiryDate":"2028-10-06"},{"type":"Method of Use","number":"11944595","applicant":"AGEPHA PHARMA FZ LLC","territory":"US","tradeName":"LODOCO","expiryDate":"2033-11-01"},{"type":"Method of Use","number":"9399036","applicant":"HIKMA INTERNATIONAL PHARMACEUTICALS LLC","territory":"US","tradeName":"MITIGARE","expiryDate":"2033-08-22"}],"pricing":[{"market":"United States","source":"CMS National Average Drug Acquisition Cost (NADAC)","asOfDate":"2024-01-03","unitCost":"$4.4559/EA","priceType":"NADAC","sourceUrl":"https://data.medicaid.gov/dataset/4j6z-xnwq","annualCost":"$1,626","description":"COLCHICINE 0.6 MG CAPSULE","retrievedDate":"2026-04-07"}],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=COLCHICINE","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T01:14:44.725611+00:00"},"patents":{"url":"","method":"deterministic","source":"FDA Orange Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-20T01:14:44.725547+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Colchicine","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-20T01:14:52.005588+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T01:14:50.527166+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-20T01:14:43.282982+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=COLCHICINE","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T01:14:50.831979+00:00"},"mechanism.drugClass":{"url":"https://api.fda.gov/drug/label.json","method":"deterministic","source":"FDA Label (EPC)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T01:14:40.202034+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T01:14:40.202063+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T01:14:40.202068+00:00"},"safety.safetySignals":{"url":"https://api.fda.gov/drug/event.json","method":"api_direct","source":"FDA FAERS","rawText":"","confidence":1,"sourceType":"fda_faers","retrievedAt":"2026-04-20T01:14:52.448722+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Tubulin inhibitor","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T01:14:52.005525+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL107/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T01:14:51.659919+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"ANDA209876","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-20T01:14:40.202071+00:00"}},"allNames":"colcrys","offLabel":[],"synonyms":["colchicine","colchisol","colcin"],"timeline":[{"date":"1961-01-01","type":"neutral","source":"FDA Orange Book","milestone":"Rights transferred from MERCK to Scilex Pharms"},{"date":"1961-07-27","type":"positive","source":"DrugCentral","milestone":"FDA approval (Merck)"},{"date":"2009-07-29","type":"positive","source":"FDA Orange Book","milestone":"Colcrys approved — 0.6MG **Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons**"},{"date":"2014-09-26","type":"positive","source":"FDA Orange Book","milestone":"Mitigare approved — 0.6MG"},{"date":"2023-06-16","type":"positive","source":"FDA Orange Book","milestone":"Lodoco approved — 0.5MG"},{"date":"2024-04-29","type":"neutral","source":"FDA Orange Book","milestone":"Generic entry — 12 manufacturers approved"}],"aiSummary":"Colcrys (Colchicine) is a small molecule alkaloid drug originally developed by Merck and currently owned by Scilex Pharmaceuticals. It targets the serine/threonine-protein kinase pim-1 and has been FDA-approved since 1961 for various indications including chronic gouty arthritis, familial Mediterranean fever, and gout. Colcrys is available as a generic medication with multiple manufacturers. Key safety considerations include its potential for gastrointestinal side effects and interactions with other medications. The commercial status of Colcrys is complex, with some formulations still under patent.","approvals":[{"date":"1961-07-27","orphan":true,"company":"MERCK","regulator":"FDA"}],"brandName":"Colcrys","ecosystem":[{"indication":"Atherosclerosis","otherDrugs":[{"name":"alirocumab","slug":"alirocumab","company":"Sanofi Aventis"}],"globalPrevalence":null},{"indication":"Cardiovascular disease","otherDrugs":[{"name":"evolocumab","slug":"evolocumab","company":"Repatha"}],"globalPrevalence":null},{"indication":"Chronic gouty arthritis","otherDrugs":[{"name":"probenecid","slug":"probenecid","company":""},{"name":"sulfinpyrazone","slug":"sulfinpyrazone","company":""}],"globalPrevalence":41000000},{"indication":"Familial Mediterranean fever","otherDrugs":[{"name":"anakinra","slug":"anakinra","company":"Biovitrum Ab"},{"name":"canakinumab","slug":"canakinumab","company":"Novartis Pharms"}],"globalPrevalence":2000000000},{"indication":"Gout","otherDrugs":[{"name":"allopurinol","slug":"allopurinol","company":"Prometheus Labs"},{"name":"indomethacin","slug":"indomethacin","company":""},{"name":"naproxen","slug":"naproxen","company":"Roche Palo"},{"name":"pegloticase","slug":"pegloticase","company":"Crealta Pharms Llc"}],"globalPrevalence":41000000},{"indication":"Gout Prevention","otherDrugs":[{"name":"febuxostat","slug":"febuxostat","company":"Takeda Pharms Usa"}],"globalPrevalence":41000000}],"mechanism":{"target":"Serine/threonine-protein kinase pim-1","novelty":"First-in-class","targets":[{"gene":"PIM1","source":"DrugCentral","target":"Serine/threonine-protein kinase pim-1","protein":"Serine/threonine-protein kinase pim-1"},{"gene":"TUBB","source":"DrugCentral","target":"Tubulin beta chain","protein":"Tubulin beta chain"},{"gene":"TUBB4B","source":"DrugCentral","target":"Tubulin beta-4B chain","protein":"Tubulin beta-4B chain"},{"gene":"BRD4","source":"DrugCentral","target":"Bromodomain-containing protein 4","protein":"Bromodomain-containing protein 4"},{"gene":"GLRA2","source":"DrugCentral","target":"Glycine receptor subunit alpha-2","protein":"Glycine receptor subunit alpha-2"},{"gene":"CYP3A4","source":"DrugCentral","target":"Cytochrome P450 3A4","protein":"Cytochrome P450 3A4"},{"gene":"ABCB1","source":"DrugCentral","target":"Multidrug resistance protein 1","protein":"Multidrug resistance protein 1"},{"gene":"GLRA1","source":"DrugCentral","target":"Glycine receptor subunit alpha-1","protein":"Glycine receptor subunit alpha-1"},{"gene":"ABCC1","source":"DrugCentral","target":"Multidrug resistance-associated protein 1","protein":"Multidrug resistance-associated protein 1"}],"moaClass":"Cytochrome P450 3A4 Inhibitors","modality":"Small Molecule","drugClass":"Alkaloid [EPC]","explanation":"The mechanism by which Colchicine Tablets, USP exert their beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1. Additionally, colchicine disrupts cytoskeletal functions through inhibition of -tubulin polymerization into microtubules, and consequently prevents the activation, degranulation and migration of neutrophils thought to mediate some gout symptoms.","oneSentence":"Colcrys works by inhibiting the activity of a specific enzyme called serine/threonine-protein kinase pim-1.","technicalDetail":"Colcrys (Colchicine) is a competitive inhibitor of the serine/threonine-protein kinase pim-1, which plays a key role in the regulation of inflammatory responses and cell proliferation.","_target_confidence":0.5},"_wikipedia":{"url":"https://en.wikipedia.org/wiki/Colchicine","title":"Colchicine","extract":"Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids in the treatment of gout. Other uses for colchicine include the management of pericarditis.","wiki_history":"== History ==\nThe plant source of colchicine, the autumn crocus (Colchicum autumnale), was described for treatment of rheumatism and swelling in the Ebers Papyrus (circa 1500 BC), an Egyptian medical text. It is a toxic alkaloid and secondary metabolite. Colchicum extract was first described as a treatment for gout in De Materia Medica by Pedanius Dioscorides, in the first century AD. Use of the bulb-like corms of Colchicum to treat gout probably dates to around 550 AD, as the \"hermodactyl\" recommended by Alexander of Tralles. Colchicum corms were used by the Persian physician Avicenna, and were recommended by Ambroise Paré in the 16th century, and appeared in the London Pharmacopoeia of 1618.\n\nColchicine was first isolated in 1820 by French chemists P. S. Pelletier and J. B. Caventou. In 1833, P. L. Geiger purified an active ingredient, which he named colchicine. It quickly became a popular remedy for gout. Its pain-relieving and anti-inflammatory effects for gout were linked to its ability to bind with tubulin.\n\nThe full synthesis of colchicine was achieved by the Swiss organic chemist Albert Eschenmoser in 1959."},"commercial":{"launchDate":"1961","_launchSource":"DrugCentral (FDA 1961-07-27, MERCK)"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/726","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=COLCHICINE","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=COLCHICINE","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://en.wikipedia.org/wiki/Colchicine","fields":["history","overview"],"source":"Wikipedia"},{"id":5,"url":"https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files","fields":["patents","exclusivity","genericManufacturers"],"source":"FDA Orange Book"}],"_enrichedAt":"2026-03-30T10:15:52.951842","_validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-20T01:14:55.461855+00:00","fieldsConflicting":1,"overallConfidence":0.8},"biosimilars":[],"competitors":[{"drugName":"abiraterone acetate","drugSlug":"abiraterone-acetate","fdaApproval":"2011-04-28","patentExpiry":"May 20, 2034","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"aliskiren","drugSlug":"aliskiren","fdaApproval":"2007-03-05","patentExpiry":"Feb 19, 2026","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"alprazolam","drugSlug":"alprazolam","fdaApproval":"1981-10-16","genericCount":24,"patentStatus":"Off-patent — generic available","relationship":"same-target"},{"drugName":"amiodarone","drugSlug":"amiodarone","fdaApproval":"1985-12-24","patentExpiry":"Mar 13, 2029","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"amprenavir","drugSlug":"amprenavir","fdaApproval":"1999-04-15","patentStatus":"Unknown","relationship":"same-target"},{"drugName":"aprepitant","drugSlug":"aprepitant","fdaApproval":"2003-03-27","patentExpiry":"Sep 26, 2027","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"astemizole","drugSlug":"astemizole","fdaApproval":"1988-12-31","relationship":"same-target"},{"drugName":"atazanavir","drugSlug":"atazanavir","fdaApproval":"2003-06-20","genericCount":8,"patentStatus":"Off-patent — generic available","relationship":"same-target"},{"drugName":"atorvastatin","drugSlug":"atorvastatin","fdaApproval":"1996-12-17","patentExpiry":"Jun 7, 2037","patentStatus":"Patent protected","relationship":"same-target"},{"drugName":"bromocriptine","drugSlug":"bromocriptine","fdaApproval":"1978-06-28","patentExpiry":"Jun 7, 2030","patentStatus":"Patent protected","relationship":"same-target"}],"dataSources":[{"url":"https://data.medicaid.gov/dataset/4j6z-xnwq","name":"CMS National Average Drug Acquisition Cost (NADAC)","fields":["pricing"],"retrievedDate":"2026-04-07"}],"genericName":"colchicine","indications":{"approved":[{"name":"Atherosclerosis","source":"DrugCentral","snomedId":38716007,"regulator":"FDA","eligibility":"Not specified"},{"name":"Cardiovascular disease","source":"DrugCentral","snomedId":49601007,"regulator":"FDA","eligibility":"Not specified"},{"name":"Chronic gouty arthritis","source":"DrugCentral","snomedId":68451005,"regulator":"FDA","eligibility":"Adults","usPrevalence":9200000,"globalPrevalence":41000000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Rheumatology, 2023"},{"name":"Familial Mediterranean fever","source":"DrugCentral","snomedId":12579009,"regulator":"FDA","eligibility":"Adults","usPrevalence":null,"globalPrevalence":2000000000,"prevalenceMethod":"curated","prevalenceSource":"Common symptom, not a disease"},{"name":"Gout","source":"DrugCentral","snomedId":90560007,"regulator":"FDA","eligibility":"Adults","usPrevalence":9200000,"globalPrevalence":41000000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Rheumatology, 2023"},{"name":"Gout Prevention","source":"DrugCentral","snomedId":"","regulator":"FDA","eligibility":"Adults","usPrevalence":9200000,"globalPrevalence":41000000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Rheumatology, 2023"}],"offLabel":[],"pipeline":[]},"currentOwner":"Scilex Pharms","drugCategory":"established","labelChanges":[],"relatedDrugs":[{"drugId":"abiraterone-acetate","brandName":"abiraterone acetate","genericName":"abiraterone acetate","approvalYear":"2011","relationship":"same-target"},{"drugId":"aliskiren","brandName":"aliskiren","genericName":"aliskiren","approvalYear":"2007","relationship":"same-target"},{"drugId":"alprazolam","brandName":"alprazolam","genericName":"alprazolam","approvalYear":"1981","relationship":"same-target"},{"drugId":"amiodarone","brandName":"amiodarone","genericName":"amiodarone","approvalYear":"1985","relationship":"same-target"},{"drugId":"amprenavir","brandName":"amprenavir","genericName":"amprenavir","approvalYear":"1999","relationship":"same-target"},{"drugId":"aprepitant","brandName":"aprepitant","genericName":"aprepitant","approvalYear":"2003","relationship":"same-target"},{"drugId":"astemizole","brandName":"astemizole","genericName":"astemizole","approvalYear":"1988","relationship":"same-target"},{"drugId":"atazanavir","brandName":"atazanavir","genericName":"atazanavir","approvalYear":"2003","relationship":"same-target"},{"drugId":"atorvastatin","brandName":"atorvastatin","genericName":"atorvastatin","approvalYear":"1996","relationship":"same-target"},{"drugId":"bromocriptine","brandName":"bromocriptine","genericName":"bromocriptine","approvalYear":"1978","relationship":"same-target"}],"trialDetails":[{"nctId":"NCT04774159","phase":"PHASE3","title":"Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk","status":"RECRUITING","sponsor":"Population Health Research Institute","startDate":"2021-05-06","conditions":["Peripheral Arterial Disease","Atherosclerosis of Extremities","Inflammation"],"enrollment":6150,"completionDate":"2029-12"},{"nctId":"NCT05850091","phase":"PHASE4","title":"Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine","status":"RECRUITING","sponsor":"Massachusetts General Hospital","startDate":"2023-12-07","conditions":["Coronary Artery Disease"],"enrollment":200,"completionDate":"2027-05-01"},{"nctId":"NCT07462325","phase":"PHASE4","title":"Proteomic and Inflammatory Omics Changes With Colchicine Therapy in Coronary Heart Disease","status":"NOT_YET_RECRUITING","sponsor":"Chinese Academy of Medical Sciences, Fuwai Hospital","startDate":"2026-03-01","conditions":["Coronary Heart Disease (CHD)"],"enrollment":176,"completionDate":"2027-03-31"},{"nctId":"NCT06212271","phase":"EARLY_PHASE1","title":"Mechanistic Clinical Trial of Colchicine in Patients With Peripheral Artery Disease","status":"RECRUITING","sponsor":"University of Pennsylvania","startDate":"2024-09-25","conditions":["Peripheral Artery Disease"],"enrollment":24,"completionDate":"2026-04"},{"nctId":"NCT07476625","phase":"NA","title":"Efficacy and Safety of Thalidomide for Pediatric PFAPA Syndrome","status":"NOT_YET_RECRUITING","sponsor":"Wenjie Zheng","startDate":"2026-04-01","conditions":["Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome"],"enrollment":106,"completionDate":"2028-03-30"},{"nctId":"NCT05618353","phase":"PHASE4","title":"The Peri-OPerative COlchicine to Reduce Negative Events (POPCORN) Trial","status":"RECRUITING","sponsor":"VA Office of Research and Development","startDate":"2023-08-21","conditions":["Coronary Artery Disease"],"enrollment":700,"completionDate":"2029-04-30"},{"nctId":"NCT07411768","phase":"NA","title":"Low-dose Colchicine for Thromboprophylaxis After Transcatheter Aortic Valve Replacement","status":"NOT_YET_RECRUITING","sponsor":"China National Center for Cardiovascular Diseases","startDate":"2026-03","conditions":["Transcatheter Aortic Valve Replacement","Transcatheter Heart Valve Thrombosis","Anti-inflammatory Therapy"],"enrollment":116,"completionDate":"2028-06"},{"nctId":"NCT05633810","phase":"PHASE3","title":"COLchicine and Non-enteric Coated Aspirin in the Cardiovascular Outcomes Trial of Patients With Type 2 Diabetes","status":"RECRUITING","sponsor":"Montreal Heart Institute","startDate":"2022-12-21","conditions":["Diabete Type 2","Cardiovascular Diseases"],"enrollment":10000,"completionDate":"2027-12"},{"nctId":"NCT05726019","phase":"PHASE2","title":"Colchicine in Patients Undergoing Coronary Artery Bypass Grafting After Acute Coronary Syndrome","status":"COMPLETED","sponsor":"University of Sao Paulo General Hospital","startDate":"2022-02-05","conditions":["Coronary Artery Disease","Acute Coronary Syndrome","Coronary Artery Bypass","Myocardial Reperfusion","Postpericardiotomy Syndrome","Postoperative Atrial Fibrilation","Perioperative Myocardial Infarction"],"enrollment":100,"completionDate":"2025-12-21"},{"nctId":"NCT06130059","phase":"PHASE2","title":"Efficacy of LoDoCo in Improving Exercise Capacity Among Patients With HFpEF and Inflammation","status":"RECRUITING","sponsor":"University of Texas Southwestern Medical Center","startDate":"2024-04-24","conditions":["Heart Failure","Inflammation"],"enrollment":60,"completionDate":"2027-12-31"},{"nctId":"NCT07232069","phase":"PHASE3","title":"PRE-EMPT: Prospective RandomizEd Evaluation and Management of Premature aTherosclerosis","status":"NOT_YET_RECRUITING","sponsor":"Duke University","startDate":"2026-07-01","conditions":["Coronary Artery Disease Risk Factors Multiple","Coronary Artery Disease Progression","Prevention & Control","Premature Atherosclerosis"],"enrollment":1500,"completionDate":"2031-07"},{"nctId":"NCT05855746","phase":"PHASE3","title":"Colchicine Versus Placebo in Acute Myocarditis Patients","status":"RECRUITING","sponsor":"Assistance Publique - Hôpitaux de Paris","startDate":"2024-07-16","conditions":["Acute Myocarditis"],"enrollment":300,"completionDate":"2028-07-16"},{"nctId":"NCT07432529","phase":"PHASE3","title":"Design and Rationale of the COLT Study","status":"NOT_YET_RECRUITING","sponsor":"Azienda Sanitaria Locale ASL 6, Livorno","startDate":"2026-06-01","conditions":["Venous Thrombosis Deep (Limbs)","Post-thrombotic Syndrome","Venous Thromboembolism (VTE)","Venous Insufficiency"],"enrollment":940,"completionDate":"2027-06-01"},{"nctId":"NCT06587737","phase":"PHASE3","title":"Colchicine for the Reduction of Dependency and Vascular Events After an Acute Intracerebral Hemorrhage","status":"NOT_YET_RECRUITING","sponsor":"Population Health Research Institute","startDate":"2026-05-30","conditions":["Colchicine","ICH - Intracerebral Hemorrhage","Stroke","Dependence"],"enrollment":1125,"completionDate":"2028-10-30"},{"nctId":"NCT06543082","phase":"PHASE4","title":"MACT (Mono Antiplatelet and Colchicine Therapy) Prospective Multicenter Study","status":"RECRUITING","sponsor":"CHA University","startDate":"2024-08-05","conditions":["Acute Coronary Syndrome"],"enrollment":490,"completionDate":"2028-12"},{"nctId":"NCT07287345","phase":"PHASE4","title":"Colchicine's Effect on Inflammatory Markers","status":"RECRUITING","sponsor":"Ayesha Ather","startDate":"2026-01-16","conditions":["Colchicine","Inflammation in Cardiac Surgery","Post Operative Atrial Fibrillation","Inflammatory Markers","Colchicine Adverse Reaction"],"enrollment":24,"completionDate":"2026-06"},{"nctId":"NCT06396858","phase":"PHASE4","title":"Anti-inflammatory and Anti-thrombotic Therapy With colcHicine and Low Dose Rivaroxaban for Major Adverse Cardiovascular Events Reduction in Ischemic Stroke","status":"NOT_YET_RECRUITING","sponsor":"Brazilian Clinical Research Institute","startDate":"2026-07","conditions":["Ischemic Stroke"],"enrollment":4500,"completionDate":"2027-12"},{"nctId":"NCT05949281","phase":"PHASE2","title":"Repurposing Colchicine for Reduction of Residual Inflammatory Risk in Type 1 Diabetes","status":"ACTIVE_NOT_RECRUITING","sponsor":"Asger Lund, MD","startDate":"2023-08-29","conditions":["Type 1 Diabetes","Cardiovascular Diseases","Chronic Inflammation"],"enrollment":102,"completionDate":"2031-01-15"},{"nctId":"NCT07362966","phase":"PHASE4","title":"Effect of Colchicine on Progression of Coronary Atherosclerosis in Patients With TET2-CHIP Variant","status":"NOT_YET_RECRUITING","sponsor":"Shenyang Northern Hospital","startDate":"2026-02-24","conditions":["Colchicine","Coronary Atherosclerosis Management","Clonal Hematopoiesis of Indeterminate Potential"],"enrollment":120,"completionDate":"2027-08-01"},{"nctId":"NCT02939573","phase":"PHASE2","title":"A Randomized Multicenter Study for Isolated Skin Vasculitis","status":"RECRUITING","sponsor":"University of Pennsylvania","startDate":"2017-01-01","conditions":["Primary Cutaneous Vasculitis","Cutaneous Polyarteritis Nodosa","IgA Vasculitis","Henoch-Schönlein Purpura"],"enrollment":90,"completionDate":"2028-12-31"},{"nctId":"NCT06930885","phase":"PHASE3","title":"Polypill and Colchicine for Risk Reduction in Atherosclerotic Cardiovascular Disease","status":"RECRUITING","sponsor":"Hospital do Coracao","startDate":"2025-06-12","conditions":["Atherothrombotic Diseases","Atherosclerotic Cardiovascular Disease (ASCVD)"],"enrollment":7713,"completionDate":"2031-05"},{"nctId":"NCT07349875","phase":"PHASE4","title":"Colchicine Treatment for Non-Flow-Limiting Coronary Plaque by Coronary CTA: A Randomized Controlled Trial","status":"RECRUITING","sponsor":"Nanjing First Hospital, Nanjing Medical University","startDate":"2026-01-01","conditions":["Coronary Artery Disease (CAD)"],"enrollment":3826,"completionDate":"2030-06-30"},{"nctId":"NCT06802926","phase":"PHASE4","title":"Pilot Trial of Colchicine for Graft Failure in CABG","status":"RECRUITING","sponsor":"Ruijin Hospital","startDate":"2025-12-29","conditions":["CABG","Graft Failure","Colchicine"],"enrollment":100,"completionDate":"2028-12"},{"nctId":"NCT06440694","phase":"PHASE3","title":"Colchicine to Quench the Inflammatory Response After Deep Vein Thrombosis (The Conquer-DVT Pilot Trial)","status":"RECRUITING","sponsor":"Ottawa Hospital Research Institute","startDate":"2025-07-07","conditions":["Venous Thromboembolism"],"enrollment":150,"completionDate":"2027-12-01"},{"nctId":"NCT06838143","phase":"","title":"Ilaris NIS in Korea","status":"RECRUITING","sponsor":"Novartis Pharmaceuticals","startDate":"2025-03-29","conditions":["Hereditary Periodic Fever Syndromes","Cryopyrin-associated Periodic Syndromes (CAPS)","Colchicine Resistance Familial Mediterranean Fever (crFMF)","TNF Receptor Associated Periodic Syndrome (TRAPS)","Hyper-IgD Syndrome / Mevalonate Kinase Deficiency (HIDS/MKD)","Systemic Juvenile Idiopathic Arthritis (sJIA)"],"enrollment":25,"completionDate":"2028-09-30"},{"nctId":"NCT03128905","phase":"PHASE3","title":"Trial of Colchicine Versus Prednisone for the Treatment of Acute CPPD Arthritis","status":"COMPLETED","sponsor":"Lille Catholic University","startDate":"2018-02-05","conditions":["Chondrocalcinosis"],"enrollment":111,"completionDate":"2022-05-13"},{"nctId":"NCT07247734","phase":"PHASE2","title":"The Effect of Colchicine, on Insulin Sensitivity in Individuals With Type 1 Diabetes and Systemic Low-grade Inflammation","status":"RECRUITING","sponsor":"Asger Lund, MD","startDate":"2025-12-01","conditions":["Type 1 Diabetes","Chronic Inflammation","Insulin Sensitivity"],"enrollment":26,"completionDate":"2027-06-22"},{"nctId":"NCT04916522","phase":"PHASE2","title":"The COlchicine HypERtENsion Trial","status":"ACTIVE_NOT_RECRUITING","sponsor":"Herlev and Gentofte Hospital","startDate":"2021-08-10","conditions":["Hypertension"],"enrollment":150,"completionDate":"2026-01"},{"nctId":"NCT07280572","phase":"PHASE3","title":"RECLAIM Adaptive Platform Trial for PCC Treatments","status":"ENROLLING_BY_INVITATION","sponsor":"Janneke van de Wijgert","startDate":"2025-02-17","conditions":["Post COVID Condition"],"enrollment":1250,"completionDate":"2027-12-01"},{"nctId":"NCT07145229","phase":"PHASE2","title":"Safety and Efficacy of ABP-745 in Participants With an Acute Gout Flare","status":"RECRUITING","sponsor":"Atom Therapeutics Co., Ltd","startDate":"2025-08-26","conditions":["Acute Gouty Arthritis","Gout Flare","Gout Flares","Acute Gout Flare"],"enrollment":380,"completionDate":"2026-06"},{"nctId":"NCT06765356","phase":"PHASE4","title":"Pragmatic Evaluation of a Pentaspline Pulsed Field Ablation System to Treat Atrial Fibrillation and Related Arrhythmias","status":"RECRUITING","sponsor":"Vivek Reddy","startDate":"2025-04-15","conditions":["Persistent Atrial Fibrillation","Paroxysmal Atrial Fibrillation","Long-standing Persistent Atrial Fibrillation"],"enrollment":275,"completionDate":"2027-03-30"},{"nctId":"NCT06118034","phase":"PHASE3","title":"Effect of Colchicine on Perioperative Anti-inflammatory Organ Injury in Cardiac Surgery","status":"RECRUITING","sponsor":"The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School","startDate":"2024-01-28","conditions":["Inflammatory Response","Cardiac Disease"],"enrollment":768,"completionDate":"2026-12-30"},{"nctId":"NCT06855433","phase":"PHASE2","title":"Colchicine to Reduce Your SympToms And Lower Levels of Inflammation, Zeroing in on Effective CPPD Disease Treatment","status":"NOT_YET_RECRUITING","sponsor":"Brigham and Women's Hospital","startDate":"2026-04-10","conditions":["CPPD - Calcium Pyrophosphate Deposition Disease"],"enrollment":150,"completionDate":"2029-10-01"},{"nctId":"NCT04420624","phase":"PHASE2,PHASE3","title":"COLchicine to Prevent Sympathetic Denervation After an Acute Myocardial Infarction","status":"TERMINATED","sponsor":"University Hospital, Montpellier","startDate":"2020-12-04","conditions":["Myocardial Infarction, Acute"],"enrollment":54,"completionDate":"2022-05-24"},{"nctId":"NCT04875702","phase":"PHASE4","title":"Treat-to-Target Serum Urate Versus Treat-to-Avoid Symptoms in Gout","status":"RECRUITING","sponsor":"Massachusetts General Hospital","startDate":"2024-02-22","conditions":["Gout"],"enrollment":650,"completionDate":"2028-10-31"},{"nctId":"NCT04500665","phase":"PHASE2","title":"Anti-Inflammatory Treatment of Uremic Cardiomyopathy With Colchicine","status":"RECRUITING","sponsor":"Brigham and Women's Hospital","startDate":"2021-11-01","conditions":["Chronic Kidney Diseases"],"enrollment":20,"completionDate":"2026-11-11"},{"nctId":"NCT07064109","phase":"NA","title":"Multi-omics Characterization and Model Construction of Colchicine Anti-inflammatory Therapy Efficacy in ACS Patients","status":"RECRUITING","sponsor":"Shanghai Tongji Hospital, Tongji University School of Medicine","startDate":"2025-07-01","conditions":["ACS - Acute Coronary Syndrome"],"enrollment":380,"completionDate":"2027-07-01"},{"nctId":"NCT05162742","phase":"PHASE3","title":"Colchicine and Inflammation in Aortic Stenosis","status":"ACTIVE_NOT_RECRUITING","sponsor":"Radboud University Medical Center","startDate":"2022-12-22","conditions":["Aortic Valve Disease","Aortic Valve Stenosis","Aortic Valve Calcification","Inflammation","Calcification","Cardiovascular Diseases"],"enrollment":150,"completionDate":"2025-12-22"},{"nctId":"NCT06798714","phase":"PHASE4","title":"The Effect of Colchicine on the Occurrence of Atrial Fibrillation After Cardiac Surgery","status":"RECRUITING","sponsor":"Tomsk Cardiology Research Institute","startDate":"2025-01-20","conditions":["Coronary Artery Disease","Atrial Fibrillation","Coronary Artery Bypass Grafting","Colchicine"],"enrollment":140,"completionDate":"2026-02-20"},{"nctId":"NCT05476991","phase":"PHASE3","title":"Evaluation of Low Dose Colchicine and Ticagrelor in Prevention of Ischemic Stroke in Patients With Stroke Due to Atherosclerosis","status":"RECRUITING","sponsor":"Assistance Publique - Hôpitaux de Paris","startDate":"2023-05-17","conditions":["Stroke","Stroke, Ischemic","Atherosclerosis","Myocardial Infarction","Coronary Syndrome","TIA","Cardiac Disease","Cerebral Infarction"],"enrollment":2800,"completionDate":"2027-09-01"},{"nctId":"NCT04264260","phase":"PHASE2","title":"Evaluation the Palliative Effects of Colchicine on Primary Hepatic Malignant Tumors Unable to Receive Curative Treatment","status":"COMPLETED","sponsor":"Kaohsiung Medical University Chung-Ho Memorial Hospital","startDate":"2019-12-24","conditions":["Hepatocellular Carcinoma Stage IIIB","Cholangiocarcinoma, Intrahepatic","Cholangiocarcinoma; With Hepatocellular Carcinoma","Hepatocellular Carcinoma Stage IV"],"enrollment":42,"completionDate":"2025-05-30"},{"nctId":"NCT05017571","phase":"PHASE2","title":"Colchicine to Suppress Inflammation and Improve Insulin Resistance in Adults and Adolescents With Obesity","status":"COMPLETED","sponsor":"Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)","startDate":"2021-11-08","conditions":["Obesity","Insulin Resistance","Inflammation"],"enrollment":152,"completionDate":"2025-09-02"},{"nctId":"NCT06847204","phase":"PHASE1,PHASE2","title":"EFFICACY OF COLCHICINE IN IMPROVING CLINICAL OUTCOMES IN PATIENTS WITH MILD TO MODERATE COVID-19 PNEUMONIA IN LAHORE: A RANDOMIZED CONTROL TRIAL","status":"COMPLETED","sponsor":"Zaeema Kanwal","startDate":"2025-02-24","conditions":["COVID - 19"],"enrollment":66,"completionDate":"2025-06-24"},{"nctId":"NCT05785429","phase":"NA","title":"The Effect of Colchicine on Food-related Effort-based Decision Making in Brain and Behaviour in Overweight and Obesity","status":"COMPLETED","sponsor":"Donders Centre for Cognitive Neuroimaging","startDate":"2022-08-02","conditions":["Overweight and Obesity"],"enrollment":59,"completionDate":"2025-01-20"},{"nctId":"NCT07143136","phase":"EARLY_PHASE1","title":"Short-Term Outcomes of Early Administration of Colchicine in Non-ST Segment Elevation Myocardial Infarction Patients Treated With Drug-Eluting Stents.","status":"RECRUITING","sponsor":"Assiut University","startDate":"2025-08-10","conditions":["Non ST-Segment Elevation Myocardial Infarction"],"enrollment":140,"completionDate":"2026-09"},{"nctId":"NCT07129538","phase":"NA","title":"Outcomes of Inspiratory Muscle Training in FMF Adolescents","status":"RECRUITING","sponsor":"Cairo University","startDate":"2025-05-10","conditions":["Familial Mediterranean Fever"],"enrollment":40,"completionDate":"2025-09-15"},{"nctId":"NCT07130305","phase":"NA","title":"is There an Effect of Adding Body Vibration to Intake of Vitamin D on Some Outcomes of Familial Mediterranean Fever","status":"RECRUITING","sponsor":"Cairo University","startDate":"2025-05-08","conditions":["Familial Mediterranean Fever"],"enrollment":40,"completionDate":"2026-01-15"},{"nctId":"NCT07130318","phase":"NA","title":"Mediterranean Diet in Familial Mediterranean Fever: Is Fatty Liver Affected by Addition of Aerobic Exercise","status":"RECRUITING","sponsor":"Cairo University","startDate":"2025-05-08","conditions":["Familial Mediterranean Fever","Non-Alcoholic Fatty Liver Disease"],"enrollment":40,"completionDate":"2026-01-08"},{"nctId":"NCT06936709","phase":"PHASE4","title":"Perioperative Colchicine for TKA","status":"NOT_YET_RECRUITING","sponsor":"Geisinger Clinic","startDate":"2025-12-01","conditions":["Osteoarthritis of Knee","Recovery Following Primary Total Knee Arthroplasty","Perioperative Pain Control"],"enrollment":75,"completionDate":"2026-03-01"},{"nctId":"NCT06567678","phase":"PHASE1","title":"The Effect of Colchicine on Platelet Function Profiles in Patients With Stable Coronary Artery Disease","status":"COMPLETED","sponsor":"The University of The West Indies","startDate":"2024-08-21","conditions":["Coronary Artery Disease"],"enrollment":22,"completionDate":"2024-11-04"},{"nctId":"NCT06090890","phase":"PHASE4","title":"Anti-inflammatory Therapy for Recurrent In-stent Restenosis","status":"RECRUITING","sponsor":"Fu Wai Hospital, Beijing, China","startDate":"2023-10-30","conditions":["In-stent Restenosis"],"enrollment":252,"completionDate":"2027-10-29"},{"nctId":"NCT03156816","phase":"PHASE2","title":"COlchicine for Left VEntricular Remodeling Treatment in Acute Myocardial Infarction","status":"COMPLETED","sponsor":"Hospices Civils de Lyon","startDate":"2018-07-23","conditions":["Myocardial Infarction"],"enrollment":194,"completionDate":"2021-08-16"},{"nctId":"NCT07074990","phase":"NA","title":"Clinical Study Evaluating the Efficacy and Safety of Colchicine in Adult Patients With Sepsis","status":"COMPLETED","sponsor":"Tanta University","startDate":"2023-11-01","conditions":["Sepsis at Intensive Care Unit"],"enrollment":46,"completionDate":"2024-08-30"},{"nctId":"NCT04879368","phase":"PHASE3","title":"RegoNivo vs Standard of Care Chemotherapy in AGOC","status":"ACTIVE_NOT_RECRUITING","sponsor":"Australasian Gastro-Intestinal Trials Group","startDate":"2021-06-01","conditions":["Gastro-Oesophageal Cancer"],"enrollment":450,"completionDate":"2026-06-01"},{"nctId":"NCT04382443","phase":"PHASE4","title":"Oral Colchicine in Argentina to Prevent Restenosis","status":"COMPLETED","sponsor":"Centro de estudios en Cardiologia Intervencionista","startDate":"2020-03-12","conditions":["Coronary Artery Disease","Restenosis of Coronary Artery Stent","Atherosclerosis","Acute Coronary Syndrome"],"enrollment":410,"completionDate":"2022-04-30"},{"nctId":"NCT07035405","phase":"PHASE3","title":"Colchicine for Secondary Prevention After Ischemic Stroke (CHANCE-3 EX)","status":"NOT_YET_RECRUITING","sponsor":"Beijing Tiantan Hospital","startDate":"2025-07-04","conditions":["Stroke"],"enrollment":7500,"completionDate":"2028-12-31"},{"nctId":"NCT07026994","phase":"PHASE2","title":"Colchicine for the Prevention of Recurrence in Cerebral Amyloid Angiopathy RElated IntraCerebral Hemorrhage","status":"RECRUITING","sponsor":"Huashan Hospital","startDate":"2025-06-18","conditions":["Cerebral Amyloid Angiopathy","Intracerebral Hemorrhage Lobar"],"enrollment":80,"completionDate":"2027-12"},{"nctId":"NCT06336733","phase":"PHASE3","title":"Randomized Controlled Trial in Patients on Long-term Colchicine With Colchicine-resistant Familial Mediterranean Fever (FMF) to Evaluate the Efficacy of On-demand Anakinra Treatment for Painful Attacks in Patients Who Refuse Continuous Daily Therapy","status":"RECRUITING","sponsor":"Assistance Publique - Hôpitaux de Paris","startDate":"2024-06-04","conditions":["FMF"],"enrollment":50,"completionDate":"2026-12-04"},{"nctId":"NCT04870424","phase":"PHASE3","title":"Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement","status":"COMPLETED","sponsor":"Insel Gruppe AG, University Hospital Bern","startDate":"2021-09-21","conditions":["Transcatheter Aortic Valve Replacement","Atrial Fibrillation New Onset","Pacemaker","Colchicine"],"enrollment":120,"completionDate":"2025-06-03"},{"nctId":"NCT05873881","phase":"PHASE3","title":"COLchicine and Thiamine in Heart Failure Due to Ischemic Heart Disease","status":"RECRUITING","sponsor":"Hamilton Health Sciences Corporation","startDate":"2024-01-29","conditions":["Heart Failure"],"enrollment":2500,"completionDate":"2027-06"},{"nctId":"NCT06666335","phase":"PHASE4","title":"A Study to Evaluate Efficacy and Safety of Anakinra in Chinese Patients With Colchicine-resistent FMF","status":"NOT_YET_RECRUITING","sponsor":"Swedish Orphan Biovitrum","startDate":"2025-09-01","conditions":["Familial Mediterranean Fever (FMF )"],"enrollment":3,"completionDate":"2027-11-30"},{"nctId":"NCT06998862","phase":"PHASE3","title":"Colchicine in Chronic Kidney Disease Patients","status":"RECRUITING","sponsor":"Hospital General Universitario Gregorio Marañon","startDate":"2025-02-12","conditions":["Chronic Kidney Disease","Cardiovascular Events"],"enrollment":744,"completionDate":"2028-12-30"},{"nctId":"NCT05472337","phase":"PHASE2","title":"Effect of Colchicine on Coronary Reperfusion in Patients With Acute Coronary Syndrome","status":"RECRUITING","sponsor":"Pontificia Universidad Catolica de Chile","startDate":"2022-08-01","conditions":["Acute Coronary Syndrome"],"enrollment":50,"completionDate":"2026-06-30"},{"nctId":"NCT05890664","phase":"PHASE3","title":"Colchicine After Electrocardioversion for Atrial Fibrillation","status":"RECRUITING","sponsor":"University Hospital, Basel, Switzerland","startDate":"2024-04-14","conditions":["Atrial Fibrillation","Cardiac Arrhythmia"],"enrollment":416,"completionDate":"2027-03"},{"nctId":"NCT06874192","phase":"PHASE1","title":"Safety and Efficacy of LOw DOse COlchicine in Patients With STatin INTolerance: the LODOCO STINT Pilot Study","status":"RECRUITING","sponsor":"Virginia Commonwealth University","startDate":"2025-03-12","conditions":["Statin Adverse Reaction"],"enrollment":30,"completionDate":"2026-04-01"},{"nctId":"NCT06279000","phase":"PHASE3","title":"Colchicine in Patients at Cardiac Risk Undergoing Major Non-Cardiac Surgery","status":"RECRUITING","sponsor":"Cantonal Hospital of St. Gallen","startDate":"2025-04-20","conditions":["Cardiovascular Diseases","Cardiovascular Complication","Perioperative Complication","Myocardial Injury","Myocardial Injury After Noncardiac Surgery (MINS)"],"enrollment":880,"completionDate":"2029-03-30"},{"nctId":"NCT05698680","phase":"PHASE4","title":"Prednisolone Versus Colchicine for Acute Gout in Primary Care","status":"RECRUITING","sponsor":"University Medicine Greifswald","startDate":"2023-01-18","conditions":["Acute Gout"],"enrollment":314,"completionDate":"2026-02-28"},{"nctId":"NCT05637398","phase":"PHASE1,PHASE2","title":"Colchicine in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction","status":"RECRUITING","sponsor":"I.M. Sechenov First Moscow State Medical University","startDate":"2022-12-15","conditions":["HFpEF - Heart Failure With Preserved Ejection Fraction","Colchicine"],"enrollment":40,"completionDate":"2025-11-01"},{"nctId":"NCT06763055","phase":"PHASE3","title":"The Fifth INTEnsive pReventing Secondary Injury in Acute Cerebral Haemorrhage Trial Within ACT-GLOBAL","status":"RECRUITING","sponsor":"The George Institute","startDate":"2025-02-27","conditions":["Intracerebral Hemorrhage","Spontaneous Intracerebral Hemorrhage","Supratentorial Intracerebral Haemorrhage","Acute Intracerebral Haemorrhage","Acute Stroke"],"enrollment":2000,"completionDate":"2028-01"},{"nctId":"NCT06472908","phase":"PHASE3","title":"Efficacy and Safety of Colchicine After PCI","status":"RECRUITING","sponsor":"Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","startDate":"2024-07-09","conditions":["Coronary Heart Disease","Percutaneous Coronary Intervention","Colchicine"],"enrollment":8862,"completionDate":"2028-08-31"},{"nctId":"NCT06280976","phase":"PHASE4","title":"Aggressive Risk-Prevention Therapies for Coronary Atherosclerotic Plaque (ART-CAP)","status":"WITHDRAWN","sponsor":"University of Louisville","startDate":"2024-03-01","conditions":["Coronary Artery Disease","Atherosclerosis","Heart Attack"],"enrollment":0,"completionDate":"2025-01-01"},{"nctId":"NCT02898610","phase":"PHASE3","title":"Colchicine for Prevention of Vascular Inflammation in Non-cardio Embolic Stroke","status":"COMPLETED","sponsor":"University College Dublin","startDate":"2016-12-12","conditions":["Ischemic Attack, Transient","Stroke"],"enrollment":3154,"completionDate":"2024-01-31"},{"nctId":"NCT06203977","phase":"PHASE1","title":"Inflammation REduction to Prevent cArdiovascular Injury in Renal Disease (REPAIR)","status":"RECRUITING","sponsor":"Hamilton Health Sciences Corporation","startDate":"2024-11-15","conditions":["Chronic Kidney Diseases","Renal Failure"],"enrollment":200,"completionDate":"2026-05-31"},{"nctId":"NCT04278404","phase":"","title":"Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)","status":"RECRUITING","sponsor":"Duke University","startDate":"2020-03-05","conditions":["Coronavirus Infection (COVID-19)","Pulmonary Arterial Hypertension","Urinary Tract Infections in Children","Hypertension","Pain","Hyperphosphatemia","Primary Hyperaldosteronism","Edema","Hypokalemia","Heart Failure","Hemophilia","Menorrhagia","Insomnia","Pneumonia","Skin Infection","Arrythmia","Asthma in Children","Bronchopulmonary Dysplasia","Adrenal Insufficiency","Fibrinolysis; Hemorrhage","Attention Deficit Hyperactivity Disorder","Multisystem Inflammatory Syndrome in Children (MIS-C)","Kawasaki Disease","Coagulation Disorder","Down Syndrome"],"enrollment":5000,"completionDate":"2027-09"},{"nctId":"NCT06837623","phase":"PHASE3","title":"Role of Colchicine as Anti-Inflammatory Therapy in HFpEF","status":"ACTIVE_NOT_RECRUITING","sponsor":"Cairo University","startDate":"2024-07-01","conditions":["HFpEF - Heart Failure With Preserved Ejection Fraction"],"enrollment":75,"completionDate":"2025-03-01"},{"nctId":"NCT06578182","phase":"PHASE3","title":"The Effect of ColcHicine on the Incidence of Knee or Hip Replacements","status":"RECRUITING","sponsor":"Sint Maartenskliniek","startDate":"2025-01-01","conditions":["Osteoarthritis, Knee","Osteoarthritis, Hip"],"enrollment":1410,"completionDate":"2029-03-31"},{"nctId":"NCT04790240","phase":"PHASE1,PHASE2","title":"Medical Herbs Inhibit Inflammation Directing T Cells to Kill the COVID-19 Virus (COVID)","status":"RECRUITING","sponsor":"All Natural Medicine Clinic, LLC","startDate":"2025-01-01","conditions":["Covid19 Virus Infection"],"enrollment":100,"completionDate":"2027-05-30"},{"nctId":"NCT06813079","phase":"PHASE2","title":"Using Tumor Models to Determine Treatments","status":"NOT_YET_RECRUITING","sponsor":"University Health Network, Toronto","startDate":"2025-02-17","conditions":["Pancreatic Ductal Carcinoma","Advanced Cancer","Epithelial Tumor"],"enrollment":25,"completionDate":"2028-02-17"},{"nctId":"NCT03913442","phase":"PHASE4","title":"Colchicine for the Treatment of Osteoarthritis of the Knee","status":"COMPLETED","sponsor":"NYU Langone Health","startDate":"2019-05-15","conditions":["Osteoarthritis","Osteo Arthritis Knee"],"enrollment":120,"completionDate":"2024-01-11"},{"nctId":"NCT05956145","phase":"NA","title":"Effect of Low Dose of Colchicine on Platelet Reactivity","status":"COMPLETED","sponsor":"University of Sao Paulo","startDate":"2021-06-17","conditions":["Platelet Aggregation, Spontaneous","Coronary Artery Disease"],"enrollment":80,"completionDate":"2024-04-03"},{"nctId":"NCT05159219","phase":"PHASE2","title":"Colchicine for the Prevention of Vascular Events After an Acute Intracerebral Hemorrhage","status":"COMPLETED","sponsor":"Population Health Research Institute","startDate":"2022-08-04","conditions":["Intracranial Hemorrhages"],"enrollment":100,"completionDate":"2024-12-03"},{"nctId":"NCT06768294","phase":"PHASE2","title":"Baricitinib in CPPD - the BAPTIST Study","status":"NOT_YET_RECRUITING","sponsor":"I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio","startDate":"2025-01","conditions":["Calcium Pyrophosphate Deposition Disease","Chondrocalcinosis"],"enrollment":32,"completionDate":"2027-01"},{"nctId":"NCT05936281","phase":"PHASE2","title":"A Study of the Efficacy of Genakumab in Prevention of Acute Flares in Gout Patients Initiating Urate-lowering TherapyUrate-lowering (GenSci048-202)","status":"COMPLETED","sponsor":"Changchun GeneScience Pharmaceutical Co., Ltd.","startDate":"2023-07-20","conditions":["Gout","Gout Initiating Urate-loweringUrate-lowering Therapy"],"enrollment":165,"completionDate":"2024-01-19"},{"nctId":"NCT05279690","phase":"PHASE1","title":"Pilot Trial of Colchicine in Urothelial Cancer and Other Solid Tumors","status":"COMPLETED","sponsor":"Icahn School of Medicine at Mount Sinai","startDate":"2022-02-14","conditions":["Urothelial Cancer","Metastatic Solid Tumor"],"enrollment":16,"completionDate":"2024-12-16"},{"nctId":"NCT05190991","phase":"PHASE2","title":"Safety and Efficacy of RPH-104 Used to Prevent Recurrent Fever Attacks in Adult Patients With Colchicine Resistant or Colchicine Intolerant Familial Mediterranean Fever","status":"RECRUITING","sponsor":"R-Pharm International, LLC","startDate":"2021-10-05","conditions":["Familial Mediterranean Fever","FMF"],"enrollment":60,"completionDate":"2029-01"},{"nctId":"NCT06158698","phase":"PHASE3","title":"CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine","status":"RECRUITING","sponsor":"Niguarda Hospital","startDate":"2023-11-14","conditions":["Cardiomyopathies","Myocarditis","Inflammatory Cardiomyopathy","Heart Failure","Ventricular Arrythmia"],"enrollment":80,"completionDate":"2028-05-02"},{"nctId":"NCT04322682","phase":"PHASE3","title":"Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)","status":"TERMINATED","sponsor":"Montreal Heart Institute","startDate":"2020-03-23","conditions":["Corona Virus Infection"],"enrollment":4506,"completionDate":"2021-01-21"},{"nctId":"NCT06731595","phase":"PHASE2","title":"Post-Ablation Pericarditis Reduction Study (PAPERS)","status":"COMPLETED","sponsor":"St. Vincent Cardiovascular Research Institute","startDate":"2021-05-20","conditions":["Atrial Fibrillation","Catheter Ablation","Pericarditis"],"enrollment":248,"completionDate":"2022-10-01"},{"nctId":"NCT05253794","phase":"PHASE2,PHASE3","title":"Effect of Colchicine on the Progression of Aortic Valve Stenosis - a Pilot Study","status":"RECRUITING","sponsor":"Ottawa Heart Institute Research Corporation","startDate":"2022-07-01","conditions":["Aortic Stenosis","Inflammation"],"enrollment":24,"completionDate":"2026-09-30"},{"nctId":"NCT05092776","phase":"PHASE2","title":"Efficacy and Safety of RPH-104 for Resolution and Prevention of Recurring Attacks in Adult Subjects With Familial Mediterranean Fever With Resistance to or Intolerance of Colchicine","status":"ACTIVE_NOT_RECRUITING","sponsor":"R-Pharm International, LLC","startDate":"2021-04-29","conditions":["Familial Mediterranean Fever","FMF"],"enrollment":84,"completionDate":"2025-10-30"},{"nctId":"NCT06352632","phase":"PHASE3","title":"ACT-GLOBAL Adaptive Platform Trial for Stroke","status":"RECRUITING","sponsor":"The George Institute","startDate":"2024-09-26","conditions":["Stroke"],"enrollment":20000,"completionDate":"2034-09"},{"nctId":"NCT05690204","phase":"PHASE2","title":"Dose Finding Study to Evaluate Safety and Efficacy of 3 Dosages of SAP 001.","status":"ACTIVE_NOT_RECRUITING","sponsor":"Shanton Pharma Pte. Ltd.","startDate":"2022-12-12","conditions":["Gout"],"enrollment":87,"completionDate":"2025-02"},{"nctId":"NCT05936268","phase":"PHASE2","title":"Safety and Efficacy of Genakumab for Injection in Patients With Gout Flare","status":"COMPLETED","sponsor":"Changchun GeneScience Pharmaceutical Co., Ltd.","startDate":"2023-07-21","conditions":["Acute Gout","Gout Flare"],"enrollment":106,"completionDate":"2024-02-28"},{"nctId":"NCT06215989","phase":"NA","title":"Treatment of ACuTe Coronary Syndromes With Low-dose colchICine","status":"RECRUITING","sponsor":"Beijing Anzhen Hospital","startDate":"2024-09-02","conditions":["Acute Coronary Syndrome","Unstable Angina","ST Elevation Myocardial Infarction","Non ST Segment Elevation Myocardial Infarction","Colchicine"],"enrollment":6574,"completionDate":"2028-06"},{"nctId":"NCT03048825","phase":"PHASE3","title":"Colchicine and Spironolactone in Patients with MI / SYNERGY Stent Registry","status":"COMPLETED","sponsor":"Population Health Research Institute","startDate":"2018-02-01","conditions":["ST Elevation Myocardial Infarction","Non ST Elevation Myocardial Infarction"],"enrollment":7264,"completionDate":"2024-08-09"},{"nctId":"NCT06342609","phase":"PHASE4","title":"Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients With Stable Coronary Artery Disease","status":"COMPLETED","sponsor":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center","startDate":"2023-03-15","conditions":["Coronary Artery Disease"],"enrollment":84,"completionDate":"2024-09-07"},{"nctId":"NCT03874338","phase":"","title":"CLEAR SYNERGY Neutrophil Substudy","status":"COMPLETED","sponsor":"NYU Langone Health","startDate":"2019-03-04","conditions":["Neutrophils.Hypersegmented | Bld-Ser-Plas","STEMI - ST Elevation Myocardial Infarction"],"enrollment":322,"completionDate":"2024-08-09"},{"nctId":"NCT06604611","phase":"PHASE4","title":"Colchicine in Patients with Heart Failure with Preserved Ejection Fraction and Inflammation","status":"NOT_YET_RECRUITING","sponsor":"Dongying Zhang","startDate":"2024-10-31","conditions":["Heart Failure","Heart Failure with Preserved Ejection Fraction (HFPEF)","Chronic Inflammation","Inflammation","Colchicine"],"enrollment":200,"completionDate":"2026-03-31"},{"nctId":"NCT04160117","phase":"PHASE3","title":"Impact of Short-course Colchicine Versus Placebo After Pulmonary Vein Isolation (IMPROVE-PVI Pilot)","status":"COMPLETED","sponsor":"Population Health Research Institute","startDate":"2020-01-14","conditions":["Atrial Fibrillation","Recurrence"],"enrollment":202,"completionDate":"2022-05-30"},{"nctId":"NCT05503225","phase":"PHASE2","title":"Colchicine Use in Intracranial Atherosclerotic Disease","status":"RECRUITING","sponsor":"Chinese University of Hong Kong","startDate":"2022-11-28","conditions":["ICAD - Intracranial Atherosclerotic Disease"],"enrollment":72,"completionDate":"2026-05-31"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"route":"Oral","formulation":"Capsule, Solution, Tablet","formulations":[{"form":"CAPSULE","route":"ORAL","productName":"Colchicine"},{"form":"CAPSULE","route":"ORAL","productName":"MITIGARE"},{"form":"SOLUTION","route":"ORAL","productName":"Gloperba"},{"form":"TABLET","route":"ORAL","productName":"COLCHICINE"},{"form":"TABLET","route":"ORAL","productName":"Colchicine"},{"form":"TABLET","route":"ORAL","productName":"Probenecid and Colchicine"},{"form":"TABLET","route":"ORAL","productName":"colchicine"},{"form":"TABLET","route":"ORAL","productName":"LODOCO"},{"form":"TABLET, FILM COATED","route":"ORAL","productName":"Colchicine"},{"form":"TABLET, FILM COATED","route":"ORAL","productName":"COLCHICINE"},{"form":"TABLET, FILM COATED","route":"ORAL","productName":"Colcrys"},{"form":"TABLET, FILM COATED","route":"ORAL","productName":"Colchicine"},{"form":"TABLET, FILM COATED","route":"ORAL","productName":"Colchicine"}]},"_patentsChecked":true,"crossReferences":{"NUI":"N0000148412","MMSL":"4493","NDDF":"002372","UNII":"SML2Y3J35T","VUID":"4020930","CHEBI":"CHEBI:27882","VANDF":"4017416","RXNORM":"2683","UMLSCUI":"C0009262","chemblId":"CHEMBL107","ChEMBL_ID":"CHEMBL107","KEGG_DRUG":"D00570","DRUGBANK_ID":"DB01394","PDB_CHEM_ID":" LOC","PUBCHEM_CID":"6167","SNOMEDCT_US":"387413002","IUPHAR_LIGAND_ID":"2367","MESH_DESCRIPTOR_UI":"D003078"},"formularyStatus":[],"_enricherVersion":"v2","developmentCodes":[],"ownershipHistory":[{"period":"1961-","companyName":"Merck","relationship":"Original Developer"},{"period":"present","companyName":"Scilex Pharms","relationship":"Current Owner"}],"pharmacokinetics":{"source":"DrugCentral","halfLife":"58.0 hours","clearance":"2.1 mL/min/kg","bioavailability":"50%","fractionUnbound":"0.61%","volumeOfDistribution":"6.1 L/kg"},"publicationCount":19684,"therapeuticAreas":["Immunology"],"atcClassification":{"source":"DrugCentral","atcCode":"M04AC01","allCodes":["M04AC01"]},"biosimilarFilings":[],"originalDeveloper":"Merck","recentPublications":[{"date":"2026 Mar 20","pmid":"41905101","title":"Multi-target pyrazolopyrimidine-coumarin derivatives as potent CA IX/XII and tubulin polymerization inhibitors: Design, synthesis, and biological evaluation.","journal":"European journal of medicinal chemistry"},{"date":"2026 Mar 29","pmid":"41904738","title":"Incidence and management of pyrexia syndrome in patients treated with dabrafenib and trametinib: a retrospective study.","journal":"Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer"},{"date":"2026 Mar 16","pmid":"41897198","title":"Effect of Colchicine Use and Usual Care Alone on the Rate of Progression to Chronic Kidney Disease and Mortality in Patients with Heat-Related Injury.","journal":"Healthcare (Basel, Switzerland)"},{"date":"2026 Mar 5","pmid":"41897084","title":"Association Between Vitamin D, Vitamin B12 and Folate Levels and Persistent Subclinical Inflammation in Pediatric Familial Mediterranean Fever.","journal":"Children (Basel, Switzerland)"},{"date":"2026","pmid":"41891111","title":"In-silico studies on effective phytochemicals of Crocus sativus, Ocimum tenuiflorum and its modifications targeting NIPAH virus.","journal":"In silico pharmacology"}],"companionDiagnostics":[],"genericManufacturers":14,"_genericFilersChecked":true,"genericManufacturerList":["Alkem Labs Ltd","Amneal Pharms","Annora Pharma","Aurobindo Pharma Ltd","Dr Reddys","Granules","Hetero Labs Ltd V","Macleods Pharms Ltd","Micro Labs","Mylan","Ph Health","Strides Pharma","Watson Labs Inc","Zydus Pharms"],"status":"approved","companyName":"Scilex Pharms","companyId":"scilex-pharms","modality":"Small molecule","firstApprovalDate":"1961","enrichmentLevel":4,"visitCount":0,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"1961-07-27T00:00:00.000Z","mah":"MERCK","brand_name_local":null,"application_number":""},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"1984-02-15T00:00:00.000Z","mah":"WATSON LABS","brand_name_local":null,"application_number":"ANDA084279"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2011-07-20T00:00:00.000Z","mah":"TAKEDA PHARMS USA","brand_name_local":null,"application_number":"NDA022352"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2020-09-15T00:00:00.000Z","mah":"ZYDUS PHARMS","brand_name_local":null,"application_number":"ANDA211519"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2022-03-10T00:00:00.000Z","mah":"STRIDES PHARMA","brand_name_local":null,"application_number":"ANDA209173"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2024-05-29T00:00:00.000Z","mah":"MYLAN","brand_name_local":null,"application_number":"ANDA209470"},{"country_code":"IN","regulator":"CDSCO","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TH","regulator":"FDA-TH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"MY","regulator":"NPRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"PH","regulator":"FDA-PH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"CO","regulator":"INVIMA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"ZA","regulator":"SAHPRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TW","regulator":"TFDA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"HK","regulator":"DH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"IL","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"SG","regulator":"HSA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AE","regulator":"MOH","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"KR","regulator":"MFDS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AU","regulator":"TGA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"BR","regulator":"ANVISA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"MX","regulator":"COFEPRIS","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"AR","regulator":"ANMAT","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"country_code":"TR","regulator":"TITCK","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null}],"trialStats":{"total":28,"withResults":0},"validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-20T01:14:55.461855+00:00","fieldsConflicting":1,"overallConfidence":0.8},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}