{"id":"levophed","rwe":[],"_fda":{"id":"240616bf-5277-ae18-dc3d-738f3bbabb55","set_id":"0ea48ab6-e166-df31-b132-70ef982a2d02","openfda":{"unii":["IFY5PE3ZRW"],"route":["INTRAVENOUS"],"rxcui":["242969"],"spl_id":["240616bf-5277-ae18-dc3d-738f3bbabb55"],"brand_name":["NOREPINEPHRINE BITARTRATE"],"spl_set_id":["0ea48ab6-e166-df31-b132-70ef982a2d02"],"package_ndc":["70377-121-11","70377-121-12"],"product_ndc":["70377-121"],"generic_name":["NOREPINEPHRINE BITARTRATE"],"product_type":["HUMAN PRESCRIPTION DRUG"],"substance_name":["NOREPINEPHRINE BITARTRATE"],"manufacturer_name":["BIOCON PHARMA INC."],"application_number":["ANDA219443"],"is_original_packager":[true]},"version":"3","pregnancy":["8.1 Pregnancy Risk Summary Limited published data consisting of a small number of case reports and multiple small trials involving the use of norepinephrine in pregnant women at the time of delivery have not identified an increased risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus from hypotension associated with septic shock, myocardial infarction and stroke which are medical emergencies in pregnancy and can be fatal if left untreated. ( see Clinical Considerations ). In animal reproduction studies, using high doses of intravenous norepinephrine resulted in lowered maternal placental blood flow. Clinical relevance to changes in the human fetus is unknown since the average maintenance dose is ten times lower ( see Data ). Increased fetal reabsorptions were observed in pregnant hamsters after receiving daily injections at approximately 2 times the maximum recommended dose on a mg/m 3 basis for four days during organogenesis ( see Data ). The estimated background risk for 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 the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypotension associated with septic shock, myocardial infarction, and stroke are medical emergencies in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic shock, myocardial infarction and stroke may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of norepinephrine on the fetus. Data Animal Data A study in pregnant sheep receiving high doses of intravenous norepinephrine (40 mcg/min, at approximately 10 times the average maintenance dose of 2 to 4 mcg/min in human, on a mg/kg basis) exhibited a significant decrease in maternal placental blood flow. Decreases in fetal oxygenation, urine and lung liquid flow were also observed. Norepinephrine administration to pregnant rats on Gestation Day 16 or 17 resulted in cataract production in rat fetuses. In hamsters, an increased number of resorptions (29.1% in study group vs. 3.4% in control group), fetal microscopic liver abnormalities and delayed skeletal ossification were observed at approximately 2 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day from Gestation Day 7 to 10)."],"overdosage":["10 OVERDOSAGE Overdosage with norepinephrine bitartrate may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. In case of overdosage, discontinue norepinephrine bitartrate until the condition of the patient stabilizes."],"description":["11 DESCRIPTION Norepinephrine (sometimes referred to as l-arterenol/Levarterenol or l-norepinephrine) is a sympathomimetic amine which differs from epinephrine by the absence of a methyl group on the nitrogen atom. Norepinephrine bitartrate, USP is (-)-α-(aminomethyl)-3,4-dihydroxybenzyl alcohol tartrate (1:1) (salt), monohydrate (molecular weight 337.28 g/mol) and has the following structural formula: Norepinephrine bitartrate injection, USP is supplied in a sterile aqueous solution in the form of the bitartrate salt to be administered by intravenous infusion. Norepinephrine is freely soluble in purified water slightly soluble in alcohol, practically insoluble in chloroform and ether. Each mL contains 1 mg of norepinephrine base (equivalent to 1.89 mg of norepinephrine bitartrate, USP anhydrous basis), sodium chloride for isotonicity, not more than 0.2 mg (vials) of sodium metabisulfite as an antioxidant. It has a pH of 3.0 to 4.5. The air in the containers has been displaced by nitrogen gas. Chemical Structure"],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING Norepinephrine Bitartrate injection, USP, is a sterile, clear, colorless to slightly yellow solution for injection intended for intravenous use. It contains the equivalent of 1 mg of norepinephrine base per 1 mL (4 mg/4 mL). It is available as 4 mg/4 mL in single-dose amber glass vials Supplied as: Unit of Sale Concentration NDC 70377-121-12 10 vials in a Carton 4 mg/4 mL (1 mg/mL) Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Store in original carton until time of administration to protect from light. Discard unused portion."],"geriatric_use":["8.5 Geriatric Use Clinical studies of norepinephrine bitartrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Avoid administration of norepinephrine bitartrate into the veins in the leg in elderly patients [see Warnings and Precautions (5.1) ] ."],"pediatric_use":["8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established."],"effective_time":"20250617","pharmacodynamics":["12.2 Pharmacodynamics The primary pharmacodynamic effects of norepinephrine are cardiac stimulation and vasoconstriction. Cardiac output is generally unaffected, although it can be decreased, and total peripheral resistance is also elevated. The elevation in resistance and pressure result in reflex vagal activity, which slows the heart rate and increases stroke volume. The elevation in vascular tone or resistance reduces blood flow to the major abdominal organs as well as to skeletal muscle. Coronary blood flow is substantially increased secondary to the indirect effects of alpha stimulation. After intravenous administration, a pressor response occurs rapidly and reaches steady state within 5 minutes. The pharmacologic actions of norepinephrine are terminated primarily by uptake and metabolism in sympathetic nerve endings. The pressor action stops within 1-2 minutes after the infusion is discontinued."],"pharmacokinetics":["12.3 Pharmacokinetics Absorption Following initiation of intravenous infusion, the steady state plasma concentration is achieved in 5 min. Distribution Plasma protein binding of norepinephrine is approximately 25%. It is mainly bound to plasma albumin and to a smaller extent to prealbumin and alpha 1-acid glycoprotein. The volume of distribution is 8.8 L. Norepinephrine localizes mainly in sympathetic nervous tissue. It crosses the placenta but not the blood-brain barrier. Elimination The mean half-life of norepinephrine is approximately 2.4 min. The average metabolic clearance is 3.1 L/min. Metabolism Norepinephrine is metabolized in the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and MAO. The major metabolites are normetanephrine and 3- methoxyl-4-hydroxy mandelic acid (vanillylmandelic acid, VMA), both of which are inactive. Other inactive metabolites include 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxymandelic acid, and 3,4- dihydroxyphenylglycol. Excretion Noradrenaline metabolites are excreted in urine primarily as sulphate conjugates and, to a lesser extent, as glucuronide conjugates. Only small quantities of norepinephrine are excreted unchanged."],"adverse_reactions":["6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Tissue Ischemia [see Warnings and Precautions (5.1) ] Hypotension [see Warnings and Precautions (5.2) ] Cardiac Arrhythmias [see Warnings and Precautions (5.3) ] The most common adverse reactions are hypertension and bradycardia. The following adverse reactions can occur: Nervous system disorders: Anxiety, headache Respiratory disorders: Respiratory difficulty, pulmonary edema Most common adverse reactions are ischemic injury, bradycardia, anxiety, transient headache, respiratory difficulty, and extravasation necrosis at injection site. (6) To report SUSPECTED ADVERSE REACTIONS, contact Biocon Pharma Inc., at 1-866-924-6266 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."],"contraindications":["4 CONTRAINDICATIONS None. None. ( 4 )"],"drug_interactions":["7 DRUG INTERACTIONS Monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types may result in hypertension. ( 7.1 ) Cyclopropane and halothane anesthetics increase cardiac autonomic irritability. ( 7.4 ) 7.1 MAO-Inhibiting Drugs Co-administration of norepinephrine bitartrate with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) can cause severe, prolonged hypertension. If administration of norepinephrine bitartrate cannot be avoided in patients who recently have received any of these drugs and in whom, after discontinuation, MAO activity has not yet sufficiently recovered, monitor for hypertension. 7.2 Tricyclic Antidepressants Co-administration of norepinephrine bitartrate with tricyclic antidepressants (including amitriptyline, nortriptyline, protriptyline, clomipramine, desipramine, imipramine) can cause severe, prolonged hypertension. If administration of norepinephrine bitartrate cannot be avoided in these patients, monitor for hypertension. 7.3 Antidiabetics Norepinephrine bitartrate can decrease insulin sensitivity and raise blood glucose. Monitor glucose and consider dosage adjustment of antidiabetic drugs. 7.4 Halogenated Anesthetics Concomitant use of norepinephrine bitartrate with halogenated anesthetics (e.g., cyclopropane, desflurane, enflurane, isoflurane, and sevoflurane) may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics."],"how_supplied_table":["
Unit of SaleConcentration
NDC 70377-121-1210 vials in a Carton4 mg/4 mL(1 mg/mL)
"],"mechanism_of_action":["12.1 Mechanism of Action Norepinephrine is a peripheral vasoconstrictor (alpha-adrenergic action) and an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action)."],"storage_and_handling":["Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Store in original carton until time of administration to protect from light. Discard unused portion."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Norepinephrine is a peripheral vasoconstrictor (alpha-adrenergic action) and an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action). 12.2 Pharmacodynamics The primary pharmacodynamic effects of norepinephrine are cardiac stimulation and vasoconstriction. Cardiac output is generally unaffected, although it can be decreased, and total peripheral resistance is also elevated. The elevation in resistance and pressure result in reflex vagal activity, which slows the heart rate and increases stroke volume. The elevation in vascular tone or resistance reduces blood flow to the major abdominal organs as well as to skeletal muscle. Coronary blood flow is substantially increased secondary to the indirect effects of alpha stimulation. After intravenous administration, a pressor response occurs rapidly and reaches steady state within 5 minutes. The pharmacologic actions of norepinephrine are terminated primarily by uptake and metabolism in sympathetic nerve endings. The pressor action stops within 1-2 minutes after the infusion is discontinued. 12.3 Pharmacokinetics Absorption Following initiation of intravenous infusion, the steady state plasma concentration is achieved in 5 min. Distribution Plasma protein binding of norepinephrine is approximately 25%. It is mainly bound to plasma albumin and to a smaller extent to prealbumin and alpha 1-acid glycoprotein. The volume of distribution is 8.8 L. Norepinephrine localizes mainly in sympathetic nervous tissue. It crosses the placenta but not the blood-brain barrier. Elimination The mean half-life of norepinephrine is approximately 2.4 min. The average metabolic clearance is 3.1 L/min. Metabolism Norepinephrine is metabolized in the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and MAO. The major metabolites are normetanephrine and 3- methoxyl-4-hydroxy mandelic acid (vanillylmandelic acid, VMA), both of which are inactive. Other inactive metabolites include 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxymandelic acid, and 3,4- dihydroxyphenylglycol. Excretion Noradrenaline metabolites are excreted in urine primarily as sulphate conjugates and, to a lesser extent, as glucuronide conjugates. Only small quantities of norepinephrine are excreted unchanged."],"indications_and_usage":["1 INDICATIONS AND USAGE Norepinephrine bitartrate injection is indicated to raise blood pressure in adult patients with severe, acute hypotension. Norepinephrine bitartrate injection is a catecholamine indicated for restoration of blood pressure in adult patients with acute hypotensive states. ( 1 )"],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS Tissue Ischemia : Avoid extravasation of norepinephrine bitartrate injection into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug. Infuse norepinephrine bitartrate injection into a large vein. To prevent sloughing and necrosis in areas in which extravasation has taken place, the area should be infiltrated as soon as possible with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of an adrenergic blocking agent. ( 5.1 ) Hypotension After Abrupt Discontinuation : Sudden cessation of the infusion rate may result in marked hypotension. Reduce the norepinephrine bitartrate injection infusion rate gradually. ( 5.2 ) Cardiac Arrhythmias: Norepinephrine bitartrate injection may cause arrhythmias. Monitor cardiac function in patients with underlying heart disease. ( 5.3 ) Allergic Reactions with Sulfite: Norepinephrine bitartrate injection contains sodium metabisulfite. Sulfite may cause allergic-type-reactions. ( 5.4 ) 5.1 Tissue Ischemia Administration of norepinephrine bitartrate to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating norepinephrine bitartrate [see Dosage and Administration (2.1) ]. Avoid norepinephrine bitartrate in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction. Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients. Extravasation of norepinephrine bitartrate may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation [see Dosage and Administration (2.1) ]. Emergency Treatment of Extravasation To prevent sloughing and necrosis in areas in which extravasation has occurred, infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. 5.2 Hypotension after Abrupt Discontinuation Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the norepinephrine bitartrate infusion rate while expanding blood volume with intravenous fluids. 5.3 Cardiac Arrhythmias Norepinephrine bitartrate elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias. 5.4 Allergic Reactions Associated with Sulfite Norepinephrine bitartrate injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people."],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis, mutagenesis, and fertility studies have not been performed."],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Advise the patient, family, or caregiver to report signs of extravasation urgently [see Warnings and Precautions (5.1)]. Manufactured by: Immacule Lifesciences Pvt. Ltd. HP, India-174 101 Manufactured for: Biocon Pharma Inc., Iselin, New Jersey, 08830-3009 United States of America"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION Initial dose of 0.25 mL to 0.375 mL (from 8 mcg to 12 mcg of base) per minute, adjust the rate of flow to establish and maintain a low to normal blood pressure (usually 80 mm Hg to 100 mm Hg systolic) sufficient to maintain the circulation of vital organs. ( 2.2 ) The average maintenance dose ranges from 0.0625 mL to 0.125 mL per minute (from 2 mcg to 4 mcg of base). ( 2.2 ) 2.1 Important Dosage and Administration Instructions Correct Hypovolemia Address hypovolemia before initiation of norepinephrine bitartrate injection therapy. If the patient does not respond to therapy, suspect occult hypovolemia [see Warnings and Precautions (5.1) ] . Administration Dilute norepinephrine bitartrate injection prior to use [see Dosage and Administration (2.3) ] . Infuse norepinephrine bitartrate injection into a large vein. Avoid infusions into the veins of the leg in the elderly or in patients with occlusive vascular disease of the legs [see Warnings and Precautions (5.1) ]. Avoid using a catheter-tie-in technique . Discontinuation When discontinuing the infusion, reduce the flow rate gradually. Avoid abrupt withdrawal. 2.2 Dosage After an initial dosage of 8 to 12 mcg per minute via intravenous infusion, assess patient response and adjust dosage to maintain desired hemodynamic effect. Monitor blood pressure every two minutes until the desired hemodynamic effect is achieved, and then monitor blood pressure every five minutes for the duration of the infusion. Typical maintenance intravenous dosage is 2 to 4 mcg per minute. 2.3 Preparation of Diluted Solution Visually inspect norepinephrine bitartrate injection for particulate matter and discoloration prior to administration (the solution is colorless). Do not use the solution if its color is pinkish or darker than slightly yellow or if it contains a precipitate. Add the content of one norepinephrine bitartrate injection vial (4 mg in 4 mL) to 1,000 mL of 5% Dextrose Injection, USP or Sodium Chloride Injection solutions that contain 5% dextrose to produce a 4 mcg per mL dilution. Dextrose reduces loss of potency due to oxidation. Administration in saline solution alone is not recommended. Use higher concentration solutions in patients requiring fluid restriction. Prior to use, store the diluted norepinephrine bitartrate injection solution for up to 24 hours at room temperature [20°C to 25°C (68°F to 77°F)] and protect from light. 2.4 Drug Incompatibilities Avoid contact with iron salts, alkalis, or oxidizing agents. Whole blood or plasma, if indicated to increase blood volume, should be administered separately."],"spl_product_data_elements":["NOREPINEPHRINE BITARTRATE NOREPINEPHRINE BITARTRATE NOREPINEPHRINE BITARTRATE NOREPINEPHRINE SODIUM CHLORIDE SODIUM METABISULFITE"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Injection: 4 mg/4 mL (1 mg/mL norepinephrine base) sterile, clear, colorless to slightly yellow solution in a single-dose amber glass vial. Injection: 4 mg/4 mL (1 mg/mL) norepinephrine base in single-dose glass vial. ( 3 )"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Elderly patients may be at greater risk of developing adverse reactions. ( 8.5 ) 8.1 Pregnancy Risk Summary Limited published data consisting of a small number of case reports and multiple small trials involving the use of norepinephrine in pregnant women at the time of delivery have not identified an increased risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus from hypotension associated with septic shock, myocardial infarction and stroke which are medical emergencies in pregnancy and can be fatal if left untreated. ( see Clinical Considerations ). In animal reproduction studies, using high doses of intravenous norepinephrine resulted in lowered maternal placental blood flow. Clinical relevance to changes in the human fetus is unknown since the average maintenance dose is ten times lower ( see Data ). Increased fetal reabsorptions were observed in pregnant hamsters after receiving daily injections at approximately 2 times the maximum recommended dose on a mg/m 3 basis for four days during organogenesis ( see Data ). The estimated background risk for 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 the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypotension associated with septic shock, myocardial infarction, and stroke are medical emergencies in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic shock, myocardial infarction and stroke may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of norepinephrine on the fetus. Data Animal Data A study in pregnant sheep receiving high doses of intravenous norepinephrine (40 mcg/min, at approximately 10 times the average maintenance dose of 2 to 4 mcg/min in human, on a mg/kg basis) exhibited a significant decrease in maternal placental blood flow. Decreases in fetal oxygenation, urine and lung liquid flow were also observed. Norepinephrine administration to pregnant rats on Gestation Day 16 or 17 resulted in cataract production in rat fetuses. In hamsters, an increased number of resorptions (29.1% in study group vs. 3.4% in control group), fetal microscopic liver abnormalities and delayed skeletal ossification were observed at approximately 2 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day from Gestation Day 7 to 10). 8.2 Lactation Risk Summary There are no data on the presence of norepinephrine in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Clinically relevant exposure to the infant is not expected based on the short half-life and poor oral bioavailability of norepinephrine. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of norepinephrine bitartrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Avoid administration of norepinephrine bitartrate into the veins in the leg in elderly patients [see Warnings and Precautions (5.1) ] ."],"package_label_principal_display_panel":["PRINCIPAL DISPLAY PANEL - 4 mL Vial Label vial-label - 4 mL Vial Label","PRINCIPAL DISPLAY PANEL - 4 mL Vial Carton PRINCIPAL DISPLAY PANEL - 4 mL Vial Carton"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis, mutagenesis, and fertility studies have not been performed."]},"tags":[],"safety":{"boxedWarnings":[],"safetySignals":[{"date":"","signal":"DRUG INEFFECTIVE","source":"FDA FAERS","actionTaken":"2743 reports"},{"date":"","signal":"HYPOTENSION","source":"FDA FAERS","actionTaken":"1392 reports"},{"date":"","signal":"OFF LABEL USE","source":"FDA FAERS","actionTaken":"1270 reports"},{"date":"","signal":"ACUTE KIDNEY INJURY","source":"FDA FAERS","actionTaken":"893 reports"},{"date":"","signal":"MULTIPLE ORGAN DYSFUNCTION SYNDROME","source":"FDA FAERS","actionTaken":"804 reports"},{"date":"","signal":"SEPSIS","source":"FDA FAERS","actionTaken":"790 reports"},{"date":"","signal":"CONDITION AGGRAVATED","source":"FDA FAERS","actionTaken":"779 reports"},{"date":"","signal":"RENAL FAILURE","source":"FDA FAERS","actionTaken":"731 reports"},{"date":"","signal":"TOXICITY TO VARIOUS AGENTS","source":"FDA FAERS","actionTaken":"708 reports"},{"date":"","signal":"CARDIAC ARREST","source":"FDA FAERS","actionTaken":"699 reports"}],"drugInteractions":[{"drug":"Monoamine oxidase (MAO) inhibitors and MAO-inhibiting drugs (e.g., linezolid)","severity":"Severe","mechanism":"Inhibition of norepinephrine metabolism","management":"Monitor for hypertension if administration cannot be avoided in patients who recently received these drugs and MAO activity has not sufficiently recovered","clinicalEffect":"Severe, prolonged hypertension"},{"drug":"Tricyclic antidepressants (amitriptyline, nortriptyline, protriptyline, clomipramine, desipramine, imipramine)","severity":"Severe","mechanism":"Potentiation of norepinephrine effects","management":"Monitor for hypertension if administration cannot be avoided","clinicalEffect":"Severe, prolonged hypertension"},{"drug":"Antidiabetic drugs","severity":"Moderate","mechanism":"Decreased insulin sensitivity","management":"Monitor glucose and consider dosage adjustment of antidiabetic drugs","clinicalEffect":"Elevated blood glucose"},{"drug":"Halogenated anesthetics (cyclopropane, desflurane, enflurane, isoflurane, sevoflurane)","severity":"Severe","mechanism":"Increased cardiac autonomic irritability","management":"Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics","clinicalEffect":"Ventricular tachycardia or ventricular fibrillation"}],"commonSideEffects":[{"effect":"Hypertension","drugRate":"Not specified","severity":"moderate"},{"effect":"Bradycardia","drugRate":"Not specified","severity":"moderate"},{"effect":"Tissue Ischemia","drugRate":"Not specified","severity":"serious"},{"effect":"Hypotension","drugRate":"Not specified","severity":"serious"},{"effect":"Cardiac Arrhythmias","drugRate":"Not specified","severity":"serious"},{"effect":"Anxiety","drugRate":"Not specified","severity":"mild"},{"effect":"Headache","drugRate":"Not specified","severity":"mild"},{"effect":"Transient Headache","drugRate":"Not specified","severity":"mild"},{"effect":"Respiratory Difficulty","drugRate":"Not specified","severity":"moderate"},{"effect":"Pulmonary Edema","drugRate":"Not specified","severity":"serious"},{"effect":"Ischemic Injury","drugRate":"Not specified","severity":"serious"},{"effect":"Extravasation Necrosis at Injection Site","drugRate":"Not specified","severity":"serious"}],"specialPopulations":{"Pregnancy":"Limited published data have not identified an increased risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. However, there are risks to the mother and fetus from hypotension associated with septic shock, myocardial infarction and stroke which are medical emergencies in pregnancy and can be fatal if left untreated. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of norepinephrine on the fetus. Animal studies showed decreased maternal placental blood flow at high doses and fetal reabsorptions in hamsters at approximately 2 times the maximum recommended dose.","Geriatric use":"Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Avoid administration of norepinephrine bitartrate into the veins in the leg in elderly patients.","Paediatric use":"Safety and effectiveness in pediatric patients have not been established.","Renal impairment":"Not addressed in the provided text","Hepatic impairment":"Not addressed in the provided text"}},"trials":[],"_chembl":null,"aliases":[],"patents":[{"type":"Formulation","number":"12097170","applicant":"BAXTER HEALTHCARE CORP","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 5% DEXTROSE","expiryDate":"2041-03-08"},{"type":"Formulation","number":"11413259","applicant":"LONG GROVE PHARMACEUTICALS LLC","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2038-01-30"},{"type":"Formulation","number":"10420735","applicant":"LONG GROVE PHARMACEUTICALS LLC","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2038-01-30"},{"type":"Formulation","number":"10226436","applicant":"LONG GROVE PHARMACEUTICALS LLC","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2038-01-30"},{"type":"Formulation","number":"10568850","applicant":"LONG GROVE PHARMACEUTICALS LLC","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2038-01-30"},{"type":"Formulation","number":"12245996","applicant":"LONG GROVE PHARMACEUTICALS LLC","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2038-01-30"},{"type":"Formulation","number":"10159657","applicant":"LONG GROVE PHARMACEUTICALS LLC","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2038-01-30"},{"type":"Formulation","number":"12290494","applicant":"BAXTER HEALTHCARE CORP","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 5% DEXTROSE","expiryDate":"2041-03-08"},{"type":"Formulation","number":"RE49443","applicant":"INFORLIFE SA","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2035-02-26"},{"type":"Formulation","number":"RE49422","applicant":"INFORLIFE SA","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2035-02-26"},{"type":"Formulation","number":"10888534","applicant":"INFORLIFE SA","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2039-04-26"},{"type":"Formulation","number":"11602508","applicant":"LONG GROVE PHARMACEUTICALS LLC","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2038-01-30"},{"type":"Formulation","number":"10251848","applicant":"INFORLIFE SA","territory":"US","tradeName":"NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE","expiryDate":"2035-02-26"}],"pricing":[],"_fixedAt":"2026-03-30T11:28:01.406366","_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=Norepinephrine Bitartrate","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-19T23:31:20.055325+00:00"},"patents":{"url":"","method":"deterministic","source":"FDA Orange Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-19T23:31:20.055249+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Norepinephrine Bitartrate","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-19T23:31:27.626044+00:00"},"aiSummary":{"url":"","method":"ai_extraction","source":"Haiku strategic summary","rawText":"","confidence":0.9,"sourceType":"ai_extraction","retrievedAt":"2026-04-20T07:55:29.338879+00:00"},"mechanism":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T08:28:20.326098+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-19T23:31:25.975481+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-19T23:31:19.179262+00:00"},"pharmacokinetics":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T08:28:20.326119+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=Norepinephrine Bitartrate","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T23:31:26.543589+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:31:18.073094+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:31:18.073113+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":"2026-04-19T23:31:28.087436+00:00"},"mechanism.oneSentence":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku extraction","aiModel":"claude-haiku-4-5","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T07:55:29.338848+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Adrenergic receptor agonist","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:31:27.625962+00:00"},"safety.drugInteractions":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T07:55:29.338876+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1434513/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:31:27.278498+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"ANDA219443","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:31:18.073117+00:00"}},"offLabel":[],"timeline":[{"date":"19500713","type":"positive","milestone":"FDA approval — HOSPIRA","regulator":"FDA","description":""}],"_dailymed":{"setId":"ddbef60d-c20a-4ada-928f-e87074c08a54","title":"NOREPINEPHRINE BITARTRATE IN SODIUM CHLORIDE (NOREPINEPHRINE BITARTRATE) INJECTION, SOLUTION [WG CRITICAL CARE, LLC]"},"aiSummary":"Norepinephrine bitartrate is a catecholamine indicated for raising blood pressure in adult patients with severe, acute hypotension through dual alpha and beta-adrenergic mechanisms. It has a short half-life of 2.4 minutes and achieves steady-state plasma concentration within 5 minutes of intravenous infusion. Significant drug interactions exist with MAO inhibitors, tricyclic antidepressants, and halogenated anesthetics, requiring careful monitoring. Close hemodynamic and cardiac monitoring is essential during administration, particularly in patients on interacting medications.","ecosystem":[],"mechanism":{"target":"Alpha-adrenergic and beta-adrenergic receptors","novelty":"me-too","targets":[{"gene":"ADRB1","source":"DrugCentral","target":"Beta-1 adrenergic receptor","protein":"Beta-1 adrenergic receptor","isPrimary":true,"activityType":"Ki","activityValue":6}],"modality":"Direct-acting adrenergic agonist","drugClass":"Catecholamine, sympathomimetic amine","explanation":"Norepinephrine bitartrate is a catecholamine that acts as a peripheral vasoconstrictor through alpha-adrenergic receptor stimulation, resulting in increased blood pressure. Simultaneously, it functions as an inotropic stimulator of the heart through beta-adrenergic action, enhancing cardiac contractility and coronary blood flow. These dual mechanisms make it effective for restoring blood pressure in acute hypotensive states.","oneSentence":"Peripheral vasoconstrictor via alpha-adrenergic action and cardiac inotropic stimulator with coronary vasodilation via beta-adrenergic action.","technicalDetail":"Norepinephrine binds to alpha-1 adrenergic receptors on vascular smooth muscle, triggering vasoconstriction through increased intracellular calcium. Beta-1 receptor activation in cardiac tissue increases cAMP levels, enhancing contractility and heart rate. The drug demonstrates dose-dependent effects, with alpha-adrenergic predominance at higher concentrations and beta-adrenergic effects more prominent at lower doses. Coronary artery dilation occurs secondary to increased metabolic demand from enhanced cardiac activity."},"_scrapedAt":"2026-03-27T23:27:52.626Z","_scrapedBy":"cloudflare-swarm","_wikipedia":{"url":"https://en.wikipedia.org/wiki/Norepinephrine_(medication)","title":"Norepinephrine (medication)","extract":"Norepinephrine, also known as noradrenaline and sold under the brand name Levophed among others, is a medication used to treat people with very low blood pressure. It is the typical medication used in sepsis if low blood pressure does not improve following intravenous fluids. It is the same molecule as the hormone and neurotransmitter norepinephrine. It is given by slow injection into a vein."},"commercial":{"launchDate":"1950","annualCostUS":"$50-200/month for generics","currentRevenue":"Generic — no single company revenue","peakSalesEstimate":"Generic — no single company revenue"},"references":[],"_validation":{"fieldsValidated":4,"lastValidatedAt":"2026-04-20T08:28:24.342853+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[],"competitors":[{"name":"Dopamine","company":"Hospira/Pfizer","advantage":"Dose-dependent effects; lower doses provide renal/mesenteric vasodilation while higher doses provide vasoconstriction similar to norepinephrine"},{"name":"Epinephrine","company":"Hospira/Pfizer","advantage":"Stronger beta-adrenergic effects increase cardiac output and heart rate; useful when both inotropy and vasoconstriction needed"},{"name":"Phenylephrine","company":"Hospira/Pfizer","advantage":"Pure alpha-1 agonist with selective vasoconstriction; minimal cardiac effects; preferred when heart rate elevation must be avoided"},{"name":"Vasopressin","company":"Par Pharmaceutical","advantage":"Non-catecholamine mechanism; effective in catecholamine-resistant shock; can be used as adjunctive therapy"},{"name":"Methoxamine","company":"Various","advantage":"Selective alpha-1 agonist with longer duration; produces sustained vasoconstriction with minimal tachycardia"}],"indications":{"approved":[{"name":"Severe, acute hypotension in adult patients","regulator":"FDA"},{"name":"Acute hypotensive states in adult patients","regulator":"FDA"},{"name":"Blood pressure restoration in adult patients","regulator":"FDA"}],"offLabel":[],"pipeline":[]},"_fixedFields":["primaryTarget","pubmed(47)","generics(19)","patents(0)"],"labelChanges":[],"patentStatus":"Off-patent — no active Orange Book patents","relatedDrugs":[],"trialDetails":[{"nctId":"NCT05997732","phase":"PHASE4","title":"Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences","status":"RECRUITING","sponsor":"University of Alberta","startDate":"2023-10-31","conditions":"Vasoconstriction, Vasodilation","enrollment":30},{"nctId":"NCT06977659","phase":"PHASE1, PHASE2","title":"Early Norepinephrine in Trauma Patients With Hemorrhagic Shock","status":"ENROLLING_BY_INVITATION","sponsor":"Visarat Palitnonkiat","startDate":"2025-05-20","conditions":"Trauma, Multiple","enrollment":40},{"nctId":"NCT05836272","phase":"PHASE4","title":"Early Administration of Norepinephrine in Sepsis","status":"RECRUITING","sponsor":"Tunis University","startDate":"2023-08-01","conditions":"Sepsis, Severe","enrollment":200},{"nctId":"NCT05355974","phase":"PHASE3","title":"Using Vasopressor Medication to Support Blood Pressure During Intubation Procedure","status":"COMPLETED","sponsor":"Wright State University","startDate":"2022-08-09","conditions":"Respiratory Failure, Hypotension and Shock, Hypotension on Induction","enrollment":42},{"nctId":"NCT05521152","phase":"PHASE3","title":"Norepinephrine for Prevention of Intraoperative Hypotension in Infants Undergoing Kasai Portoenterostomy","status":"COMPLETED","sponsor":"Kasr El Aini Hospital","startDate":"2022-08-28","conditions":"Anesthesia, Pediatrics, Biliary Atresia","enrollment":31},{"nctId":"NCT05049278","phase":"NA","title":"Effects of Vasopressor on the Graft Blood Flow in TRAM","status":"COMPLETED","sponsor":"Seoul National University Hospital","startDate":"2021-09-24","conditions":"Blood Flow, Anastomotic Failure of Flap, Flap Necrosis","enrollment":20},{"nctId":"NCT05502146","phase":"PHASE4","title":"Comparison of Two Different Norepinephrine Bolus Doses for Management of Spinal Anesthesia-Induced Maternal Hypotension","status":"COMPLETED","sponsor":"Mersin University","startDate":"2022-08-17","conditions":"Spinal Anesthetic Toxicity, Hypotension Drug-Induced, Cesarean Section Complications","enrollment":200},{"nctId":"NCT05637164","phase":"NA","title":"Determination of the ED50 and ED95 of Prophylactic Norepinephrine Infusion for Preventing Post-induction Hypotension in Elderly Patients Undergoing Major Abdominal Surgery","status":"UNKNOWN","sponsor":"Second Affiliated Hospital, School of Medicine, Zhejiang University","startDate":"2022-12-01","conditions":"Norepinephrine, Post-induction Hypotension","enrollment":40},{"nctId":"NCT03182088","phase":"PHASE4","title":"Norepinephrine Infusion Different Doses in Cesarean Delivery","status":"COMPLETED","sponsor":"Cairo University","startDate":"2017-06-15","conditions":"Cesarean Section Complications","enrollment":284},{"nctId":"NCT03328533","phase":"PHASE4","title":"Norepinephrine Versus Phenylephrine Continuous Variable Infusion in Cesarean Delivery","status":"COMPLETED","sponsor":"Cairo University","startDate":"2017-11-10","conditions":"Cesarean Section Complications, Spinal Anesthesia","enrollment":123},{"nctId":"NCT02962986","phase":"NA","title":"A Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent Spinal-induced Hypotension in Cesarean Deliveries","status":"COMPLETED","sponsor":"Samuel Lunenfeld Research Institute, Mount Sinai Hospital","startDate":"2017-01","conditions":"Hypotension","enrollment":112},{"nctId":"NCT02654847","phase":"NA","title":"Norepinephrine To Prevent Hypotension After Spinal Anesthesia For Cesarean Delivery: A Dose Finding Study","status":"COMPLETED","sponsor":"Samuel Lunenfeld Research Institute, Mount Sinai Hospital","startDate":"2016-01","conditions":"Hypotension","enrollment":40}],"_emaApprovals":[],"_faersSignals":[{"count":341,"reaction":"RENAL FAILURE"},{"count":321,"reaction":"PAIN"},{"count":283,"reaction":"INJURY"},{"count":267,"reaction":"ANXIETY"},{"count":255,"reaction":"UNEVALUABLE EVENT"},{"count":237,"reaction":"FEAR"},{"count":223,"reaction":"EMOTIONAL DISTRESS"},{"count":198,"reaction":"RENAL INJURY"},{"count":191,"reaction":"DEATH"},{"count":186,"reaction":"STRESS"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"route":"Intravenous"},"_patentsChecked":true,"crossReferences":{"unii":"IFY5PE3ZRW","rxcui":"7508","splId":"240616bf-5277-ae18-dc3d-738f3bbabb55","chemblId":"CHEMBL1434513","pubchemSID":"126632799"},"formularyStatus":[],"_approvalHistory":[{"date":"20200615","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19870527","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"20070926","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19890406","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19990920","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19910612","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"20201021","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19770214","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19500713","type":"ORIG","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19880302","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19850114","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19780414","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"},{"date":"19910913","type":"SUPPL","sponsor":"HOSPIRA","applicationNumber":"NDA007513"}],"developmentCodes":[],"ownershipHistory":[],"pharmacokinetics":{"tmax":"5 minutes to steady state","halfLife":"2.4 minutes","clearance":"3.1 L/min","excretion":"Urinary excretion primarily as sulfate conjugates and glucuronide conjugates; only small quantities excreted unchanged","metabolism":"Hepatic and tissue metabolism via catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) to inactive metabolites including normetanephrine and vanillylmandelic acid (VMA)","proteinBinding":"Approximately 25%","bioavailability":"","volumeOfDistribution":"8.8 L"},"publicationCount":47,"therapeuticAreas":["Metabolic"],"biosimilarFilings":[],"recentPublications":[],"companionDiagnostics":[],"genericManufacturers":19,"_genericFilersChecked":true,"genericManufacturerList":["Amneal","Anthea Pharma","Aspiro","Baxter Hlthcare Corp","Biocon Pharma","Breckenridge","Caplin","Fresenius Kabi Usa","Gland","Hikma","Meitheal","Metrics Pharm","Msn","Mylan Labs Ltd","Rising","Sagent","Sandoz","Sun Pharm","Zydus Pharms"],"phase":"marketed","status":"approved","brandName":"Levophed","genericName":"Norepinephrine Bitartrate","companyName":"Pfizer Inc.","companyId":"pfizer","modality":"Small molecule","firstApprovalDate":"1950","enrichmentLevel":5,"visitCount":9,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2015-08-31T00:00:00.000Z","mah":"MEITHEAL","brand_name_local":null,"application_number":"ANDA040455"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2018-10-04T00:00:00.000Z","mah":"MYLAN LABS LTD","brand_name_local":null,"application_number":"ANDA211242"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2018-12-17T00:00:00.000Z","mah":"AMNEAL","brand_name_local":null,"application_number":"ANDA210839"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2022-10-06T00:00:00.000Z","mah":"LONG GROVE PHARMS","brand_name_local":null,"application_number":"NDA214628"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2023-09-15T00:00:00.000Z","mah":"CAPLIN","brand_name_local":null,"application_number":"ANDA217575"},{"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":"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":"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":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"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}],"patentsNormalised":[{"patent_number":"10251848","territory":"US","patent_type":"Formulation","expiry_date":"2035-02-26T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"RE49422","territory":"US","patent_type":"Formulation","expiry_date":"2035-02-26T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"RE49443","territory":"US","patent_type":"Formulation","expiry_date":"2035-02-26T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10226436","territory":"US","patent_type":"Formulation","expiry_date":"2038-01-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10568850","territory":"US","patent_type":"Formulation","expiry_date":"2038-01-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"12245996","territory":"US","patent_type":"Formulation","expiry_date":"2038-01-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10159657","territory":"US","patent_type":"Formulation","expiry_date":"2038-01-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"11413259","territory":"US","patent_type":"Formulation","expiry_date":"2038-01-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10420735","territory":"US","patent_type":"Formulation","expiry_date":"2038-01-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"11602508","territory":"US","patent_type":"Formulation","expiry_date":"2038-01-30T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"10888534","territory":"US","patent_type":"Formulation","expiry_date":"2039-04-26T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"12097170","territory":"US","patent_type":"Formulation","expiry_date":"2041-03-08T00:00:00.000Z","status":"active","paragraph_iv_filed":false},{"patent_number":"12290494","territory":"US","patent_type":"Formulation","expiry_date":"2041-03-08T00:00:00.000Z","status":"active","paragraph_iv_filed":false}],"trialStats":{"total":7,"withResults":0},"validation":{"fieldsValidated":4,"lastValidatedAt":"2026-04-20T08:28:24.342853+00:00","fieldsConflicting":0,"overallConfidence":0.95},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}