{"id":"aldactone","rwe":[],"_fda":{"id":"76b5d6ad-0b7b-4781-b990-5ba036cf5a67","set_id":"08738ad4-1607-4d55-af71-6790477353bd","openfda":{"nui":["N0000175557","N0000011310"],"unii":["27O7W4T232"],"route":["ORAL"],"rxcui":["198222"],"spl_id":["76b5d6ad-0b7b-4781-b990-5ba036cf5a67"],"brand_name":["Spironolactone"],"spl_set_id":["08738ad4-1607-4d55-af71-6790477353bd"],"package_ndc":["50090-6539-0","50090-6539-1"],"product_ndc":["50090-6539"],"generic_name":["SPIRONOLACTONE"],"product_type":["HUMAN PRESCRIPTION DRUG"],"substance_name":["SPIRONOLACTONE"],"pharm_class_epc":["Aldosterone Antagonist [EPC]"],"pharm_class_moa":["Aldosterone Antagonists [MoA]"],"manufacturer_name":["A-S Medication Solutions"],"application_number":["ANDA040750"],"original_packager_product_ndc":["69584-854"]},"version":"5","pregnancy":["8.1 Pregnancy Risk Summary Based on mechanism of action and findings in animal studies, spironolactone may affect sex differentiation of the male during embryogenesis [see Data ] . Rat embryofetal studies report feminization of male fetuses and endocrine dysfunction in females exposed to spironolactone in utero. Limited available data from published case reports and case series did not demonstrate an association of major malformations or other adverse pregnancy outcomes with spironolactone . There are risks to the mother and fetus associated with heart failure, cirrhosis and poorly controlled hypertension during pregnancy [see Clinical Considerations ] . Because of the potential risk to the male fetus due to anti-androgenic properties of spironolactone and animal data, avoid spironolactone in pregnant women or advise a pregnant woman of the potential risk to a male fetus. 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%-4% and 15%-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with congestive heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. Clinical classification of heart disease may worsen with pregnancy and lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure . Pregnant women with symptomatic cirrhosis generally have poor outcomes including hepatic failure, variceal hemorrhage, preterm delivery, fetal growth restriction and maternal death. Outcomes are worse with coexisting esophageal varices. Pregnant women with cirrhosis of the liver should be carefully monitored and managed accordingly. Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Data Animal Data Teratology studies with spironolactone have been carried out in mice and rabbits at doses of up to 20 mg/kg/day. On a body surface area basis, this dose in the mouse is substantially below the maximum recommended human dose and, in the rabbit, approximates the maximum recommended human dose. No teratogenic or other embryotoxic effects were observed in mice, but the 20 mg/kg dose caused an increased rate of resorption and a lower number of live fetuses in rabbits. Because of its antiandrogenic activity and the requirement of testosterone for male morphogenesis, spironolactone may have the potential for adversely affecting sex differentiation of the male during embryogenesis. When administered to rats at 200 mg/kg/day between gestation days 13 and 21 (late embryogenesis and fetal development), feminization of male fetuses was observed. Offspring exposed during late pregnancy to 50 and 100 mg/kg/day doses of spironolactone exhibited changes in the reproductive tract including dose-dependent decreases in weights of the ventral prostate and seminal vesicle in males, ovaries and uteri that were enlarged in females, and other indications of endocrine dysfunction, that persisted into adulthood. Spironolactone has known endocrine effects in animals including progestational and antiandrogenic effects."],"overdosage":["10 OVERDOSAGE The oral LD 50 of spironolactone is greater than 1000 mg/kg in mice, rats, and rabbits. Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Rarely, instances of hyponatremia, hyperkalemia, or hepatic coma may occur in patients with severe liver disease, but these are unlikely due to acute overdosage. Hyperkalemia may occur, especially in patients with impaired renal function. Treatment: Induce vomiting or evacuate the stomach by lavage. There is no specific antidote. Treatment is supportive to maintain hydration, electrolyte balance, and vital functions. Patients who have renal impairment may develop hyperkalemia. In such cases, discontinue spironolactone."],"description":["11 DESCRIPTION Spironolactone oral tablets contain 25 mg, 50 mg, or 100 mg of the aldosterone antagonist spironolactone, 17­ hydroxy-7α-mercapto-3-oxo-17α-pregn-4-ene-21-carboxylic acid γ-lactone acetate, which has the following structural formula: Spironolactone is practically insoluble in water, soluble in alcohol, and freely soluble in benzene and in chloroform. Inactive ingredients include calcium sulfate, hypromellose, magnesium stearate, microcrystalline cellulose, N & A mint flavor, polyethylene glycol, povidone, pregelatinized corn starch, sodium starch glycolate, talc, and titanium dioxide 20"],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-6539 NDC: 50090-6539-0 90 TABLET, COATED in a BOTTLE NDC: 50090-6539-1 30 TABLET, COATED in a BOTTLE"],"geriatric_use":["8.5 Geriatric Use Spironolactone is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, monitor renal function."],"pediatric_use":["8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established."],"effective_time":"20251119","clinical_studies":["14 CLINICAL STUDIES 14.1 Heart Failure The Randomized Spironolactone Evaluation Study was a placebo controlled, double-blind study of the effect of spironolactone on mortality in patients with highly symptomatic heart failure and reduced ejection fraction. To be eligible to participate patients had to have an ejection fraction of ≤ 35%, NYHA class III-IV symptoms, and a history of NYHA class IV symptoms within the last 6 months before enrollment. Patients with a baseline serum creatinine of >2.5 mg/dL or a recent increase of 25% or with a baseline serum potassium of >5.0 mEq/L were excluded. Follow-up visits and laboratory measurements (including serum potassium and creatinine) were performed every four weeks for the first 12 weeks, then every 3 months for the first year, and then every 6 months thereafter. The initial dose of spironolactone was 25 mg once daily. Patients who were intolerant of the initial dosage regimen had their dose decreased to one 25 mg tablet every other day at one to four weeks. Patients who were tolerant of one tablet daily at 8 weeks may have had their dose increased to 50 mg daily at the discretion of the investigator. The mean daily dose at study end for patients randomized to spironolactone was 26 mg. 1663 patients were randomized 1:1 to spironolactone or placebo. 87% of patients were white, 7% black, 2% Asian. 73% were male and median age was 67. The median ejection fraction was 26%. 70% were NYHA class III and 29% class IV. The etiology of heart failure was ischemic in 55%, and non-ischemic in 45%. There was a history of myocardial infarction in 28%, of hypertension in 24%, and of diabetes in 22%. The median baseline serum creatinine was 1.2 mg/dL and the median baseline creatinine clearance was 57 mL/min. At baseline 100% of patients were taking loop diuretic and 95% were taking an ACE inhibitor. Other medications used at any time during the study included digoxin (78%), anticoagulants (58%), aspirin (43%), and beta-blockers (15%). The primary endpoint for Randomized Spironolactone Evaluation Study was time to all-cause mortality. Randomized Spironolactone Evaluation Study was terminated early because of significant mortality benefit demonstrated during a planned interim analysis. Compared to placebo, spironolactone reduced the risk of death by 30% (p<0.001; 95% confidence interval 18% to 40%). Spironolactone also reduced the risk of hospitalization for cardiac causes (defined as worsening heart failure, angina, ventricular arrhythmias, or myocardial infarction) by 30% (p <0.001; 95% confidence interval 18% to 41%). The survival curves by treatment group are shown in Figure 1 . Figure 1. Survival by Treatment Group in Randomized Spironolactone Evaluation Study Mortality hazard ratios for some subgroups are shown in Figure 2 . The favorable effect of spironolactone on mortality appeared similar for both genders and all age groups except patients younger than 55. There were too few non-whites in Randomized Spironolactone Evaluation Study to evaluate if the effects differ by race. Spironolactone’s benefit appeared greater in patients with low baseline serum potassium levels and less in patients with ejection fractions <0.2. These subgroup analyses must be interpreted cautiously. Figure 2. Hazard Ratios of All-Cause Mortality by Subgroup in Randomized Spironolactone Evaluation Study Figure 2 : The size of each box is proportional to the sample size as well as the event rate. LVEF denotes left ventricular ejection fraction, Ser Creatinine denotes serum creatinine, Cr Clearance denotes creatinine clearance, and ACEI denotes angiotensin-converting enzyme inhibitor. 14.2 Hypertension The dose response of spironolactone for hypertension has not been well characterized. In patients with hypertension, decreases in systolic blood pressure have been observed at doses ranging from 25 to 100 mg/day. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure [see Dosage and Administration (2.3) ] ."],"pharmacodynamics":["12.2 Pharmacodynamics Aldosterone antagonist activity: Increased levels of the mineralocorticoid, aldosterone, are present in primary and secondary hyperaldosteronism. Edematous states in which secondary aldosteronism is usually involved include congestive heart failure, hepatic cirrhosis, and nephrotic syndrome. By competing with aldosterone for receptor sites, spironolactone provides effective therapy for the edema and ascites in those conditions. Spironolactone counteracts secondary aldosteronism induced by the volume depletion and associated sodium loss caused by active diuretic therapy."],"pharmacokinetics":["12.3 Pharmacokinetics Absorption The mean time to reach peak plasma concentration of spironolactone and the active metabolite, canrenone, in healthy volunteers is 2.6 and 4.3 hours, respectively. Effect of food : Food increased the bioavailability of spironolactone (as measured by AUC) by approximately 95.4%. Patients should establish a routine pattern for taking spironolactone with regard to meals [see Dosage and Administration (2.1) ] . Distribution Spironolactone and its metabolites are more than 90% bound to plasma proteins. Elimination The mean half-life of spironolactone is 1.4 hour. The mean half-life values of its metabolites including canrenone, 7-α-(thiomethyl) spirolactone (TMS), and 6-ß-hydroxy-7-α-(thiomethyl) spirolactone (HTMS) are 16.5, 13.8, and 15 hours, respectively. Metabolism: Spironolactone is rapidly and extensively metabolized. Metabolites can be divided into two main categories: those in which sulfur of the parent molecule is removed (e.g., canrenone) and those in which the sulfur is retained (e.g., TMS and HTMS). In humans, the potencies of TMS and 7-α-thiospirolactone in reversing the effects of the synthetic mineralocorticoid, fludrocortisone, on urinary electrolyte composition were approximately a third relative to spironolactone. However, since the serum concentrations of these steroids were not determined, their incomplete absorption and/or first-pass metabolism could not be ruled out as a reason for their reduced in vivo activities. Excretion: The metabolites are excreted primarily in the urine and secondarily in bile. Specific Populations The impact of age, sex, race/ethnicity, and renal impairment on the pharmacokinetics of spironolactone have not been specifically studied. Patients with Hepatic Impairment: The terminal half-life of spironolactone has been reported to be increased in patients with cirrhotic ascites [see Use in Specific Populations (8.7) ] . Drug Interaction Studies: Drugs and Supplements Increasing Serum Potassium: Concomitant administration of spironolactone with potassium supplementation, salt substitutes containing potassium, a diet rich in potassium, or drugs that can increase potassium, including ACE inhibitors, angiotensin II antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), heparin and low molecular weight heparin, may lead to severe hyperkalemia [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ] . Lithium: Spironolactone reduces the renal clearance of lithium, inducing a high risk of lithium toxicity [see Drug Interactions (7.2) ] . Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing, and thiazide diuretics [see Drug Interactions (7.3) ] . Acetylsalicylic acid: A single dose of 600 mg of acetylsalicylic acid inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone [see Drug Interactions (7.6) ] ."],"adverse_reactions":["6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hyperkalemia [see Warnings and Precautions (5.1) ] Hypotension and Worsening Renal Function [see Warnings and Precautions (5.2) ] Electrolyte and Metabolic Abnormalities [see Warnings and Precautions (5.3) ] Gynecomastia [see Warnings and Precautions (5.4) ] Impaired neurological function/ coma in patients with hepatic impairment, cirrhosis and ascites [see Use in Specific Populations (8.7) ] The following adverse reactions associated with the use of spironolactone were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency, reliably, or to establish a causal relationship to drug exposure. Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting. Reproductive: Decreased libido, inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding, breast and nipple pain. Hematologic: Leukopenia (including agranulocytosis), thrombocytopenia. Hypersensitivity: Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis. Metabolism: Hyperkalemia, electrolyte disturbances [see Warnings and Precautions (5.1 , 5.3) ] , hyponatremia, hypovolemia. Musculoskeletal : Leg cramps. Nervous system/psychiatric: Lethargy, mental confusion, ataxia, dizziness, headache, drowsiness. Liver/biliary: A very few cases of mixed cholestatic/hepatocellular toxicity, with one reported fatality, have been reported with spironolactone administration. Renal: Renal dysfunction (including renal failure). Skin: Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, pruritis. The most common adverse reaction with spironolactone treatment is gynecomastia ( 5.4 , 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Oxford, at 1-844-508-1455, 8:00 am – 4:30 ET, Monday – Friday or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."],"contraindications":["4 CONTRAINDICATIONS Spironolactone is contraindicated in the patients with: Hyperkalemia Addison’s disease Concomitant use of eplerenone Spironolactone is contraindicated in patients with ( 4 ): Hyperkalemia Addison’s disease Concomitant use of eplerenone"],"drug_interactions":["7 DRUG INTERACTIONS Agents increasing serum potassium: Concomitant administration can lead to hyperkalemia ( 5.1 , 7.1 ). Lithium: Increased risk of lithium toxicity ( 7.2 ). NSAIDs: May reduce the diuretic, natriuretic and antihypertensive effect of spironolactone ( 7.3 ). Digoxin: spironolactone can interfere with radioimmunologic assays of digoxin exposure ( 7.4) . Cholestyramine: Hyperkalemic metabolic acidosis has been reported with concomitant use ( 7.5 ). Acetylsalicylic Acid (ASA): ASA may reduce the efficacy of spironolactone ( 7.6 ) Abiraterone: May increase prostate-specific antigen (PSA) levels ( 7.7 ). 7.1 Drugs and Supplements Increasing Serum Potassium Concomitant administration of spironolactone with potassium supplementation or drugs that can increase potassium may lead to severe hyperkalemia. In general, discontinue potassium supplementation in heart failure patients who start spironolactone [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ] . Check serum potassium levels when ACE inhibitor or ARB therapy is altered in patients receiving spironolactone. Examples of drugs that can increase potassium include: ACE inhibitors angiotensin receptor blockers non-steroidal anti-inflammatory drugs (NSAIDs) heparin and low molecular weight heparin trimethoprim 7.2 Lithium Like other diuretics, spironolactone reduces the renal clearance of lithium, thus increasing the risk of lithium toxicity. Monitor lithium levels periodically when spironolactone is coadministered [see Clinical Pharmacology (12.3) ] . 7.3 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of diuretics. Therefore, when spironolactone and NSAIDs are used concomitantly, monitor closely to determine if the desired effect of the diuretic is obtained [see Clinical Pharmacology (12.3) ] . 7.4 Digoxin Spironolactone and its metabolites interfere with radioimmunoassays for digoxin and increase the apparent exposure to digoxin. It is unknown to what extent, if any, spironolactone may increase actual digoxin exposure. In patients taking concomitant digoxin, use an assay that does not interact with spironolactone. 7.5 Cholestyramine Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine. 7.6 Acetylsalicylic Acid Acetylsalicylic acid may reduce the efficacy of spironolactone. Therefore, when spironolactone and acetylsalicylic acid are used concomitantly, spironolactone may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained [see Clinical Pharmacology (12.3) ] . 7.7 Abiraterone Spironolactone binds to the androgen receptor and may increase prostate-specific antigen (PSA) levels in abiraterone-treated prostate cancer patients. Concomitant use of spironolactone and abiraterone is not recommended."],"mechanism_of_action":["12.1 Mechanism of Action Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents that act more proximally in the renal tubule."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents that act more proximally in the renal tubule. 12.2 Pharmacodynamics Aldosterone antagonist activity: Increased levels of the mineralocorticoid, aldosterone, are present in primary and secondary hyperaldosteronism. Edematous states in which secondary aldosteronism is usually involved include congestive heart failure, hepatic cirrhosis, and nephrotic syndrome. By competing with aldosterone for receptor sites, spironolactone provides effective therapy for the edema and ascites in those conditions. Spironolactone counteracts secondary aldosteronism induced by the volume depletion and associated sodium loss caused by active diuretic therapy. 12.3 Pharmacokinetics Absorption The mean time to reach peak plasma concentration of spironolactone and the active metabolite, canrenone, in healthy volunteers is 2.6 and 4.3 hours, respectively. Effect of food : Food increased the bioavailability of spironolactone (as measured by AUC) by approximately 95.4%. Patients should establish a routine pattern for taking spironolactone with regard to meals [see Dosage and Administration (2.1) ] . Distribution Spironolactone and its metabolites are more than 90% bound to plasma proteins. Elimination The mean half-life of spironolactone is 1.4 hour. The mean half-life values of its metabolites including canrenone, 7-α-(thiomethyl) spirolactone (TMS), and 6-ß-hydroxy-7-α-(thiomethyl) spirolactone (HTMS) are 16.5, 13.8, and 15 hours, respectively. Metabolism: Spironolactone is rapidly and extensively metabolized. Metabolites can be divided into two main categories: those in which sulfur of the parent molecule is removed (e.g., canrenone) and those in which the sulfur is retained (e.g., TMS and HTMS). In humans, the potencies of TMS and 7-α-thiospirolactone in reversing the effects of the synthetic mineralocorticoid, fludrocortisone, on urinary electrolyte composition were approximately a third relative to spironolactone. However, since the serum concentrations of these steroids were not determined, their incomplete absorption and/or first-pass metabolism could not be ruled out as a reason for their reduced in vivo activities. Excretion: The metabolites are excreted primarily in the urine and secondarily in bile. Specific Populations The impact of age, sex, race/ethnicity, and renal impairment on the pharmacokinetics of spironolactone have not been specifically studied. Patients with Hepatic Impairment: The terminal half-life of spironolactone has been reported to be increased in patients with cirrhotic ascites [see Use in Specific Populations (8.7) ] . Drug Interaction Studies: Drugs and Supplements Increasing Serum Potassium: Concomitant administration of spironolactone with potassium supplementation, salt substitutes containing potassium, a diet rich in potassium, or drugs that can increase potassium, including ACE inhibitors, angiotensin II antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), heparin and low molecular weight heparin, may lead to severe hyperkalemia [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ] . Lithium: Spironolactone reduces the renal clearance of lithium, inducing a high risk of lithium toxicity [see Drug Interactions (7.2) ] . Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing, and thiazide diuretics [see Drug Interactions (7.3) ] . Acetylsalicylic acid: A single dose of 600 mg of acetylsalicylic acid inhibited the natriuretic effect of spironolactone, which was hypothesized be due to inhibition of tubular secretion of canrenone, causing decreased effectiveness of spironolactone [see Drug Interactions (7.6) ] ."],"indications_and_usage":["1 INDICATIONS AND USAGE Spironolactone is an aldosterone antagonist indicated for: The treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and to reduce the need for hospitalization for heart failure ( 1.1 ). Use as an add-on therapy for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions ( 1.2 ). The management of edema in adult patients who are cirrhotic when edema is not responsive to fluid and sodium restrictions and in the setting of nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics produce an inadequate response ( 1.3 ). Treatment of primary hyperaldosteronism for: ( 1.4 ) Short-term preoperative treatment Long-term maintenance for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery and patients with bilateral micro or macronodular adrenal hyperplasia 1.1 Heart Failure Spironolactone is indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. Spironolactone is usually administered in conjunction with other heart failure therapies. 1.2 Hypertension Spironolactone is indicated as add-on therapy for the treatment of hypertension, to lower blood pressure in patients who are not adequately controlled on other agents. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. 1.3 Edema Associated with Hepatic Cirrhosis or Nephrotic Syndrome Spironolactone is indicated for the management of edema in the following settings: Cirrhosis of the liver when edema is not responsive to fluid and sodium restriction. Nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics produce an inadequate response. Because it increases serum potassium, spironolactone may be useful for treating edema when administration of other diuretics has caused hypokalemia. 1.4 Primary Hyperaldosteronism Spironolactone is indicated in the following settings: Short-term preoperative treatment of patients with primary hyperaldosteronism. Long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery. Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism)."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS Hyperkalemia: Monitor serum potassium within one week of initiation and regularly thereafter ( 5.1 ). Hypotension and Worsening Renal Function: Monitor volume status and renal function periodically ( 5.2 ). Electrolyte and Metabolic Abnormalities: Monitor serum electrolytes, uric acid and blood glucose periodically ( 5.3 ). Gynecomastia: Spironolactone can cause gynecomastia ( 5.4 ). 5.1 Hyperkalemia Spironolactone can cause hyperkalemia. This risk is increased by impaired renal function or concomitant potassium supplementation, potassium-containing salt substitutes or drugs that increase potassium, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers [see Drug Interactions (7.1) ] . Monitor serum potassium within 1 week of initiation or titration of spironolactone and regularly thereafter. More frequent monitoring may be needed when spironolactone is given with other drugs that cause hyperkalemia or in patients with impaired renal function. If hyperkalemia occurs, decrease the dose or discontinue spironolactone and treat hyperkalemia. 5.2 Hypotension and Worsening Renal Function Excessive diuresis may cause symptomatic dehydration, hypotension and worsening renal function, particularly in salt-depleted patients or those taking angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Worsening of renal function can also occur with concomitant use of nephrotoxic drugs (e.g., aminoglycosides, cisplatin, and NSAIDs). Monitor volume status and renal function periodically. 5.3 Electrolyte and Metabolic Abnormalities In addition to causing hyperkalemia, spironolactone can cause hyponatremia, hypomagnesemia, hypocalcemia, hypochloremic alkalosis, and hyperglycemia. Asymptomatic hyperuricemia can occur and rarely gout is precipitated. Monitor serum electrolytes, uric acid and blood glucose periodically. 5.4 Gynecomastia Spironolactone can cause gynecomastia. In Randomized Spironolactone Evaluation Study, patients with heart failure treated with a mean dose of 26 mg of spironolactone once daily, about 9% of the male subjects developed gynecomastia. The risk of gynecomastia increases in a dose-dependent manner with an onset that varies widely from 1-2 months to over a year. Gynecomastia is usually reversible."],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Orally administered spironolactone has been shown to be a tumorigen in dietary administration studies performed in Sprague Dawley rats, with its proliferative effects manifested on endocrine organs and the liver. In an 18-month study using doses of about 50, 150, and 500 mg/kg/day, there were statistically significant increases in benign adenomas of the thyroid and testes and, in male rats, a dose-related increase in proliferative changes in the liver (including hepatocytomegaly and hyperplastic nodules). In 24-month studies in which rats were administered doses of about 10, 30, 100, and 150 mg spironolactone/kg/day, the range of proliferative effects included significant increases in hepatocellular adenomas and testicular interstitial cell tumors in males, and significant increases in thyroid follicular cell adenomas and carcinomas in both sexes. There was also a statistically significant increase in benign uterine endometrial stromal polyps in females. Mutagenesis Neither spironolactone nor potassium canrenoate produced mutagenic effects in tests using bacteria or yeast. In the absence of metabolic activation, neither spironolactone nor potassium canrenoate has been shown to be mutagenic in mammalian tests in vitro. In the presence of metabolic activation, spironolactone has been reported to be negative in some mammalian mutagenicity tests in vitro and inconclusive (but slightly positive) for mutagenicity in other mammalian tests in vitro. In the presence of metabolic activation, potassium canrenoate has been reported to test positive for mutagenicity in some mammalian tests in vitro, inconclusive in others, and negative in still others. Impairment of Fertility In a three-litter reproduction study in which female rats received dietary doses of 15 and 50 mg spironolactone/kg/day, there were no effects on mating and fertility, but there was a small increase in incidence of stillborn pups at 50 mg/kg/day. When injected into female rats (100 mg/kg/day for 7 days, i.p.), spironolactone was found to increase the length of the estrous cycle by prolonging diestrus during treatment and inducing constant diestrus during a two-week post-treatment observation period. These effects were associated with retarded ovarian follicle development and a reduction in circulating estrogen levels, which would be expected to impair mating, fertility, and fecundity. Spironolactone (100 mg/kg/day), administered i.p. to female mice during a two-week cohabitation period with untreated males, decreased the number of mated mice that conceived (effect shown to be caused by an inhibition of ovulation) and decreased the number of implanted embryos in those that became pregnant (effect shown to be caused by an inhibition of implantation), and at 200 mg/kg, also increased the latency period to mating."],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Patients who receive spironolactone should be advised to avoid potassium supplements and foods containing high levels of potassium, including salt substitutes. For more information, call Oxford Pharmaceuticals, LLC at 1-844-508-1455, 8:00 am – 4:30 pm ET, Monday – Friday Manufactured by: OXFORD PHARMACEUTICALS Birmingham, AL 35211 8200024 Rev 03/24 R04"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION Heart Failure: Initiate treatment at 25 mg once daily ( 2.2 ). Hypertension: Initiate treatment at 25 to 100 mg daily in either single or divided doses ( 2.3 ). Edema: Initiate therapy in a hospital setting and titrate slowly. The recommended initial daily dose is 100 mg in single or divided doses ( 2.4 ). Primary hyperaldosteronism: Initiate treatment at 100 to 400 mg in preparation for surgery. In patients unsuitable for surgery use the lowest effective dosage determined for the individual patient ( 2.5 ). 2.1 General Considerations Spironolactone can be taken with or without food, but should be taken consistently with respect to food [see Clinical Pharmacology (12.3) ] . 2.2 Treatment of Heart Failure In patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m², initiate treatment at 25 mg once daily. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily as clinically indicated. Patients who develop hyperkalemia on 25 mg once daily may have their dosage reduced to 25 mg every other day [see Warnings and Precautions (5.1) ] . In patients with an eGFR between 30 and 50 mL/min/1.73 m 2 , consider initiating therapy at 25 mg every other day because of the risk of hyperkalemia [see Use in Specific Populations (8.6) ]. 2.3 Treatment of Essential Hypertension The recommended initial daily dose is 25 to 100 mg of spironolactone administered in either single or divided doses is recommended. Dosage can be titrated at two-week intervals. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure. 2.4 Treatment of Edema In patients with cirrhosis, initiate therapy in a hospital setting and titrate slowly [see Use in Specific Populations (8.7) ] . The recommended initial daily dosage is 100 mg of spironolactone administered in either single or divided doses, but may range from 25 to 200 mg daily. When given as the sole agent for diuresis, administer for at least five days before increasing dose to obtain desired effect. 2.5 Treatment of Primary Hyperaldosteronism Administer spironolactone in doses of 100 to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone can be used as long-term maintenance therapy at the lowest effective dosage determined for the individual patient."],"spl_product_data_elements":["Spironolactone Spironolactone SPIRONOLACTONE SPIRONOLACTONE Calcium Sulfate Dihydrate HYDROXYPROPYL METHYLCELLULOSE Magnesium Stearate Microcrystalline Cellulose 101 Mint Polyethylene Glycol, Unspecified Povidone K30 ZEA MAYS (CORN) STARCH Sodium Starch Glycolate Type A Potato Talc CI 77891 white to off-white 854;O Figure 1 Figure 2"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Tablets: 25 mg round, white to off-white, convex, coated, debossed with 852 on one side and debossed with “O” on the other side. Tablets: 50 mg oval, white to off-white, scored, convex, coated, debossed with 853 left of the bisect on one side and debossed with “O” on the other side. Tablets: 100 mg round, white to off-white, scored, convex, coated, debossed with 854 above the bisect on one side and debossed with “O” on the other side. Tablets: 25 mg, 50 mg, and 100 mg ( 3 )."],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, spironolactone may affect sex differentiation of the male during embryogenesis ( 8.1 ). 8.1 Pregnancy Risk Summary Based on mechanism of action and findings in animal studies, spironolactone may affect sex differentiation of the male during embryogenesis [see Data ] . Rat embryofetal studies report feminization of male fetuses and endocrine dysfunction in females exposed to spironolactone in utero. Limited available data from published case reports and case series did not demonstrate an association of major malformations or other adverse pregnancy outcomes with spironolactone . There are risks to the mother and fetus associated with heart failure, cirrhosis and poorly controlled hypertension during pregnancy [see Clinical Considerations ] . Because of the potential risk to the male fetus due to anti-androgenic properties of spironolactone and animal data, avoid spironolactone in pregnant women or advise a pregnant woman of the potential risk to a male fetus. 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%-4% and 15%-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with congestive heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. Clinical classification of heart disease may worsen with pregnancy and lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure . Pregnant women with symptomatic cirrhosis generally have poor outcomes including hepatic failure, variceal hemorrhage, preterm delivery, fetal growth restriction and maternal death. Outcomes are worse with coexisting esophageal varices. Pregnant women with cirrhosis of the liver should be carefully monitored and managed accordingly. Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Data Animal Data Teratology studies with spironolactone have been carried out in mice and rabbits at doses of up to 20 mg/kg/day. On a body surface area basis, this dose in the mouse is substantially below the maximum recommended human dose and, in the rabbit, approximates the maximum recommended human dose. No teratogenic or other embryotoxic effects were observed in mice, but the 20 mg/kg dose caused an increased rate of resorption and a lower number of live fetuses in rabbits. Because of its antiandrogenic activity and the requirement of testosterone for male morphogenesis, spironolactone may have the potential for adversely affecting sex differentiation of the male during embryogenesis. When administered to rats at 200 mg/kg/day between gestation days 13 and 21 (late embryogenesis and fetal development), feminization of male fetuses was observed. Offspring exposed during late pregnancy to 50 and 100 mg/kg/day doses of spironolactone exhibited changes in the reproductive tract including dose-dependent decreases in weights of the ventral prostate and seminal vesicle in males, ovaries and uteri that were enlarged in females, and other indications of endocrine dysfunction, that persisted into adulthood. Spironolactone has known endocrine effects in animals including progestational and antiandrogenic effects. 8.2 Lactation Risk Summary Spironolactone is not present in breastmilk; however, limited data from a lactating woman at 17 days postpartum reports the presence of the active metabolite, canrenone, in human breast milk in low amounts that are expected to be clinically inconsequential. In this case, there were no adverse effects reported for the breastfed infant after short term exposure to spironolactone; however, long term effects on a breastfed infant are unknown. There are no data on spironolactone effects on milk production. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for spironolactone and any potential adverse effects on the breastfed child from spironolactone or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Spironolactone is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, monitor renal function. 8.6 Use in Renal Impairment Spironolactone is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Patients with renal impairment are at increased risk of hyperkalemia. Monitor potassium closely. 8.7 Use in Hepatic Impairment Spironolactone can cause sudden alterations of fluid and electrolyte balance which may precipitate impaired neurological function, worsening hepatic encephalopathy and coma in patients with hepatic disease with cirrhosis and ascites. In these patients, initiate spironolactone in the hospital [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] . Clearance of spironolactone and its metabolites is reduced in patients with cirrhosis. In patients with cirrhosis, start with lowest initial dose and titrate slowly [ see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] ."],"package_label_principal_display_panel":["SPIRONOLACTONE Label Image"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Orally administered spironolactone has been shown to be a tumorigen in dietary administration studies performed in Sprague Dawley rats, with its proliferative effects manifested on endocrine organs and the liver. In an 18-month study using doses of about 50, 150, and 500 mg/kg/day, there were statistically significant increases in benign adenomas of the thyroid and testes and, in male rats, a dose-related increase in proliferative changes in the liver (including hepatocytomegaly and hyperplastic nodules). In 24-month studies in which rats were administered doses of about 10, 30, 100, and 150 mg spironolactone/kg/day, the range of proliferative effects included significant increases in hepatocellular adenomas and testicular interstitial cell tumors in males, and significant increases in thyroid follicular cell adenomas and carcinomas in both sexes. There was also a statistically significant increase in benign uterine endometrial stromal polyps in females. Mutagenesis Neither spironolactone nor potassium canrenoate produced mutagenic effects in tests using bacteria or yeast. In the absence of metabolic activation, neither spironolactone nor potassium canrenoate has been shown to be mutagenic in mammalian tests in vitro. In the presence of metabolic activation, spironolactone has been reported to be negative in some mammalian mutagenicity tests in vitro and inconclusive (but slightly positive) for mutagenicity in other mammalian tests in vitro. In the presence of metabolic activation, potassium canrenoate has been reported to test positive for mutagenicity in some mammalian tests in vitro, inconclusive in others, and negative in still others. Impairment of Fertility In a three-litter reproduction study in which female rats received dietary doses of 15 and 50 mg spironolactone/kg/day, there were no effects on mating and fertility, but there was a small increase in incidence of stillborn pups at 50 mg/kg/day. When injected into female rats (100 mg/kg/day for 7 days, i.p.), spironolactone was found to increase the length of the estrous cycle by prolonging diestrus during treatment and inducing constant diestrus during a two-week post-treatment observation period. These effects were associated with retarded ovarian follicle development and a reduction in circulating estrogen levels, which would be expected to impair mating, fertility, and fecundity. Spironolactone (100 mg/kg/day), administered i.p. to female mice during a two-week cohabitation period with untreated males, decreased the number of mated mice that conceived (effect shown to be caused by an inhibition of ovulation) and decreased the number of implanted embryos in those that became pregnant (effect shown to be caused by an inhibition of implantation), and at 200 mg/kg, also increased the latency period to mating."]},"tags":[],"safety":{"boxedWarnings":[],"safetySignals":[{"date":"","signal":"DYSPNOEA","source":"FDA FAERS","actionTaken":"10467 reports"},{"date":"","signal":"FATIGUE","source":"FDA FAERS","actionTaken":"8228 reports"},{"date":"","signal":"NAUSEA","source":"FDA FAERS","actionTaken":"7871 reports"},{"date":"","signal":"DIARRHOEA","source":"FDA FAERS","actionTaken":"7473 reports"},{"date":"","signal":"ACUTE KIDNEY INJURY","source":"FDA FAERS","actionTaken":"6792 reports"},{"date":"","signal":"DIZZINESS","source":"FDA FAERS","actionTaken":"6274 reports"},{"date":"","signal":"HEADACHE","source":"FDA FAERS","actionTaken":"5905 reports"},{"date":"","signal":"HYPOTENSION","source":"FDA FAERS","actionTaken":"5843 reports"},{"date":"","signal":"OFF LABEL USE","source":"FDA FAERS","actionTaken":"5587 reports"},{"date":"","signal":"DRUG INEFFECTIVE","source":"FDA FAERS","actionTaken":"5232 reports"}],"drugInteractions":[{"drug":"Potassium supplementation, salt substitutes containing potassium, ACE inhibitors, angiotensin II antagonists, NSAIDs, heparin, low molecular weight heparin, trimethoprim","severity":"Severe","mechanism":"Concomitant administration increases serum potassium","management":"Discontinue potassium supplementation in heart failure patients who start spironolactone; check serum potassium levels when ACE inhibitor or ARB therapy is altered","clinicalEffect":"Severe hyperkalemia"},{"drug":"Lithium","severity":"High","mechanism":"Spironolactone reduces renal clearance of lithium","management":"Monitor lithium levels periodically when coadministered","clinicalEffect":"High risk of lithium toxicity"},{"drug":"NSAIDs","severity":"Moderate","mechanism":"NSAIDs reduce diuretic effect","management":"Monitor closely to determine if desired diuretic effect is obtained","clinicalEffect":"Reduced diuretic, natriuretic, and antihypertensive effect of spironolactone"},{"drug":"Digoxin","severity":"Moderate","mechanism":"Spironolactone and metabolites interfere with radioimmunoassays","management":"","clinicalEffect":"Interference with radioimmunologic assays of digoxin exposure"},{"drug":"Cholestyramine","severity":"Moderate","mechanism":"Concomitant use","management":"","clinicalEffect":"Hyperkalemic metabolic acidosis"},{"drug":"Acetylsalicylic acid (ASA)","severity":"Moderate","mechanism":"ASA inhibits tubular secretion","management":"","clinicalEffect":"Reduced natriuretic effect and efficacy of spironolactone"},{"drug":"Abiraterone","severity":"Moderate","mechanism":"Concomitant use","management":"","clinicalEffect":"May increase prostate-specific antigen (PSA) levels"}],"commonSideEffects":[{"effect":"Hyperkalaemia","drugRate":"25.3%","placeboRate":"","totalAtRisk":801,"totalAffected":203,"trialsReporting":2},{"effect":"Hypokalaemia","drugRate":"8.2%","placeboRate":"","totalAtRisk":801,"totalAffected":66,"trialsReporting":2},{"effect":"Diarrhoea","drugRate":"4.3%","placeboRate":"","totalAtRisk":439,"totalAffected":19,"trialsReporting":1},{"effect":"Hypomagnesaemia","drugRate":"4.3%","placeboRate":"","totalAtRisk":439,"totalAffected":19,"trialsReporting":1},{"effect":"Hypotension","drugRate":"3.4%","placeboRate":"","totalAtRisk":439,"totalAffected":15,"trialsReporting":1},{"effect":"Glomerular filtration rate decreased","drugRate":"3.4%","placeboRate":"","totalAtRisk":439,"totalAffected":15,"trialsReporting":1},{"effect":"Anaemia","drugRate":"2.5%","placeboRate":"","totalAtRisk":439,"totalAffected":11,"trialsReporting":1},{"effect":"Constipation","drugRate":"2.5%","placeboRate":"","totalAtRisk":439,"totalAffected":11,"trialsReporting":1},{"effect":"Cardiac failure","drugRate":"2.3%","placeboRate":"","totalAtRisk":439,"totalAffected":10,"trialsReporting":1},{"effect":"Back pain","drugRate":"2.3%","placeboRate":"","totalAtRisk":439,"totalAffected":10,"trialsReporting":1},{"effect":"Hyperglycaemia","drugRate":"2.3%","placeboRate":"","totalAtRisk":439,"totalAffected":10,"trialsReporting":1},{"effect":"Iron deficiency anaemia","drugRate":"2.1%","placeboRate":"","totalAtRisk":439,"totalAffected":9,"trialsReporting":1},{"effect":"Headache","drugRate":"2.1%","placeboRate":"","totalAtRisk":439,"totalAffected":9,"trialsReporting":1},{"effect":"Hypertension","drugRate":"1.8%","placeboRate":"","totalAtRisk":439,"totalAffected":8,"trialsReporting":1},{"effect":"Diabetes mellitus","drugRate":"1.6%","placeboRate":"","totalAtRisk":439,"totalAffected":7,"trialsReporting":1},{"effect":"Pneumonia","drugRate":"1.6%","placeboRate":"","totalAtRisk":439,"totalAffected":7,"trialsReporting":1},{"effect":"Gynaecomastia","drugRate":"1.4%","placeboRate":"","totalAtRisk":439,"totalAffected":6,"trialsReporting":1},{"effect":"Hydrothorax","drugRate":"1.4%","placeboRate":"","totalAtRisk":439,"totalAffected":6,"trialsReporting":1},{"effect":"Arthralgia","drugRate":"1.4%","placeboRate":"","totalAtRisk":439,"totalAffected":6,"trialsReporting":1},{"effect":"Iron deficiency","drugRate":"1.4%","placeboRate":"","totalAtRisk":439,"totalAffected":6,"trialsReporting":1},{"effect":"COVID-19","drugRate":"1.4%","placeboRate":"","totalAtRisk":439,"totalAffected":6,"trialsReporting":1},{"effect":"Asthenia","drugRate":"1.1%","placeboRate":"","totalAtRisk":439,"totalAffected":5,"trialsReporting":1},{"effect":"Oedema peripheral","drugRate":"0.6%","placeboRate":"","totalAtRisk":801,"totalAffected":5,"trialsReporting":2},{"effect":"Atrial fibrillation","drugRate":"1.1%","placeboRate":"","totalAtRisk":439,"totalAffected":5,"trialsReporting":1},{"effect":"Acute respiratory failure","drugRate":"1.1%","placeboRate":"","totalAtRisk":439,"totalAffected":5,"trialsReporting":1},{"effect":"Chronic kidney disease","drugRate":"1.1%","placeboRate":"","totalAtRisk":439,"totalAffected":5,"trialsReporting":1},{"effect":"Renal impairment","drugRate":"1.1%","placeboRate":"","totalAtRisk":439,"totalAffected":5,"trialsReporting":1},{"effect":"Dyspnoea","drugRate":"0.9%","placeboRate":"","totalAtRisk":439,"totalAffected":4,"trialsReporting":1},{"effect":"Blood creatinine increased","drugRate":"0.5%","placeboRate":"","totalAtRisk":439,"totalAffected":2,"trialsReporting":1},{"effect":"Abdominal pain upper","drugRate":"0.5%","placeboRate":"","totalAtRisk":439,"totalAffected":2,"trialsReporting":1},{"effect":"Hyponatraemia","drugRate":"0.0%","placeboRate":"","totalAtRisk":439,"totalAffected":0,"trialsReporting":1},{"effect":"Respiratory tract infection viral","drugRate":"0.0%","placeboRate":"","totalAtRisk":439,"totalAffected":0,"trialsReporting":1}],"contraindications":["Hyperkalemia","Addison's disease","Concomitant use of eplerenone"],"specialPopulations":{"Lactation":"Spironolactone is not present in breastmilk; however, the active metabolite canrenone is present in low amounts expected to be clinically inconsequential. Long-term effects on breastfed infants are unknown. Consider developmental benefits of breastfeeding along with mother's clinical need and potential adverse effects.","Pregnancy":"Based on mechanism of action and animal studies, spironolactone may affect sex differentiation of the male during embryogenesis. Rat studies report feminization of male fetuses and endocrine dysfunction in females exposed in utero. Limited human data did not demonstrate association with major malformations. Avoid spironolactone in pregnant women or advise of potential risk to male fetus. Pregnant women with heart failure, cirrhosis, or poorly controlled hypertension require close monitoring due to increased maternal and fetal risks.","Geriatric use":"Spironolactone is substantially excreted by the kidney. Elderly patients are more likely to have decreased renal function. Monitor renal function.","Pediatric use":"Safety and effectiveness in pediatric patients have not been established.","Renal impairment":"Spironolactone is substantially excreted by the kidney and risk of adverse reactions is greater in patients with impaired renal function. Patients with renal impairment are at increased risk of hyperkalemia. Monitor potassium closely.","Hepatic impairment":"Spironolactone can cause sudden alterations of fluid and electrolyte balance which may precipitate impaired neurological function, worsening hepatic encephalopathy and coma in patients with cirrhosis and ascites. Initiate in hospital. Clearance is reduced in cirrhosis; start with lowest initial dose and titrate slowly."}},"trials":[],"_chembl":null,"aliases":[],"patents":[{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":true,"patentNumber":"9757394","drugSubstance":false},{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":false,"patentNumber":"11395828","drugSubstance":false},{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":true,"patentNumber":"10888570","drugSubstance":false},{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":true,"patentNumber":"11389461","drugSubstance":false},{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":true,"patentNumber":"10660907","drugSubstance":false},{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":true,"patentNumber":"10624906","drugSubstance":false},{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":true,"patentNumber":"10493083","drugSubstance":false},{"applNo":"N209478","source":"FDA Orange Book","status":"Active","expires":"Oct 28, 2036","territory":"US","drugProduct":true,"patentNumber":"11491166","drugSubstance":false}],"pricing":[{"market":"United States","source":"CMS National Average Drug Acquisition Cost (NADAC)","asOfDate":"2024-01-03","unitCost":"$0.2016/EA","priceType":"NADAC","sourceUrl":"https://data.medicaid.gov/dataset/4j6z-xnwq","annualCost":"$74","description":"SPIRONOLACTONE 100 MG TABLET","retrievedDate":"2026-04-07"}],"_fixedAt":"2026-03-30T11:26:40.479835","_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=Spironolactone","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-19T23:28:05.358792+00:00"},"patents":{"url":"","method":"deterministic","source":"FDA Orange Book","rawText":"","confidence":1,"sourceType":"fda_orange_book","retrievedAt":"2026-04-19T23:28:05.358717+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Spironolactone","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-19T23:28:07.309427+00:00"},"aiSummary":{"url":"","method":"ai_extraction","source":"Haiku strategic summary","rawText":"","confidence":0.9,"sourceType":"ai_extraction","retrievedAt":"2026-04-20T07:55:37.701891+00:00"},"mechanism":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T08:33:43.148260+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-19T23:28:06.035976+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-19T23:28:03.898690+00:00"},"pharmacokinetics":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T08:33:43.148282+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=Spironolactone","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T23:28:06.280937+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":"2026-04-19T23:27:56.547593+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:27:56.547626+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:27:56.547632+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":"2026-04-19T23:28:07.892255+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":"2026-04-20T07:55:37.701858+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Mineralocorticoid receptor antagonist","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:28:07.309370+00:00"},"safety.drugInteractions":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T07:55:37.701889+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1393/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:28:06.975850+00:00"},"safety.contraindications":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T07:55:37.701883+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"ANDA040750","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:27:56.547636+00:00"}},"offLabel":[],"timeline":[{"date":"19600121","type":"positive","milestone":"FDA approval — PFIZER","regulator":"FDA","description":""}],"_dailymed":{"setId":"2efb4720-625f-6616-b6f0-8b13a17c9d7e","title":"SPIRONOLACTONE TABLET [BRYANT RANCH PREPACK]"},"aiSummary":"Spironolactone is a potassium-sparing diuretic and aldosterone antagonist indicated for heart failure with reduced ejection fraction, hypertension, edema management, and primary hyperaldosteronism. It demonstrates strong efficacy through competitive aldosterone receptor antagonism, increasing sodium and water excretion while retaining potassium. The primary risk is severe hyperkalemia, particularly when combined with ACE inhibitors, ARBs, NSAIDs, or potassium supplementation, requiring careful monitoring of serum potassium levels. Long-term metabolite half-lives (13.8-16.5 hours) support once-daily dosing and sustained therapeutic effects in heart failure and hypertension management.","ecosystem":[],"mechanism":{"target":"Aldosterone receptors at aldosterone-dependent sodium-potassium exchange site in distal convoluted renal tubule","novelty":"me-too","modality":"Competitive receptor antagonist","drugClass":"Potassium-sparing diuretic, aldosterone antagonist","explanation":"Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. This mechanism causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism and may be given alone or with other diuretic agents that act more proximally in the renal tubule.","oneSentence":"Aldosterone antagonist causing increased sodium and water excretion while retaining potassium.","technicalDetail":"Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule."},"_scrapedAt":"2026-03-27T23:28:22.645Z","_scrapedBy":"cloudflare-swarm","_wikipedia":{"url":"https://en.wikipedia.org/wiki/Spironolactone","title":"Spironolactone","extract":"Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat fluid build-up due to liver disease or kidney disease. It is also used to reduce risk of disease progression, hospitalization, and death due to some types of heart failure. Other uses include acne and excessive hair growth in women, low blood potassium that does not improve with supplementation, high blood pressure that is difficult to treat, and early puberty in boys. It can also be used to block the effects of testosterone as a part of feminizing hormone therapy. Spironolactone is usually available in tablets, taken by mouth, though topical forms are also available."},"commercial":{"launchDate":"1960","annualCostUS":"$50-200/yr for generics","currentRevenue":"Generic — no single company revenue","peakSalesEstimate":"$500M"},"references":[],"_validation":{"fieldsValidated":7,"lastValidatedAt":"2026-04-20T08:33:47.248717+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[],"competitors":[{"name":"Eplerenone (Inspra)","company":"Pfizer","advantage":"Selective aldosterone antagonist with fewer hormonal side effects (less gynecomastia and sexual dysfunction) compared to spironolactone"},{"name":"Amiloride (Midamor)","company":"Merck","advantage":"Potassium-sparing diuretic that works through different mechanism; alternative for patients who cannot tolerate aldosterone antagonists"},{"name":"Triamterene (Dyrenium)","company":"Various","advantage":"Potassium-sparing diuretic with rapid onset; used as alternative in patients with spironolactone intolerance"},{"name":"Finerenone (Kerendia)","company":"Bayer","advantage":"Non-steroidal selective aldosterone antagonist with improved renal and cardiovascular outcomes in diabetic kidney disease"}],"dataSources":[{"url":"https://data.medicaid.gov/dataset/4j6z-xnwq","name":"CMS National Average Drug Acquisition Cost (NADAC)","fields":["pricing"],"retrievedDate":"2026-04-07"}],"indications":{"approved":[{"name":"NYHA Class III-IV heart failure with reduced ejection fraction","regulator":"FDA"},{"name":"Hypertension as add-on therapy","regulator":"FDA"},{"name":"Edema in cirrhotic patients unresponsive to fluid and sodium restriction","regulator":"FDA"},{"name":"Edema in nephrotic syndrome with inadequate response to other treatments","regulator":"FDA"},{"name":"Short-term preoperative treatment of primary hyperaldosteronism","regulator":"FDA"},{"name":"Long-term maintenance therapy for discrete aldosterone-producing adrenal adenomas in non-surgical candidates","regulator":"FDA"},{"name":"Long-term maintenance therapy for bilateral micro or macronodular adrenal hyperplasia","regulator":"FDA"}],"offLabel":[],"pipeline":[]},"_fixedFields":["generics(25)","patents(8)"],"labelChanges":[],"relatedDrugs":[],"trialDetails":[{"nctId":"NCT04760717","phase":"PHASE2","title":"Regulating Blood Pressure During Recovery From Intracerebral Hemorrhage and Ischemic Stroke","status":"ACTIVE_NOT_RECRUITING","sponsor":"Yale University","startDate":"2021-03-19","conditions":"Intracerebral Hemorrhage, Ischemic Stroke, Spironolactone","enrollment":160},{"nctId":"NCT01712620","phase":"PHASE2","title":"Spironolactone for Pulmonary Arterial Hypertension","status":"RECRUITING","sponsor":"National Institutes of Health Clinical Center (CC)","startDate":"2014-01-10","conditions":"Pulmonary Arterial Hypertension","enrollment":70},{"nctId":"NCT06678685","phase":"PHASE2, PHASE3","title":"Spironolactone Improved Children With Gene Mutations Related to NCOR","status":"COMPLETED","sponsor":"Qilu Hospital of Shandong University","startDate":"2024-10-30","conditions":"NCOR Gene Mutations, Spironolactone, ASD","enrollment":2},{"nctId":"NCT07483151","phase":"","title":"Venous Congestion And Cognitive Dysfunction After Cardiac Surgery","status":"RECRUITING","sponsor":"Zhuan Zhang","startDate":"2024-11-01","conditions":"Intraoperative Venous Congestion And Cognitive Dysfunction After Cardiac Surgery","enrollment":110},{"nctId":"NCT07483177","phase":"PHASE1, PHASE2","title":"HEART: Pilot Randomized Controlled Trial","status":"NOT_YET_RECRUITING","sponsor":"Mayo Clinic","startDate":"2026-05","conditions":"Thoracic Aortic Aneurysm","enrollment":50},{"nctId":"NCT07473895","phase":"PHASE2","title":"Topical 5% Spironolactone Gel Versus 0.1% Adapalene Gel for Acne Vulgaris: A Randomized Split-Face Study","status":"NOT_YET_RECRUITING","sponsor":"Assiut University","startDate":"2026-04","conditions":"Acne Vulgaris","enrollment":40},{"nctId":"NCT07046975","phase":"PHASE3","title":"Bioavailability and Bioequivalence Study of Extended Release Torsemide and Spironolactone","status":"COMPLETED","sponsor":"Sarfez Pharmaceuticals, Inc.","startDate":"2025-06-15","conditions":"Bioavailability Heathy Volunteers","enrollment":24},{"nctId":"NCT07223502","phase":"PHASE3","title":"A Study Comparing the Clinical Benefit of Finerenone Versus a Fixed Dose Combination (FDC) of Extended-Release Torsemide and Spironolactone in Patients With Hypertension and Chronic Kidney Disease","status":"RECRUITING","sponsor":"Sarfez Pharmaceuticals, Inc.","startDate":"2025-12-01","conditions":"Hypertension (HTN)","enrollment":30},{"nctId":"NCT07015671","phase":"PHASE3","title":"Bioavailability and Bioequivalence Study of ER Torsemide and Spironolactone FDC Tablet in Healthy Subjects","status":"COMPLETED","sponsor":"Sarfez Pharmaceuticals, Inc.","startDate":"2025-07-01","conditions":"Bioequivalence Study in Healthy Subjects, PK/PD","enrollment":24},{"nctId":"NCT04582383","phase":"PHASE4","title":"Comparative Effectiveness Study of Spironolactone Versus Doxycycline for Acne","status":"ACTIVE_NOT_RECRUITING","sponsor":"University of Pennsylvania","startDate":"2022-03-30","conditions":"Acne","enrollment":350},{"nctId":"NCT07043634","phase":"PHASE3","title":"A Study to Evaluate the Effect of Food or no Food on the Bioavailability of an Extended Release (ER) Torsemide and Spironolactone Fixed Dose Combination (FDC) Tablet in Healthy Adult Subjects","status":"COMPLETED","sponsor":"Sarfez Pharmaceuticals, Inc.","startDate":"2025-06-15","conditions":"Bioavailability Heathy Volunteers","enrollment":24},{"nctId":"NCT07431216","phase":"PHASE1, PHASE2","title":"A Phase 1b/2a Study to Evaluate the Safety, Pharmacokinetics, and Objective Response of STAR-001 (LP-184) in Combination With Spironolactone in Supratentorial Glioblastoma at First Progression","status":"NOT_YET_RECRUITING","sponsor":"Lantern Pharma Inc.","startDate":"2026-04-01","conditions":"Histopathology Confirmed Supratentorial GBM at First Recurrence, IDHwt GBM, IDHm Grade 4 Astrocytoma","enrollment":68},{"nctId":"NCT07422948","phase":"NA","title":"Efficacy and Safety of Early Initiation of Midodrine for Control and Prevention of Ascites and Its Related Complications in Acute-on-chronic Liver Failure.","status":"NOT_YET_RECRUITING","sponsor":"Institute of Liver and Biliary Sciences, India","startDate":"2026-02-05","conditions":"Acute on Chronic Liver Failure","enrollment":113},{"nctId":"NCT05807139","phase":"PHASE1","title":"Spironolactone in Alcohol Use Disorder (SAUD)","status":"RECRUITING","sponsor":"National Institute on Drug Abuse (NIDA)","startDate":"2023-07-13","conditions":"Alcohol Use Disorder","enrollment":20},{"nctId":"NCT07281014","phase":"PHASE4","title":"Unmitigated Aldosterone Signaling During Standard Clinical MRA Dosing","status":"RECRUITING","sponsor":"Yale University","startDate":"2026-01-27","conditions":"Heart Failure","enrollment":20},{"nctId":"NCT07415811","phase":"NA","title":"Spironolactone and XPB-1 Integrity in the TFIIH Complex","status":"ENROLLING_BY_INVITATION","sponsor":"University of Sao Paulo General Hospital","startDate":"2024-07-24","conditions":"HIV","enrollment":12},{"nctId":"NCT03593317","phase":"PHASE2","title":"Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD","status":"RECRUITING","sponsor":"Hospices Civils de Lyon","startDate":"2024-12-20","conditions":"Arrhythmogenic Right Ventricular Dysplasia","enrollment":120},{"nctId":"NCT07335900","phase":"NA","title":"A Clinical Study Using FAPI-PET Imaging to Assess the Postoperative Effects of TAVI in Patients With Aortic Stenosis","status":"RECRUITING","sponsor":"RenJi Hospital","startDate":"2025-12-19","conditions":"Severe Aortic Valve Stenosis","enrollment":25},{"nctId":"NCT06004830","phase":"PHASE2","title":"Off-Label Medications for Alcohol Use Disorder Among Patients With HIV: Pilot Study 1","status":"RECRUITING","sponsor":"Yale University","startDate":"2023-11-06","conditions":"Alcohol Use Disorder, Hiv","enrollment":30},{"nctId":"NCT07331220","phase":"NA","title":"Pulmonary Artery Denervation for Heart Failure With Preserved Left Ventricular Ejection Fraction","status":"NOT_YET_RECRUITING","sponsor":"Nanjing First Hospital, Nanjing Medical University","startDate":"2025-12-30","conditions":"Heart Failure With Preserved Ejection Fraction","enrollment":310},{"nctId":"NCT07328230","phase":"NA","title":"Superselective Adrenal Arterial Embolization Versus Oral Spironolactone for Treatment of Idiopathic Hyperaldosteronism","status":"RECRUITING","sponsor":"Chinese Academy of Medical Sciences, Fuwai Hospital","startDate":"2022-08-01","conditions":"Idiopathic Hyperaldosteronism, Hyperaldosteronism","enrollment":172},{"nctId":"NCT03429946","phase":"PHASE4","title":"Hypoglycemia and Autonomic Nervous System Function-B","status":"COMPLETED","sponsor":"Brigham and Women's Hospital","startDate":"2013-07-17","conditions":"Hypoglycemia, Healthy","enrollment":28},{"nctId":"NCT07304817","phase":"PHASE2","title":"Comparative Study on the Mode of Action of Vicadrostat and Spironolactone on Protein Profiles and Renal Hemodynamic Effects (COMPARE-VS)","status":"NOT_YET_RECRUITING","sponsor":"University Medical Center Groningen","startDate":"2026-02","conditions":"CKD, Cardiovascular Diseases, Heart Failure","enrollment":100},{"nctId":"NCT07285187","phase":"","title":"Venous Congestion And Delirium After Cardiac Surgery","status":"RECRUITING","sponsor":"Zhuan Zhang","startDate":"2024-11-01","conditions":"Intraoperative, Venous Congestion, Postoperative Delirium (POD)","enrollment":120},{"nctId":"NCT05561361","phase":"","title":"The Effect of SAAE on Vascular Endothelial Function in PA Patients","status":"RECRUITING","sponsor":"Second Affiliated Hospital of Nanchang University","startDate":"2022-10-01","conditions":"Primary Aldosteronism","enrollment":200},{"nctId":"NCT04251780","phase":"","title":"Tissue K+ in Primary Hyperaldosteronism","status":"COMPLETED","sponsor":"University of Erlangen-Nürnberg Medical School","startDate":"2018-01-01","conditions":"Primary Hyperaldosteronism, Electrolyte Disturbance","enrollment":21},{"nctId":"NCT04633005","phase":"PHASE2","title":"Polypill Strategy for Heart Failure With Reduced Ejection Fraction","status":"COMPLETED","sponsor":"University of Texas Southwestern Medical Center","startDate":"2021-11-15","conditions":"Heart Failure","enrollment":212},{"nctId":"NCT07235891","phase":"PHASE4","title":"Retinal Protective Effects of Novel Finerenone in Patients With Chronic Kidney Disease","status":"NOT_YET_RECRUITING","sponsor":"Alexandria University","startDate":"2025-11-20","conditions":"Retinal Nerve Fiber Layer Thickness, Chronic Kidney Disease","enrollment":40},{"nctId":"NCT07232277","phase":"","title":"Venous Congestion and Cardiac Surgery-Associated Acute Kidney Injury","status":"RECRUITING","sponsor":"Zhuan Zhang","startDate":"2024-10-15","conditions":"Intraoperative, Venous Congestion, Cardiac Surgery-associated Acute Kidney Injury","enrollment":114},{"nctId":"NCT04980716","phase":"PHASE3","title":"Early Specialized Cardiovascular Intervention Based on Impedance Cardiography in Locally Advanced Non-small Cell Lung Cancer Patients","status":"RECRUITING","sponsor":"Sun Yat-sen University","startDate":"2021-06-01","conditions":"Non-small Cell Lung Cancer, Cardiovascular Complication","enrollment":524},{"nctId":"NCT04522739","phase":"PHASE4","title":"Spironolactone Safety in African Americans With Mild Cognitive Impairment and Early Dementia","status":"COMPLETED","sponsor":"Emory University","startDate":"2022-09-06","conditions":"Mild Cognitive Impairment, Alzheimer Disease","enrollment":25},{"nctId":"NCT07041281","phase":"PHASE2","title":"Spironolactone to Improve Pregnancy-Associated Hypertension Trajectories","status":"RECRUITING","sponsor":"Massachusetts General Hospital","startDate":"2025-10-16","conditions":"Preeclampsia, Gestational Hypertension","enrollment":204},{"nctId":"NCT05014087","phase":"PHASE2","title":"Digoxin In Treatment of Alcohol Associated Hepatitis","status":"TERMINATED","sponsor":"Yale University","startDate":"2021-10-08","conditions":"Acute Alcoholic Hepatitis, Chemical and Drug Induced Liver Injury, Alcohol-Induced Disorders","enrollment":23},{"nctId":"NCT06697353","phase":"","title":"An Observational Study to Learn More About the Real-world Outcomes in Patients With Heart Failure Who Initiate Treatment With Vericiguat in Japan","status":"COMPLETED","sponsor":"Bayer","startDate":"2024-11-01","conditions":"Chronic Heart Failure, Chronic Heart Failure With Reduced Ejection Fraction","enrollment":4936},{"nctId":"NCT05754684","phase":"PHASE2","title":"Quadruple Immunotherapy for Neuroblastoma","status":"RECRUITING","sponsor":"Hong Kong Children's Hospital","startDate":"2022-01-01","conditions":"Neuroblastoma Recurrent","enrollment":29},{"nctId":"NCT01552044","phase":"PHASE1, PHASE2","title":"Effect of Spironolactone in Treating Chronic Non-resolutive Central Serous Chorioretinitis","status":"COMPLETED","sponsor":"Institut National de la Santé Et de la Recherche Médicale, France","startDate":"2012-01","conditions":"Central Serous Chorioretinitis","enrollment":17},{"nctId":"NCT07137364","phase":"","title":"Efficacy of Spironolactone Combined With Antihypertensive Drugs in Patients With Primary Aldosteronism","status":"RECRUITING","sponsor":"Third Military Medical University","startDate":"2022-05-01","conditions":"Primary Aldosteronism, Hypertension","enrollment":350},{"nctId":"NCT07130175","phase":"NA","title":"Radiofrequency Ablation for Polymorphic Ventricular Tachycardia With Heart Failure (RFCA for PMVT-HF)","status":"COMPLETED","sponsor":"Qian Feng","startDate":"2022-12-31","conditions":"Polymorphic Ventricular Tachycardia, Heart Failure","enrollment":118},{"nctId":"NCT05676684","phase":"PHASE2, PHASE3","title":"Dapagliflozin With or Without Spironolactone for HFpEF","status":"COMPLETED","sponsor":"Universidade do Porto","startDate":"2022-09-15","conditions":"Heart Failure With Preserved Ejection Fraction","enrollment":108},{"nctId":"NCT05411991","phase":"PHASE4","title":"Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment","status":"COMPLETED","sponsor":"Vrije Universiteit Brussel","startDate":"2022-06-12","conditions":"Acute Heart Failure, Diuretics Drug Reactions","enrollment":107},{"nctId":"NCT03068910","phase":"EARLY_PHASE1","title":"Hyperandrogenemia and Altered Day-night LH Pulse Patterns","status":"RECRUITING","sponsor":"University of Virginia","startDate":"2016-07-21","conditions":"Hyperandrogenism, Polycystic Ovary Syndrome, Puberty","enrollment":32},{"nctId":"NCT04723862","phase":"EARLY_PHASE1","title":"Does Spironolactone Normalize Sleep-wake Luteinizing Hormone Pulse Frequency in Pubertal Girls With Hyperandrogenism?","status":"RECRUITING","sponsor":"University of Virginia","startDate":"2021-11-12","conditions":"Hyperandrogenism, Polycystic Ovary Syndrome, Puberty","enrollment":32},{"nctId":"NCT06247267","phase":"","title":"The Effect of Sex Steroid Replacement Therapy in the Hypogonadism and Transgender Active-Duty Population","status":"RECRUITING","sponsor":"Walter Reed National Military Medical Center","startDate":"2021-03-09","conditions":"Hypogonadism, Gender Identity Dysphoria","enrollment":75},{"nctId":"NCT04676646","phase":"PHASE4","title":"Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone","status":"COMPLETED","sponsor":"AstraZeneca","startDate":"2021-03-08","conditions":"Hyperkalaemia, Heart Failure With Reduced Ejection Fraction","enrollment":366},{"nctId":"NCT07020104","phase":"NA","title":"The Role of Skin Sodium Accumulation in Chronic Kidney Disease","status":"RECRUITING","sponsor":"Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)","startDate":"2025-01-07","conditions":"Chronic Kidney Diseases","enrollment":60},{"nctId":"NCT04901975","phase":"PHASE1, PHASE2","title":"Fibrosis and the Fontan","status":"RECRUITING","sponsor":"Children's Hospital of Philadelphia","startDate":"2021-02-11","conditions":"Single-ventricle","enrollment":145},{"nctId":"NCT03929718","phase":"EARLY_PHASE1","title":"Efficacy of Aldosterone Antagonist Therapy for Prevention of New Atrial Fibrillation","status":"ACTIVE_NOT_RECRUITING","sponsor":"Piedmont Healthcare","startDate":"2019-04-24","conditions":"AFib","enrollment":50},{"nctId":"NCT05501080","phase":"NA","title":"The Effect of SAAE on Ventricular Remodeling in PA Patients","status":"RECRUITING","sponsor":"Second Affiliated Hospital of Nanchang University","startDate":"2022-09-01","conditions":"Primary Aldosteronism","enrollment":112},{"nctId":"NCT06495710","phase":"NA","title":"Arterial Stiffness and Blood Pressure","status":"RECRUITING","sponsor":"VA Office of Research and Development","startDate":"2025-05-01","conditions":"Hypertension, Vascular Stiffness, Aging","enrollment":228},{"nctId":"NCT05637853","phase":"PHASE4","title":"Telemonitored Fast Track Medical Sequencing for Heart Failure With Reduced Ejection Fraction","status":"ACTIVE_NOT_RECRUITING","sponsor":"Göteborg University","startDate":"2022-10-22","conditions":"Heart Failure With Reduced Ejection Fraction","enrollment":60},{"nctId":"NCT05797558","phase":"NA","title":"Unilateral Primary Aldosteronism, Mineralocorticoid Antagonists Versus Surgical Treatment","status":"RECRUITING","sponsor":"Göteborg University","startDate":"2023-04-28","conditions":"Primary Hyperaldosteronism Due to Adrenal Adenoma","enrollment":80},{"nctId":"NCT04727073","phase":"PHASE3","title":"Spironolactone in the Treatment of Heart Failure","status":"TERMINATED","sponsor":"Charite University, Berlin, Germany","startDate":"2018-11-01","conditions":"Heart Failure with Mid-range Ejection Fraction, Heart Failure with Preserved Ejection Fraction","enrollment":743},{"nctId":"NCT03576755","phase":"PHASE1, PHASE2","title":"Spironolactone Therapy In Young Women With NASH","status":"COMPLETED","sponsor":"University of California, San Francisco","startDate":"2019-01-09","conditions":"NASH - Nonalcoholic Steatohepatitis","enrollment":20},{"nctId":"NCT04283656","phase":"PHASE1","title":"Evaluating Drug Interactions Between Doravirine With Estradiol and Spironolactone in Healthy Transgender Women","status":"COMPLETED","sponsor":"Thomas Jefferson University","startDate":"2022-01-04","conditions":"Transgender Health, Gender Dysphoria, Transgender Women","enrollment":8},{"nctId":"NCT06641284","phase":"","title":"Gender-Based Differences in Heart Failure Hospitalizations Among Patients With Heart Failure Treated With Spironolactone","status":"COMPLETED","sponsor":"Ahmad Abdullah Salawi","startDate":"2023-10-01","conditions":"Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure NYHA Class II","enrollment":509},{"nctId":"NCT06205407","phase":"PHASE1","title":"A Study to Learn How the Body Processes Spironolactone and Hydrochlorothiazide Film Coated Tablets Manufactured at Two Sites: Viatris and Neolpharma","status":"COMPLETED","sponsor":"Pfizer","startDate":"2023-12-26","conditions":"Healthy Participants","enrollment":42},{"nctId":"NCT03020303","phase":"PHASE3","title":"Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease","status":"COMPLETED","sponsor":"Population Health Research Institute","startDate":"2017-07-07","conditions":"Endstage Renal Disease","enrollment":2538},{"nctId":"NCT05092984","phase":"PHASE3","title":"Evaluation of Spironolactone Efficacy in Patient with Rheumatoid Arthritis (RA)","status":"RECRUITING","sponsor":"University Hospital, Strasbourg, France","startDate":"2022-06-22","conditions":"Rheumatoid Arthritis","enrollment":154},{"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","enrollment":5000},{"nctId":"NCT05933265","phase":"PHASE1, PHASE2","title":"Study of LP-184 in Patients With Advanced Solid Tumors","status":"RECRUITING","sponsor":"Lantern Pharma Inc.","startDate":"2023-06-09","conditions":"Advanced Solid Tumor, Metastatic Solid Tumor, GBM","enrollment":175},{"nctId":"NCT02378805","phase":"","title":"Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome","status":"RECRUITING","sponsor":"University Hospital Goettingen","startDate":"1995-07","conditions":"Alport Syndrome, Hereditary Kidney Disease, Pediatric Kidney Disease","enrollment":800},{"nctId":"NCT04142788","phase":"PHASE4","title":"RELieving Increasing oEdema Due to Heart Failure","status":"TERMINATED","sponsor":"NHS Greater Glasgow and Clyde","startDate":"2020-08-26","conditions":"Heart Failure，Congestive","enrollment":19},{"nctId":"NCT03122834","phase":"","title":"Effect of Genetic Polymorphism on the Clinical Outcome of Patients With Heart Failure","status":"COMPLETED","sponsor":"Ain Shams University","startDate":"2020-04-15","conditions":"Heart Failure","enrollment":246},{"nctId":"NCT06377449","phase":"NA","title":"Influence of Lung Ultrasonography on the Prognosis and Postoperative Outcomes in Cardiac Surgical Patients","status":"RECRUITING","sponsor":"Saint Petersburg State University, Russia","startDate":"2024-05-15","conditions":"Ischemic Heart Disease, Aortic Stenosis, Severe, Aortic Insufficiency","enrollment":186},{"nctId":"NCT05010707","phase":"PHASE2","title":"Transgender Estradiol Affirming Therapy","status":"COMPLETED","sponsor":"Washington University School of Medicine","startDate":"2021-08-02","conditions":"Transgenderism","enrollment":39},{"nctId":"NCT06523465","phase":"PHASE4","title":"Statin Combined with Amlodipine Treats Primary Aldosteronism","status":"RECRUITING","sponsor":"Third Military Medical University","startDate":"2024-09-10","conditions":"Primary Aldosteronism, Statin, Mineralocorticoid Receptor Antagonist","enrollment":180},{"nctId":"NCT05318755","phase":"","title":"China Gender-affirming Hormone Therapy Study","status":"RECRUITING","sponsor":"Peking University Third Hospital","startDate":"2022-04-16","conditions":"Transgender, Gender Incongruence","enrollment":240},{"nctId":"NCT02901184","phase":"PHASE3","title":"Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction","status":"RECRUITING","sponsor":"Uppsala University","startDate":"2017-11-23","conditions":"Heart Failure With Preserved Ejection Fraction","enrollment":2000},{"nctId":"NCT05849766","phase":"PHASE3","title":"Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction","status":"COMPLETED","sponsor":"October 6 University","startDate":"2023-04-27","conditions":"Dilated Cardiomyopathy","enrollment":150},{"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},{"nctId":"NCT05663892","phase":"PHASE4","title":"Drug-Drug Interaction Study in Trans Women Living With HIV","status":"ACTIVE_NOT_RECRUITING","sponsor":"Maple Leaf Research","startDate":"2022-11-23","conditions":"Hiv, Transgenderism","enrollment":45},{"nctId":"NCT04331691","phase":"PHASE4","title":"Comparison of Spironolactone and Amiloride on Home Blood Pressure in Resistant Hypertension","status":"COMPLETED","sponsor":"Yonsei University","startDate":"2020-11-16","conditions":"Resistant Hypertension","enrollment":118},{"nctId":"NCT05195164","phase":"","title":"The Effects of Orchiectomy and Age on Vascular and Metabolic Health in Older Versus Younger Transgender Women","status":"COMPLETED","sponsor":"University of Colorado, Denver","startDate":"2021-03-22","conditions":"Transgender, Gender Identity, Vascular Stiffness","enrollment":17},{"nctId":"NCT04066283","phase":"","title":"Effects of Aging and Gender-Affirming Hormone Therapy on Vascular Endothelial Function and Metabolic Profiles in Transgender Women","status":"COMPLETED","sponsor":"University of Colorado, Denver","startDate":"2019-04-17","conditions":"Transgender, Gender Identity, Vascular Stiffness","enrollment":29},{"nctId":"NCT04100083","phase":"PHASE4","title":"Spironolactone for Hidradenitis Suppurativa","status":"WITHDRAWN","sponsor":"Medical University of South Carolina","startDate":"2020-09-21","conditions":"Hidradenitis Suppurativa","enrollment":""},{"nctId":"NCT03874338","phase":"","title":"CLEAR SYNERGY Neutrophil Substudy","status":"COMPLETED","sponsor":"NYU Langone Health","startDate":"2019-03-04","conditions":"Neutrophils.Hypersegmented &#X7C; Bld-Ser-Plas, STEMI - ST Elevation Myocardial Infarction","enrollment":322},{"nctId":"NCT06091475","phase":"NA","title":"Therapy to Maintain Remission in Dilated Cardiomyopathy","status":"RECRUITING","sponsor":"Imperial College London","startDate":"2023-12-02","conditions":"Heart Failure, Cardiomyopathy, Dilated, Cardiomyopathies","enrollment":50},{"nctId":"NCT03953209","phase":"PHASE1","title":"Spironolactone for the Treatment of Melasma","status":"WITHDRAWN","sponsor":"Medical University of South Carolina","startDate":"2020-03-05","conditions":"Melasma","enrollment":""},{"nctId":"NCT06457074","phase":"PHASE4","title":"Finerenone for Patients With Primary Aldosteronism (FAIRY)","status":"RECRUITING","sponsor":"Qifu Li","startDate":"2024-06-04","conditions":"Primary Aldosteronism","enrollment":306},{"nctId":"NCT06579053","phase":"PHASE1","title":"Bioequivalence Study of Spironolactone Tablets in Healthy Subjects","status":"COMPLETED","sponsor":"SPH Sine Pharmaceutical Laboratories Co., Ltd.","startDate":"2023-03-22","conditions":"Bioequivalence Study","enrollment":64},{"nctId":"NCT04409431","phase":"NA","title":"Effects of Adrenal Artery Ablation and Spironolactone in Patients With Primary Aldosteronism","status":"RECRUITING","sponsor":"Third Military Medical University","startDate":"2019-12-01","conditions":"Primary Aldosteronism, Hypertension","enrollment":60},{"nctId":"NCT01294319","phase":"PHASE2","title":"Evaluation of Cortisol Resistance in Young Sedentary and Endurance-Trained Men","status":"COMPLETED","sponsor":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","startDate":"2011-01-24","conditions":"Cortisol Resistance, Negative Feedback, ACTH","enrollment":51},{"nctId":"NCT06499948","phase":"PHASE4","title":"Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients with Alport Syndrome (COMBINE-ALPORT)","status":"RECRUITING","sponsor":"Stefan Lujinschi","startDate":"2024-02-26","conditions":"Alport Syndrome, Thin Basement Membrane Disease, Alport Nephropathy","enrollment":34},{"nctId":"NCT03344159","phase":"PHASE4","title":"Spironolactone Therapy in Chronic Stable Right HF Trial","status":"COMPLETED","sponsor":"Ottawa Heart Institute Research Corporation","startDate":"2018-04-01","conditions":"Chronic Right-Sided Heart Failure, Pulmonary Arterial Hypertension, Pulmonary Hypertension, Primary, 2","enrollment":15},{"nctId":"NCT04643691","phase":"PHASE2","title":"Losartan and Spironolactone Treatment for ICU Patients With COVID-19 Suffering From ARDS","status":"TERMINATED","sponsor":"Assistance Publique Hopitaux De Marseille","startDate":"2020-09-11","conditions":"COVID-19, ARDS","enrollment":78},{"nctId":"NCT05924620","phase":"PHASE4","title":"Efficacy and Safety of Finerenone in Patients With Primary Aldosteronism","status":"COMPLETED","sponsor":"Chongqing Medical University","startDate":"2023-06-21","conditions":"Primary Aldosteronism","enrollment":60},{"nctId":"NCT06413082","phase":"PHASE3","title":"Pharmacogenetics of Torasemide and Spironolactone in Hypertension Treatment","status":"COMPLETED","sponsor":"Ospedale San Raffaele","startDate":"2021-02-15","conditions":"Hypertension, Genetic Predisposition, Drug Effect","enrollment":38},{"nctId":"NCT04199910","phase":"","title":"4beta-hydroxycholesterol in Cirrhosis","status":"SUSPENDED","sponsor":"University of Oulu","startDate":"2019-12-01","conditions":"Cirrhosis, Liver","enrollment":120},{"nctId":"NCT05394142","phase":"PHASE2","title":"A Clinical Trial to Evaluate the Efficacy, Tolerability, and Safety of a Fixed Dose Combination of Spironolactone, Pioglitazone & Metformin (SPIOMET) in Polycystic Ovary Syndrome (PCOS)","status":"RECRUITING","sponsor":"Fundació Sant Joan de Déu","startDate":"2022-05-24","conditions":"Polycystic Ovary Syndrome (PCOS)","enrollment":364},{"nctId":"NCT03652623","phase":"PHASE1, PHASE2","title":"Transgender Youth and PrEP: PK, Safety, Uptake & Adherence - PK Study","status":"COMPLETED","sponsor":"Hektoen Institute for Medical Research","startDate":"2018-07-23","conditions":"HIV/AIDS, Gender, Behavior and Behavior Mechanisms","enrollment":49},{"nctId":"NCT06233695","phase":"","title":"Gender-based Differences in the Outcome of Treatment With Aldosterone Antagonists in Patients With Heart Failure","status":"COMPLETED","sponsor":"Alexandria University","startDate":"2022-10-15","conditions":"Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure NYHA Class II","enrollment":100},{"nctId":"NCT06275763","phase":"PHASE4","title":"Optimal Medical Treatment of Difficult-to-treat Hypertension","status":"UNKNOWN","sponsor":"National Institute of Cardiology, Warsaw, Poland","startDate":"2023-10-20","conditions":"Hypertension","enrollment":2500},{"nctId":"NCT06035978","phase":"PHASE4","title":"Determination of Drug Levels for Pharmacotherapy of Heart Failure","status":"NOT_YET_RECRUITING","sponsor":"University Hospital Ostrava","startDate":"2024-03","conditions":"Cardiovascular Diseases, Heart Failure With Reduced Ejection Fraction","enrollment":100},{"nctId":"NCT06204640","phase":"PHASE3","title":"SPironolactONe for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation","status":"NOT_YET_RECRUITING","sponsor":"University Hospital, Caen","startDate":"2024-03-01","conditions":"Atrial Fibrillation Recurrent","enrollment":580},{"nctId":"NCT06164379","phase":"PHASE4","title":"Efficacy and Safety of Finerenone vs. Spironolactone in Patients With Primary Aldosteronism","status":"UNKNOWN","sponsor":"Shanghai Jiao Tong University School of Medicine","startDate":"2023-12-16","conditions":"Primary Aldosteronism","enrollment":150},{"nctId":"NCT01422759","phase":"NA","title":"Effect of Spironolactone on Adrenal or Ovarian Androgen Production in Overweight Pubertal Girls With Androgen Excess","status":"UNKNOWN","sponsor":"University of Virginia","startDate":"2016-12-09","conditions":"Obesity, Hyperandrogenemia, Polycystic Ovary Syndrome","enrollment":20},{"nctId":"NCT04075149","phase":"EARLY_PHASE1","title":"Does Treatment of Androgen Excess Using Spironolactone Improve Ovulatory Rates in Girls With Androgen Excess?","status":"UNKNOWN","sponsor":"University of Virginia","startDate":"2019-12-18","conditions":"Polycystic Ovary Syndrome, Puberty Disorders, Ovulation Disorder","enrollment":24},{"nctId":"NCT03777319","phase":"PHASE1","title":"Spironolactone Versus Prednisolone in DMD","status":"TERMINATED","sponsor":"Kevin Flanigan","startDate":"2018-12-05","conditions":"Muscular Dystrophy, Duchenne","enrollment":2},{"nctId":"NCT01848639","phase":"PHASE3","title":"ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial","status":"COMPLETED","sponsor":"University Hospital, Brest","startDate":"2013-06","conditions":"End Stage Renal Failure on Dialysis","enrollment":823},{"nctId":"NCT05287100","phase":"NA","title":"To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation.","status":"COMPLETED","sponsor":"Institute of Liver and Biliary Sciences, India","startDate":"2022-01-01","conditions":"Cirrhosis, Liver","enrollment":35}],"whoEssential":true,"_emaApprovals":[],"_faersSignals":[{"count":2271,"reaction":"DYSPNOEA"},{"count":1730,"reaction":"HYPERKALAEMIA"},{"count":1684,"reaction":"DIARRHOEA"},{"count":1634,"reaction":"NAUSEA"},{"count":1572,"reaction":"ACUTE KIDNEY INJURY"},{"count":1558,"reaction":"FATIGUE"},{"count":1465,"reaction":"HYPOTENSION"},{"count":1377,"reaction":"DRUG INTERACTION"},{"count":1362,"reaction":"CARDIAC FAILURE"},{"count":1343,"reaction":"ANAEMIA"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"administration":{"route":"Oral"},"_patentsChecked":true,"crossReferences":{"unii":"27O7W4T232","rxcui":"9997","splId":"76b5d6ad-0b7b-4781-b990-5ba036cf5a67","chemblId":"CHEMBL1393","pubchemSID":"9518"},"formularyStatus":[],"_approvalHistory":[{"date":"19950531","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20130612","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19870615","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19920507","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19860113","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20021126","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19900315","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19850815","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19820503","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19840322","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19970730","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19830729","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19831129","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19810304","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20120917","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20160411","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20251114","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19960514","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20141022","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19970730","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19871123","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20081125","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19900123","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19600121","type":"ORIG","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19850926","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19990326","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19821230","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19891030","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19841105","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19831129","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19881109","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19831220","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19810622","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19830407","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20221219","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20200728","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19810630","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19761110","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20180306","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20110922","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"19990113","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"},{"date":"20150501","type":"SUPPL","sponsor":"PFIZER","applicationNumber":"NDA012151"}],"developmentCodes":[],"ownershipHistory":[],"pharmacokinetics":{"tmax":"Spironolactone: 2.6 hours; Canrenone: 4.3 hours","halfLife":"Spironolactone: 1.4 hours; Canrenone: 16.5 hours; TMS: 13.8 hours; HTMS: 15 hours","clearance":"","excretion":"Metabolites excreted primarily in urine and secondarily in bile","metabolism":"Rapidly and extensively metabolized into two main categories: those with sulfur removed (e.g., canrenone) and those with sulfur retained (e.g., TMS and HTMS). TMS and 7-α-thiospirolactone potencies approximately one-third relative to spironolactone in reversing fludrocortisone effects.","proteinBinding":"More than 90% bound to plasma proteins","bioavailability":"Food increased bioavailability by approximately 95.4%","volumeOfDistribution":""},"publicationCount":7697,"therapeuticAreas":["Metabolic"],"biosimilarFilings":[],"companionDiagnostics":[{"biomarker":"Serum potassium","requirement":"required","diagnosticId":"cdx-0","diagnosticName":"FDA-approved test"},{"biomarker":"Lithium levels","requirement":"recommended","diagnosticId":"cdx-1","diagnosticName":"FDA-approved test"}],"genericManufacturers":25,"_genericFilersChecked":true,"genericManufacturerList":["Accord Hlthcare","Actavis Elizabeth","Amneal","Amneal Pharms","Annora Pharma","Ascot","Aurobindo Pharma","Chartwell Rx","Graviti Pharms","Hetero Labs Ltd Iii","Ivax Pharms","Jubilant Generics","Lederle","Mutual Pharm","Mylan","Oxford Pharms","Pharmobedient","Purepac Pharm","Sun Pharm Industries","Superpharm","Upsher Smith","Vangard","Warner Chilcott","Watson Labs","Zydus Pharms"],"phase":"marketed","status":"approved","brandName":"Aldactone","genericName":"Spironolactone","companyName":"Pfizer Inc.","companyId":"pfizer","modality":"Small molecule","firstApprovalDate":"1960","enrichmentLevel":5,"visitCount":9,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2002-06-05T00:00:00.000Z","mah":"SUN PHARM INDUSTRIES","brand_name_local":null,"application_number":"ANDA089424"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2014-09-22T00:00:00.000Z","mah":"OXFORD PHARMS","brand_name_local":null,"application_number":"ANDA040750"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2015-05-01T00:00:00.000Z","mah":"PFIZER","brand_name_local":null,"application_number":"NDA012151"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2017-08-04T00:00:00.000Z","mah":"CMP DEV LLC","brand_name_local":null,"application_number":"NDA209478"},{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"2025-02-21T00:00:00.000Z","mah":"HETERO LABS LTD III","brand_name_local":null,"application_number":"ANDA218085"},{"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":"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":"CA","regulator":"Health Canada","status":"approved","approval_date":null,"mah":"","brand_name_local":"","application_number":""},{"country_code":"GB","regulator":"MHRA","status":"likely_approved","approval_date":null,"mah":null,"brand_name_local":null,"application_number":null},{"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}],"pricingByCountry":[{"country_code":"Un","currency":"USD","price_amount":"74.00","price_per":"year","price_type":"NADAC","annual_cost_usd":null,"reimbursement_status":null},{"country_code":"UN","currency":"USD","price_amount":"74.00","price_per":"year","price_type":"NADAC","annual_cost_usd":null,"reimbursement_status":null},{"country_code":"UN","currency":"USD","price_amount":"74.00","price_per":"year","price_type":"NADAC","annual_cost_usd":null,"reimbursement_status":null},{"country_code":"UN","currency":"USD","price_amount":"74.00","price_per":"year","price_type":"NADAC","annual_cost_usd":null,"reimbursement_status":null},{"country_code":"UN","currency":"USD","price_amount":"74.00","price_per":"year","price_type":"NADAC","annual_cost_usd":null,"reimbursement_status":null}],"trialStats":{"total":35,"withResults":11},"validation":{"fieldsValidated":7,"lastValidatedAt":"2026-04-20T08:33:47.248717+00:00","fieldsConflicting":0,"overallConfidence":0.95},"verificationStatus":"verified","dataCompleteness":{"mechanism":true,"indications":true,"safety":true,"trials":true,"score":4}}