Spironolactone: uses, appearance and warnings

Spironolactone tablets are 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 hyperaldosternism 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 tablets are 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 tablets are usually administered in conjunction with other heart failure therapies. 1.2 Hypertension Spironolactone tablets are 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. …

Tablets: 25 mg white, round, unscored, debossed MP 35 Tablets: 50 mg white, round, film coated, scored, debossed MP 542 Tablets: 100 mg white, oval shape, film coated, scored, debossed MP 303 Tablets: 25 mg, 50 mg, and 100 mg ( 3 )

Spironolactone tablets, USP are supplied as follows: Spironolactone tablets 25 mg, white, round, unscored, debossed MP 35 Bottles of 100 NDC 53489-143-01 Bottles of 500 NDC 53489-143-05 Bottles of 1000 NDC 53489-143-10 Spironolactone tablets 50 mg, white, round, film coated, scored, debossed MP 542 Bottles of 30 NDC 53489-328-07 Bottles of 50 NDC 53489-328-02 Bottles of 60 NDC 53489-328-06 Bottles of 100 NDC 53489-328-01 Bottles of 250 NDC 53489-328-03 Bottles of 500 NDC 53489-328-05 Bottles of 1000 NDC 53489-328-10 Spironolactone tablets 100 mg, white, oval shape, film coated, scored, debossed MP 303 Bottles of 30 NDC 53489-329-07 Bottles of 50 NDC 53489-329-02 Bottles of 60 NDC 53489-329-06 Bottles of 100 NDC 53489-329-01 Bottles of 250 NDC 53489-329-03 Bottles of 500 NDC 53489-329-05 Bottles of 1000 NDC 53489-329-10 Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature] DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

Spironolactone tablets are contraindicated in the patients with: Hyperkalemia Addison’s disease Concomitant use of eplerenone Spironolactone Tablets are contraindicated in patients with ( 4 ): Hyperkalemia Addison’s disease Concomitant use of eplerenone

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 tablets can cause gynecomastia (5.4). 5.1 Hyperkalemia Spironolactone tablets 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 tablets and regularly thereafter. More frequent monitoring may be needed when spironolactone tablets are given with other drugs that cause hyperkalemia or in patients with impaired renal function. If hyperkalemia occurs, decrease the dose or discontinue spironolactone tablets 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 tablets 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 tablets can cause gynecomastia. In the 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.

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. …

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 tablets ( 7.3 ). Digoxin: Spironolactone tablets 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 tablets ( 7.6 ). Abiraterone: May increase prostate-specific antigen (PSA) levels ( 7.7 ). Mitotane: Avoid concomitant use of spironolactone tablets and mitotane ( 7.8 ). …