1 INDICATIONS AND USAGE Spironolactone oral suspension is an antagonist of aldosterone 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 cirrhotic patients when edema is not responsive to fluid and sodium restrictions ( 1.3 ) 1.1 Heart Failure Spironolactone oral suspension is indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction in adult patients to increase survival, manage edema, and to reduce the need for hospitalization for heart failure.

Spironolactone oral suspension is usually administered in conjunction with other heart failure therapies.

1.2 Hypertension Spironolactone oral suspension is indicated as an add-on therapy for the treatment of hypertension, to lower blood pressure in adult 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 caused by Cirrhosis Spironolactone oral suspension is indicated for the management of edema in adult cirrhotic patients when edema is not responsive to fluid and sodium restriction.

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: Gynecomastia [see Warnings and Precautions ( 5.4 )] , 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, chloasma.

The most common adverse reaction (incidence > 5%) with spironolactone oral suspension treatment is gynecomastia ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact CMP Pharma at 1-844-321-1443 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.