Carospir
FDA Drug Information • Also known as: Carospir
- Brand Names
- Carospir
- Drug Class
- Aldosterone Antagonist [EPC]
- Route
- ORAL
- Dosage Form
- SUSPENSION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION CAROSPIR Oral Suspension contains 25 mg of the aldosterone antagonist spironolactone, 17-hydroxy-7α-mercapto-3-oxo-17α-pregn-4-ene-21- carboxylic acid γ-lactone acetate per 5 mL, 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 sorbic acid, potassium sorbate, citric acid anhydrous, sodium citrate dihydrate, simethicone emulsion, saccharin sodium, xanthan gum, Magnasweet 110, glycerin, banana flavor, and purified water. Chemical Structure
What Is Carospir Used For?
1 INDICATIONS AND USAGE CAROSPIR 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 CAROSPIR 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. CAROSPIR is usually administered in conjunction with other heart failure therapies. 1.2 Hypertension CAROSPIR 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,...
Dosage and Administration
2 DOSAGE AND ADMINISTRATION CAROSPIR is not therapeutically equivalent to Aldactone ( 2.1 ) Heart Failure: Initiate treatment at 20 mg once daily. ( 2.2 ) Hypertension: Initiate treatment at 20 to 75 mg daily in either single or divided doses ( 2.3 ) Edema associated with Hepatic Cirrhosis: Initiate therapy in a hospital setting and titrate slowly. The initial recommended daily dose is 75 mg in either single or divided doses ( 2.4 ) 2.1 General Considerations CAROSPIR is not therapeutically equivalent to Aldactone. Follow dosing instructions given here. In patients requiring a dose greater than 100 mg, use another formulation. Doses of the suspension greater than 100 mg may result in spironolactone concentrations higher than expected [see Clinical Pharmacology (12.3) ] . CAROSPIR 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/1.73m 2 , initiate treatment at 20 mg (4 mL) once daily. Patients who tolerate 20 mg (4 mL) once daily may have their dosage increased to 37.5 mg (7.5 mL) once daily as clinically indicated. Patients who develop hyperkalemia on 20 mg (4 mL) once daily may have their dosage reduced to 20 mg (4 mL) every other day [see Warning and Precautions 5.1) ] . In patients with an eGFR between 30 and 50 mL/min/1.73m 2 , consider initiating treatment at 10 mg (2 mL) 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 20 mg (4 mL) to 75 mg (15 mL) administered in either single or divided doses. Dosage can be titrated at two-week intervals. Doses >75 mg/day generally do not provide additional reductions in blood pressure. 2.4 Treatment of Edema associated with Hepatic Cirrhosis In patients with cirrhosis, initiate therapy in a hospital setting and titrate slowly [see Use in Specific Populations (8.6)] and Clinical Pharmacology (12.3) ] . The recommended initial daily dose is 75 mg (15 mL) administered in either single or divided doses. In patients requiring titration above 100 mg, use another formulation [see Dosage and Administration (2.1) ] . When given as the sole agent for diuresis, administer for at least five days before increasing dose to obtain desired effect.
Side Effects (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: 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 CAROSPIR 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.
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 CAROSPIR ( 7.3 ) Digoxin: CAROSPIR 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 ) 7.1 Drugs and Supplements Increasing Serum Potassium Concomitant administration of CAROSPIR 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 CAROSPIR [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 CAROSPIR. Examples of drugs that can increase potassium include: ACE inhibitors angiotensin receptor blockers aldosterone blockers non-steroidal anti-inflammatory drugs (NSAIDs) heparin and low molecular weight heparin trimethoprim 7.2 Lithium Like other diuretics, CAROSPIR reduces the renal clearance of lithium, thus increasing the risk of lithium toxicity. Monitor lithium levels periodically when CAROSPIR 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 loop, potassium-sparing, and thiazide diuretics. Therefore, when CAROSPIR 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 increase the apparent exposure to digoxin. In patients taking concomitant digoxin, measure serum digoxin concentrations before initiating spironolactone using an assay that does not interact with spironolactone. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring [see Clinical Pharmacology (12.3) ] . 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 CAROSPIR and acetylsalicylic acid are used concomitantly, CAROSPIR 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 CYP2C8 and CYP3A Substrates Spironolactone is an irreversible inhibitor for CYP2C8 and CYP3A4/5 in vitro [see Clinical Pharmacology (12.3) ] . Therefore, spironolactone may increase the exposure of other coadministered...
Contraindications
4 CONTRAINDICATIONS CAROSPIR is contraindicated for patients with the following conditions: Hyperkalemia Addison’s disease Concomitant use of eplerenone CAROSPIR is contraindicated in patients with ( 4 ) Hyperkalemia Addison’s disease Concomitant use of eplerenone
Pregnancy and Breastfeeding
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 Clinical Pharmacology (12.1) ] . 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 congenital anomalies 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 congenital anomalies and miscarriage in the clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk 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....
Overdosage
10 OVERDOSAGE The oral LD50 of spironolactone is greater than 1000 mg/kg in mice, rats, and rabbits. Acute overdosage of CAROSPIR 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 CAROSPIR.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING CAROSPIR (spironolactone) Oral Suspension 25 mg/5 mL is a white to off-white, opaque, banana-flavored suspension. It is available in a 118 mL bottle (NDC 46287-020-04), a 473 mL bottle (NDC 46287-020-01), and a 5 mL unit dose cup (NDC 46287-020-20) available in a 10 count carton (NDC 46287-020-50). Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature] . Shake well before use. Dispense in a tight container as defined in the USP.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.