Carospir (spironolactone)

Carospir (spironolactone) oral suspension is an antagonist of aldosterone used to treat heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. It is also used 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; and for the management of edema in adult hepatic cirrhosis patients when edema is not responsive to fluid and sodium restrictions.

The following are clinically significant adverse reactions:

• Hyperkalemia 
• Hypotension and Worsening Renal Function 
• Electrolyte and Metabolic Abnormalities 
• Gynecomastia
• Impaired neurological function/ coma in patients with hepatic impairment, cirrhosis and ascites 

The following adverse reactions associated with the use of Carospir 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, 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, 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.

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.
• Carospir can be taken with or without food, but should be taken consistently with respect to food.

Treatment Of Heart Failure

• In patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73m2, 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. In patients with an eGFR between 30 and 50 mL/min/1.73m2, consider initiating treatment at 10 mg (2 mL) because of the risk of hyperkalemia.

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.

Treatment Of Edema Associated With Hepatic Cirrhosis

• In patients with cirrhosis, initiate therapy in a hospital setting and titrate slowly. 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. When given as the sole agent for diuresis, administer for at least five days before increasing dose to obtain the desired effect.

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. 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
• 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.

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.

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. 

Cholestyramine

Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.

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.

Pregnancy

There are risks to the mother and fetus associated with heart failure, cirrhosis and poorly controlled hypertension during pregnancy. 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.

Breastfeeding

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.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Carospir 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.

Use In Renal Impairment

Carospir 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.

Use In Hepatic Impairment

Carospir 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 Carospir in the hospital.

Clearance of spironolactone and its metabolites is reduced in patients with cirrhosis. In patients with cirrhosis, start with lowest initial dose and titrate slowly