- Pharmaceutical Form : Oral Solution
- Composition : Each 5 mL oral suspension contains: spironolactone 25 mg.
- Active Substance : spironolactone
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.
Spironolactone is rapidly and extensively metabolized.
The peak plasma concentration (Cmax) of spironolactone is reached 0.5 to 1.5 hours after dosing.
Spironolactone and its metabolites are more than 90% bound to plasma proteins. The metabolites are excreted primarily in the urine and secondarily in bile.
A high fat and high calorie meal increased the bioavailability of spironolactone.
SPIRONOLACTONE is indicated for treatment of NYHA Class III-IV (the New York Heart Association Class III-IV) heart failure and reduced ejection fraction to increase survival, manage edema, and to reduce the need for hospitalization for heart failure.
SPIRONOLACTONE is usually administered in conjunction with other heart failure therapies.
SPIRONOLACTONE 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.
Edema Caused by Cirrhosis:
SPIRONOLACTONE is indicated for the management of edema in adult cirrhotic patients when edema is not responsive to fluid and sodium restriction.
SPIRONOLACTONE is contraindicated for patients with the following conditions:
- Addison’s disease
- Concomitant use of eplerenone.
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.
Monitor serum potassium within 1 week of initiation or titration of SPIRONOLACTONE and regularly thereafter.
Closer 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.
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.
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.
SPIRONOLACTONE can cause 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.
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.
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.
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.
Safety and effectiveness in pediatric patients have not been established.
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.
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.
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.
Clearance of spironolactone and its metabolites is reduced in patients with cirrhosis. In patients with cirrhosis, start with lowest initial dose and titrate.
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. 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
- aldosterone blockers
- non-steroidal anti-inflammatory drugs (NSAIDs)
- heparin and low molecular weight heparin
Like other diuretics, SPIRONOLACTONE reduces the renal clearance of lithium, thus increasing the risk of lithium toxicity. Monitor lithium levels periodically when CAROSPIR is co administered.
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
Spironolactone and its metabolites interfere with radioimmune assays 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.
Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.
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.
-Hypotension and Worsening Renal Function
-Electrolyte and Metabolic Abnormalities
-Impaired neurological function/ coma in patients with hepatic impairment, cirrhosis and ascites.
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.
DOSAGE AND ADMINISTRATION:
SPIRONOLACTONE is not therapeutically equivalent to Aldactone.
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.
SPIRONOLACTONE 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 (Estimated glomerular filtration rate) >50 mL/min/1.73m, 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/1.73m, 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 desired effect.
STORAGE CONDITIONS: Store at 15°to 30°C
PACKAGING: 100 mL