Spironolactone is a specific antagonist 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. ALDACTONE acts both as a diuretic and as an antihypertensive drug
Pharmacokinetics:
– spironolactone is rapidly and extensively metabolized
-Mean Peak Serum Concentration: 80 ng/mL at 2.6 hr , Half-Life: Approximately 1.4 hr
-Spironolactone and its metabolites are more than 90% bound to plasma proteins. The metabolites are excreted primarily in the urine and secondarily in bile.
-Food increased the bioavailability of unmetabolized spironolactone by almost 100%.
INDICATIONS:
Spironolactone is indicated in the management of:
-Primary hyperaldosteronism for: Establishing the diagnosis of primary hyperaldosteronism –Short term preoperative treatment of patients with primary hyperaldosteronism.
-Long term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas -Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).
-Edematous conditions for patients with: Congestive heart failure: spironolactone is also indicated for patients with congestive heart failure taking digitalis -Cirrhosis of the liver accompanied by edema and/or ascites-Nephrotic syndrome
-Essential Hypertension
-Hypokalemia: spironolactone is also indicated for the prophylaxis of hypokalemia in patients taking digitalis
-Severe Heart Failure
-Usage In Pregnancy: spironolactone is indicated in pregnancy when edema is due to pathologic causes.
CONTRAINDICATIONS:
Spironolactone is contraindicated for patients with anuria, acute renal insufficiency, significant impairment of renal excretory function, hyperkalemia, Addison’s disease, and with concomitant use of eplerenone.
SIDE EFFECTS:
Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea,vomiting,Gynecomastia ,inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding, breast pain. Carcinoma of the breast ,Leukopenia (including agranulocytosis), thrombocytopenia,Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis,Hyperkalemia, electrolyte disturbances ,Leg cramps,Lethargy, mental confusion, ataxia, dizziness, headache, drowsiness,cholestatic/hepatocellular toxicity,Renal dysfunction (including renal failure),Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, pruritis.
DRUG INTERACTIONS:
ACE inhibitors: Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia.
Angiotensin II antagonists, aldosterone blockers, heparin, low molecular weight heparin, and other drugs known to cause hyperkalemia: Concomitant administration may lead to severe hyperkalemia.
Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur.
Pressor amines (e.g., norepinephrine): spironolactone reduces the vascular responsiveness to norepinephrine. Therefore, caution should be exercised in the management of patients subjected to regional or general anesthesia while they are being treated with spironolactone.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to the muscle relaxant may result.
Lithium: Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
Nonsteroidal anti-inflammatory drugs (NSAIDs): administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing, and thiazide diuretics. Combination of NSAIDs, e.g., indomethacin, with potassium-sparing diuretics has been associated with severe hyperkalemia.
Digoxin: spironolactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity.
Cholestyramine: Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine.
WARNINGS:
-Potassium Supplementation:Excessive potassium intake may cause hyperkalemia in patients receiving spironolactone
-Concomitant administration of spironolactone with the following drugs or potassium sources may lead to severe hyperkalemia:
other drugs or conditions known to cause hyperkalemia
potassium supplements
diet rich in potassium
salt substitutes containing potassium
– spironolactone should not be administered concurrently with other potassium-sparing diuretics.
– spironolactone should be used with caution in patients with impaired hepatic function because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
-Lithium generally should not be given with diuretics
PRECAUTIONS:
General:
-All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance, e.g., hypomagnesemia, hyponatremia, hypochloremic alkalosis, and hyperkalemia.
-Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hyperkalemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities, which may be fatal.
-hyperkalemia (warning signs include paresthesia, muscle weakness, fatigue, flaccid paralysis of the extremities, bradycardia, and shock),If hyperkalemia is present, spironolactone should be discontinued immediately
-Reversible hyperchloremic metabolic acidosis, usually in association with hyperkalemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.
-hyponatremia, manifested by dryness of the mouth, thirst, lethargy, and drowsiness and hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than administration of sodium
– spironolactone therapy may cause a transient elevation of BUN, especially in patients with pre-existing renal impairment. Spironolactone may cause mild acidosis
–Gynecomastia may develop in association with the use of spironolactone
–Somnolence and dizziness have been reported to occur in some patients. Caution is advised when driving or operating machinery.
Pregnancy: Category C: the use of spironolactone in pregnant women requires that the anticipated benefit be weighed against the possible hazards to the fetus.
Nursing Mothers: a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother, if use of the drug is essential, an alternative method of infant feeding should be instituted.
Laboratory Tests:
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals, particularly in the elderly and those with significant renal or hepatic impairments.
DOSAGE AND ADMINISTRATION:
–Primary Hyperaldosteronism
Long Test: spironolactone is administered at a daily dosage of 400 mg for three to four weeks
Short Test: spironolactone is administered at a daily dosage of 400 mg for four days
–After the diagnosis of hyperaldosteronism: spironolactone may be administered in doses of 100 to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone may be employed for long-term maintenance therapy at the lowest effective dosage determined for the individual patient.
–Edema In Adults (Congestive Heart Failure, Hepatic Cirrhosis, Or Nephrotic Syndrome):An initial daily dosage of 100 mg of spironolactone administered in either single or divided doses is recommended, but may range from 25 to 200 mg daily.
–Essential Hypertension:For adults, an initial daily dosage of 50 to 100 mg of spironolactone administered in either single or divided doses is recommended.
–Hypokalemia: spironolactone in a dosage ranging from 25 mg to 100 mg daily is useful in treating a diuretic-induced hypokalemia.
–Severe Heart Failure In Conjunction With Standard Therapy:Treatment should be initiated with spironolactone 25 mg once daily if the patient’s serum potassium is ≤ 5 mEq/L and the patient’s serum creatinine is ≤ 2.5 mg/dL. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily. Patients who do not tolerate 25 mg once daily may have their dosage reduced to 25 mg every other day.
OVERDOSE:
Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea.
Treatment: Induce vomiting or evacuate the stomach by lavage. Treatment is supportive to maintain hydration, electrolyte balance, and vital functions.
Storage Condition:
Keep in a dry place below 30°C – Out of reach of children.
