Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia.
Alcohol, barbiturates, or narcotics
Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (eg, oral agents, insulin)
Dosage adjustment of the antidiabetic drug may be required.
Intensified electrolyte depletion, particularly hypokalemia, may occur.
Pressor amines (eg, norepinephrine)
Both spironolactone and hydrochlorothiazide reduce 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 Aldactazide.
Skeletal muscle relaxants, nondepolarizing (eg, tubocurarine)
Possible increased responsiveness to the muscle relaxant may result.
Lithium generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
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. Combination of NSAIDs, eg, indomethacin, with potassium-sparing diuretics has been associated with severe hyperkalemia. Therefore, when Aldactazide and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
Spironolactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity. It may be necessary to reduce the maintenance and digitalization doses when spironolactone is administered, and the patient should be carefully monitored to avoid over- or underdigitalization.
The oral LD50 of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.
Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Rarely, instances of hyponatremia, hyperkalemia (less commonly seen with Aldactazide because the hydrochlorothiazide component tends to produce hypokalemia), or hepatic coma may occur in patients with severe liver disease, but these are unlikely due to acute overdosage.
However, because Aldactazide contains both spironolactone and hydrochlorothiazide, the toxic effects may be intensified, and signs of thiazide overdosage may be present. These include electrolyte imbalance such as hypokalemia and/or hyponatremia. The potassium-sparing action of spironolactone may predominate and hyperkalemia may occur, especially in patients with impaired renal function. BUN determinations have been reported to rise transiently with hydrochlorothiazide. There may be CNS depression with lethargy or even coma.
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 spironolactone-induced hyperkalemia. In such cases, Aldactazide should be discontinued immediately. With severe hyperkalemia, the clinical situation dictates the procedures to be employed. These include the intravenous administration of calcium chloride solution, sodium bicarbonate solution and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation. These are temporary measures to be repeated as required. Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis.
Aldactazide is contraindicated in patients with anuria, acute renal insufficiency, significant impairment of renal excretory function, or hyperkalemia, and in patients who are allergic to thiazide diuretics or to other sulfonamide-derived drugs. Aldactazide may also be contraindicated in acute or severe hepatic failure.
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