Hydrochlorothiazide and Spironolactone

Spironolactone, an ingredient of spironolactone and hydrochlorothiazide tablets, has been shown to be a tumorigen in chronic toxicity studies in rats. Spironolactone and hydrochlorothiazide tablets should be used only in those conditions described below. Unnecessary use of this drug should be avoided. Spironolactone and hydrochlorothiazide tablets are indicated for: Edematous conditions for patients with: Congestive heart failure: • For the management of edema and sodium retention when the patient is only partially responsive to, or is intolerant of, other therapeutic measures, • The treatment of diuretic-induced hypokalemia in patients with congestive heart failure when other measures are considered inappropriate, • The treatment of patients with congestive heart failure taking digitalis when other therapies are considered inadequate or inappropriate.

Spironolactone and hydrochlorothiazide tablets are a combination of two diuretic agents with different but complementary mechanisms and sites of action, thereby providing additive diuretic and antihypertensive effects. Additionally, the spironolactone component helps to minimize the potassium loss characteristically induced by the thiazide component. The diuretic effect of spironolactone is mediated through its action as a specific pharmacologic antagonist of aldosterone, primarily by competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Hydrochlorothiazide promotes the excretion of sodium and water primarily by inhibiting their reabsorption in the cortical diluting segment of the distal renal tubule.

Optimal dosage should be established by individual titration of the components. Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome) The usual maintenance dose of spironolactone and hydrochlorothiazide tablets is 100 mg each of spironolactone and hydrochlorothiazide daily, administered in a single dose or in divided doses, but may range from 25 mg to 200 mg of each component daily depending on the response to the initial titration. In some instances it may be desirable to administer separate tablets of either spironolactone or hydrochlorothiazide in addition to spironolactone and hydrochlorothiazide tablets in order to provide optimal individual therapy.

Spironolactone and hydrochlorothiazide tablets are contraindicated in patients with anuria, acute renal insufficiency, significant impairment of renal excretory function, hypercalcemia, hyperkalemia, Addison's disease, and in patients who are allergic to thiazide diuretics or to other sulfonamide-derived drugs. Spironolactone and hydrochlorothiazide tablets may also be contraindicated in acute or severe hepatic failure.

Potassium supplementation, either in the form of medication or as a diet rich in potassium, should not ordinarily be given in association with spironolactone and hydrochlorothiazide tablet therapy. Excessive potassium intake may cause hyperkalemia in patients receiving spironolactone and hydrochlorothiazide tablets.

The following adverse reactions have been reported and, within each category (body system), are listed in order of decreasing severity. Hydrochlorothiazide Body as a whole: Weakness. Cardiovascular: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics, or antihypertensive drugs). Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialoadenitis, cramping, constipation, gastric irritation, nausea, anorexia. Eye Disorders: Acute myopia and acute angle-closure glaucoma. Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia. Hypersensitivity: Anaphylactic reactions, necrotizing angitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura.

ACE inhibitors, Angiotensin II receptor antagonists, aldosterone blockers, potassium supplements, 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. Antidiabetic drugs (e.g., oral agents, insulin): Dosage adjustment of the antidiabetic drug may be required. Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia, may occur. Pressor amines (e.g., 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 spironolactone and hydrochlorothiazide tablets.

Store below 77°F (25°C).