FDA label 5bed9894-93fd-3e64-e053-2a91aa0a301b

WARNING Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats (see PRECAUTIONS ). Spironolactone and hydrochlorothiazide should be used only in those conditions described under INDICATIONS AND USAGE . Unnecessary use of this drug should be avoided. Fixed-dose combination drugs are not indicated for initial therapy of edema or hypertension. Edema or hypertension requires therapy titrated to the individual patient. If the fixed combination represents the dosage so determined, its use may be more convenient in patient management. The treatment of hypertension and edema is not static but must be reevaluated as conditions in each patient warrant.

WARNINGS 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 therapy. Excessive potassium intake may cause hyperkalemia in patients receiving spironolactone and hydrochlorothiazide (see PRECAUTIONS: General ). Concomitant administration of spironolactone and hydrochlorothiazide with the following drugs or potassium sources may lead to severe hyperkalemia: other potassium-sparing diuretics ACE inhibitors angiotensin II receptor antagonists aldosterone blockers non-steroidal anti-inflammatory drugs (NSAIDs), e.g., indomethacin heparin and low molecular weight heparin other drugs or conditions known to cause hyperkalemia potassium supplements diet rich in potassium salt substitutes containing potassium Spironolactone and hydrochlorothiazide should not be administered concurrently with other potassium-sparing diuretics. Spironolactone, when used with ACE inhibitors or indomethacin, even in the presence of a diuretic, has been associated with severe hyperkalemia. Extreme caution should be exercised when spironolactone and hydrochlorothiazide is given concomitantly with these drugs (see PRECAUTIONS: Drug Interactions ). Spironolactone and hydrochlorothiazide 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 (see PRECAUTIONS: Drug Interactions ). Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function. Thiazides may add to or potentiate the action of other antihypertensive drugs. Sensitivity reactions to thiazides may occur in patients with or without a history of allergy or bronchial asthma. Sulfonamide derivatives, including thiazides, have been reported to exacerbate or activate systemic lupus erythematosus. Acute Myopia and Secondary Angle-Closure Glaucoma Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

ADVERSE REACTIONS 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 (see WARNINGS ). 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. Metabolic: Electrolyte imbalance (see PRECAUTIONS ), hyperglycemia, glycosuria, hyperuricemia. Musculoskeletal: Muscle spasm. Nervous System/Psychiatric: Vertigo, paresthesias, dizziness, headache, restlessness. Renal: Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS ). Skin: Erythema multiforme, pruritus. Special Senses: Transient blurred vision, xanthopsia. Spironolactone Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting. Reproductive: Gynecomastia (see PRECAUTIONS ), inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding, breast pain. Carcinoma of the breast has been reported in patients taking spironolactone but a cause and effect relationship has not been established. Hematologic: Leukopenia (including agranulocytosis), thrombocytopenia. Hypersensitivity: Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis. Metabolism: Hyperkalemia, electrolyte disturbances (see WARNINGS and PRECAUTIONS ). 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, pruritus.