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.
Post Marketing Experience
Non-melanoma Skin Cancer
Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.