Applies to hydrochlorothiazide: oral capsules, oral oral solution, oral tablets.

Side effects include:

Potassium depletion, hyperuricemia (usually asymptomatic rarely leading to gout). Hypochloremic alkalosis in patients at risk (e.g., hypokalemic patients). Hyperglycemia and glycosuria in diabetics.

For Healthcare Professionals

Applies to hydrochlorothiazide: compounding powder, oral capsule, oral solution, oral tablet.

Metabolic

Frequency not reported: Electrolyte imbalance, hyperglycemia, glycosuria, hyperuricemia, mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50% of patients (and may predispose patients to cardiac arrhythmias), metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, elevated serum uric acid levels, glucose intolerance and a potentially deleterious effect on the lipid profile (i.e., increased serum cholesterol)^[Ref]

Since hydrochlorothiazide may increase total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, and VLDL lipoprotein cholesterol levels by 50%, and may reduce insulin secretion, it should be used with caution in diabetic patients and in those with hypercholesterolemia. True glucose intolerance may develop in approximately 3% of patients. It is typically reversible within six months after discontinuation of therapy.

Hyperuricamia may be an important consideration in patients with a history of gout. Hypophosphatasemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.^[Ref]

Hypersensitivity

Frequency not reported: Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress (including pneumonitis and pulmonary edema), photosensitivity, fever, urticaria, rash, purpura, toxic epidermal necrolysis^[Ref]

There have been approximately 34 known cases of thiazide-induced pulmonary edema, encompassing 52 episodes of pulmonary edema, as of 1991 (per a 1996 review). In some cases, doses as small as 12.5 mg were associated with the development of pulmonary edema. The average time to onset of this adverse reaction is 44 minutes, women carry a relative risk of 9:1, and the average age is 56 years. The mortality rate is 6%. Some experts consider this side effect grossly underreported.^[Ref]

Dermatologic

Frequency not reported: Erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis (including toxic epidermal necrolysis), alopecia, erythema annular centrifugum, acute eczematous dermatitis, morbilliform and leukocytoclastic vasculitis, phototoxic dermatitis^[Ref]

A 67-year-old woman with hypothyroidism, hypercalcemia, depression, and hypertension developed facial erythema, headaches, tremors, confusion and personality changes associated with a new positive ANA and anti-nRNP, and a skin biopsy consistent with lupus erythematosus while taking hydrochlorothiazide (HCTZ), levothyroxine, and amitriptyline. The eruption resolved upon discontinuation of HCTZ, but she later developed a higher ANA titer associated with symptomatic diffuse interstitial pulmonary infiltrates. She was successfully treated with corticosteroids.^[Ref]

Renal

Frequency not reported: Renal insufficiency (manifest as an increase in serum creatinine and BUN may occur due to hydrochlorothiazide-induced intravascular volume depletion), interstitial nephritis, renal failure^[Ref]

Although hydrochlorothiazide has been used to treat nephrogenic diabetes insipidus, a case report in which the drug was believed to have caused this condition has been reported.^[Ref]

Cardiovascular

The incidence of premature ventricular contractions as measured by 48-hour ambulatory ECG monitoring is the same in both patients with and without left ventricular hypertrophy despite a similar fall in serum potassium concentrations.^[Ref]

Frequency not reported: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs), cardiac arrhythmias (including ventricular ectopy and complete AV heart block)^[Ref]

Gastrointestinal

Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in increased risk of cholesterol gallstone formation. Reports of bowel strictures associated with thiazide ingestion were reported in the 1960s although these patients were on a combination hydrochlorothiazide-potassium product.^[Ref]

Frequency not reported: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia, acute cholecystitis^[Ref]

Respiratory

Although rare, nearly 40 cases of hydrochlorothiazide-induced noncardiogenic pulmonary edema have been reported including at least two fatalities. Onset of symptoms can occur within minutes (range 10 to 150 minutes) of first exposure to the drug. Associated symptoms include dyspnea, hypoxia, respiratory distress, wheezing, cough, tachypnea, dizziness, nausea, vomiting, diarrhea, and hypotension. Ninety percent of cases have occurred in women at a mean dose of 38.7 mg. Treatment varies, but following discontinuation of hydrochlorothiazide most patients respond, with symptoms resolving in a mean 3.5 days. Rechallenge can result in a more severe reaction, even months to years after the initial exposure. Rechallenge with any thiazide diuretic is not recommended.^[Ref]

Rare (less than 0.1%): Acute noncardiogenic pulmonary edema^[Ref]

Immunologic

There are rare case reports of hydrochlorothiazide-induced immune hemolytic anemia. The following illustrates a fatal case:

A 53-year-old man with hypertension developed nausea, vomiting, diarrhea, and progressive anorexia and weakness associated with scleral icterus, anemia with spherocytosis, dark red urine with proteinuria, bilirubinuria, hemoglobinuria, and elevated lactic dehydrogenase levels 18 months after beginning hydrochlorothiazide and methyldopa. Haptoglobin was less than 50 mg per dl. Direct and indirect Coombs tests were positive. The patient died suddenly; autopsy revealed no obvious cause of death, left ventricular hypertrophy, and mild coronary atherosclerosis.^[Ref]

Rare (less than 0.1%): Allergic vasculitis, hemolytic anemia, development of a rash histologically identical to subacute cutaneous lupus^[Ref]

Hematologic

Frequency not reported: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia^[Ref]

Musculoskeletal

Frequency not reported: Muscle spasm, myalgias^[Ref]

Nervous system

Frequency not reported: Weakness, vertigo, paresthesias, dizziness, headache, restlessness, chills^[Ref]

Ocular

Frequency not reported: Transient blurred vision, idiosyncratic reactions to hydrochlorothiazide resulting in acute transient myopia and acute angle-closure glaucoma, xanthopsia

Genitourinary

Frequency not reported: Impotence