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Applies to hydrochlorothiazide: oral capsule, oral tablet
Along with its needed effects, hydrochlorothiazide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking hydrochlorothiazide:
Incidence not known
Some side effects of hydrochlorothiazide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Incidence not known
For Healthcare Professionals
Applies to hydrochlorothiazide: compounding powder, oral capsule, oral solution, oral tabletMetabolic
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)
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.Hypersensitivity
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.
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 necrolysisDermatologic
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.
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 dermatitisRenal
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.
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 failureCardiovascular
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)
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.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.
Frequency not reported: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia, acute cholecystitisRespiratory
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.
Rare (less than 0.1%): Acute noncardiogenic pulmonary edemaImmunologic
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.
Rare (less than 0.1%): Allergic vasculitis, hemolytic anemia, development of a rash histologically identical to subacute cutaneous lupusHematologic
Frequency not reported: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopeniaMusculoskeletal
Frequency not reported: Muscle spasm, myalgiasNervous system
Frequency not reported: Weakness, vertigo, paresthesias, dizziness, headache, restlessness, chillsOcular
Frequency not reported: Transient blurred vision, idiosyncratic reactions to hydrochlorothiazide resulting in acute transient myopia and acute angle-closure glaucoma, xanthopsiaGenitourinary
Frequency not reported: Impotence
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