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Some side effects of hydrochlorothiazide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Get emergency medical help if you have any of these signs of an allergic reaction while taking hydrochlorothiazide: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Stop using this medication and call your doctor at once if you have a serious side effect such as:
· eye pain, vision problems;
· dry mouth, thirst, nausea, vomiting;
· feeling weak, drowsy, restless, or light-headed;
· fast or uneven heartbeat;
· muscle pain or weakness;
· numbness or tingly feeling;
· a red, blistering, peeling skin rash; or
· nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
Less serious side effects of hydrochlorothiazide may include:
· mild stomach pain;
· constipation; or
· blurred vision.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.
Metabolic side effects are common, especially when doses greater than 50 mg per day are used. 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, and elevated serum uric acid levels are also relatively common. Metabolic problems associated with thiazide diuretics also includes glucose intolerance and a potentially deleterious effect on the lipid profile (i.e., increased serum cholesterol).
Since HCTZ 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.
In contrast, a 3 year study involving healthy older men and women (n=320; 60 to 79 years of age; primarily Caucasian), low dose (12.5 to 25 mg/day) hydrochlorothiazide had minimal effects on lipid metabolism (i.e., triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol).
A prospective study of 34 patients who received oral thiazide-type diuretics for 14 years without interruption revealed an increased average fasting blood glucose level after treatment. Withdrawal of thiazide therapy for 7 months in 10 of the patients resulted in average reductions of 10% in the fasting blood glucose and 25% in the 2-hour glucose tolerance test values. A control group was not reported.
Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.
Hypersensitivity (usually nausea, vomiting, diarrhea, and rash) has been reported in less than 1% of patients. Rare cases of acute pulmonary edema, interstitial cystitis, and interstitial nephritis, and anaphylaxis have been reported.
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.
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.
Dermatologic reactions include case reports of erythema annular centrifugum, acute eczematous dermatitis, and morbilliform and leukocytoclastic vasculitis. Thiazides may induce phototoxic dermatitis. In addition, a rare, distinct entity with clinical and laboratory features indistinguishable from those of subacute cutaneous lupus erythematosus is associated with HCTZ.
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.
Renal insufficiency, manifest as an increase in serum creatinine and BUN may occur due to HCTZ-induced intravascular volume depletion. Rare cases of interstitial nephritis have been reported.
Cardiac arrhythmias, including ventricular ectopy and complete AV heart block, are associated with hypokalemia and hyponatremia due to HCTZ. Hypotension has been reported in association with HCTZ-induced pulmonary edema. Orthostatic hypotension may occur and may rarely be associated with syncope, particularly in the elderly.
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.
Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in increased risk of cholesterol gallstone formation. Reports of bowel strictures associated with thiazide ingestion have been reported in the 1960's although these patients were on a combination HCTZ-potassium product.
Gastrointestinal side effects are unusual, and include case reports of pancreatitis, nausea, and acute cholecystitis.
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.
Respiratory side effects are rare, and include approximately 40 case reports of acute noncardiogenic pulmonary edema. These cases are thought to be due to idiosyncrasy or a hypersensitivity mechanism.
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.
Immunologic side effects are rare, and include case reports of allergic vasculitis and hemolytic anemia. There are numerous case reports of patients developing a rash histologically identical to subacute cutaneous lupus following HCTZ administration.
Hematologic side effects are rare. Cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been reported.
Musculoskeletal side effects are unusual, and include case reports of myalgias and chills. Preservation of mineral bone density has also been observed in older patients.
Nervous system side effects including cerebrovascular insufficiency have been associated with HCTZ-induced plasma volume contraction. At least one case of cognitive and neurologic impairment (i.e., confusion, somnolence, feeling dazed) has been reported. Symptoms immediately resolved following discontinuation of hydrochlorothiazide.
Endocrinologic side effects associated with thiazide diuretics include a single case of recurrent parathyroid adenoma, although the association is probably coincidental.
Ocular side effects have included idiosyncratic reactions to hydrochlorothiazide resulting in acute transient myopia and acute angle-closure glaucoma.
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