Hydrochlorothiazide / triamterene Side Effects
Not all side effects for hydrochlorothiazide / triamterene may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
Applies to hydrochlorothiazide / triamterene: oral capsule, oral tablet
Hydrochlorothiazide (HCTZ)-triamterene is generally well-tolerated, especially in patients with adequate urine output. Serious side effects have been reported in less than 0.1% of patients.
Patients with sulfa sensitivity may develop an allergic reaction to drugs containing hydrochlorothiazide.
Hypersensitivity reactions include rare cases of drug fever, anaphylaxis, photosensitive dermatitis, and erythema multiforme. Cases of acute pulmonary edema, interstitial cystitis, and interstitial nephritis have been associated with HCTZ.
A 67-year-old white 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 or 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 has been associated with HCTZ.
Postmarketing reports of dermatologic reactions have included Stevens-Johnson syndrome and exfoliative dermatitis, including toxic epidermal necrolysis.
Cardiovascular side effects include hypotension, orthostatic hypotension, and cardiac arrhythmias. Arrhythmias have been associated with HCTZ-induced hypokalemia; hypokalemia is much less likely with the addition of triamterene. See "metabolic" side effects below.
The presence of an arrhythmia or widened QRS complex associated with hyperkalemia requires prompt administration of 10% calcium gluconate 10 to 20 mL intravenously over a 20 to 30 minute interval. Noncardiotoxic hyperkalemia usually responds to 10 units of regular insulin plus glucose 25 grams (as a 20% solution infused over 30 minutes) and consideration of sodium bicarbonate 40 to 150 mEq infused over a 30 to 60 minute interval. Insulin-dependent diabetic patients with preexisting hyperglycemia may not require the glucose infusion.
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 is recommended that hydrochlorothiazide be used with caution in patients with hypercholesterolemia or diabetes. A case of hyperosmolar hyperglycemic coma is associated with hydrochlorothiazide.
Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and hypomagnesemia may occur, but are usually clinically insignificant except in malnourished patients.
Metabolic abnormalities include acidosis and hyperkalemia, which is more likely in the elderly, diabetic, or renally insufficient. It is recommended that serum potassium concentrations be monitored, and an electrocardiogram be obtained if hyperkalemia is suspected to check for peaked T waves and QRS complex changes.
Hyponatremia, hypokalemia, hypercalcemia, hyperglycemia, and elevated serum uric acid and cholesterol levels have been associated with hydrochlorothiazide.
Gastrointestinal side effects, such as nausea and vomiting, may be lessened by administering the drug after meals. Due to the diuretic action of the drug some patients complain of dry mouth.
Rare cases of pancreatitis associated with the combination drug have been reported. Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in increased risk of cholesterol gallstone formation. Reports of bowel strictures associated with thiazide ingestion are reported in the 1960's, although these patients were on a combination hydrochlorothiazide-potassium product.
Hepatic side effects are rare. A case of cholestatic jaundice and centrilobular necrosis of the liver has been associated with triamterene (probably related to hypersensitivity to the drug). Triamterene may cause a spurious elevation in serum lactate dehydrogenase concentrations.
A case of obstructive renal tubular triamterene calculi is reported. Triamterene is less soluble in solutions with a pH less than 6.0. In addition, triamterene alone, and when combined with hydrochlorothiazide, is associated with acute interstitial nephritis and acute renal failure in rare cases.
Renal side effects including new or worsened renal insufficiency has been reported in less than 1% of patients. Triamterene renal calculi has been estimated to occur in 1/1,500 to 1/2,000 patients. Rare cases of interstitial nephritis and bladder calculi have been reported.
Hematologic side effects include thrombocytopenia and macrocytic anemia.
Rare cases of triamterene-induced dose-dependent hemagglutination resulting in acute intravascular hemolysis are reported. Hydrochlorothiazide-associated immune-complex hemolytic anemia and aplastic anemia are reported.
Triamterene inhibits dihydrofolate reductase, resulting in decreased folate production. This may be important in patients who have borderline folate stores, such as pregnant women and alcohol abusers.
Musculoskeletal side effects include myalgias.
Rare cases of cerebrovascular insufficiency are associated with hydrochlorothiazide-induced plasma volume contraction.
Nervous system side effects include fatigue and headache.
Endocrinologic problems associated with thiazide diuretics include glucose intolerance and a potentially deleterious effect on the lipid profile. This may be important in some patients with or who are at risk for diabetes or coronary artery disease. A single case of recurrent parathyroid adenoma has been associated with HCTZ, although the association was probably coincidental.
A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed an increased average fasting blood glucose level after treatment. Withdrawal of thiazide therapy for seven months in 10 of the patients resulted in average reductions of 10% in fasting blood glucose and 25% in the 2-hour glucose tolerance test value. A control group was not reported.
A laboratory abnormality associated with triamterene is spurious elevation of lactate dehydrogenase concentrations. Triamterene interferes with the fluorescent measurement of quinidine, resulting in erroneous values of the serum quinidine concentration.
Respiratory side effects have rarely been associated with HCTZ. Some cases of acute pulmonary edema were thought to be due to idiosyncrasy or hypersensitivity to the drug.
Ocular side effects including acute transient myopia with shallowing of the anterior chamber has rarely been associated with HCTZ-triamterene, HCTZ, chlorthalidone, trichlormethiazide, and other sulfonamides, as well as aspirin, ethoxzolamide and acetazolamide. Ocular side effects have also included idiosyncratic reactions to the hydrochlorothiazide component resulting in acute transient myopia and acute angle-closure glaucoma.
Transient myopia with anterior chamber flattening and choroidal detachment has been associated with hydrochlorothiazide-triamterene. Other mechanisms that have been proposed or described include (a) spasm of accommodation, (b) changes in lens structure resulting from altered sodium chloride metabolism, (c) edema of the ciliary body (which produces increased curvature of the lens surface), (d) inhibition of fluid by the lens, (e) increased lenticular index of refraction because of dry salt retention, (f) changes in the refractive index of the vitreous and aqueous because of differential sugar levels, and (h) stretching of the sclera.
More about hydrochlorothiazide/triamterene
- Hydrochlorothiazide and triamterene
- Triamterene and hydrochlorothiazide (Advanced Reading)
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