Hydrochlorothiazide/Olmesartan Side Effects

Please note - some side effects for Hydrochlorothiazide/Olmesartan may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Hydrochlorothiazide/Olmesartan - for the Consumer

Hydrochlorothiazide/Olmesartan

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Hydrochlorothiazide/Olmesartan:

Dizziness; nausea.

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; confusion; decrease in sexual ability; decreased urination; depression; drowsiness; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; hoarseness; muscle pain, tenderness, or cramps; red, swollen, blistered, or peeling skin; restlessness; seizures; severe or persistent dry mouth; shortness of breath; swelling of the arms or legs; unusual bruising or bleeding; unusual thirst, tiredness, or weakness; vomiting; yellowing of the skin or eyes.

Side Effects by Body System

Cardiovascular

Cardiovascular side effects of olmesartan have been reported in 0.5% to 1% of patients, including tachycardia, chest pain, and peripheral edema. Symptomatic hypotension may occur in volume- or salt-depleted patients. Facial edema has been reported in 5 patients. Other angiotensin II antagonists have been associated with angioedema. Cardiac arrhythmias, including ventricular ectopy and complete AV heart block, are associated with hypokalemia and hyponatremia due to hydrochlorothiazide (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 associated with HCTZ 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.

Dermatologic

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 side effects of olmesartan have included rash (0.5% to 1%), alopecia, pruritus, and urticaria.

Dermatologic reactions associated with hydrochlorothiazide 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.

Endocrine

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.

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 is reported, although the association is probably coincidental.

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 have been reported in the 1960's although these patients were on a combination HCTZ-potassium product.

Gastrointestinal side effects of olmesartan have been reported in 0.5% to 1% of patients, including abdominal pain, dyspepsia, gastroenteritis, and nausea. Vomiting has also been reported in postmarketing experience.

Gastrointestinal side effects associated with HCTZ are unusual, and include case reports of pancreatitis and acute cholecystitis.

Genitourinary

Genitourinary side effects of olmesartan have included urinary tract infection (0.5% to 1%).

Hematologic

Hematologic side effects of olmesartan have included small decreases in hemoglobin (0.3 g/dL) and hematocrit (0.3 vol%). Cases of immune complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been reported following HCTZ administration.

Hepatic

Hepatic side effects of olmesartan have rarely included liver enzyme and serum bilirubin elevations.

Hypersensitivity

Hypersensitivity (usually nausea, vomiting, diarrhea, and rash) has been reported in less than 1% of patients taking HCTZ. Rare cases of acute pulmonary edema, interstitial cystitis, and interstitial nephritis, and anaphylaxis have been reported. Rare cases of angioedema have been reported in patients receiving olmesartan.

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.

Immunologic

Immunologic side effects reported during HCTZ therapy 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.

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.

Metabolic

Metabolic side effects of olmesartan have been reported in 0.5% to 1% of patients, including hypercholesterolemia, hyperlipidemia, and hyperuricemia. Metabolic side effects during HCTZ therapy 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. Hydrochlorothiazide may increase serum cholesterol. Hyperkalemia has also been reported in postmarketing experience.

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.

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.

Musculoskeletal

Musculoskeletal side effects of olmesartan have been reported in 0.5% to 1% of patients, including arthralgia, arthritis, myalgia, and skeletal pain. In addition, rare reports of rhabdomyolysis have been reported during postmarketing experience in patients receiving angiotensin II receptor blockers.

Musculoskeletal side effects associated with HCTZ are unusual, and include case reports of myalgias and chills. Preservation of mineral bone density has also been observed in older patients.

Nervous system

Nervous system side effects of olmesartan have included dizziness (3% vs. 1% with placebo), vertigo (0.5% to 1%), and insomnia (0.5% to 1%). Asthenia has also been reported in postmarketing experience.

A nervous system side effect, cerebrovascular insufficiency, has been associated with HCTZ-induced plasma volume contraction.

Other

Other side effects of olmesartan that have been reported in more than 1% of patients but at the same or greater incidence than placebo included back pain, bronchitis, increased creatine phosphokinase, diarrhea, headache, hematuria, hyperglycemia, hypertriglyceridemia, inflicted injury, influenza-like symptoms, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection. Fatigue and pain have been reported in 0.5% to 1% of patients.

Renal

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 side effects associated with ACE inhibitors have included increases in serum creatinine or BUN in patients with renal artery stenosis. Acute renal failure and increased serum creatinine levels have been reported in postmarketing experience with olmesartan.

Renal insufficiency, manifesting 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.

Respiratory

Respiratory side effects of olmesartan have included cough (0.9% vs 0.7% with placebo). Respiratory side effects associated with HCTZ are rare, and include approximately 30 case reports of acute noncardiogenic pulmonary edema. These cases are thought to be due to idiosyncrasy or a hypersensitivity mechanism.

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