Hydrochlorothiazide and captopril Side Effects
Please note - some side effects for Hydrochlorothiazide and captopril may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects by Body System - for Healthcare Professionals
Applies to: oral tablet
Captopril-hydrochlorothiazide (HCTZ) is generally well tolerated. In some studies, side effects associated with captopril were not seen with the combination because lower doses of captopril were needed to achieve the desired effects. Approximately 3% of patients choose to discontinue therapy due to adverse side effects.
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.
Metabolic side effects including hypokalemia and hypercholesterolemia that are sometimes associated with HCTZ are uncommon with the addition of captopril. In fact, total cholesterol may decrease in some patients with pretreatment hypercholesterolemia. HCTZ monotherapy is associated with hypomagnesemia, hypercalcemia, and elevated serum uric acid levels.
Gastrointestinal side effects include dysgeusia in approximately 0.3% to 4.0% of patients. This is probably related to the captopril component, and is usually self-limited and reversible. Nausea is reported in 1% to 4% of patients.
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.
Nervous system side effects include minor dizziness in 5% to 10% of patients.
Cardiovascular side effects have included hypotension or angina pectoris in 1% to 5% of patients. Less common cardiovascular complaints include tachycardia or palpitations in less than 2% of patients.
Hypotension and presyncopal symptoms are more common in patients with congestive heart failure or hyponatremia. "First dose" hypotension may be minimized by starting with lower doses with the patient supine.
A retrospective study has revealed a significantly higher incidence of discontinuation of angiotensin converting enzyme inhibitor therapy due to cough among black patients compared with non-black patients (9.6% vs. 2.4%).
Respiratory side effects including a dry, persistent cough has been associated with captopril therapy in approximately 4% of patients. Rare reports of asthma associated with captopril suggest that angiotensin-converting enzyme plays a role in the genesis and metabolism of bronchodilatory mediators.
Although HCTZ has been used to treat nephrogenic diabetes insipidus, a case in which the drug was believed to have caused this condition has been reported.
Renal side effects have included new renal insufficiency (in less than 3% of patients) and proteinuria (1%). When used judiciously in many circumstances, captopril and other ACE inhibitors may contribute to improved renal function. Risk factors for the development of renal insufficiency are hypovolemia, hypotension, hyponatremia, concomitant use of other potentially nephrotoxic medications, and renal artery stenosis. Rare cases of allergic nephritis, membranous glomerulonephritis, and nephrotic syndrome are reported during captopril monotherapy.
A 68-year-old man with a history of myocardial infarction (MI) developed dyspnea, chest tightness, a low grade fever, dizziness, sweating, and vomiting associated with cyanosis, a mild leukocytosis, radiographic evidence of pulmonary edema, clinical evidence of hypovolemia, and respiratory acidosis. MI and infection were ruled out; the patient recovered after restoration of his intravascular volume with saline and albumin. The only known precipitating factor was the ingestion of HCTZ, which the patient had taken without incident for two years. Rechallenge resulted in recurrent acute pulmonary edema. Other signs of hypersensitivity, such as rash and eosinophilia, were absent.
Patients with intestinal angioedema generally present with abdominal pain (with or without nausea or vomiting) and in some cases there was no prior history of facial angioedema, and C-1 esterase levels were normal. These symptoms resolve after stopping the ACE inhibitor.
Hypersensitivity reactions to captopril, as with some other angiotensin converting enzyme (ACE) inhibitors, may be life-threatening. Angioedema of the face, extremities, lips, tongue, glottis and/or pharynx have been reported rarely in patients receiving ACE inhibitors. Obstructive laryngeal and glossal angioedema due to captopril is a rare, but potentially fatal reaction. In addition, intestinal angioedema has been reported in patients treated with ACE inhibitors. It is recommended that any patient with dyspnea, dysphagia, or significant facial angioedema stop therapy immediately and avoid ACE inhibitor therapy in general. Other hypersensitivity reactions including hepatitis, allergic vasculitis, pruritus, and mild to severe skin rashes have been reported.
Rare cases of acute pulmonary edema, interstitial cystitis, interstitial nephritis and anaphylaxis are associated with HCTZ.
The neutropenia and agranulocytosis associated with captopril typically occur within 3 to 12 weeks after starting therapy, and are usually reversible within 3 weeks after stopping the drug. While most cases are described in patients who are receiving high doses of captopril (600 mg per day), agranulocytosis has been described in patients on 12.5 to 100 mg per day.
Hematologic side effects have rarely been associated with captopril monotherapy. These include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, eosinophilia, or thrombocytopenia in approximately 0.02% of patients. Extremely rare cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia are associated with HCTZ monotherapy.
Musculoskeletal complaints are limited to muscular cramping, described almost exclusively with dosage greater than captopril 100 mg-HCTZ 50 mg per day.
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.
A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed a significantly increased average fasting blood glucose level after treatment. Withdrawal of thiazide therapy for seven months in 10 of the patients resulted in mean reductions of 10% in fasting blood glucose and 25% in the 2-hour glucose tolerance test value. A control group was not reported.
A review of 19 cases of captopril-associated hepatic injury revealed the most common dosage of captopril was 450 mg per day, the mean age was 61 years, and the most common interval between starting the drug and the onset of symptoms was 14 weeks. Jaundice was the most common presenting symptom, and approximately one third of the patients had concomitant fever, rash, or eosinophilia. Because of these associated findings, the suspected mechanism of injury was hypersensitivity.
Hepatic side effects associated with the use of ACE inhibitors have included a rare syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. Experts recommend discontinuation of therapy with this drug if jaundice or markedly elevated hepatic serum enzymes develop.
A 53-year-old man with diabetes mellitus, hypertension, and heart failure developed arthralgias, fever, and malaise associated with bilateral pleural effusion, elevated liver function tests, a pericardial rub, and elevated C-reactive protein. After other causes of systemic lupus erythematosus were ruled out, captopril was stopped, and these signs and symptoms resolved.
In a study of 78 patients who were treated with captopril for 11 months, 13 developed a positive antinuclear antibody titer. Only one of the 13, however, developed a serum sickness-like illness.
There are rare case reports of HCTZ-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 HCTZ 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 reactions rarely associated with captopril monotherapy have included lymphadenopathy, systemic lupus erythematosus, and Henoch-Schonlein Purpura. Serum sickness-like illness has also been reported.Top
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