Hydrochlorothiazide and bisoprolol Side Effects
Please note - some side effects for Hydrochlorothiazide and bisoprolol 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
Cardiovascular side effects have included bradycardia, dizziness, and dyspnea. Like other beta-blockers, bisoprolol may decrease myocardial contractility, which may be important in some patients with poor left ventricular systolic function. The drug has, however, been used safely in patients with chronic stable heart failure.
Unusual side effects include palpitations, mild heart rhythm disturbances, and orthostatic hypotension. Claudication is reported, and may be more likely in patients with peripheral vascular disease.
The incidence of premature ventricular depolarizations associated with HCTZ, as measured by 48-hour ECG monitoring, is the same in patients with and without left ventricular hypertrophy despite a similar fall in serum potassium concentrations.
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.
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 changes are common during HCTZ therapy, but are not expected due to the relatively low dose (6.25 mg) in each combination tablet. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50% of patients who are receiving at least 50 mg per day of HCTZ. This may predispose some patients to develop cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, hypercholesterolemia, and hyperuricemia are also relatively common with these higher doses.
Hypersensitivity reactions are reported in 1% of patients who are taking HCTZ. These may present as nausea, vomiting, diarrhea, or rash. Rare cases of acute pulmonary edema, interstitial cystitis, and interstitial nephritis, and anaphylaxis have been associated with HCTZ.
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 this intravascular volume with saline and albumin. The only precipitating factor per history was the ingestion of HCTZ, which the patient had taken without incidence for two years. Rechallenge resulted in recurrent acute pulmonary edema. Other signs of hypersensitivity, such as rash and eosinophilia, were absent.
Nervous system side effects have included dizziness, vertigo, headache, paresthesias, somnolence, decreased concentration or memory, and anxiety. One case of ischemic stroke is associated with HCTZ-induced plasma volume contraction.
Respiratory system side effects associated with beta-blockers have included rare reports of wheezing. This is due to beta-blockade of bronchial dilation, and may be important in patients with reactive airway disease. Approximately 30 case reports of acute noncardiogenic pulmonary edema 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 skin biopsy consistent with lupus erythematosus while taking 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 associated with bisoprolol have included rash, acne, eczema, skin irritation, pruritus, flushing, sweating, alopecia, angioedema, and exfoliative dermatitis. Reactions associated with HCTZ have included skin -erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, 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 has been associated with HCTZ.
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% and 25% in fasting blood glucose and 2-hour glucose tolerance test values, respectively. A control group was not reported.
Endocrinologic side effects associated with both bisoprolol and HCTZ have included hyperglycemia and hyperlipidemia. In one study, patients treated with the combination had an average increase of 32.6 mg/dl in serum triglycerides and an average decrease of 3.3 mg in HDL cholesterol. This may be important in patients with or at risk of diabetes or coronary artery disease. Thyroid function tests are unaffected by bisoprolol. This may be relevant if bisoprolol is used to treat the symptoms of hyperthyroidism.
The incidence of elevated liver function tests (SGOT and SGPT) of between one and two times normal is approximately 6%, of greater than two times normal is approximately 2%.
Renal side effects have included renal insufficiency due to HCTZ-induced intravascular volume depletion, but is unlikely due to the relative small doses of drug in the combination product. Rare cases of interstitial nephritis have been associated with HCTZ.
Although HCTZ 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.
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. Diarrhea has been reported in up to 5% and 6% of patients taking bisoprolol alone and bisoprolol-HCTZ, respectively. Rare cases of pancreatitis and acute cholecystitis have been associated with HCTZ.
Genitourinary side effects have included decreased libido, impotence, Peyronie's disease, cystitis, and renal colic.
Psychiatric side effects associated with bisoprolol have included vivid dreams, hallucinations, and insomnia. Rare cases of catatonia or depression have been associated with bisoprolol.
Hematologic side effects are rare. Purpura, agranulocytosis, and thrombocytopenia have been associated with bisoprolol, and rare cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with HCTZ.
Musculoskeletal side effects have included pain in rare cases. Gout and elevated serum uric acid levels are reported in at least 1% of patients. Myalgias and chills are rarely reported in patients who are receiving HCTZ.
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, and hemoglobinuria, and elevated serum 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.
Clinically significant immunologic side effects are rare. Approximately 15% of patients on long-term bisoprolol therapy develop a positive ANA titer. Rare cases of allergic vasculitis and hemolytic anemia are associated with HCTZ.
Ocular side effects have included idiosyncratic reactions to the hydrochlorothiazide component resulting in acute transient myopia and acute angle-closure glaucoma.Top
Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.