Ziac Side Effects

Generic Name: bisoprolol / hydrochlorothiazide

Note: This page contains side effects data for the generic drug bisoprolol / hydrochlorothiazide. It is possible that some of the dosage forms included below may not apply to the brand name Ziac.

It is possible that some side effects of Ziac may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to bisoprolol / hydrochlorothiazide: oral tablet

As well as its needed effects, bisoprolol / hydrochlorothiazide may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking bisoprolol / hydrochlorothiazide, check with your doctor immediately:

Less common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • chest pain or discomfort
  • lightheadedness, dizziness, or fainting
  • rapid weight gain
  • shortness of breath
  • slow or irregular heartbeat
  • tingling of the hands or feet
  • unusual tiredness or weakness
  • unusual weight gain or loss

If any of the following symptoms of overdose occur while taking bisoprolol / hydrochlorothiazide, get emergency help immediately:

Symptoms of overdose
  • Anxiety
  • blurred vision
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • change in consciousness
  • chills
  • cold, clammy skin
  • cold sweats
  • confusion as to time, place, or person
  • cool, pale skin
  • cough
  • decrease in amount of urine
  • depression
  • difficulty breathing
  • dilated neck veins
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • drowsiness
  • dry mouth
  • extreme fatigue
  • fast or pounding heartbeat or pulse
  • fast, weak pulse
  • frequent urination
  • hallucinations
  • holding false beliefs that cannot be changed by fact
  • increased hunger
  • increased thirst
  • increased volume of pale, dilute urine
  • irregular breathing
  • irritability
  • loss of appetite
  • loss of consciousness
  • mood changes
  • muscle pain or cramps
  • nausea or vomiting
  • nervousness
  • nightmares
  • no breathing
  • noisy breathing
  • not able to pass urine
  • numbness or tingling in the hands, feet, or lips
  • pain or aching in the lower legs
  • seizures
  • shakiness
  • slurred speech
  • sweating
  • swelling of the face, hands, fingers, feet, ankles, or lower legs
  • tightness in the chest
  • trembling
  • troubled breathing
  • unconsciousness
  • unusual drowsiness, dullness, or feeling of sluggishness
  • unusual excitement, nervousness, or restlessness
  • very drowsy or sleepy
  • weakness and heaviness of legs
  • weight gain
  • wheezing

Some bisoprolol / hydrochlorothiazide side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

Less common
  • Acid or sour stomach
  • belching
  • decreased interest in sexual intercourse
  • diarrhea
  • difficulty with moving
  • heartburn
  • inability to have or keep an erection
  • indigestion
  • joint pain
  • loss in sexual ability, desire, drive, or performance
  • muscle aching or stiffness
  • sleepiness
  • stomach discomfort, upset, or pain
  • swollen joints
Rare
  • Runny nose
  • sneezing
  • stuffy nose

For Healthcare Professionals

Applies to bisoprolol / hydrochlorothiazide: oral tablet

Cardiovascular

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.[Ref]

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.[Ref]

Metabolic

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.[Ref]

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.[Ref]

Hypersensitivity

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.[Ref]

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.[Ref]

Nervous system

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.[Ref]

Respiratory

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.[Ref]

Dermatologic

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.[Ref]

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.[Ref]

Endocrine

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.[Ref]

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.[Ref]

Hepatic

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%.[Ref]

Renal

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

Genitourinary

Genitourinary side effects have included decreased libido, impotence, Peyronie's disease, cystitis, and renal colic.[Ref]

Psychiatric

Psychiatric side effects associated with bisoprolol have included vivid dreams, hallucinations, and insomnia. Rare cases of catatonia or depression have been associated with bisoprolol.[Ref]

Hematologic

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.[Ref]

Musculoskeletal

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.[Ref]

Immunologic

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.[Ref]

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.[Ref]

Ocular

Ocular side effects have included idiosyncratic reactions to the hydrochlorothiazide component resulting in acute transient myopia and acute angle-closure glaucoma.

References

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41. Shirey RS, Bartholomew J, Bell W, Pollack B, Kickler TS, Ness PM "Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia." Transfusion 28 (1988): 70-2

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