Bisoprolol-Hydrochlorothiazide

Bisoprolol-Hydrochlorothiazide is a combination medication used to treat the symptoms of high blood pressure (hypertension). 

• Bisoprolol-Hydrochlorothiazide is available under the following different brand names: Ziac 

Common side effects of Bisoprolol-Hydrochlorothiazide include:

• Dizziness,
• Spinning sensation,
• Feeling weak or tired,
• Diarrhea,
• Nausea,
• Upset stomach,
• Headache,
• Cough,
• Runny nose, and
• Sleep problems (insomnia)

Serious side effects of Bisoprolol-Hydrochlorothiazide include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Chest pain,
• Fast, slow, or uneven heartbeats,
• Lightheadedness,
• Blurred vision,
• Tunnel vision,
• Eye pain,
• Seeing halos around light,
• Shortness of breath,
• Swelling,
• Rapid weight gain,
• Leg cramps,
• Constipation,
• Irregular heartbeats,
• Fluttering in the chest,
• Extreme thirst,
• Increased urination,
• Numbness or tingling,
• Muscle weakness,
• Limp feeling,
• Nausea,
• Upper stomach pain,
• Itching,
• Tiredness,
• Loss of appetite,
• Dark urine,
• Clay-colored stools,
• Yellowing of the skin or eyes (jaundice),
• Headache,
• Hunger,
• Weakness,
• Sweating,
• Confusion,
• Irritability,
• Dizziness,
• Feeling jittery,
• Sore throat,
• Burning in the eyes,
• Skin pain, and
• Red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling

Rare side effects of Bisoprolol-Hydrochlorothiazide include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 2.5 mg/6.25 mg
• 5 mg/6.25 mg
• 10 mg/6.25 mg

Hypertension

Adult dosage

• Initial: 2.5 mg/6.25 mg tablet orally once a day
• Increase based on clinical response every 2 week
• Maximum: 20 mg bisoprolol /12.5 mg hydrochlorothiazide orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Bisoprolol-Hydrochlorothiazide has severe interactions with no other drugs.
• Bisoprolol-Hydrochlorothiazide has serious interactions with at least 34 other drugs.
• Bisoprolol-Hydrochlorothiazide has moderate interactions with at least 248 other drugs.
• Bisoprolol-Hydrochlorothiazide has minor interactions with at least 164 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Anuria
• Cardiogenic shock
• Heart block 2°/3°
• Hypersensitivity to either component or sulfonamide derivatives
• Overt cardiac failure
• Marked sinus bradycardia

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Bisoprolol-Hydrochlorothiazide?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Bisoprolol-Hydrochlorothiazide?”

Cautions

• Although the probability of developing hypokalemia is reduced with therapy because of a very low dose of HCTZ employed, periodic determination of serum electrolytes should be performed, and patients should be observed for signs of fluid or electrolyte disturbances, .g, hyponatremia, hyperchloremic alkalosis, hypokalemia, and hypomagnesemia
• Thiazides have been shown to increase urinary excretion of magnesium; this may result in hypomagnesemia; warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting
• Hypokalemia may develop, especially with brisk diuresis when severe cirrhosis is present, during concomitant use of corticosteroids or adrenocorticotropic hormone (ACTH), or after prolonged therapy; interference with adequate oral electrolyte intake will also contribute to hypokalemia; hypokalemia and hypomagnesemia can provoke ventricular arrhythmias or sensitize or exaggerate the response of the heart to the toxic effects of digitalis; hypokalemia may be avoided or treated by potassium supplementation or increased intake of potassium-rich foods
• Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than salt administration, except in rare instances when the hyponatremia is life-threatening; in actual salt depletion, appropriate replacement is the therapy of choice
• Calcium excretion is decreased by thiazides, and pathologic changes in parathyroid glands, with hypercalcemia and hypophosphatemia, have been observed in a few patients on prolonged thiazide therapy
• Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics; bisoprolol fumarate, alone or in combination with HCTZ, has been associated with increases in uric acid; however, in U.S. clinical trials, the incidence of treatment-related increases in uric acid was higher during therapy with HCTZ 25 mg (25%) than with B/H 6.25 mg (10%); because of the very low dose of HCTZ employed, hyperuricemia may be less likely with this drug combination
• In general, beta-blocking agents should be avoided in patients with overt congestive failure; however, in some patients with compensated cardiac failure, it may be necessary to utilize these agents; in such situations, they must be used cautiously
• Continued depression of the myocardium with beta-blockers can, in some patients, precipitate cardiac failure; at the first signs or symptoms of heart failure, discontinuation of therapy should be considered; in some cases, therapy can be continued while heart failure is treated with other drugs
• Exacerbations of angina pectoris and, in some instances, myocardial infarction or ventricular arrhythmia, are observed in patients with coronary artery disease following abrupt cessation of therapy with beta-blockers; such patients should be cautioned against interruption or discontinuation of therapy without a physician’s advice; even in patients without overt coronary artery disease, it may be advisable to taper therapy with over approximately 1 week with the patient under careful observation; if withdrawal symptoms occur, beta-blocking agent therapy should be reinstituted, at least temporarily
• Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease, exercise caution in such individuals
• Patients with bronchospastic pulmonary disease should, in general, not receive beta-blockers; because of the relative beta1 selectivity of bisoprolol fumarate, the drug may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate other antihypertensive treatment; Since beta1- selectivity is not absolute, the lowest possible dose of ZIAC should be used. Abeta2 agonist (bronchodilator) should be made available
• Chronically administered beta-blocking therapy should not be routinely withdrawn before major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures
• Beta-blockers may mask some manifestations of hypoglycemia, particularly tachycardia; nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels; because of its beta1-selectivity, this is less likely with bisoprolol fumarate; however, patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned about these possibilities; also, latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of insulin dose; because of the very low dose of HCTZ employed, this may be less likely with this drug combination
• Beta-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia; abrupt withdrawal of beta-blockade may be followed by an exacerbation of symptoms of hyperthyroidism or may precipitate a thyroid storm
• Cumulative effects of thiazides may develop in patients with impaired renal function; in such patients, thiazides may precipitate azotemia; in subjects with creatinine clearance < 40 mL/min, the plasma half-life of bisoprolol fumarate is increased up to threefold, as compared to healthy subjects; if progressive renal impairment becomes apparent, therapy should be discontinued
• This drug combination should be used with caution in patients with impaired hepatic function or progressive liver disease; thiazides may alter fluid and electrolyte balance, which may precipitate hepatic coma; also, elimination of bisoprolol fumarate is significantly slower in patients with cirrhosis than in healthy subjects
• Angle-closure glaucoma
  • Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute angle-closure glaucoma and elevated intraocular pressure with or without a noticeable acute myopic shift and/or choroidal effusions
  • Symptoms may include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation
  • Untreated, the acute angle-closure glaucoma may result in permanent visual field loss
  • The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible; prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled
  • Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy
  • Instruct patients taking hydrochlorothiazide to immediately consult their healthcare provider if visual field defects, decreased visual acuity, or ocular pain occurs.

Pregnancy and Lactation

• There are no adequate and well-controlled studies on pregnant women; therapy should be used during pregnancy only if the potential benefit justifies its risk to the fetus
• Impairment of fertility
  • Reproduction studies in rats did not show impairment of fertility with bisoprolol fumarate/hydrochlorothiazide combination doses containing up to 30 mg/kg/day of bisoprolol fumarate in combination with 75 mg/kg/day of hydrochlorothiazide
  • On a bodyweight basis, these doses are 75 and 300 times, respectively, MRHD of bisoprolol fumarate and hydrochlorothiazide; on a body surface area basis, these study doses are 15 and 62 times, respectively, MRHD
• Lactation
  • Bisoprolol fumarate alone or in combination with HCTZ has not been studied in nursing mothers; thiazides are excreted in human breast milk; small amounts of bisoprolol fumarate (below 2% of the dose) have been detected in the milk of lactating rats; because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to mother.