Bisoprolol and hydrochlorothiazide

Bisoprolol and hydrochlorothiazide is a prescription medication used to treat high blood pressure. Bisoprolol and hydrochlorothiazide is a single product containing 2 medications: bisoprolol and hydrochlorothiazide. Bisoprolol belongs to a group of drugs called beta blockers. It works to decrease blood pressure and heart rate by blocking beta receptors in the body. Hydrochlorothiazide belongs to a group of drugs called thiazide diuretics, which work by stopping reabsorption of salt into your body. This prevents fluid from building up in the body.

This medication comes in a tablet form and is typically taken once daily with or without food. 

Common side effects of bisoprolol and hydrochlorothiazide include dizziness, tiredness (fatigue), and cough. Do not drive or operate heavy machinery until you know how this medication affects you. 

Bisoprolol and Hydrochlorothiazide may be found in some form under the following brand names:

• Ziac

In the U.S.

• Ziac

Available Dosage Forms:

• Tablet

Therapeutic Class: Beta-Adrenergic Blocker, Cardioselective/Thiazide Combination

Pharmacologic Class: Bisoprolol

Chemical Class: Thiazide

• If you have an allergy to bisoprolol, hydrochlorothiazide, or any other part of bisoprolol and hydrochlorothiazide.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Heart block, shock caused by heart problems, or slow heartbeat.
• If you have heart failure (weak heart).
• If you have kidney disease.
• If you are not able to pass urine.
• If you are taking dofetilide.
• If you are using another drug like this one.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take bisoprolol and hydrochlorothiazide with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use bisoprolol and hydrochlorothiazide as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.
• This medicine may cause you to pass urine more often. To keep from having sleep problems, try to take before 6 pm.
• Take bisoprolol and hydrochlorothiazide at the same time of day.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• If you take cholestyramine or colestipol, talk with your pharmacist about how to take them with this medicine.
• If you are on a low-salt or salt-free diet, talk with your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Chest pain.
• Slow heartbeat.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Dark urine or yellow skin or eyes.
• A burning, numbness, or tingling feeling that is not normal.
• This medicine can cause certain eye problems. If left untreated, this can lead to lasting eyesight loss. If eye problems happen, signs like change in eyesight or eye pain most often happen within hours to weeks of starting bisoprolol and hydrochlorothiazide. Call your doctor right away if you have these signs.
• If you have lupus, this medicine can make your lupus active or get worse. Tell your doctor right away if you get any new or worse signs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about bisoprolol and hydrochlorothiazide, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about bisoprolol and hydrochlorothiazide. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using bisoprolol and hydrochlorothiazide.

Review Date: October 4, 2017

Hypertension: Management of hypertension.

Concerns related to adverse events:

• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia can occur. As appropriate, correct electrolyte disturbances prior to initiation.

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses ≥25 mg (Gurwitz 1997).

• Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma.

• Ocular effects: Hydrochlorothiazide may cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain. Additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy.

• Photosensitivity: Photosensitization may occur with hydrochlorothiazide.

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; however, bisoprolol, with B1 selectivity, has been used cautiously with close monitoring. Ensure patient has an inhaled beta2-agonist immediately available.

• Conduction abnormality: Consider preexisting conditions such as sick sinus syndrome before initiating. Use is contraindicated in patients with second- or third-degree AV block or marked sinus bradycardia (unless a functioning artificial pacemaker is in place).

• Diabetes: Use with caution in patients with diabetes mellitus; bisoprolol may potentiate hypoglycemia and/or mask signs and symptoms. Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Heart failure: Use bisoprolol with caution in patients with compensated heart failure (HF) and monitor for a worsening of the condition. Use is contraindicated in patients with cardiogenic shock or overt HF.

• Hepatic impairment: Use with caution in patients with impaired hepatic function or progressive liver disease. Thiazides may alter fluid and electrolyte balance, which may precipitate hepatic coma; elimination of bisoprolol is significantly slower in patients with cirrhosis.

• Hypercalcemia: Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia.

• Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations.

• Myasthenia gravis: Use bisoprolol with caution in patients with myasthenia gravis.

• Peripheral vascular disease and Raynaud disease: Bisoprolol can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease (PVD) and Raynaud disease. Use with caution and monitor for progression of arterial obstruction.

• Parathyroid disease: Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use; should be discontinued prior to testing for parathyroid function.

• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.

• Prinzmetal variant angina: Beta-blockers without alpha1-adrenergic receptor blocking activity should be avoided in patients with Prinzmetal variant angina since unopposed alpha1-adrenergic receptors mediate coronary vasoconstriction and can worsen anginal symptoms (Mayer, 1998).

• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.

• Psychiatric disease: Use bisoprolol with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.

• Renal impairment: Use with caution in patients with renal impairment; plasma half-life of bisoprolol is increased threefold in patients with CrCl <40 mL/minute; hydrochlorothiazide may precipitate azotemia. Discontinue use with progressive renal impairment. Cumulative effects may develop, including azotemia, in patients with impaired renal function. Use is contraindicated in patients with anuria.

• Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

• Thyroid disease: Bisoprolol may mask signs of hyperthyroidism (eg, tachycardia); use caution if hyperthyroidism is suspected, abrupt withdrawal may precipitate thyroid storm.

Concurrent drug therapy issues:

• Drug/drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD); gradually taper over ~1 week to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.

• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.

More frequently reported side effects include: diarrhea, dizziness, headache, and rhinitis. See below for a comprehensive list of adverse effects.

Applies to bisoprolol / hydrochlorothiazide: oral tablet

General

Frequency not reported side effects were seen with hydrochlorothiazide doses of generally 25 mg and higher.[Ref]

The more commonly reported side effects observed with this drug are fatigue, dizziness, and diarrhea.[Ref]

Cardiovascular

Common (1% to 10%): Bradycardia, chest pain, peripheral edema
Frequency not reported: Arrhythmia, peripheral ischemia

Bisoprolol:
Frequency not reported: Bradycardia, palpitations, rhythm disturbances, cold extremities, claudication, hypotension, orthostatic hypotension, chest pain, congestive heart failure, exertional dyspnea, edema

Hydrochlorothiazide:
Frequency not reported: Orthostatic hypotension, necrotizing angiitis, vasculitis[Ref]

Orthostatic hypotension may be potentiated by alcohol, barbiturates, or narcotics.[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, nausea, dyspepsia

Bisoprolol:
Frequency not reported: Gastric pain, epigastric pain, abdominal pain, peptic ulcer, gastritis, dyspepsia, nausea, vomiting, diarrhea, constipation, dry mouth, mesenteric arterial thrombosis, ischemic colitis

Hydrochlorothiazide:
Frequency not reported: Gastric irritation, constipation, pancreatitis, sialadenitis, dry mouth[Ref]

Nervous system

Common (1% to 10%): Dizziness, somnolence
Frequency not reported: Headache

Bisoprolol:
Frequency not reported: Unsteadiness, dizziness, vertigo, headache, syncope, paresthesia, hypoesthesia, hyperesthesia, somnolence, decreased concentration, decreased memory, tremor, taste abnormality, slightly clouded sensorium

Hydrochlorothiazide:
Frequency not reported: Vertigo, paresthesia[Ref]

Musculoskeletal

Common (1% to 10%): Muscle cramps, myalgia

Bisoprolol:
Frequency not reported: Arthralgia, muscle pain, joint pain, back pain, neck pain, muscle cramps, twitching

Hydrochlorothiazide:
Frequency not reported: Cramping, muscle spasm[Ref]

Respiratory

Common (1% to 10%): Cough, upper respiratory tract infection
Uncommon (0.1% to 1%): Rhinitis

Bisoprolol:
Frequency not reported: Asthma, bronchospasm, bronchitis, dyspnea, pharyngitis, rhinitis, sinusitis, upper respiratory infection, sore throat, laryngospasm, respiratory distress

Hydrochlorothiazide:
Frequency not reported: Respiratory distress, pneumonitis, pulmonary edema[Ref]

Other

Common (1% to 10%): Fatigue

Bisoprolol:
Frequency not reported: Tinnitus, decreased hearing, earache, fatigue, asthenia, malaise, fever, aching

Hydrochlorothiazide:
Frequency not reported: Weakness, fever[Ref]

Genitourinary

Common (1% to 10%): Impotence

Bisoprolol:
Frequency not reported: Impotence, polyuria, Peyronie's disease

Hydrochlorothiazide:
Frequency not reported: Sexual dysfunction[Ref]

Metabolic

Uncommon (0.1% to 1%): Hypokalemia
Frequency not reported: Increased uric acid, increased serum triglycerides, decreased HDL

Bisoprolol:
Frequency not reported: Gout, weight gain, increased serum triglycerides, increased uric acid, increased serum potassium, increased glucose, increased phosphorus

Hydrochlorothiazide:
Common (1% to 10%): Hypokalemia
Frequency not reported: Anorexia, gout, hyperglycemia, hyperuricemia, hyperlipidemia, hypercalcemia, increased uric acid, other electrolyte imbalances[Ref]

Bisoprolol: Uric acid, serum potassium, glucose, and phosphorus increases associated with use of this drug were not of clinical importance and rarely resulted in discontinuation.[Ref]

Psychiatric

Frequency not reported: Insomnia, loss of libido

Bisoprolol:
Frequency not reported: Sleep disturbance, vivid dreams, insomnia, depression, anxiety, restlessness, decreased libido, hallucination, disorientation to time and space, emotional lability

Hydrochlorothiazide:
Frequency not reported: Restlessness[Ref]

Immunologic

Of the 15% of patients who converted to a positive ANA status, one-third of the patients converted back to a negative ANA titer with continued use.[Ref]

Bisoprolol:
Very common: Antinuclear antibody (ANA) conversions to a positive titer (up to 15%)[Ref]

Renal

Bisoprolol:
Frequency not reported: Cystitis, renal colic, increased creatinine, increased BUN

Hydrochlorothiazide:
Frequency not reported: Renal failure, renal dysfunction, interstitial nephritis, glycosuria[Ref]

Creatinine and BUN were associated with slightly increased levels, but these effects were generally not of clinical importance and rarely resulted in discontinuation.[Ref]

Dermatologic

Bisoprolol:
Frequency not reported: Rash, acne, eczema, psoriasis, skin irritation, pruritus, flushing, sweating, alopecia, dermatitis, cutaneous vasculitis, exfoliative dermatitis

Hydrochlorothiazide:
Frequency not reported: Photosensitivity, rash, cutaneous vasculitis, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis[Ref]

Ocular

Bisoprolol:
Frequency not reported: Visual disturbances, ocular pain, ocular pressure, abnormal lacrimation

Hydrochlorothiazide:
Frequency not reported: Transient blurred vision, xanthopsia[Ref]

Hematologic

Bisoprolol:
Frequency not reported: Purpura, decreased WBCs, decreased platelets, eosinophilia, agranulocytosis, thrombocytopenia

Hydrochlorothiazide:
Frequency not reported: Purpura, leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia[Ref]

During treatment with this drug, eosinophilia and decreased levels of WBCs and platelets were not of clinical importance and rarely resulted in discontinuation.[Ref]

Hypersensitivity

Bisoprolol:
Frequency not reported: Angioedema

Hydrochlorothiazide:
Frequency not reported: Urticaria, anaphylactic reactions[Ref]

Hepatic

SGOT and SGPT elevations of 1 to 2 times the upper limit of normal were reported in 6.2% of patients, with a multiple occurrence rate of 1.9%. Generally, this increase was the result of underlying disorders or resolved with continued use of this drug.[Ref]

Bisoprolol:
Common (1% to 10%): Increased serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)

Hydrochlorothiazide:
Frequency not reported: Intrahepatic cholestatic jaundice, cholecystitis[Ref]

Some side effects of bisoprolol / hydrochlorothiazide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Use caution with dose-titration