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Ziac Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 8/10/2015

Ziac (bisoprolol fumarate and hydrochlorothiazide) is a combination of a thiazide diuretic (water pill) and a beta-blocker used to treat high blood pressure (hypertension). Ziac is available in generic form. Common side effects of Ziac include dizziness, spinning sensation, lightheadedness, tiredness, and drowsiness as your body adjusts to the medication. Nausea, stomach upset, diarrhea, cough, runny nose, constipation, ringing in your ears, blurred vision, and trouble sleeping may also occur.

Ziac is comes in tablets of 2.5 mg/6.25 mg (bisoprolol fumarate 2.5 mg and hydrochlorothiazide 6.25 mg): 5 mg/6.25 mg or 10 mg/6.25 mg. The dose is based on the individual patient's needs. Adverse interactions may occur between Ziac and many medications including insulin or diabetes medicine you take by mouth, colestipol or cholestyramine, steroids, lithium, rifampin, NSAIDs, other heart or blood pressure medications or calcium channel blockers. During pregnancy, this medication should be used only when prescribed by your doctor. This drug passes into breast milk and could have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Our Ziac Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Ziac in Detail - Patient Information: Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using this medication and call your doctor at once if you have any of these serious side effects:

  • eye pain, vision problems;
  • swelling, rapid weight gain, feeling short of breath, even with mild exertion;
  • fast, slow, or uneven heartbeat;
  • easy bruising or bleeding;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden severe headache, confusion, problems with speech or balance;
  • chest pain, sudden cough, wheezing, rapid breathing, coughing up blood;
  • pain, swelling, warmth, or redness in one or both legs;
  • numbness or tingly feeling in your hands or feet;
  • feeling weak, drowsy, restless, or light-headed;
  • dry mouth, extreme thirst, confusion, increased urination, leg discomfort, muscle weakness or limp feeling, nausea and vomiting;
  • urinating less than usual or not at all;
  • fever, sore throat, and headache with a severe blistering, peeling, and red skin rash; or
  • upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • diarrhea, constipation, upset stomach;
  • dizziness, spinning sensation;
  • cough, runny nose;
  • ringing in your ears; or
  • blurred vision.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Ziac (Bisoprolol and Hydrochlorothiazide)

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.

Ziac Overview - Patient Information: Side Effects

SIDE EFFECTS: See also Precautions section.

Dizziness, lightheadedness, tiredness, and drowsiness may occur as your body adjusts to the medication. Nausea, stomach upset, diarrhea, cough, constipation and trouble sleeping may also occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This product may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

The hydrochlorothiazide in this product may cause too much body water and salts to be lost (dehydration). Tell your doctor immediately if you have any of these unlikely but serious symptoms of dehydration: very dry mouth, extreme thirst, muscle cramps/weakness, fast heartbeat, severe dizziness, unusual decrease in the amount of urine, fainting, seizures.

Tell your doctor immediately if any of these unlikely but serious side effects occur: very slow/irregular heartbeat, swelling of the ankles/feet, sudden/unexplained weight gain, loss of feeling/tingling in the fingers/toes, hair loss, decrease in vision, eye pain, mental/mood changes, decreased sexual ability/interest, muscle/joint pain, persistent nausea/vomiting, yellowing eyes/skin, severe stomach/abdominal pain, dark urine, nervousness, shaking, confusion, easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), change in the amount of urine (not including the normal increase in urine when you first start this drug).

Seek immediate medical attention if this rare but very serious side effect occurs: trouble breathing.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Ziac (Bisoprolol and Hydrochlorothiazide)

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Ziac FDA Prescribing Information: Side Effects
(Adverse Reactions)



Bisoprolol fumarate/HCTZ 6.25 mg is well tolerated in most patients. Most adverse effects (AEs) have been mild and transient. In more than 65,000 patients treated worldwide with bisoprolol fumarate, occurrences of bronchospasm have been rare. Discontinuation rates for AEs were similar for bisoprolol fumarate/HCTZ 6.25 mg and placebo-treated patients.

In the United States, 252 patients received bisoprolol fumarate (2.5, 5, 10, or 40 mg)/HCTZ 6.25 mg and 144 patients received placebo in two controlled trials. In Study 1, bisoprolol fumarate 5/HCTZ 6.25 mg was administered for 4 weeks. In Study 2, bisoprolol rumarate 2.5, 10, or 40/HCTZ 6.25 mg was administered for 12 weeks. All adverse experiences, whether drug related or not, and drug related adverse experiences in patients treated with bisoprolol fumarate 2.5-10/HCTZ 6.25 mg, reported during comparable, 4 week treatment periods by at least 2% of bisoprolol fumarate/HCTZ 6.25 mg-treated patients (plus additional selected adverse experiences) are presented in the following table:

% of Patients with Adverse Experiencesa

Body System/Adverse Experience All Adverse Experiences Drug Related
Adverse Experiences
Placebob B2.5-40/H6.25b Placebob B2.5-10/H6.25b
(n=144) (n=252) (n=144) (n=221)
% % % %
  bradycardia 0.7 1.1 0.7 0.9
  arrhythmia 1.4 0.4 0.0 0.0
  peripheral ischemia 0.9 0.7 0.9 0.4
  chest pain 0.7 1.8 0.7 0.9
  bronchospasm 0.0 0.0 0.0 0.0
  cough 1.0 2.2 0.7 1.5
  rhinitis 2.0 0.7 0.7 0.9
  URI 2.3 2.1 0.0 0.0
Body as a Whole
  asthenia 0.0 0.0 0.0 0.0
  fatigue 2.7 4.6 1.7 3.0
  peripheral edema 0.7 1.1 0.7 0.9
Central Nervous System
  dizziness 1.8 5.1 1.8 3.2
  headache 4.7 4.5 2.7 0.4
  muscle cramps 0.7 1.2 0.7 1.1
  myalgia 1.4 2.4 0.0 0.0
  insomnia 2.4 1.1 2.0 1.2
  somnolence 0.7 1.1 0.7 0.9
  loss of libido 1.2 0.4 1.2 0.4
  impotence 0.7 1.1 0.7 1.1
  diarrhea 1.4 4.3 1.2 1.1
  nausea 0.9 1.1 0.9 0.9
  dyspepsia 0.7 1.2 0.7 0.9
a) Averages adjusted to combine across studies, b) Combined across studies.

Other adverse experiences that have been reported with the individual components are listed below.

Bisoprolol Fumarate

In clinical trials worldwide, or in postmarketing experience, a variety of other AEs, in addition to those listed above, have been reported. While in many cases it is not known whether a causal relationship exists between bisoprolol and these AEs, they are listed to alert the physician to a possible relationship.

Central Nervous System

Unsteadiness, dizziness, vertigo, headache, syncope, paresthesia, hypoesthesia, hyperesthesia, sleep disturbance/vivid dreams, insomnia, somnolence, depression, anxiety/restlessness, decreased concentration/memory.


Bradycardia, palpitations and other rhythm disturbances, cold extremities, claudication, hypotension, orthostatic hypotension, chest pain, congestive heart failure, dyspnea on exertion.


Gastric/epigastric/abdominal pain, peptic ulcer, gastritis, dyspepsia, nausea, vomiting, diarrhea, constipation, dry mouth.


Arthralgia, muscle/joint pain, back/neck pain, muscle cramps, twitching/tremor.


Rash, acne, eczema, psoriasis, skin irritation, pruritus, purpura, flushing, sweating, alopecia, dermatitis, exfoliative dermatitis (very rarely), cutaneous vasculitis.

Special Senses

Visual disturbances, ocular pain/pressure, abnormal lacrimation, tinnitus, decreased hearing, earache, taste abnormalities.




Asthma, bronchospasm, bronchitis, dyspnea, pharyngitis, rhinitis, sinusitis, URI (upper respiratory infection).


Decreased libido/impotence, Peyronie's disease (very rarely), cystitis, renal colic, polyuria.


Fatigue, asthenia, chest pain, malaise, edema, weight gain, angioedema.

In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and should be considered potential adverse effects:

Central Nervous System

Reversible mental depression progressing to catatonia, hallucinations, an acute reversible syndrome characterized by disorientation to time and place, emotional lability, slightly clouded sensorium.


Fever, combined with aching and sore throat, laryngospasm, and respiratory distress.


Agranulocytosis, thrombocytopenia.


Mesenteric arterial thrombosis and ischemic colitis.


The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with bisoprolol fumarate during investigational use or extensive foreign marketing experience.


The following adverse experiences, in addition to those listed in the above table, have been reported with hydrochlorothiazide (generally with doses of 25 mg or greater).



Central Nervous System

Vertigo, paresthesia, restlessness.


Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics).


Anorexia, gastric irritation, cramping, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, cholecystitis, sialadenitis, dry mouth.


Muscle spasm.

Hypersensitive Reactions

Purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions.

Special Senses

Transient blurred vision, xanthopsia.




Sexual dysfunction, renal failure, renal dysfunction, interstitial nephritis.


Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis.

Laboratory Abnormalities


Because of the low dose of hydrochlorothiazide in ZIAC (bisoprolol fumarate and hydrochlorothiazide), adverse metabolic effects with bisoprolol fumarate/HCTZ 6.25 mg are less frequent and of smaller magnitude than with HCTZ 25 mg. Laboratory data on serum potassium from the U.S. placebo-controlled trials are shown in the following table:

Serum Potassium Data from U.S. Placebo Controlled Studies

  Placeboa B2.5/H6.25 mg B5/H6.25 mg B10/H6.25 mg HCTZ 25mga
  (N=130b) (N=28b) (N=149b) (N=28b) (N=142b)
Mean Changec (mEq/L) +0.04 +0.11 -0.08 0.00 -0.30%
Hypokalemiad 0.0% 0.0% 0.7% 0.0% 5.5%
a) Combined across studies.
b) Patients with normal serum potassium at baseline.
c) Mean change from baseline at Week 4.
d) Percentage of patients with abnormality at Week 4.

Treatment with both beta blockers and thiazide diuretics is associated with increases in uric acid. However, the magnitude of the change in patients treated with B/H 6.25 mg was smaller than in patients treated with HCTZ 25 mg. Mean increases in serum triglycerides were observed in patients treated with bisoprolol fumarate and hydrochlorothiazide 6.25 mg. Total cholesterol was generally unaffected, but small decreases in HDL cholesterol were noted.

Other laboratory abnormalities that have been reported with the individual components are listed below.

Bisoprolol Fumarate

In clinical trials, the most frequently reported laboratory change was an increase in serum triglycerides, but this was not a consistent finding.

Sporadic liver test abnormalities have been reported. In the U.S. controlled trials experience with bisoprolol fumarate treatment for 4-12 weeks, the incidence of concomitant elevations in SGOT and SGPT from 1 to 2 times normal was 3.9%, compared to 2.5% for placebo. No patient had concomitant elevations greater than twice normal.

In the long-term, uncontrolled experience with bisoprolol fumarate treatment for 6-18 months, the incidence of one or more concomitant elevations in SGOT and SGPT from 1 to 2 times normal was 6.2%. The incidence of multiple occurrences was 1.9%. For concomitant elevations in SGOT and SGPT of greater than twice normal, the incidence was 1.5%. The incidence of multiple occurrences was 0.3%. In many cases these elevations were attributed to underlying disorders, or resolved during continued treatment with bisoprolol fumarate.

Other laboratory changes included small increases in uric acid, creatinine, BUN, serum potassium, glucose, and phosphorus and decreases in WBC and platelets. There have been occasional reports of eosinophilia. These were generally not of clinical importance and rarely resulted in discontinuation of bisoprolol fumarate.

As with other beta-blockers, ANA conversions have also been reported on bisoprolol fumarate. About 15% of patients in long-term studies converted to a positive titer, although about one-third of these patients subsequently reconverted to a negative titer while on continued therapy.


Hyperglycemia, glycosuria, hyperuricemia, hypokalemia and other electrolyte imbalances (see PRECAUTIONS), hyperlipidemia, hypercalcemia, leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, and hemolytic anemia have been associated with HCTZ therapy.

Read the entire FDA prescribing information for Ziac (Bisoprolol and Hydrochlorothiazide)

Ziac - User Reviews

Ziac User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Ziac sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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