Dosing and uses of Ziac (bisoprolol/hydrochlorothiazide)
Adult dosage forms and strengths
bisoprolol/hydrochlorothiazide
tablet
- 2.5mg/6.25mg
- 5mg/6.25mg
- 10mg/6.25mg
Hypertension
Initial: 2.5 mg/6.25 mg tablet PO qd
Increase based on clinical response q2 week
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy
Maximum: bisoprolol 20 mg/hydrochlorothiazide 12.5 mg PO qd
Renal Impairment
Use caution in dosing/titrating patients with renal dysfunction
Cumulative effects of thiazides may develop with impaired renal function
CrCl <40mL/min: half-life of bisoprolol fumarate is increased up to threefold
Other Information
Combination may be substituted for the titrated individual components
Withdraw gradually over about 2 weeks
Dosage adjustment for geriatric patients usually not necessary
Pediatric dosage forms and strengths
<18 years: Safety/efficacy not established
Ziac (bisoprolol/hydrochlorothiazide) adverse (side) effects
No adverse effects specific to the combination have been observed; adverse effects limited to those previously reported with bisoprolol fumarate and hydrochlorothiazide
1-10%
Bisoprolol fumarate
- Arthralgia (3%), asthenia (2%), cough (3%), diarrhea (4%), dizziness (10%), dry mouth (1%), dyspnea (2%), fatigue (8%), headache (11%), hypoaesthesia (2%), insomnia (3%), nausea (2%), peripheral edema (4%), pharyngitis (2%), rhinitis (4%), sinusitis (2%), upper respiratory infection (5%), vomiting (2% )
Hydrochlorothiazide
- Anorexia
- Epigastric distress
- Hypokalemia
- Hypotension
- Orthostatic hypotension
- Phototoxicity
Frequency not defined
Bisoprolol fumarate
- Aggravate CHF, cold extremeties, decrease HDL, depression, hypotension, increase bronchospasm, increase triglycerides, mask symptoms of hypoglycemia, muscle & joint pain
Hydrochlorothiazide
- Agranulocytosis, anaphylaxis, anemia
- Confusion, erythema multiforme skin reactions including Stevens-Johnson syndrome
- Exfoliative dermatitis including toxic epidermal necrolysis
- Hypomagnesemia, hyponatremia, hypochloremia, dizziness, fatigue, headache, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypercholesterolemia, muscle weakness or cramps, nausea, purpura, rash, vertigo, vomiting
Warnings
Contraindications
anuria
cardiogenic shock
heart block 2°/3°
hypersensitivity to either component or sulfonamides
overt cardiac failure
sinus bradycardia
Cautions
Anesthesia/surgery (myocardial depression): chronically administered beta-blocking therapy should not be routinely withdrawn prior to 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
Bronchospastic disease
Cerebrovascular insufficiency
CHF, cardiomegaly
DM, fluid or electrolyte imbalance, hyperuricemia or gout, SLe
Hyperthyroidism or thyrotoxicosis
Liver disease
May aggravate digitalis toxicity
Peripheral vascular disease
Renal impairment
Risk of male sexual dysfunction
Sensitivity reactions may occur with or without history of allergy or asthma
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
Pregnancy and lactation
Pregnancy category: C
Lactation: excreted in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ziac (bisoprolol/hydrochlorothiazide)
Half-Life
bisoprolol fumarate: 9-12 hr
hydrochlorothiazide: 6-15 hr
Absorption
Rate and extent of absorption of bisoprolol fumarate and hydrochlorothiazide from combination product are not different, respectively, from rate and extent of absorption of bisoprolol fumarate and hydrochlorothiazide monotherapy
bisoprolol fumarate: 80% bioavailability
hydrochlorothiazide: 70% bioavailability
Onset
hydrochlorothiazide initial diuresis 2 hr; HTN 3-4 days
Duration
hydrochlorothiazide diuresis 6-12 hr; HTN up to 1 week
Vd
hydrochlorothiazide 3-4 L/kg
Peak Plasma Time
bisoprolol fumarate: 2-4 hr
hydrochlorothiazide: 1.5-2.5 hr
Protein Bound
bisoprolol fumarate: 30%
hydrochlorothiazide: 40%
Metabolism
bisoprolol fumarate: hepatic, not metabolized by P450 CYP2D6; about 20% first-pass metabolism
hydrochlorothiazide minimally metabolized
Clearance
hydrochlorothiazide 335 mL/min
Excretion
bisoprolol fumarate: urine 50%
hydrochlorothiazide: urine 50-70%
Dialyzable
bisoprolol fumarate: no evidence
hydrochlorothiazide: no
Mechanism of action
bisoprolol fumarate/hydrochlorothiazide is a fixed-combination tablet that combines a Beta adrenergic receptor blocker, bisoprolol fumarate, and a thiazide diuretic, hydrochlorothiazide
bisoprolol fumarate, a cardioselective inhibitor of beta(1)-adrenoceptor, has no significant intrinsic sympathomimetic activity or membrane stabilizing activity in its therapeutic dosage; exhibits beta(2)-adrenoceptors inhibition and negative chronotropic effect
hydrochlorothiazide is a thiazide diuretic that inhibits Na reabsorption in distal renal tubules resulting in increased excretion of Na+ and water, also K+ and H+ ions
