ZIAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZIAC (ZIAC).
ZIAC is a combination of bisoprolol, a cardioselective beta1-adrenergic receptor blocker, and hydrochlorothiazide, a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, reducing blood volume.
| Metabolism | Bisoprolol is metabolized primarily by CYP2D6; hydrochlorothiazide is not extensively metabolized. |
| Excretion | Renal: bisoprolol (50% unchanged), HCTZ (≥95% unchanged); biliary/fecal: bisoprolol (≤2%) |
| Half-life | Bisoprolol: 9–12 h (terminal); HCTZ: 6–15 h (terminal); prolonged in renal impairment; steady state by 5 days |
| Protein binding | Bisoprolol: 26–33% (albumin); HCTZ: 40–68% (albumin) |
| Volume of Distribution | Bisoprolol: 3.5 L/kg (extensive tissue distribution); HCTZ: 3–4 L/kg |
| Bioavailability | Bisoprolol: 80% (oral); HCTZ: 65–75% (oral) |
| Onset of Action | Oral: antihypertensive effect within 1–2 h; maximal effect at 2–4 weeks |
| Duration of Action | Oral: 24 h (once-daily dosing); sustained BP reduction over 24 h |
| Molecular Weight | 266.34 |
ZIAC (bisoprolol fumarate/hydrochlorothiazide) 2.5 mg/6.25 mg to 10 mg/6.25 mg orally once daily, titrated at 2-week intervals based on blood pressure response. Maximum dose: 20 mg/12.5 mg per day.
| Dosage form | TABLET |
| Renal impairment | For CrCl 30-49 mL/min: use caution, consider dose reduction. CrCl <30 mL/min: avoid use; hydrochlorothiazide is ineffective and bisoprolol may accumulate. For CrCl 30-89 mL/min: no adjustment for bisoprolol; avoid hydrochlorothiazide if severe dysfunction. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce bisoprolol dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. Alternative agents recommended. |
| Geriatric use | Start at lowest dose (2.5 mg/6.25 mg). Titrate slowly; monitor renal function, electrolytes, and orthostatic hypotension. Avoid if CrCl <30 mL/min. |
| 1st trimester | Risk of fetal bradycardia and hypotension; use only if clearly needed. |
| 2nd trimester | Risk of fetal bradycardia, growth restriction; monitor fetal growth and heart rate. |
| 3rd trimester | Risk of neonatal bradycardia, hypotension, and hypoglycemia; discontinue before delivery if possible. |
Clinical note
Comprehensive clinical and safety monograph for ZIAC (ZIAC).
| Placental transfer | Crosses placenta; achieves fetal concentrations similar to maternal. |
| Breastfeeding | Small amounts appear in breast milk; monitor infant for bradycardia and hypotension. |
| Lactation Rating | L3 - Moderately Safe |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Bronchial asthmaCardiogenic shockSinus bradycardiaHeart block greater than first degreeOvert cardiac failureHypersensitivity to any component
| Precautions | Beta-blocker withdrawal: abrupt cessation may exacerbate angina or precipitate myocardial infarction., Bradycardia and heart block: avoid in patients with severe bradycardia or heart block greater than first degree., Bronchospasm: use with caution in patients with bronchospastic diseases (e.g., asthma)., Electrolyte disturbances: hydrochlorothiazide may cause hypokalemia, hyponatremia, and hypomagnesemia., Renal impairment: monitor renal function; may precipitate azotemia., Diabetes: beta-blockers may mask hypoglycemia symptoms; hydrochlorothiazide may increase blood glucose., Thyroid storm: beta-blockers may mask signs of hyperthyroidism. |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, spinach) in excessive amounts, as thiazides may cause potassium imbalances. Limit salt intake to control blood pressure. Use salt substitutes with caution; they often contain potassium. Grapefruit juice may increase bisoprolol effects; avoid large quantities. |
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| Teratogenic Risk | First trimester: Association with intrauterine growth restriction (IUGR), oligohydramnios, and preterm birth, but no consistent evidence of major malformations; beta-blockers may cause fetal bradycardia. Second/third trimester: Continued risk of IUGR, placental hypoperfusion, and neonatal bradycardia, hypotension, and hypoglycemia. Avoid use after 20 weeks if possible; use lowest effective dose. |
| Fetal Monitoring | Maternal: Blood pressure and heart rate, serum electrolytes (especially potassium with HCTZ), renal function, and signs of heart failure. Fetal: Ultrasound for growth restriction and amniotic fluid index (oligohydramnios risk). Neonatal: Monitor for bradycardia, hypotension, hypoglycemia, and respiratory depression for 24-48 hours postpartum. |
| Fertility Effects | No direct evidence of impaired fertility. Beta-blockers may interfere with sympathetic nervous system regulation of reproductive function, but clinically insignificant. Thiazide diuretics may rarely affect libido or cause impotence in males, but no female fertility impact reported. |
| Clinical Pearls | ZIAC is a fixed-dose combination of bisoprolol (beta-blocker) and hydrochlorothiazide (thiazide diuretic). It is indicated for hypertension. Do not use for initial therapy; titrate individual components first. Monitor serum potassium and renal function; thiazides can cause hypokalemia and hyperuricemia. Bisoprolol should not be abruptly discontinued due to risk of exacerbation of angina or myocardial infarction. Use with caution in patients with asthma, COPD, or peripheral vascular disease. |
| Patient Advice | Take exactly as prescribed, usually once daily, with or without food. · Do not stop taking suddenly; this can worsen chest pain or cause heart attack. Consult your doctor before stopping. · May cause dizziness or lightheadedness; avoid driving or hazardous activities until you know how the medication affects you. · Notify your doctor if you experience symptoms of low potassium (muscle cramps, weakness, irregular heartbeat) or dehydration (excessive thirst, dry mouth, decreased urination). · Limit alcohol intake as it may increase dizziness. · Monitor blood pressure regularly and keep appointments for blood tests. · Avoid over-the-counter medications unless approved by your doctor, especially NSAIDs, decongestants, and potassium supplements. |