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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZIAC (ZIAC).
| Breastfeeding | Bisoprolol (beta-blocker in ZIAC) is excreted in breast milk in low amounts (M/P ratio not established; estimated ~0.3-0.5 based on similar beta-blockers). Hydrochlorothiazide is excreted in small amounts. Consider alternative antihypertensives with better safety data; monitor infant for bradycardia, hypotension, and feeding difficulties. |
| 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. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["Cardiogenic shock","Decompensated heart failure","Sick sinus syndrome or sinoatrial block (without pacemaker)","Second- or third-degree AV block (without pacemaker)","Severe bradycardia (<45 bpm)","Anuria","Hypersensitivity to bisoprolol, hydrochlorothiazide, or sulfonamide-derived drugs"]
| 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."] |
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| 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. |