BISOPROLOL FUMARATE AND HYDROCHLOROTHIAZIDE
Clinical safety rating: safe
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
Bisoprolol is a cardioselective beta-1 adrenergic receptor antagonist that reduces heart rate and myocardial contractility, decreasing cardiac output. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium-chloride symporter in distal convoluted tubule, reducing plasma volume.
| Metabolism | Bisoprolol is primarily metabolized by CYP2D6 (minor CYP3A4) to inactive metabolites. Hydrochlorothiazide is not extensively metabolized; excreted unchanged in urine. |
| Excretion | Bisoprolol: 50% unchanged in urine, remainder as inactive metabolites; Hydrochlorothiazide: 95% unchanged in urine. Fecal elimination: negligible. |
| Half-life | Bisoprolol: terminal half-life 10-12 hours (up to 15 hours in elderly/clinically significant for once-daily dosing); Hydrochlorothiazide: terminal half-life 6-15 hours (prolonged in renal impairment). |
| Protein binding | Bisoprolol: 30% bound to albumin; Hydrochlorothiazide: 40-70% bound to albumin. |
| Volume of Distribution | Bisoprolol: Vd 3 L/kg (extensive tissue distribution); Hydrochlorothiazide: Vd 0.8-1.4 L/kg (distributes into extracellular fluid). |
| Bioavailability | Bisoprolol: oral bioavailability 80-90%; Hydrochlorothiazide: oral bioavailability 65-75% (reduced in heart failure). |
| Onset of Action | Bisoprolol: oral, beta-blockade effects begin within 1-2 hours; Hydrochlorothiazide: oral, diuretic effect within 2 hours. |
| Duration of Action | Bisoprolol: 24 hours (supports once-daily dosing); Hydrochlorothiazide: 12-24 hours (antihypertensive effect lasts 24 hours). |
| Molecular Weight | 325.42 |
One tablet orally once daily. Initial dose: 2.5 mg/6.25 mg to 10 mg/25 mg, titrated based on response. Maximum: 20 mg/50 mg per day.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if CrCl <30 mL/min. If CrCl 30-50 mL/min: use with caution; maximum bisoprolol dose 10 mg/day. No adjustment for CrCl >50 mL/min. |
| Liver impairment | No specific guidelines for Child-Pugh. Use caution in severe hepatic impairment; consider reducing initial dose of bisoprolol (e.g., 2.5 mg). |
| Pediatric use | Not established; safety and efficacy not determined in pediatric patients. |
| Geriatric use | Start at low end of dosing range (e.g., 2.5 mg/6.25 mg daily). Titrate slowly due to increased risk of hypotension, bradycardia, and electrolyte imbalance. Monitor renal function. |
| 1st trimester | Bisoprolol fumarate: first-trimester use may be associated with fetal bradycardia and growth restriction; limited human data. Hydrochlorothiazide: first-trimester use associated with increased risk of neural tube defects and other congenital anomalies. |
| 2nd trimester | Bisoprolol: may cause fetal bradycardia, growth restriction, and hypoglycemia; use only if benefit outweighs risk. Hydrochlorothiazide: second-trimester use may cause fetal electrolyte disturbances, jaundice, and thrombocytopenia; generally avoided. |
| 3rd trimester | Bisoprolol: near term may cause neonatal bradycardia, hypotension, and hypoglycemia; avoid if possible or taper before delivery. Hydrochlorothiazide: third-trimester use may cause neonatal jaundice, thrombocytopenia, and electrolyte imbalances; avoid. |
Clinical note
Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.
| FDA category | Animal |
| Placental transfer |
■ FDA Black Box Warning
Abrupt cessation may exacerbate angina and precipitate myocardial infarction in patients with coronary artery disease.
| Common Effects | edema |
| Serious Effects |
Hypersensitivity to bisoprolol, hydrochlorothiazide, or sulfonamide-derived drugsSevere bradycardia (heart rate < 45-50 bpm)Cardiogenic shockSick sinus syndrome without pacemakerSecond- or third-degree AV block without pacemakerDecompensated heart failure (NYHA class III-IV)Severe hypotension (systolic BP < 90 mmHg)Severe asthma or COPD with bronchospasmPheochromocytoma without alpha-blockadeAnuriaRenal failure with creatinine clearance < 30 mL/minHepatic comaElectrolyte disturbances (severe hypokalemia, hypercalcemia, hyponatremia)
| Precautions | Beta-blocker withdrawal: taper gradually, Bronchospasm: avoid in asthma/COPD, Bradycardia/heart block: monitor heart rate, Electrolyte imbalances: hypokalemia, hyponatremia, Hyperuricemia: may precipitate gout, Exacerbation of peripheral vascular disease, May mask hypoglycemia in diabetes, Sulfonamide allergy cross-reactivity (hydrochlorothiazide) |
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| Bisoprolol crosses the placenta (molecular weight 325 Da). Hydrochlorothiazide crosses the placenta and is detected in fetal blood and amniotic fluid. |
| Breastfeeding | Bisoprolol is excreted into breast milk in low amounts; theoretical risk of bradycardia and hypotension in the infant. Hydrochlorothiazide is excreted in breast milk; may suppress lactation and cause neonatal electrolyte disturbances. Use with caution; monitor infant for signs of bradycardia, hypotension, and electrolyte imbalance. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Beta-blocker exposure associated with possible fetal bradycardia and growth restriction; thiazide diuretic exposure not strongly associated with major malformations but may cause electrolyte disturbances. Second and third trimesters: Beta-blocker may cause fetal bradycardia, hypoglycemia, and growth restriction; thiazide diuretic may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte imbalances. Use only if potential benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, serum electrolytes, and renal function. Fetal ultrasound for growth, amniotic fluid volume, and fetal heart rate monitoring. Neonatal monitoring for bradycardia, hypoglycemia, and electrolyte disturbances. |
| Fertility Effects | No significant adverse effects on fertility reported. Beta-blockers may rarely affect spermatogenesis; hydrochlorothiazide has no known impact. |
| Food/Dietary | Avoid grapefruit juice as it may increase bisoprolol effects. Limit high-potassium foods and salt substitutes due to risk of hyperkalemia with bisoprolol and hypokalemia with HCTZ. Avoid excessive alcohol. Maintain adequate hydration but do not overhydrate. |
| Clinical Pearls | Monitor heart rate and blood pressure closely; avoid abrupt withdrawal due to risk of exacerbation of angina or MI. Check serum potassium, sodium, and renal function periodically due to HCTZ. Use cautiously in patients with asthma or COPD due to beta-blockade. May mask symptoms of hypoglycemia in diabetics. |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning. · Do not stop suddenly; taper under doctor's supervision to avoid rebound hypertension or chest pain. · Report slow heart rate, dizziness, or fainting. · May cause drowsiness; avoid driving until effects are known. · Limit alcohol intake. · Monitor for signs of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat. · Use sun protection; hydrochlorothiazide increases photosensitivity. · Inform all healthcare providers you are taking this medication. |