Bisocam

Approved Indications:

• Hypertension (Primary/Essential): Used for the treatment of mild to moderate essential hypertension when monotherapy with either agent is inadequate.
• Chronic Stable Angina: Especially in patients with concomitant hypertension and angina.
• Ischemic Heart Disease (IHD): For long-term management and prevention of recurrent ischemic episodes in patients requiring both heart rate control and vasodilation.

Clinically Accepted Off-label Uses:

• Post-Myocardial Infarction with Hypertension: For cardiovascular risk reduction when dual control of BP and cardiac workload is needed.
• Left Ventricular Hypertrophy (LVH): As part of an antihypertensive regimen in patients at risk of LVH-related complications.

General Guidelines:

• Administered orally once daily, with or without food.
• Fixed-dose combination should be individualized based on patient response to monotherapy components.

Adults (Initial & Maintenance Dose):

• Common starting dose: Bisoprolol 5 mg + Amlodipine 5 mg once daily.
• Titration: May be increased to Bisoprolol 10 mg + Amlodipine 10 mg once daily, based on clinical response after 1–2 weeks.

Elderly:

• Start at the lower end of the dosage range due to increased sensitivity.
• Monitor blood pressure and heart rate carefully.

Renal Impairment:

• Mild to Moderate (CrCl ≥30 mL/min): No dose adjustment generally required.
• Severe (CrCl <30 mL/min): Caution advised; consider initiating with individual components.

Hepatic Impairment:

• Amlodipine may accumulate in hepatic impairment; initiate at low doses with close monitoring.

Pediatrics:

• Safety and efficacy not established in children.

Bisoprolol Fumarate is a selective β1-adrenergic receptor blocker that reduces myocardial oxygen demand by decreasing heart rate, contractility, and cardiac output. It also inhibits renin release, leading to mild antihypertensive effects.

Amlodipine Besilate is a long-acting dihydropyridine calcium channel blocker (CCB) that inhibits calcium influx in vascular smooth muscle and myocardium. This causes vasodilation, resulting in decreased peripheral vascular resistance and blood pressure.

Combined, these agents complement each other by targeting both heart rate and vascular resistance—providing comprehensive control of blood pressure and angina symptoms.

Bisoprolol Fumarate:

• Absorption: ~90% oral bioavailability.
• Distribution: Widely distributed; ~30% plasma protein binding.
• Metabolism: Primarily hepatic (CYP3A4); no active metabolites.
• Half-life: 10–12 hours.
• Excretion: ~50% renal and 50% hepatic elimination.

Amlodipine Besilate:

• Absorption: ~64–90% bioavailability; peak plasma in 6–12 hrs.
• Distribution: High volume of distribution; ~93% protein bound.
• Metabolism: Extensively metabolized in liver via CYP3A4 to inactive metabolites.
• Half-life: 30–50 hours (allowing once-daily dosing).
• Excretion: 60% in urine (mostly as metabolites), 10% unchanged.

• Pregnancy: Not classified under FDA pregnancy categories post-2015; avoid use unless absolutely necessary. Animal studies show potential fetal risk; human data limited.
• Lactation: Both components may be excreted in breast milk in small amounts. Use with caution during breastfeeding; alternatives may be preferred for nursing mothers.

• Primary Class: Antihypertensive Combination
• Subclasses:
• Bisoprolol: Selective Beta-1 Blocker
• Amlodipine: Dihydropyridine Calcium Channel Blocker (long-acting)

• Hypersensitivity to bisoprolol, amlodipine, or formulation excipients
• Severe bradycardia
• Cardiogenic shock
• Second- or third-degree AV block (without pacemaker)
• Decompensated heart failure
• Severe hypotension (systolic BP <90 mmHg)

• Heart Failure: May worsen pre-existing heart failure; monitor for signs of decompensation.
• Bradycardia: Monitor heart rate; avoid in patients with low resting HR.
• Hepatic Impairment: Amlodipine exposure increases; dose cautiously.
• Peripheral Edema: Common with amlodipine; monitor and manage accordingly.
• Drug Withdrawal: Sudden discontinuation of bisoprolol may cause rebound hypertension or angina.
• Monitoring: Regular blood pressure, heart rate, renal function, and signs of fluid retention.

Common (≥1%):

• Cardiovascular: Bradycardia, hypotension, palpitations, flushing
• General: Fatigue, dizziness, headache
• GI: Nausea, abdominal discomfort
• Musculoskeletal: Peripheral edema (more common with amlodipine)

Less Common:

• Dyspnea, insomnia, rash, cold extremities

Serious (Rare):

• AV block, severe hypotension, heart failure exacerbation
• Hepatic dysfunction (elevated liver enzymes)
• Angioedema (rare with amlodipine)

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase plasma levels of amlodipine → hypotension risk
• Other Antihypertensives or Beta-blockers: Additive hypotensive or bradycardic effects
• NSAIDs: May reduce antihypertensive efficacy
• Insulin or oral hypoglycemics: Enhanced glucose-lowering effect (with bisoprolol)
• Digoxin: Additive bradycardia or AV block risk
• Alcohol: May enhance hypotensive effect

• ESC/ESH 2023 Guidelines: Endorses combination therapy in hypertension, including beta-blocker + CCB combinations for patients with specific cardiovascular comorbidities.
• FDA & EMA Updates: No major recent changes in safety warnings or dosing for this fixed combination.
• Clinical Recommendation: Preferred in patients with co-existing hypertension and coronary artery disease (CAD) requiring heart rate control.

• Temperature: Store below 25°C (77°F)
• Humidity & Light: Protect from moisture and direct light
• Handling: Keep in original container; do not freeze
• Reconstitution: Not applicable (oral tablets)