Acubis

1. Indications

Approved Indications:

• Hypertension (High Blood Pressure): For the management of essential hypertension, either as monotherapy or in combination with other antihypertensive agents.
• Chronic Stable Angina: To reduce the frequency and severity of anginal attacks and improve exercise tolerance.
• Chronic Heart Failure (CHF): Indicated for stable, moderate to severe chronic heart failure (NYHA Class II-III) with reduced ejection fraction, typically in combination with ACE inhibitors, diuretics, and/or digitalis.

Clinically Accepted Off-label Uses:

• Atrial Fibrillation (Rate Control): Used to manage ventricular rate in atrial fibrillation, especially in patients with hypertension or heart failure.
• Premature Ventricular Contractions (PVCs): Sometimes used for symptomatic relief in benign PVCs.
• Post-Myocardial Infarction (MI): Utilized for secondary prevention and cardiac remodeling in stable patients.

Route of Administration: Oral (tablets)

Adult Dosage:

• Hypertension/Angina: Start with 5 mg once daily. Maintenance dose: 5–10 mg once daily. Maximum dose: 20 mg/day.
• Chronic Heart Failure: Start with 1.25 mg once daily. Double the dose every 1–2 weeks as tolerated to a target dose of 10 mg once daily.

Elderly:

• No specific dose adjustment is necessary, but initiate therapy at the lower end of the dosing range due to greater sensitivity.

Renal Impairment:

• CrCl <40 mL/min: Maximum recommended dose is 10 mg once daily.

Hepatic Impairment:

• Caution is advised; start with a low dose and titrate slowly.

Pediatric Use:

• Safety and efficacy have not been established; not routinely recommended.

Missed Dose:

• If a dose is missed, take as soon as remembered unless it is close to the next dose. Do not double the dose.

Bisoprolol is a cardioselective β1-adrenergic receptor blocker. It reduces sympathetic nervous system stimulation of the heart, leading to decreased heart rate, myocardial contractility, and cardiac output. In hypertension, this results in lowered blood pressure. In heart failure, it improves ventricular function by reducing myocardial oxygen demand and neurohormonal activation. Its selective action on β1 receptors reduces the likelihood of bronchospasm seen with non-selective beta-blockers.

• Absorption: Rapid and almost complete oral absorption (≈90%) with minimal first-pass metabolism.
• Bioavailability: ~88%
• Time to Peak Plasma Concentration: 2–4 hours
• Distribution: Volume of distribution: ~3.5 L/kg; moderate plasma protein binding (~30%)
• Metabolism: Primarily hepatic via CYP3A4 to inactive metabolites
• Elimination Half-life: 10–12 hours, allowing for once-daily dosing
• Excretion: 50% excreted unchanged by kidneys; 50% metabolized by liver and excreted as inactive metabolites in urine

• Pregnancy: Category C (U.S. FDA). There are no adequate studies in pregnant women; use only if the potential benefit justifies the potential risk to the fetus.
• Lactation: Bisoprolol is excreted in breast milk. Use with caution; if therapy is essential, consider monitoring the infant for signs of beta-blockade (e.g., bradycardia, hypotension).

• Primary Class: Beta-Adrenergic Blocker (Beta-Blocker)
• Subclass: Selective β1-Adrenergic Receptor Antagonist
• Generation: Second-generation beta-blocker

• Known hypersensitivity to bisoprolol or any component of the formulation
• Acute decompensated heart failure requiring IV inotropes
• Cardiogenic shock
• Severe bradycardia (<45 bpm)
• Second or third-degree AV block (without pacemaker)
• Sick sinus syndrome (without pacemaker)
• Severe peripheral arterial circulatory disorders

• Heart Failure Worsening: Initiate only in stable CHF; monitor closely during titration.
• Bronchospastic Diseases: Use with caution in patients with asthma or COPD due to risk of bronchospasm, though β1 selectivity lowers this risk.
• Diabetes Mellitus: May mask symptoms of hypoglycemia (e.g., tachycardia); caution required.
• Peripheral Vascular Disease: May worsen symptoms; monitor circulation.
• Thyrotoxicosis: May mask signs (e.g., tachycardia).
• Surgery/Anesthesia: Do not abruptly discontinue before surgery; may blunt response to beta-agonists.
• Renal/Hepatic Impairment: Use lower initial doses and titrate cautiously.

Common:

• Fatigue
• Dizziness
• Bradycardia
• Headache
• Cold extremities

Less Common:

• Hypotension
• Sleep disturbances
• Nausea, diarrhea
• Erectile dysfunction
• Depression

Serious (Rare):

• Severe bradycardia or AV block
• Heart failure exacerbation
• Bronchospasm
• Anaphylaxis (very rare)

• Calcium Channel Blockers (e.g., Verapamil, Diltiazem): Additive negative chronotropic effects; risk of AV block or bradycardia.
• Other Antihypertensives/Diuretics: May increase risk of hypotension.
• Insulin and Oral Antidiabetics: May enhance hypoglycemic effect and mask hypoglycemic symptoms.
• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase bisoprolol plasma levels.
• CYP3A4 Inducers (e.g., rifampin, carbamazepine): May reduce bisoprolol efficacy.
• NSAIDs: May blunt antihypertensive effect.
• Anesthetic Agents: Increased risk of bradycardia and hypotension.

• ESC 2021 & ACC/AHA 2022 Guidelines: Confirmed bisoprolol’s role as a first-line beta-blocker for stable CHF with reduced ejection fraction.
• EMA Label Update: Reinforced dosing recommendations and emphasized careful initiation in CHF patients.

• Storage Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C.
• Protection: Protect from moisture and light. Keep in tightly closed containers.
• Handling Precautions: No special reconstitution or refrigeration needed.
• Disposal: Dispose of unused medication according to local pharmaceutical waste guidelines.