Probis 5

Indications

Probis Tablet is prescribed for the treatment of:

• Hypertension (High Blood Pressure)
• Angina (Chest Pain)
• Moderate to Severe Heart Failure

Please note that Probis is not intended for the emergency management of hypertensive crises.
Use this medication only as directed by a registered healthcare professional.

Pharmacology

Bisoprolol Hemifumarate is a highly selective ß1-adrenergic blocker, exhibiting a stronger affinity for ß1 receptors compared to other beta-blockers. By selectively targeting ß1 receptors in the heart and vascular smooth muscle, it reduces heart rate and cardiac output, ultimately lowering blood pressure. Unlike non-selective beta-blockers, Bisoprolol has no significant impact on lipid metabolism, including levels of protective HDL-cholesterol, even during long-term treatment.

Bisoprolol’s pharmacokinetics support a once-daily dosing schedule with minimal variation in plasma concentration between individuals. This makes Bisoprolol a reliable and consistent treatment option for hypertension.

Absorption and Bioavailability

• Bisoprolol is almost entirely absorbed (>90%) from the gastrointestinal tract, with minimal first-pass effect (<10%), leading to a bioavailability of 88%.
• Food intake does not affect its absorption.

Distribution

• Bisoprolol is widely distributed throughout the body, with a distribution volume of 3.51 L/kg.

Metabolism

• Bisoprolol is metabolized primarily by oxidative pathways in the liver without conjugation.
• The resulting metabolites are highly polar and excreted via the kidneys.
• It is primarily metabolized by the CYP3A4 enzyme, with minimal involvement of CYP2D6.

Elimination

• Bisoprolol is cleared from the body through both renal and hepatic processes, with approximately 50% eliminated unchanged via the kidneys.
• Its half-life ranges between 10-12 hours, allowing for once-daily dosing.

Dosage & Administration

Adults: For mild to moderate hypertension, the typical starting dose is 5 mg once daily, either alone or in combination with a diuretic. If the response is insufficient, the dose can be increased to 10 mg, and then to a maximum of 20 mg once daily, with a minimum 2-week interval between dose adjustments.

Children: The safety and efficacy of Bisoprolol have not been established for pediatric use.

Renal and Hepatic Impairment: In patients with liver conditions (e.g., cirrhosis) or renal dysfunction (creatinine clearance <40 mL/min), the initial dose should be 5 mg daily. Dose adjustments should be made cautiously to avoid accumulation. Bisoprolol is not dialyzable, so no dose adjustment is required in dialysis patients.

Elderly: Dose adjustment is generally not necessary unless there is significant renal or hepatic impairment.

Always use this medication as prescribed by a healthcare professional.

Drug Interactions

• Other Beta-Blockers: Combining Probis with other beta-blockers is not recommended.
• Catecholamine-Depleting Drugs: Patients on drugs like reserpine should be monitored carefully as the combined beta-adrenergic blocking effects may lead to excessive reduction in sympathetic activity.
• Centrally Acting Antihypertensives: When used with clonidine, beta-blockers may intensify rebound hypertension. It is advised to discontinue the beta-blocker several days before stopping clonidine.
• Antiarrhythmic Agents: Caution is advised when combining with myocardial depressants or AV-conduction inhibitors like verapamil, diltiazem, or disopyramide.
• Calcium Channel Blockers: Concurrent use with beta-blockers and calcium channel blockers may cause prolonged heart conduction, potentially leading to severe hypotension, bradycardia, or cardiac failure.

Contraindications

Probis should not be used in patients with:

• Cardiogenic shock
• Severe heart failure
• Second or third-degree AV block
• Right ventricular failure due to pulmonary hypertension
• Sinus bradycardia

Side Effects

Possible side effects may include:

• Fatigue, dizziness, or headaches
• Gastrointestinal issues like nausea, vomiting, diarrhea, constipation, or abdominal pain
• Cold or numb extremities
• Muscle weakness or cramps
• Bradycardia (slower heart rate)
• Respiratory difficulties, especially in patients with asthma or COPD (bronchospasm)

Not everyone will experience these side effects. If any adverse reactions occur, consult your healthcare provider.

Pregnancy and Lactation

• Pregnancy: Bisoprolol was not teratogenic in animal studies but showed some fetotoxicity at high doses. Use during pregnancy should be limited to situations where the benefits outweigh the risks.
• Lactation: Bisoprolol may be present in breast milk in small amounts. It is not known if it passes into human milk, so breastfeeding mothers should discontinue nursing if Bisoprolol therapy is essential.

Precautions and Warnings

Caution should be exercised when adjusting the dose in patients with impaired renal or hepatic function. Patients with a history of severe allergic reactions may be less responsive to usual doses of epinephrine when taking beta-blockers.

Therapeutic Class

Anti-adrenergic Agent (Beta-Blockers)

Storage Conditions

Store in a cool, dry place, away from light and heat. Keep out of reach of children.