Bisoprolol Fumarate tablet is indicated for:

• Hypertension (high blood pressure)
• Angina (chest pain due to reduced blood flow to the heart)
• Moderate to severe heart failure

Note: Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Bisoprolol Fumarate is a highly selective β1-adrenergic receptor blocker. It demonstrates a strong affinity for β1 receptors compared with other beta-blockers. It selectively blocks β1 receptors in the heart and vascular smooth muscle, thereby reducing heart rate and cardiac output, which leads to a reduction in arterial blood pressure. While β-blockers may adversely affect lipid metabolism, Bisoprolol, being β1-selective, does not significantly alter cholesterol fractions, including cardioprotective HDL-cholesterol, during long-term therapy.

The pharmacokinetic profile of Bisoprolol supports once-daily dosing and ensures minimal inter- and intra-individual variability in plasma concentrations. These properties contribute to its reliable therapeutic effect.

Absorption and bioavailability: Bisoprolol is almost completely absorbed (>90%) from the gastrointestinal tract. Due to a low first-pass effect (<10%), its absolute bioavailability is approximately 88%. Food intake does not significantly affect absorption.

Distribution: Bisoprolol is widely distributed in the body, with an apparent volume of distribution of approximately 3.5 L/kg.

Metabolism: Bisoprolol undergoes metabolism primarily via oxidative pathways without subsequent conjugation. The metabolites are highly polar and are excreted via the kidneys. These metabolites are pharmacologically inactive. In vitro studies indicate that Bisoprolol is mainly metabolized by CYP3A4 (~95%), with CYP2D6 playing a minor role.

Elimination: The clearance of Bisoprolol is evenly divided between renal excretion of unchanged drug (~50%) and hepatic metabolism (~50%) to metabolites that are also excreted renally. The total clearance is approximately 15 L/h, and the elimination half-life ranges from 10 to 12 hours.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily, either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit. 

Children: Safety and effectiveness in children have not been established.

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min), as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction.

Other β-blocking Agents: Bisoprolol Fumarate should not be used in combination with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored, as the additional β-adrenergic blocking effect of bisoprolol fumarate may lead to an excessive reduction in sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may enhance rebound hypertension following withdrawal of clonidine. If both drugs are used together, the β-blocker should be discontinued several days before stopping clonidine. When switching from clonidine to β-blocker therapy, initiation of the β-blocker should be delayed for several days after clonidine has been discontinued (refer to prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with caution when administered with myocardial depressants or A-V conduction inhibitors, such as certain calcium antagonists (particularly phenylalkylamines like verapamil and benzothiazepines like diltiazem), or antiarrhythmic drugs such as disopyramide.

Calcium Channel Blockers: The combined use of β-blockers and calcium channel blockers with negative inotropic effects may prolong S-A and A-V conduction, especially in patients with impaired ventricular function or conduction abnormalities. This combination may result in severe hypotension, bradycardia, and cardiac failure.

Contraindicated in patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension, and sinus bradycardia.

Medicines and their potential side effects may affect individuals differently. The following are some of the known side effects associated with this medicine; however, not all patients will experience them. These may include fatigue, dizziness, headache, and gastrointestinal disturbances such as nausea, vomiting, diarrhea, constipation, or abdominal pain. Cold or numb extremities (e.g., hands and feet) may occur. Muscle weakness or cramps may also be reported. Slower than normal heart rate and breathing difficulties due to airway narrowing (bronchospasm) may occur, particularly in patients with asthma or COPD.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day (approximately 375 times the maximum recommended human daily dose). However, it showed fetotoxic effects (increased late resorptions) at 50 mg/kg/day and maternal toxicity (reduced food intake and body-weight gain) at 150 mg/kg/day. In rabbits, it was not teratogenic up to 12.5 mg/kg/day (about 31 times the maximum recommended human dose), but embryolethal effects (increased early resorptions) were observed at this dose. There are no adequate studies in pregnant women. Therefore, bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If treatment is considered essential, breastfeeding should be discontinued.

Caution is required when adjusting the dose of bisoprolol in patients with impaired renal or hepatic function. Patients taking beta-blockers who have a history of severe anaphylactic reactions to various allergens may be more reactive to repeated exposure (whether accidental, diagnostic, or therapeutic) and may not respond adequately to usual doses of epinephrine used to treat allergic reactions.

Anti-adrenergic agent (beta-blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Keep in a dry place away from light and heat. Keep out of the reach of children.