BILOCOR 10

Indications

• Hypertension
• Heart failure
• Angina pectoris
• Arrhythmias

Dosage

Children: Refer to BNF for Children for specific pediatric dosing.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Though the precise mechanism of action of bisoprolol in hypertension is not fully understood, it is believed to primarily exert its therapeutic effects through the antagonism of β-1 adrenoceptors. This leads to a reduction in cardiac output by decreasing heart rate and myocardial contractility. Additionally, bisoprolol may lower renin output from the kidneys and exert some central nervous system effects that contribute to decreased sympathetic nervous system activity, further lowering blood pressure and heart rate.

Pharmacodynamics

Bisoprolol significantly decreases heart rate (chronotropy), reduces myocardial contractility (inotropy), and lowers blood pressure. Clinical studies have shown that bisoprolol can effectively reduce cardiovascular mortality and overall mortality in patients suffering from heart failure with reduced ejection fraction.

Pharmacokinetics

Bisoprolol is well absorbed from the gastrointestinal tract and has a bioavailability of approximately 80%. It is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, and has an elimination half-life of about 10-12 hours, allowing for once-daily dosing. The drug is primarily excreted via the kidneys, with a small portion eliminated unchanged.

Contra-indications

• Severe bradycardia
• Second or third degree AV block
• Cardiogenic shock
• Uncontrolled heart failure
• Hypersensitivity to bisoprolol or any excipients

Adverse effects

• Fatigue
• Dizziness
• Bradycardia
• Hypotension
• Cold extremities
• Gastrointestinal disturbances
• Sleep disturbances
• Depression

Interactions

• Propafenone: Moderate (increases risk of cardiovascular adverse effects)
• Rifampicin: Unknown (decreases exposure)

Precautions

• Caution in patients with asthma or chronic obstructive pulmonary disease (COPD)
• Caution in patients with diabetes mellitus (may mask hypoglycemia)
• Caution in patients with peripheral vascular disease
• Monitor heart rate and blood pressure regularly

Pregnancy

Bisoprolol should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. It may cause fetal bradycardia, hypotension, and neonatal withdrawal symptoms.

Breast-feeding

Bisoprolol is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Formulations

• Oral tablets: 1.25 mg, 2.5 mg, 5 mg, 10 mg

Indications

• Hypertension
• Angina pectoris
• Heart failure (adjunctive therapy)

Dosage

Children: Refer to BNF for Children for appropriate dosing information, as specific pediatric doses are not provided.

Adults: Initial dose: 5 mg once daily. Maintenance dose: may be increased to a maximum of 10 mg once daily depending on response and tolerability.

Mechanism of action

Bisoprolol fumarate selectively inhibits beta-1 adrenergic receptors located primarily in the heart. This results in a decrease in heart rate, myocardial contractility, and conduction velocity through the atrioventricular node, leading to reduced cardiac output and lower blood pressure. It does not significantly affect beta-2 adrenergic receptors, which are found in the lungs and vascular smooth muscle, resulting in a lower risk of bronchospasm in susceptible individuals.

Pharmacodynamics

The pharmacological effects of bisoprolol include a reduction in heart rate, myocardial oxygen demand, and blood pressure. The onset of action occurs within 1-2 hours after oral administration, with peak effects observed around 4-6 hours. The antihypertensive effect lasts for 24 hours, allowing for once-daily dosing. Bisoprolol also has a favorable safety profile compared to non-selective beta-blockers, particularly in patients with respiratory conditions.

Pharmacokinetics

Bisoprolol fumarate is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 90%. It is primarily metabolized in the liver via cytochrome P450 enzymes, predominantly CYP2D6, and has a half-life of around 10-12 hours, allowing for once-daily dosing. Excretion occurs mainly through the kidneys, with approximately 50% of the drug eliminated unchanged in urine. Dosage adjustments may be necessary in patients with significant renal impairment.

Contra-indications

• Acute or decompensated heart failure requiring intravenous inotropes
• Sino-atrial block

Adverse effects

• Fatigue
• Dizziness
• Bradycardia
• Hypotension
• Cold extremities
• Depression
• Nausea
• Diarrhea
• Shortness of breath
• Sleep disturbances

Interactions

• Other beta-blockers
• Calcium channel blockers
• Antiarrhythmic agents
• CYP2D6 inhibitors
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Digoxin
• Insulin or oral antidiabetic agents

Precautions

• Caution in patients with a history of bronchospasm
• Careful monitoring in patients with renal impairment
• Caution in patients with hepatic impairment
• Gradual withdrawal recommended to avoid rebound hypertension
• Assess heart failure status before initiation and during titration

Pregnancy

Bisoprolol fumarate is not recommended during pregnancy unless the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as bisoprolol fumarate is excreted in breast milk; monitor the infant for adverse effects.

Storage

Store below 25 degrees Celsius in a dry place, away from light.

Formulations

• Bisoprolol fumarate 1.25 mg tablets
• Bisoprolol fumarate 2.5 mg tablets
• Bisoprolol fumarate 5 mg tablets
• Bisoprolol fumarate 7.5 mg tablets
• Bisoprolol fumarate solution for injection

Mechanism of action

Though the mechanism of action of bisoprolol has not been fully elucidated in hypertension, it is thought that therapeutic effects are achieved through the antagonism of β-1adrenoceptors to result in lower cardiac output. Bisoprolol is a competitive, cardioselective β1-adrenergic antagonist. When β1-receptors (located mainly in the heart) are activated by adrenergic neurotransmitters such as epinephrine, both the blood pressure and heart rate increase, leading to greater cardiovascular work, increasing the demand for oxygen. Bisoprolol reduces cardiac workload by decreasing contractility and the need for oxygen through competitive inhibition of β1-adrenergic receptors. Bisoprolol is also thought to reduce the output of renin in the kidneys, which normally increases blood pressure. Additionally, some central nervous system effects of bisoprolol may include diminishing sympathetic nervous system output from the brain, decreasing blood pressure and heart rate.

Pharmacodynamics

Bisoprolol decreases heart rate (chronotropy), decreases contractility (inotropy), and reduces blood pressure. The results of various clinical studies indicate that bisoprolol reduces cardiovascular mortality and all-cause mortality in patients with heart failure and decreased cardiac ejection fraction (EF).