Bisoprolol Hemifumarate
Indications
Bisoprolol Hemifumarate tablet is indicated in-
- Hypertension
- Angina
- Moderate to severe heart failure
Pharmacology
Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.
The pharmacokinetic properties of Bisoprolol provide the prerequisite for a single daily dose and ensure an extremely low inter and intra-individual variability of the plasma concentration profiles. The high therapeutic reliability of Bisoprolol is based on these properties.
Absorption and bioavailability: Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract. The high absorption rate and the small first-pass effect (<10%) lead to an absolute bioavailability of 88%. Concomitant food intake does not affect the absorption. Distribution: Bisoprolol is extensively distributed. The medium distribution volume is 3.51/kg.
Metabolism: Bisoprolol is metabolized via oxidative pathways with no subsequent conjugation. All metabolites, being very polar, are renally eliminated. The major metabolites in human plasma and urine were found to be without pharmacological activity. In vitro data from studies in human liver microsomes show that Bisoprolol is primarily metabolized via CYPSA4 (-95%) with CYP2D6 having only a minor role.
Elimination: The clearance of Bisoprolol is balanced between renal elimination of the unchanged molecule (-50%) and hepatic metabolism (-50%) to metabolites which are also renally excreted. The total clearance of Bisoprolol is approximately 15 I/h. Bisoprolol has an elimination half-life of 10-12 hours.
The pharmacokinetic properties of Bisoprolol provide the prerequisite for a single daily dose and ensure an extremely low inter and intra-individual variability of the plasma concentration profiles. The high therapeutic reliability of Bisoprolol is based on these properties.
Absorption and bioavailability: Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract. The high absorption rate and the small first-pass effect (<10%) lead to an absolute bioavailability of 88%. Concomitant food intake does not affect the absorption. Distribution: Bisoprolol is extensively distributed. The medium distribution volume is 3.51/kg.
Metabolism: Bisoprolol is metabolized via oxidative pathways with no subsequent conjugation. All metabolites, being very polar, are renally eliminated. The major metabolites in human plasma and urine were found to be without pharmacological activity. In vitro data from studies in human liver microsomes show that Bisoprolol is primarily metabolized via CYPSA4 (-95%) with CYP2D6 having only a minor role.
Elimination: The clearance of Bisoprolol is balanced between renal elimination of the unchanged molecule (-50%) and hepatic metabolism (-50%) to metabolites which are also renally excreted. The total clearance of Bisoprolol is approximately 15 I/h. Bisoprolol has an elimination half-life of 10-12 hours.
Dosage & Administration
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
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
Interaction
Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.
Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.
Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).
Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.
Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.
Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.
Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).
Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.
Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.
Contraindications
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.
Side Effects
Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect. Fatigue, dizziness, headache, disturbances of the gut such as nausea, vomiting, diarrhea, constipation or abdominal pain. Cold or numb extremities, e.g; hands and feet. Muscle weakness or cramps. Slower than normal heart breathing difficulties due to a narrowing of the airways (bronchospasm) in people with asthma or COPD.
Pregnancy & Lactation
Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. 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 use of bisoprolol fumarate is considered essential, then mothers should stop nursing.
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 use of bisoprolol fumarate is considered essential, then mothers should stop nursing.
Precautions & Warnings
Impaired renal or hepatic function use caution in adjusting the dose of Bisoprolol in patients with renal or hepatic impairment. While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
Therapeutic Class
Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers
Storage Conditions
Keep in a dry place away from light and heat. Keep out of the reach of children.
Chemical Structure
| Molecular Formula : | C18H31NO4 |
| Chemical Structure : |  |
Common Questions about Bisoprolol Hemifumarate
What is Bisoprolol?
Bisoprolol is a beta-blocker medication. Beta-blockers work by blocking the effects of adrenaline. Bisoprolol helps to lower blood pressure, reduce the workload on the heart, and prevent chest pain.
What is Bisoprolol used for?
Bisoprolol is used to make your heart beat slower and your blood vessels wider. It's a medication for High blood pressure (hypertension), Chest pain (angina), and Heart failure.
How should I take Bisoprolol?
You should take Bisoprolol by mouth, with or without food, once daily. It's best practice to take the medicine at the same time each day.
What are the side effects of Bisoprolol?
Bisoprolol can have several side effects, including: Dizziness, Fatigue, Headache, Slow heart rate, Difficulty breathing, and Cold hands and feet.
Is Bisoprolol safe to take?
Bisoprolol is generally safe to take, but you should talk to your doctor before taking it if you have any health conditions, such as- Asthma, Diabetes, Heart problems, Liver or kidney problems, Low blood pressure, and Depression.
Should I use Bisoprolol empty stomach, before food or after food?
Bisoprolol should be taken after food in a prescribed dosage.
What are the instructions for the storage and disposal of Bisoprolol?
Bisoprolol should be kept in a cool dry place and in its original packaging. Make sure this medication remains unreachable to children and pets.
Quick Tips
- Bisoprolol may cause dizziness. If this happens to you, get up slowly when rising from a sitting or lying position.
- Bisoprolol can hide symptoms of low blood sugar if you are diabetic. Monitor your blood sugar levels regularly.
- Do not stop taking Bisoprolol suddenly as it can cause your blood pressure to rise suddenly, thereby increasing the risk of heart attack and stroke.
