Usage
- Medical Conditions: Bisoprolol + Perindopril Arginine is prescribed for the treatment of hypertension (high blood pressure) and stable coronary artery disease (CAD). In hypertension, it is used when treatment with individual components (bisoprolol and perindopril) has already stabilized the patient’s blood pressure. In CAD, it helps to reduce the risk of cardiac events in patients with a prior history of myocardial infarction and/or revascularization. It may also be used in patients with stable chronic heart failure.
- Pharmacological Classification: This combination drug belongs to two classes: beta-1-selective adrenergic blocking agents (bisoprolol) and angiotensin-converting enzyme (ACE) inhibitors (perindopril).
- Mechanism of Action: Bisoprolol lowers blood pressure and heart rate by blocking the beta-1 adrenergic receptors in the heart, decreasing myocardial contractility and reducing cardiac output. Perindopril inhibits the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This vasodilatory effect contributes to lower blood pressure and also reduces aldosterone secretion, leading to sodium and water excretion. The combination of these mechanisms results in a synergistic antihypertensive effect.
Alternate Names
- International or Regional Variations: The combination may be referred to as bisoprolol/perindopril arginine in some regions.
- Brand Names: Cosyrel, Cosimprel, Bipressil.
How It Works
- Pharmacodynamics: Bisoprolol selectively blocks beta-1 adrenergic receptors in the heart, reducing heart rate, myocardial contractility, and cardiac output. Perindopril inhibits ACE, leading to decreased angiotensin II and aldosterone levels, resulting in vasodilation and increased sodium and water excretion.
- Pharmacokinetics:
- Bisoprolol: Well absorbed orally (approximately 90%), with peak plasma concentrations reached within 1-4 hours. Metabolized primarily in the liver, with approximately 50% excreted unchanged in urine and 50% as metabolites. Elimination half-life is 10-12 hours.
- Perindopril: Absorbed orally (about 65-70%), hydrolyzed in the liver to perindoprilat, its active metabolite. Peak plasma concentration of perindoprilat is reached within 3-7 hours. Excreted primarily in the urine. Elimination half-life of perindoprilat is approximately 25 hours.
- Mode of Action: Bisoprolol exerts its effects through competitive antagonism of beta-1 adrenergic receptors. Perindopril blocks the active site of ACE preventing the conversion of angiotensin I to angiotensin II.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Bisoprolol binds to beta-1 adrenergic receptors. Perindopril inhibits ACE.
- Elimination Pathways: Bisoprolol undergoes hepatic metabolism, and both bisoprolol and its metabolites are eliminated renally. Perindopril is also metabolized in the liver to its active form, perindoprilat, and primarily eliminated renally.
Dosage
Standard Dosage
Adults:
- The usual dose is one tablet once daily, taken in the morning before a meal. Tablets are available in several strengths combining bisoprolol fumarate and perindopril arginine (2.5 mg/2.5 mg, 5 mg/5 mg, 5mg/10mg, 10 mg/5 mg, 10 mg/10 mg).
- The fixed-dose combination is not suitable for initial therapy. Patients should be stabilized with bisoprolol and perindopril as individual medications at the same dose level for at least 4 weeks before switching to the combination tablet.
- If dosage adjustment is needed, it should be done by titrating the individual components.
Children:
- Not recommended for use in children and adolescents younger than 18 years.
Special Cases:
- Elderly Patients: Administer based on renal function. Dose reductions might be required based on creatinine clearance.
- Patients with Renal Impairment: Dosage adjustments are necessary depending on the degree of impairment (creatinine clearance). Refer to specific product prescribing information for detailed guidance. The combination is not suitable for patients with severe renal impairment (creatinine clearance < 30 mL/min).
- Patients with Hepatic Dysfunction: No dosage adjustment is required.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, severe heart failure, or other serious cardiovascular conditions.
Clinical Use Cases
- The combination tablet is not indicated for use in acute settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dose adjustments may be needed based on patient response, renal function, and other clinical factors. Refer to the specific product prescribing information for detailed guidance.
Side Effects
Common Side Effects:
- Headache, dizziness, hypotension, fatigue, nausea, vomiting, diarrhea, cough, peripheral edema, and bradycardia.
Rare but Serious Side Effects:
- Angioedema, severe hypotension, acute heart failure, hepatic dysfunction, hyperkalemia, and blood dyscrasias.
Long-Term Effects:
- Chronic kidney disease, electrolyte imbalances, and persistent cough (with perindopril).
Adverse Drug Reactions (ADR):
- Angioedema, severe hypotension, and anaphylactic reactions require immediate medical attention.
Contraindications
- Hypersensitivity to bisoprolol, perindopril, other ACE inhibitors, or any component of the formulation.
- History of angioedema related to ACE inhibitor use.
- Cardiogenic shock, second or third-degree AV block (without pacemaker), sick sinus syndrome, severe bradycardia, or symptomatic hypotension.
- Pregnancy (especially after the first trimester).
- Concomitant use with sacubitril/valsartan or aliskiren (in patients with diabetes).
Drug Interactions
- Clinically Significant Drug Interactions: Potassium-sparing diuretics, potassium supplements, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), other antihypertensive medications, certain anesthetics, tricyclic antidepressants, and antipsychotics.
- CYP450 Interactions: Bisoprolol is primarily metabolized by CYP2D6 but is not a major substrate or inhibitor. Perindopril is not significantly metabolized by CYP450 enzymes.
- Interactions with other medications: Use with caution in combination with drugs affecting potassium levels, centrally acting antihypertensives, vasodilators, and other medications that can lower blood pressure. Consult comprehensive drug interaction resources for specific information.
- Food and lifestyle factors: Alcohol may enhance the hypotensive effects of the drug. High potassium intake should be avoided, especially with perindopril.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category D (first trimester) and Category X (second and third trimesters). Contraindicated during the second and third trimesters. ACE inhibitors can cause fetal harm and even death when administered during pregnancy.
- Fetal Risks: Renal failure, oligohydramnios, growth retardation, fetal death, and neonatal hypotension.
- Drug Excretion in Breast Milk: Both bisoprolol and perindopril can be excreted in breast milk. Breastfeeding is generally not recommended.
- Alternative Safer Options: Other antihypertensive medications with better-established safety profiles during pregnancy and breastfeeding are available and should be considered.
Drug Profile Summary
- Mechanism of Action: Bisoprolol: Beta-1 adrenergic blocker. Perindopril: ACE inhibitor.
- Side Effects: Headache, dizziness, hypotension, cough, fatigue. Serious side effects: Angioedema, severe hypotension.
- Contraindications: Hypersensitivity, history of angioedema, pregnancy (second and third trimesters), cardiogenic shock.
- Drug Interactions: Potassium-sparing diuretics, other antihypertensives, lithium, NSAIDs.
- Pregnancy & Breastfeeding: Contraindicated in the second and third trimesters of pregnancy and generally not recommended during breastfeeding.
- Dosage: Adult: One tablet daily, starting dose dependent on individual component titration. Not for initial therapy. Pediatric: Not recommended.
- Monitoring Parameters: Blood pressure, heart rate, renal function, electrolytes (especially potassium), and signs of angioedema.
Popular Combinations
This medication is a popular combination of bisoprolol and perindopril, offering the convenience of a single-pill dosage. It is generally not combined with other antihypertensives in fixed-dose combinations. Individual component dose titration is usually done prior to initiation of the combination tablet, rather than using it in combination with other agents initially.
Precautions
- General Precautions: Monitor renal function, electrolytes, and blood pressure regularly. Assess for signs of angioedema.
- Specific Populations: See Dosage section.
- Lifestyle Considerations: Advise patients to limit alcohol intake and avoid driving or operating hazardous machinery until the drug’s effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Bisoprolol + Perindopril Arginine?
A: The usual dose is one tablet once daily, available in strengths of 2.5/2.5mg, 5/5mg, 5/10mg, 10/5mg, and 10/10mg of bisoprolol fumarate and perindopril arginine, respectively. The choice of strength is based on the stabilized doses of the individual components.
Q2: Can Bisoprolol + Perindopril Arginine be used as initial therapy for hypertension?
A: No, this combination is not suitable for initial hypertension therapy. Patients should first be stabilized on individual doses of bisoprolol and perindopril.
Q3: What are the most common side effects of this medication?
A: Common side effects include headache, dizziness, hypotension, fatigue, cough, and gastrointestinal disturbances.
Q4: What is the most serious side effect to watch out for?
A: Angioedema is a rare but serious side effect. Patients should seek immediate medical attention if they experience swelling of the face, lips, tongue, or throat, or difficulty breathing.
Q5: Can this medication be used during pregnancy?
A: Bisoprolol + Perindopril Arginine is contraindicated during the second and third trimesters of pregnancy due to the risk of fetal harm. Use during the first trimester requires careful consideration of the potential risks and benefits.
Q6: What are the key drug interactions with this medication?
A: Important drug interactions occur with potassium-sparing diuretics, potassium supplements, lithium, and other antihypertensive agents.
Q7: How should the dosage be adjusted in patients with renal impairment?
A: Dosage adjustments are necessary in patients with renal impairment based on creatinine clearance. Refer to the product’s prescribing information for specific guidance.
Q8: Can this drug be crushed or chewed?
A: The tablets should generally be swallowed whole and should not be crushed or chewed, as this may alter the release characteristics of the medication. Consult with a pharmacist or refer to the specific product information for specific administration instructions.
Q9: How should the medication be stored?
A: Store at room temperature away from moisture and heat.
Q10: What should a patient do if they miss a dose?
A: If a dose is missed, the patient should take it as soon as they remember unless it is close to the time of their next dose. They should not double the dose to catch up.
