Usage
- Amlodipine + Bisoprolol is prescribed for the treatment of hypertension (high blood pressure). It is used as a substitution therapy in patients whose blood pressure is adequately controlled with the individual components given concurrently, but as separate tablets. It is also used in patients whose blood pressure isn’t adequately managed by either amlodipine or bisoprolol alone.
- Pharmacological Classification: This combination drug includes a calcium channel blocker (Amlodipine) and a beta-blocker (Bisoprolol).
- Mechanism of Action: Amlodipine, a dihydropyridine calcium channel blocker, inhibits calcium ion influx across cell membranes, leading to vasodilation. Bisoprolol, a cardioselective beta-1 adrenergic receptor blocker, decreases heart rate and myocardial contractility, reducing cardiac output and blood pressure. The combined effect results in synergistic blood pressure reduction.
Alternate Names
- No widely recognized alternate names exist for this combination specifically. The individual components are sometimes referred to as amlodipine besylate and bisoprolol fumarate, denoting the salt forms used in formulations.
- Brand Names: Concor AM, Concor AMLO, Zebapril-AM5.
How It Works
- Pharmacodynamics: Amlodipine relaxes vascular smooth muscle, causing vasodilation and reducing peripheral resistance. Bisoprolol reduces heart rate and myocardial contractility, decreasing cardiac output. Both contribute to lower blood pressure.
- Pharmacokinetics: Amlodipine is well absorbed orally, reaching peak plasma concentrations in 6-12 hours. It undergoes extensive hepatic metabolism and has a half-life of about 30-50 hours, permitting once-daily dosing. Bisoprolol is also well absorbed orally, with a peak plasma concentration in 2-4 hours. It is partially metabolized in the liver, with both the parent drug and metabolites contributing to its effect. Its half-life is 9–12 hours.
- Mode of Action: Amlodipine blocks L-type calcium channels in vascular smooth muscle, inhibiting calcium influx needed for muscle contraction. Bisoprolol competitively binds to beta-1 adrenergic receptors in the heart, blocking the stimulatory effects of catecholamines.
- Receptor Binding/Enzyme Inhibition: Amlodipine targets L-type calcium channels. Bisoprolol targets beta-1 adrenergic receptors.
- Elimination Pathways: Amlodipine is primarily eliminated via hepatic metabolism, with about 60% excreted in the urine and 20-25% in feces. Bisoprolol is eliminated approximately equally by renal and hepatic routes.
Dosage
Standard Dosage
Adults:
- Initial dose: Amlodipine 5 mg + Bisoprolol 5 mg once daily.
- Titration: If the desired response is not achieved after 6 weeks, the dose may be increased to Amlodipine 10 mg + Bisoprolol 5 mg, Amlodipine 5 mg + Bisoprolol 10 mg, or if both components need up-titration, up to 10 mg of each component (Amlodipine 10 mg + Bisoprolol 10 mg). The dosage should be adjusted based on the patient’s response and tolerability.
- Maximum dose: Amlodipine 10 mg + Bisoprolol 10 mg once daily.
Children:
- Not recommended for children under 6 years of age. Limited data is available regarding pediatric use. For children above six, the dosage needs to be adjusted according to their condition and should only be administered under strict medical supervision.
Special Cases:
- Elderly Patients: Start with the lowest dose and titrate cautiously.
- Patients with Renal Impairment: No dosage adjustment is generally needed for mild to moderate renal impairment. In severe renal impairment (creatinine clearance < 20 mL/min), the maximum daily dose of Bisoprolol should not exceed 10 mg.
- Patients with Hepatic Dysfunction: Caution is advised in patients with hepatic impairment, especially those with severe hepatic impairment, where the daily dose of Bisoprolol should not exceed 10 mg. Dosage adjustments for Amlodipine are not well-established in hepatic impairment.
- Patients with Comorbid Conditions: Careful monitoring is needed in patients with diabetes, asthma, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, and other cardiovascular conditions.
Clinical Use Cases
- The combination is generally not indicated for acute situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It’s primarily used for chronic hypertension management.
Dosage Adjustments
- Adjust dosage based on patient response, blood pressure control, and tolerability.
- Consider renal and hepatic function for dosage adjustments, specifically for Bisoprolol.
Side Effects
Common Side Effects
- Headache, dizziness, fatigue, edema (especially ankle swelling), nausea, bradycardia, and cold extremities.
Rare but Serious Side Effects
- Severe hypotension, bronchospasm (in susceptible individuals), heart block, new or worsening heart failure.
Long-Term Effects
- Long-term use of beta-blockers might be linked to metabolic changes, but further research is needed with this particular combination.
Adverse Drug Reactions (ADR)
- Angioedema, severe allergic reactions, and significant bradycardia.
Contraindications
- Hypersensitivity to amlodipine, bisoprolol, or any component of the formulation.
- Cardiogenic shock, second- or third-degree heart block, sick sinus syndrome (unless a functioning pacemaker is present), severe bradycardia, severe heart failure, and severe hypotension.
Drug Interactions
- Other antihypertensives (additive hypotensive effects).
- Beta-blockers (additive bradycardia and negative inotropic effects).
- Calcium channel blockers (additive effects on heart rate and blood pressure).
- CYP3A4 inhibitors (may increase amlodipine levels).
- CYP2D6 inhibitors (may increase bisoprolol levels).
- Digoxin, insulin, and oral hypoglycemic agents.
Pregnancy and Breastfeeding
- Pregnancy: Use only if clearly needed and the potential benefit outweighs the risk to the fetus. Not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Amlodipine: Calcium channel blocker causing vasodilation. Bisoprolol: Beta-blocker reducing heart rate and contractility.
- Side Effects: Headache, dizziness, edema, fatigue, bradycardia.
- Contraindications: Hypersensitivity, severe bradycardia, heart block, cardiogenic shock.
- Drug Interactions: Other antihypertensives, beta-blockers, calcium channel blockers.
- Pregnancy & Breastfeeding: Use with caution during pregnancy if clearly needed. Not recommended for breastfeeding.
- Dosage: Start with Amlodipine 5 mg + Bisoprolol 5 mg once daily, titrate as needed up to 10 mg of each component.
- Monitoring Parameters: Blood pressure, heart rate, signs of heart failure.
Popular Combinations
- Not applicable, since it is already a combination drug. This medication often follows monotherapy with amlodipine or bisoprolol if the blood pressure target is not reached.
Precautions
- General Precautions: Monitor heart rate and blood pressure. Monitor for signs of heart failure. Assess renal and hepatic function.
- Specific Populations: Caution is advised in pregnancy and lactation. Use cautiously in older adults and patients with comorbidities.
- Lifestyle Considerations: Limit alcohol consumption.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Bisoprolol?
A: Initial dose: Amlodipine 5 mg + Bisoprolol 5 mg once daily. Titrate up to 10 mg of each component as needed based on blood pressure control and tolerability.
Q2: Can Amlodipine + Bisoprolol be used in patients with asthma?
A: Use with caution in patients with asthma or COPD, as beta-blockers can potentially exacerbate bronchospasm. Cardioselective beta-blockers like Bisoprolol are preferred if a beta-blocker is necessary.
Q3: How should the dose be adjusted in renal impairment?
A: For mild to moderate renal impairment, no dosage adjustment is usually needed. In severe renal impairment (creatinine clearance <20 ml/min), the maximum Bisoprolol dose should not exceed 10mg.
Q4: What are the major drug interactions to consider?
A: Other antihypertensives, beta-blockers, calcium channel blockers, CYP3A4 inhibitors (for amlodipine), and CYP2D6 inhibitors (for bisoprolol).
Q5: What is the mechanism by which Amlodipine + Bisoprolol lowers blood pressure?
A: Amlodipine causes vasodilation by blocking calcium channels. Bisoprolol reduces heart rate and contractility by blocking beta-1 receptors.
Q6: Can Amlodipine + Bisoprolol be stopped abruptly?
A: No, especially in patients with ischemic heart disease. Abrupt discontinuation can lead to rebound hypertension or other cardiovascular complications. Tapering the dose gradually is recommended.
Q7: Is this combination safe in pregnancy?
A: Use only if clearly needed and the potential benefit outweighs the fetal risk. Discuss with a healthcare provider.
Q8: What are the most common side effects patients experience?
A: Headache, dizziness, fatigue, ankle swelling (edema), nausea, slow heart rate (bradycardia), and cold extremities.
Q9: Are there any specific monitoring parameters for this combination?
A: Yes, regularly monitor blood pressure, heart rate, and watch for signs of worsening heart failure. In diabetic patients, blood sugar monitoring is also necessary to prevent beta-blocker-masked hypoglycemic episodes.
