Usage
Ivabradine + Metoprolol Succinate is prescribed for the treatment of chronic heart failure and angina pectoris (chest pain due to reduced blood flow to the heart caused by coronary artery disease). It belongs to the pharmacological classifications of selective If current inhibitor (Ivabradine) and beta-blocker (Metoprolol). Ivabradine works by selectively inhibiting the If current in the sinoatrial node, which slows the heart rate. Metoprolol blocks beta-adrenergic receptors in the heart, reducing heart rate and myocardial contractility. The combination of these two mechanisms improves cardiac function and reduces angina symptoms.
Alternate Names
Ivabradine/Metoprolol, Ivabradine and Metoprolol Succinate. Brand names: Ivables M 25.
How It Works
Pharmacodynamics: Ivabradine selectively inhibits the If (‘funny’) current in the sinoatrial node, slowing the heart’s pacemaker activity and thus reducing heart rate. It does not affect myocardial contractility or conduction. Metoprolol, a beta-1 selective adrenergic receptor blocker, reduces heart rate, myocardial contractility, and blood pressure.
Pharmacokinetics: Ivabradine is rapidly absorbed after oral administration and extensively metabolized by the liver, primarily via CYP3A4. It is eliminated through both renal and hepatic pathways. Metoprolol succinate is an extended-release formulation that provides slow and consistent release of the drug. It is metabolized by the liver and eliminated renally.
Mode of Action: Ivabradine acts by binding to the If channels in the sinoatrial node cells, inhibiting the inward sodium-potassium current responsible for the slow diastolic depolarization phase of the pacemaker potential. Metoprolol competitively binds to beta-1 adrenergic receptors in the heart, preventing the binding of catecholamines like norepinephrine and epinephrine, leading to reduced sympathetic activity on the heart.
Elimination Pathways: Ivabradine is eliminated through hepatic metabolism (CYP3A4) and renal excretion. Metoprolol is predominantly eliminated through hepatic metabolism.
Dosage
Standard Dosage
Adults:
The starting dose of Ivabradine + Metoprolol Succinate is typically Ivabradine 5mg + Metoprolol 25mg twice daily. The dose may be adjusted based on the patient’s heart rate, blood pressure and tolerability.
Children: The combination is not generally recommended for children, however for Metoprolol alone: for children 6 years and older the dose is based on body weight (usually 1mg/kg once daily, not exceeding 50mg). For children under 6, usage should be determined by the doctor. Ivabradine is usually given to children aged 6 months and over, with dosing based on weight and response, under careful medical supervision.
Special Cases:
- Elderly Patients: The dosage may need to be adjusted based on individual tolerance and renal/hepatic function.
- Patients with Renal Impairment: Careful monitoring is required, and dose adjustments may be necessary.
- Patients with Hepatic Dysfunction: Ivabradine dosage should be reduced due to its dependence on liver metabolism. Careful monitoring and dose adjustments may be needed for Metoprolol.
- Patients with Comorbid Conditions: Adjust dose cautiously in patients with diabetes, other cardiovascular diseases, and respiratory issues.
Clinical Use Cases
The combination is not typically administered in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or during emergencies like cardiac arrest. Individual components (e.g., intravenous Metoprolol) might be used in these settings.
Dosage Adjustments
Dose adjustments may be necessary in patients with renal or hepatic dysfunction. Monitor heart rate, blood pressure, and ECG regularly.
Side Effects
Common Side Effects:
- Headache
- Dizziness
- Blurred vision
- Bradycardia (slow heart rate)
- Hypotension (low blood pressure)
- Fatigue
Rare but Serious Side Effects:
- Severe bradycardia
- Atrioventricular block
- Heart failure exacerbation
- Angioedema
- Bronchospasm
Long-Term Effects:
Data on specific long-term side effects from combined use is limited, but may include chronic bradycardia or hypotension.
Adverse Drug Reactions (ADR): Severe bradycardia, syncope, worsening heart failure.
Contraindications
- Severe bradycardia (heart rate <60 bpm before treatment)
- Sick sinus syndrome
- Second or third-degree atrioventricular block (unless a pacemaker is present)
- Cardiogenic shock
- Severe hypotension (blood pressure <90/50 mmHg)
- Acute decompensated heart failure
- Severe hepatic impairment
- Hypersensitivity to Ivabradine or Metoprolol.
- Pregnancy and breastfeeding
Drug Interactions
Ivabradine is primarily metabolized by CYP3A4, therefore, drugs inhibiting or inducing CYP3A4 can alter Ivabradine levels. Concomitant use with other drugs that lower heart rate (e.g., calcium channel blockers, digoxin, amiodarone, other beta-blockers) can increase the risk of bradycardia. Avoid grapefruit juice.
Metoprolol can interact with several medications, including calcium channel blockers, insulin, antidiabetic drugs, and certain antidepressants.
Pregnancy and Breastfeeding
Ivabradine + Metoprolol Succinate is contraindicated in pregnancy and breastfeeding due to potential risks to the fetus or infant.
Drug Profile Summary
- Mechanism of Action: Ivabradine: selective If current inhibition, reducing heart rate. Metoprolol: beta-1 adrenergic receptor blocker, reducing heart rate and myocardial contractility.
- Side Effects: Bradycardia, hypotension, dizziness, blurred vision, headache, fatigue.
- Contraindications: Severe bradycardia, heart block, hypotension, hepatic impairment, pregnancy, breastfeeding.
- Drug Interactions: CYP3A4 inhibitors/inducers, other bradycardic agents.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Initial: Ivabradine 5mg + Metoprolol 25mg twice daily, adjustable based on patient response.
- Monitoring Parameters: Heart rate, blood pressure, ECG.
Popular Combinations
Although a fixed-dose combination exists, Ivabradine and Metoprolol Succinate are often used individually and in combination with other heart failure medications such as ACE inhibitors, ARBs, and diuretics.
Precautions
- Monitor heart rate, blood pressure, and ECG.
- Pre-existing heart conditions need careful evaluation before prescribing.
- Caution with hepatic and renal impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ivabradine + Metoprolol Succinate?
A: The starting dose is typically Ivabradine 5mg + Metoprolol 25 mg twice daily. This may be adjusted by a physician based on the patient’s heart rate, blood pressure, and tolerability.
Q2: What are the major side effects of this combination?
A: Common side effects include bradycardia, hypotension, dizziness, blurred vision, and headaches.
Q3: Who should not take Ivabradine + Metoprolol Succinate?
A: Patients with severe bradycardia, sick sinus syndrome, heart block, severe hypotension, acute decompensated heart failure, severe hepatic impairment, hypersensitivity to either drug, and pregnant or breastfeeding women.
Q4: Are there any significant drug interactions with this combination?
A: Yes, interactions can occur with CYP3A4 inhibitors/inducers and other medications that slow heart rate, such as calcium channel blockers, digoxin, and other beta-blockers.
Q5: Can this combination be used during pregnancy or breastfeeding?
A: No, it is contraindicated in both pregnancy and breastfeeding.
Q6: How does Ivabradine + Metoprolol Succinate help in managing heart failure?
A: By reducing heart rate and myocardial workload, the combination improves cardiac efficiency and reduces the risk of hospitalization for worsening heart failure.
Q7: What should I monitor in patients taking Ivabradine + Metoprolol Succinate?
A: Closely monitor heart rate, blood pressure, and ECG for signs of bradycardia, hypotension, or conduction abnormalities.
Q8: How is the dose of Ivabradine + Metoprolol Succinate adjusted?
A: The dose is adjusted based on the patient’s resting heart rate, blood pressure, and overall clinical response. Dosage adjustments should be made gradually and under medical supervision.
Q9: What is the difference between Metoprolol tartrate and Metoprolol succinate in this combination?
A: Metoprolol succinate is an extended-release formulation providing a more stable blood concentration over time, while tartrate is an immediate-release form. The combination medication uses the succinate form.
