Usage
- This fixed-dose combination (FDC) is prescribed for the treatment of essential hypertension (high blood pressure) in adults. It may be used when monotherapy with either drug is insufficient to control blood pressure.
- Pharmacological classification: Antihypertensive (combining a calcium channel blocker (CCB) and a beta-blocker).
- Mechanism of Action: Cilnidipine, a dihydropyridine CCB, inhibits calcium influx into vascular smooth muscle cells, leading to vasodilation and reduced peripheral resistance. Metoprolol succinate, a cardioselective beta-1 adrenergic receptor blocker, reduces heart rate, cardiac output, and renin release, further contributing to blood pressure reduction.
Alternate Names
- While no specific international non-proprietary names (INN) exist for the combination, the individual components have their established INNs: Cilnidipine and Metoprolol Succinate.
- Brand names: The combination is marketed under various brand names, which can vary regionally. Some examples include Cilacar-M, Cilinitab M, StayHappi, and others.
How It Works
- Pharmacodynamics: Cilnidipine primarily affects peripheral arteries, causing vasodilation and reducing blood pressure. Metoprolol succinate reduces heart rate and myocardial contractility, lowering cardiac output and blood pressure.
- Pharmacokinetics: Both drugs are orally absorbed. Cilnidipine undergoes extensive first-pass metabolism in the liver, while metoprolol succinate has lower first-pass metabolism. Both are metabolized in the liver, primarily by CYP enzymes. Elimination pathways are mainly hepatic, with some renal excretion.
- Mode of Action: Cilnidipine blocks L-type calcium channels in vascular smooth muscle. Metoprolol succinate competitively binds to beta-1 adrenergic receptors in the heart, inhibiting the effects of catecholamines.
Dosage
Standard Dosage
Adults:
- The standard dose is one tablet containing 10 mg cilnidipine and either 25 mg or 50 mg metoprolol succinate, taken orally once daily.
- The dosage can be adjusted based on individual patient response and blood pressure control, up to a maximum dose determined by the physician.
Children:
- This FDC is not recommended for use in children under 18 years of age, as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose of cilnidipine (e.g., 5 mg) and titrate cautiously while monitoring for hypotension.
- Patients with Renal Impairment: Dose adjustment is generally not necessary for cilnidipine but may be needed for metoprolol succinate in severe renal impairment.
- Patients with Hepatic Dysfunction: Exercise caution and consider dose adjustments, particularly for cilnidipine, as it is extensively metabolized by the liver.
- Patients with Comorbid Conditions: Careful monitoring is required in patients with diabetes, asthma, chronic obstructive pulmonary disease (COPD), or peripheral vascular disease.
Clinical Use Cases The provided source documents focus primarily on managing hypertension using cilnidipine + metoprolol succinate, and there are no specific clinical use cases mentioned for intubation, surgical procedures, mechanical ventilation, or ICU scenarios with this fixed-dose combination.
Dosage Adjustments
- Dosage should be individualized based on the patient’s blood pressure response and tolerability.
- Consider renal and hepatic function, concomitant medications, and other medical conditions.
Side Effects
Common Side Effects
- Headache, dizziness, fatigue, peripheral edema (ankle swelling), nausea, flushing, and bradycardia.
Rare but Serious Side Effects
- Severe hypotension, heart block, bronchospasm (in susceptible individuals), and acute heart failure.
Long-Term Effects
- While generally safe for long-term use, regular monitoring of blood pressure, heart rate, and electrolyte levels is advised.
Adverse Drug Reactions (ADR)
- Angioedema, Stevens-Johnson syndrome (rare).
Contraindications
- Hypersensitivity to cilnidipine, metoprolol, or any component of the formulation.
- Severe bradycardia, second- or third-degree heart block, sick sinus syndrome (unless a pacemaker is present), cardiogenic shock, decompensated heart failure, and severe aortic stenosis.
- Pregnancy.
Drug Interactions
- Other antihypertensive medications (additive effects).
- Calcium channel blockers (additive effects).
- Beta-blockers (additive bradycardia and hypotension).
- CYP3A4 inhibitors (increased cilnidipine levels).
- CYP2D6 inhibitors (increased metoprolol levels).
- Alcohol (enhanced hypotension).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated in pregnancy due to the potential for fetal harm.
- Breastfeeding: Not recommended during breastfeeding as both drugs can be excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Cilnidipine: Calcium channel blockade; Metoprolol: Beta-1 adrenergic receptor blockade.
- Side Effects: Headache, dizziness, fatigue, edema, nausea, bradycardia.
- Contraindications: Severe bradycardia, heart block, heart failure, pregnancy.
- Drug Interactions: Other antihypertensives, CCBs, beta-blockers, CYP3A4/2D6 inhibitors.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended during breastfeeding.
- Dosage: 10/25 or 10/50 mg once daily, adjusted based on patient response.
- Monitoring Parameters: Blood pressure, heart rate, electrolytes.
Precautions
- Assess renal and hepatic function before initiating therapy.
- Monitor for hypotension, bradycardia, and signs of heart failure.
- Caution in patients with diabetes, asthma, COPD, or peripheral vascular disease.
- Avoid abrupt discontinuation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cilnidipine + Metoprolol Succinate?
A: The usual starting dose is one tablet of 10 mg cilnidipine and 25 mg or 50 mg metoprolol succinate once daily, adjusted as needed based on blood pressure response.
Q2: Can this combination be used in children?
A: No, it is not recommended for children under 18 years of age.
Q3: What are the common side effects?
A: Headache, dizziness, fatigue, ankle swelling, nausea, and slow heart rate are common side effects.
Q4: Are there any serious side effects to watch out for?
A: Yes, rare but serious side effects include severe low blood pressure, heart block, and worsening of heart failure.
Q5: What are the contraindications to using this combination?
A: Contraindications include hypersensitivity, severe bradycardia, heart block, heart failure, and pregnancy.
Q6: Does this combination interact with other medications?
A: Yes, it can interact with other blood pressure medications, certain heart medications, and some antibiotics. Consult with a pharmacist or physician for specific interactions.
Q7: Can I take this medication if I am pregnant or breastfeeding?
A: It is contraindicated during pregnancy and not recommended during breastfeeding.
Q8: What precautions should I take while on this medication?
A: Avoid abrupt discontinuation, monitor blood pressure regularly, and report any unusual symptoms to your doctor.
Q9: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember, unless it is almost time for the next dose. Do not double the dose.
Q10: How does this combination help control blood pressure?
A: Cilnidipine widens blood vessels, while metoprolol slows the heart rate and reduces its workload. Together, they effectively lower blood pressure.
