Cilnidipine + Metoprolol Succinate + Telmisartan

Usage

• This fixed-dose combination (FDC) medication is primarily prescribed for the treatment of hypertension (high blood pressure) in adults. It is particularly beneficial for patients who require multiple antihypertensive agents to achieve their blood pressure goals or those already taking the individual components separately. This combination therapy may also be used in patients who are at high risk of cardiovascular events like heart attacks and strokes.
• Pharmacological Classification: Antihypertensive (a combination of a calcium channel blocker, a beta-blocker, and an angiotensin II receptor blocker).
• Mechanism of Action: This FDC lowers blood pressure through three distinct mechanisms:
  • Cilnidipine: Inhibits calcium influx into vascular smooth muscle cells, causing vasodilation and reducing peripheral resistance. It also possesses a dual L/N-type calcium channel blocking activity.
  • Metoprolol Succinate: A beta-1 selective adrenergic receptor blocker that decreases heart rate, cardiac output, and renin release, thereby lowering blood pressure. The succinate formulation provides extended release.
  • Telmisartan: An angiotensin II receptor blocker that inhibits the binding of angiotensin II to its receptor, leading to vasodilation and a reduction in aldosterone secretion.

Alternate Names

• There is no officially recognized alternate name for this specific FDC. However, it may be referred to by the names of its individual components or the combination described as a triple therapy for hypertension.
• Brand Names: This FDC is marketed under various brand names like Cadmet Trio 25, Met XL Trio 25, Metosartan LN 25, Telista MCL 25, Cilacar TM 25, Tsart MCL 25, Telma LNB 25.

How It Works

• Pharmacodynamics: The combined effect of the three drugs results in a synergistic reduction in blood pressure. Cilnidipine acts on the peripheral vasculature, Metoprolol reduces cardiac output, and Telmisartan blocks the renin-angiotensin-aldosterone system (RAAS).
• Pharmacokinetics:
  • Absorption: All three drugs are absorbed orally. Metoprolol succinate is formulated for extended release, providing a more consistent blood level.
  • Metabolism: Cilnidipine and Metoprolol are primarily metabolized by the liver, specifically by CYP3A4 and CYP2D6 enzymes respectively. Telmisartan undergoes glucuronidation in the liver.
  • Elimination: The drugs and their metabolites are eliminated primarily through renal and hepatic routes.
• Mode of Action:
  • Cilnidipine: Blocks L-type and N-type calcium channels in vascular smooth muscle, preventing calcium influx and thus muscle contraction.
  • Metoprolol: Competitively binds to beta-1 adrenergic receptors in the heart, reducing sympathetic stimulation and lowering heart rate and contractility.
  • Telmisartan: Selectively blocks the AT1 receptor subtype, preventing angiotensin II from binding and exerting its vasoconstrictor effects.
• Receptor Binding/Enzyme Inhibition:
  • Cilnidipine: Calcium channel blocker.
  • Metoprolol: Beta-1 adrenergic receptor blocker.
  • Telmisartan: Angiotensin II receptor blocker.
• Elimination Pathways: Predominantly renal and hepatic excretion.

Dosage

Standard Dosage

Adults: The typical starting dose is one tablet containing Cilnidipine 10mg, Metoprolol Succinate 25mg (extended-release), and Telmisartan 40mg, taken orally once daily. The dosage may be adjusted based on individual patient response and blood pressure control.

Children: This FDC is not recommended for use in children, as the safety and efficacy have not been established.

Special Cases:

• Elderly Patients: Dosage should be initiated cautiously in elderly patients due to potential age-related decline in renal and hepatic function.
• Patients with Renal Impairment: Dosage adjustment may be necessary in patients with moderate to severe renal impairment.
• Patients with Hepatic Dysfunction: Use with caution in patients with hepatic impairment, as it may affect the metabolism of Cilnidipine and Metoprolol.
• Patients with Comorbid Conditions: Careful monitoring is recommended in patients with diabetes, heart failure, or other cardiovascular diseases.

Clinical Use Cases

The use of this FDC in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations has not been established and is generally not recommended.

Dosage Adjustments

Dosage adjustments are made based on individual patient response to therapy, renal and hepatic function, and the presence of other medical conditions.

Side Effects

Common Side Effects:

Headache, dizziness, fatigue, nausea, edema, hypotension, bradycardia, gastrointestinal disturbances (diarrhea, constipation).

Rare but Serious Side Effects:

Severe hypotension, bradycardia, heart block, angioedema, liver dysfunction, renal failure.

Long-Term Effects:

The long-term effects of this FDC are still being studied. However, maintaining good blood pressure control through appropriate medication can significantly reduce the risk of long-term complications associated with hypertension, such as cardiovascular disease and renal failure.

Adverse Drug Reactions (ADR):

Angioedema, severe hypotension, acute renal failure, hepatotoxicity.

Contraindications

• Hypersensitivity to any of the components (Cilnidipine, Metoprolol, Telmisartan).
• Cardiogenic shock, decompensated heart failure, sick sinus syndrome, severe bradycardia, second or third-degree atrioventricular block (unless a functioning pacemaker is present), severe hepatic impairment.

Drug Interactions

• CYP3A4 inhibitors (ketoconazole, ritonavir) and CYP2D6 inhibitors (fluoxetine, paroxetine) may increase the plasma concentrations of Cilnidipine and Metoprolol, respectively.
• Other antihypertensive medications can have additive effects.
• NSAIDs can reduce the antihypertensive effect and increase the risk of kidney problems.
• Alcohol can potentiate the hypotensive effects.
• Grapefruit juice can affect the metabolism of Cilnidipine.
• Potassium supplements and a high-potassium diet should be avoided.

Pregnancy and Breastfeeding

• This FDC is contraindicated during pregnancy due to the potential for fetal harm.
• The safety during breastfeeding has not been established. It is advisable to avoid this medication during breastfeeding or discontinue breastfeeding.

Drug Profile Summary

• Mechanism of Action: See above.
• Side Effects: See above.
• Contraindications: See above.
• Drug Interactions: See above.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy; safety during breastfeeding not established.
• Dosage: See above.
• Monitoring Parameters: Blood pressure, heart rate, renal function tests, liver function tests, electrolyte levels.

Popular Combinations

This particular combination itself is frequently utilized, exploiting the synergistic effects of the different antihypertensive mechanisms. Individual components may be combined with other antihypertensives like diuretics or ACE inhibitors based on individual patient needs.

Precautions

• General Precautions: Assess renal and hepatic function, monitor blood pressure and heart rate regularly.

• Specific Populations:

  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Not recommended.
  • Children & Elderly: Not recommended for children; use with caution in the elderly.

• Lifestyle Considerations: Limit alcohol intake, avoid smoking, adopt a healthy diet (low sodium, low fat).

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Cilnidipine + Metoprolol Succinate + Telmisartan?

A: The typical starting dose is Cilnidipine 10mg + Metoprolol Succinate 25mg (ER) + Telmisartan 40mg once daily. Dosage can be adjusted according to patient response and blood pressure control.

Q2: What are the common side effects?

A: Common side effects include headache, dizziness, fatigue, nausea, edema, hypotension, and bradycardia.

Q3: Can this medication be used during pregnancy or breastfeeding?

A: No, this FDC is contraindicated during pregnancy and should be avoided during breastfeeding.

Q4: What are the serious side effects that require immediate medical attention?

A: Severe hypotension, bradycardia, angioedema, liver or kidney dysfunction are serious adverse effects.

Q5: Are there any dietary restrictions while taking this medication?

A: Patients should limit alcohol intake, avoid grapefruit juice, and limit potassium intake. A low-sodium diet is generally recommended for hypertension management.

Q6: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember. If it is close to the time for the next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.

Q7: Can this medicine be taken with other blood pressure medications?

A: It may interact with other antihypertensives. Consult your doctor before combining with other blood pressure medications.

Q8: What should I discuss with my doctor before starting this medication?

A: Discuss your complete medical history, including any existing conditions, allergies, other medications, and whether you are pregnant, planning pregnancy, or breastfeeding.

Q9: How does this combination work differently than taking each medicine individually?

A: The combination provides synergistic blood pressure control by targeting multiple mechanisms involved in blood pressure regulation. It can be more effective than taking each medication individually for some patients and simplifies the treatment regimen.

Q10: Can this medication cause hypotension?

A: Yes, hypotension (low blood pressure) is a possible side effect, especially at the start of treatment or with dosage increases.