Chlorthalidone + Cilnidipine

Usage

• Chlorthalidone + Cilnidipine is prescribed for the treatment of hypertension (high blood pressure). It is also used to help reduce the risks associated with hypertension, such as stroke and heart attack. It’s often prescribed when monotherapy (treatment with a single drug) isn’t sufficient for blood pressure control.

• Pharmacological Classification: Antihypertensive (combination drug containing a thiazide-like diuretic and a calcium channel blocker).

• Mechanism of Action: This combination medication works through two distinct mechanisms:

  • Chlorthalidone: This thiazide-like diuretic increases urine production by inhibiting sodium reabsorption in the kidneys. This decreases blood volume, thus lowering blood pressure. It also helps relax blood vessels.

  • Cilnidipine: This calcium channel blocker inhibits calcium influx into vascular smooth muscle cells and cardiac myocytes, leading to vasodilation (widening of blood vessels). This lowers peripheral resistance and reduces cardiac workload, further contributing to a decrease in blood pressure.

Alternate Names

• There are no widely recognized alternate generic names.
• Brand Names: Cilacar-C, StayHappi Cilnidipine+Chlorthalidone.

How It Works

• Pharmacodynamics: The combined effect of vasodilation (from cilnidipine) and diuresis (from chlorthalidone) leads to a significant reduction in blood pressure. Cilnidipine primarily acts on peripheral arterioles, reducing peripheral resistance. Chlorthalidone reduces blood volume and also has some vasodilatory effects.

• Pharmacokinetics:

  • Absorption: Both drugs are absorbed orally. Cilnidipine is best absorbed after a meal. Chlorthalidone’s absorption is not significantly affected by food.

  • Metabolism: Cilnidipine undergoes hepatic metabolism. Chlorthalidone is not extensively metabolized.

  • Elimination: Cilnidipine metabolites are primarily eliminated in the feces, with a small amount in the urine. Chlorthalidone is primarily excreted unchanged in the urine.

• Mode of Action:

  • Cilnidipine blocks L-type calcium channels in vascular smooth muscle, preventing calcium influx and subsequent vasoconstriction.

  • Chlorthalidone inhibits sodium reabsorption in the distal convoluted tubule of the nephron.

• Elimination Pathways:

  • Cilnidipine: Primarily hepatic metabolism followed by fecal excretion.
  • Chlorthalidone: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• The typical starting dose is Cilnidipine 10 mg + Chlorthalidone 12.5 mg once daily, preferably in the morning.
• The dose can be increased to a maximum of Cilnidipine 20 mg + Chlorthalidone 25 mg per day if needed.

Children:

• Not recommended for use in patients under 18 years of age due to lack of data on safety and efficacy.

Special Cases:

• Elderly Patients: Initiate therapy with a lower dose (e.g., Cilnidipine 5 mg) and monitor closely. Excessive hypotensive effects should be avoided.
• Patients with Renal Impairment: Dose adjustment may be necessary depending on the degree of impairment. In severe renal impairment, the drug may be ineffective.
• Patients with Hepatic Dysfunction: Exercise caution and monitor closely, especially in severe hepatic dysfunction. Start with a lower dose of cilnidipine.
• Patients with Comorbid Conditions: Careful monitoring is required in patients with diabetes, gout, lupus, heart failure, and other conditions.

Clinical Use Cases

• Dosage recommendations for specific medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations haven’t been specifically defined in the provided research. Dosage adjustments must be made on a case-by-case basis considering the patient’s overall condition and hemodynamic status.

Dosage Adjustments

• Dosage should be adjusted based on the patient’s response to therapy and the presence of any comorbidities.

Side Effects

Common Side Effects:

• Dizziness
• Headache
• Fatigue
• Swelling in the ankles/feet (peripheral edema)
• Flushing
• Palpitations
• Increased urination

Rare but Serious Side Effects:

• Severe hypotension (low blood pressure) potentially leading to syncope (fainting).
• Electrolyte imbalances (hypokalemia – low potassium levels).
• Allergic reactions.
• Liver dysfunction.
• Angina pectoris (chest pain).

Long-Term Effects:

• Potential for electrolyte disturbances with long-term use, particularly hypokalemia.

Adverse Drug Reactions (ADR):

• Severe hypotension, angioedema (swelling of face, lips, tongue), and other allergic reactions require immediate medical attention.

Contraindications

• Hypersensitivity to cilnidipine or chlorthalidone or any component of the formulation.
• Anuria (inability to produce urine).
• Severe hepatic or renal impairment.
• Cardiogenic shock.
• Severe aortic stenosis.
• Unstable angina or recent myocardial infarction.
• Second and third trimesters of pregnancy.

Drug Interactions

• Other antihypertensives: Additive effects may occur, leading to hypotension.
• Diuretics: May potentiate electrolyte imbalances, particularly hypokalemia.
• NSAIDs (e.g., ibuprofen): May decrease the antihypertensive effect.
• Drugs affecting potassium levels (e.g., digoxin, potassium supplements): May increase the risk of hyperkalemia or hypokalemia.
• Alcohol: May potentiate the hypotensive effects.
• Grapefruit juice: May increase cilnidipine levels.
• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May increase cilnidipine levels.

Pregnancy and Breastfeeding

• Pregnancy: Not recommended during pregnancy, especially during the 2nd and 3rd trimesters. May cause harm to the fetus.
• Breastfeeding: Chlorthalidone is excreted in breast milk and may suppress lactation. Cilnidipine use during breastfeeding is also not recommended. Use with caution if clearly necessary, and consider the potential risks to the infant.

Drug Profile Summary

• Mechanism of Action: Cilnidipine (calcium channel blocker) causes vasodilation; Chlorthalidone (thiazide-like diuretic) increases urine output and reduces blood volume.
• Side Effects: Dizziness, headache, edema, flushing, palpitations, increased urination, hypotension, hypokalemia.
• Contraindications: Hypersensitivity, anuria, severe hepatic/renal impairment, cardiogenic shock, aortic stenosis, pregnancy.
• Drug Interactions: Other antihypertensives, diuretics, NSAIDs, drugs affecting potassium, alcohol, grapefruit juice.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: Adults: 10/12.5 mg once daily, adjustable up to 20/25 mg.
• Monitoring Parameters: Blood pressure, heart rate, electrolytes (especially potassium), renal function, and signs of edema.

Popular Combinations

• Sometimes used in combination with Telmisartan (an angiotensin II receptor blocker) for more comprehensive blood pressure control in resistant hypertension.

Precautions

• General Precautions: Monitor blood pressure, electrolytes, renal and hepatic function. Assess for signs of edema and other side effects.
• Specific Populations: As outlined in the “Special Cases” section of Dosage.
• Lifestyle Considerations: Encourage lifestyle modifications, including a healthy diet, regular exercise, and limiting alcohol intake. Avoid driving or operating machinery if experiencing dizziness or drowsiness.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Chlorthalidone + Cilnidipine?

A: The standard adult starting dose is Cilnidipine 10 mg + Chlorthalidone 12.5 mg once daily, taken orally. This can be increased to a maximum of 20/25 mg per day as needed and tolerated.

Q2: What are the common side effects?

A: Common side effects include dizziness, headache, peripheral edema, flushing, palpitations, and increased urination.

Q3: Is this combination safe in pregnancy?

A: No, it’s generally not recommended during pregnancy, especially in the second and third trimesters, due to potential fetal harm.

Q4: What are the major contraindications?

A: Contraindications include hypersensitivity to either drug, anuria, severe liver or kidney disease, cardiogenic shock, and severe aortic stenosis.

Q5: Are there any significant drug interactions?

A: Yes, it can interact with other antihypertensives, diuretics, NSAIDs, drugs affecting potassium levels (e.g., digoxin), and alcohol. Grapefruit juice may also affect cilnidipine levels.

Q6: How should the dose be adjusted in elderly patients?

A: Start with a lower dose of cilnidipine (e.g., 5 mg) and titrate cautiously, monitoring closely for hypotension.

Q7: Can this combination be used in patients with renal impairment?

A: Use with caution. Dosage adjustments may be needed, and it may be ineffective in severe renal impairment.

Q8: What monitoring is required during treatment?

A: Monitor blood pressure, electrolytes (especially potassium), renal function, and signs of edema.

Q9: What should patients be advised regarding lifestyle?

A: Patients should be advised to maintain a healthy lifestyle, including regular exercise, a balanced diet (low sodium is beneficial), and limit alcohol consumption. Caution regarding driving and operating machinery if dizziness or drowsiness occur.

Q10: What should I do if a patient misses a dose?

A: Take the missed dose as soon as remembered unless it is close to the time for the next dose. Do not double the dose to catch up.