Usage
- Amlodipine + Indapamide is prescribed for the treatment of essential hypertension (high blood pressure) as substitution therapy in patients already controlled with the individual components given concurrently. It is not suitable for initial therapy.
- Pharmacological classification: Antihypertensive; combination of a calcium channel blocker (Amlodipine) and a thiazide-like diuretic (Indapamide).
- Mechanism of Action: Amlodipine blocks calcium entry into vascular smooth muscle, causing vasodilation and reducing peripheral resistance. Indapamide inhibits sodium reabsorption in the distal convoluted tubule, increasing sodium and water excretion, further lowering blood pressure.
Alternate Names
- No internationally recognized non-proprietary name for the combination.
- Brand names: Amlodac D, Natrixam.
How It Works
- Pharmacodynamics: Amlodipine causes vasodilation, reducing peripheral resistance and blood pressure. Indapamide increases excretion of sodium, chloride, and water, lowering blood volume and thus blood pressure.
- Pharmacokinetics: Amlodipine is well absorbed orally. Peak plasma concentrations are reached in 6-12 hours. It is highly protein-bound and extensively metabolized by the liver. It’s primarily excreted in the feces. Indapamide is well absorbed orally and extensively metabolized in the liver; primarily excreted in urine and some feces.
- Mode of Action: Amlodipine acts by blocking L-type calcium channels in vascular smooth muscle, which inhibits calcium influx. Indapamide acts by inhibiting sodium reabsorption in the distal convoluted tubule.
- Receptor Binding/Enzyme Inhibition: Amlodipine binds to L-type calcium channels. Indapamide inhibits sodium reabsorption via the sodium-chloride transporter
- Elimination Pathways: Amlodipine is extensively metabolized by the liver, primarily by CYP3A4, and then excreted in the feces. Indapamide is metabolized by the liver and excreted primarily in urine and some feces.
Dosage
Standard Dosage
Adults:
- One tablet containing a fixed combination of Amlodipine and Indapamide daily, taken orally, preferably in the morning before meals. The specific strengths of Amlodipine and Indapamide in the combination tablet will depend on the previously titrated and stabilized doses of the individual components.
Children: Not recommended for use in children and adolescents as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Dose adjustments may be needed based on renal function, as perindopril elimination is decreased in elderly patients. Start at the lower end of the dosing range.
- Patients with Renal Impairment: Contraindicated in severe renal impairment (creatinine clearance < 30 mL/min). Dose adjustment may be necessary in moderate renal impairment.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution should be exercised in mild to moderate hepatic impairment, and the dose should be initiated at the lower end of the dosing range.
- Patients with Comorbid Conditions: Caution in patients with heart failure, electrolyte imbalances, diabetes, gout, or abnormal heart rhythms.
Clinical Use Cases The provided sources do not offer dosage recommendations for this combination specifically for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dose adjustments should be made based on renal and hepatic function.
Side Effects
Common Side Effects:
- Headache, dizziness, edema (especially of the ankles and feet), fatigue, flushing, palpitations, and nausea.
Rare but Serious Side Effects:
- Angioedema, hypotension, Stevens-Johnson syndrome, hepatic encephalopathy, acute angle-closure glaucoma, worsening angina, myocardial infarction.
Long-Term Effects:
- Electrolyte imbalances (hypokalemia, hyponatremia).
Adverse Drug Reactions (ADR):
- Angioedema, severe hypotension, and hepatotoxicity require immediate medical attention.
Contraindications
- Hypersensitivity to amlodipine, indapamide, other sulfonamides, or dihydropyridines.
- Severe renal or hepatic impairment.
- Anuria, hypovolemia.
- Pregnancy and breastfeeding (generally not recommended).
- Concomitant use with aliskiren (especially in patients with diabetes or renal impairment).
Drug Interactions
- Other antihypertensives (additive hypotensive effect).
- Potassium-sparing diuretics (risk of hyperkalemia).
- NSAIDs (may reduce antihypertensive effect).
- Lithium (increased lithium levels).
- CYP3A4 inhibitors (may increase amlodipine levels).
- Alcohol (may enhance hypotensive effect).
- Grapefruit juice (may increase amlodipine levels).
- Corticosteroids, laxatives (risk of hypokalemia).
Pregnancy and Breastfeeding
- Not recommended during pregnancy due to potential fetal harm.
- Not recommended during breastfeeding as both drugs are excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Amlodipine: Calcium channel blocker; Indapamide: Thiazide-like diuretic.
- Side Effects: Edema, headache, dizziness, fatigue, flushing, nausea.
- Contraindications: Hypersensitivity, severe renal/hepatic impairment, pregnancy, breastfeeding.
- Drug Interactions: Other antihypertensives, potassium-sparing diuretics, NSAIDs, lithium.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: One tablet daily containing previously stabilized doses of each component.
- Monitoring Parameters: Blood pressure, renal function, electrolytes (especially potassium), liver enzymes.
Popular Combinations
- Although this itself is a popular combination, it may be sometimes prescribed with other antihypertensive agents like ACE inhibitors or ARBs if blood pressure control is inadequate.
Precautions
- General Precautions: Monitor blood pressure, renal function, and electrolytes.
- Specific Populations: Use with caution in elderly patients and patients with renal or hepatic impairment. Avoid in pregnancy and breastfeeding.
- Lifestyle Considerations: Encourage lifestyle modifications such as diet, exercise, and smoking cessation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Indapamide?
A: One tablet daily, orally, containing the fixed combination of amlodipine and indapamide corresponding to individually titrated component doses, preferably taken in the morning before a meal. It’s not intended for initial hypertension therapy.
Q2: What are the common side effects?
A: Common side effects include headache, dizziness, peripheral edema, flushing, palpitations, and fatigue.
Q3: Can this combination be used in patients with renal impairment?
A: It is contraindicated in severe renal impairment. Use cautiously in moderate renal impairment with appropriate dosage adjustments.
Q4: Is Amlodipine + Indapamide safe during pregnancy?
A: It is generally not recommended during pregnancy. Consult a physician.
Q5: What are the major drug interactions to be aware of?
A: Interactions can occur with other antihypertensives, potassium-sparing diuretics, NSAIDs, and lithium.
Q6: What should patients be monitored for during therapy?
A: Blood pressure, renal function, electrolyte levels (potassium), liver function tests.
Q7: What is the mechanism of action of this combination?
A: Amlodipine blocks calcium channels causing vasodilation. Indapamide increases sodium and water excretion, reducing blood volume.
Q8: Can I start a patient directly on Amlodipine + Indapamide combination therapy?
A: No. This combination is meant as a substitution therapy for patients already stabilized on the individual components.
Q9: How is amlodipine + indapamide administered?
A: Orally, preferably once a day in the morning with water before a meal. Tablets should be swallowed whole and not chewed.
Q10: What if a patient misses a dose?
A: If a patient misses a dose, the missed dose should be skipped, and the next dose should be taken at the regular scheduled time. Patients should not double the dose.
