Natrixam

• Essential (primary) hypertension
• Treatment of adults with elevated blood pressure when monotherapy is insufficient or when initial combination therapy is appropriate. Fixed-dose combination is indicated for improved blood-pressure control and adherence.
• Hypertension with high cardiovascular risk
• Patients requiring greater BP reduction or with coexisting conditions (e.g., elderly patients, isolated systolic hypertension) where a diuretic + calcium-channel blocker regimen is appropriate.
• Edema associated with heart failure (adjunct) — clinically accepted off-label in some settings when diuretic effect is required together with BP control (use with caution; treat underlying heart-failure recommendations supersede).
• Important note: Not indicated for hypertensive emergencies. Use for children is not established; use in pregnancy and lactation only when benefits outweigh risks (see Section 5).

General principles

• Oral administration once daily, preferably in the morning. Take with or without food. Maintain consistent administration time.

Typical recommended adult dosing (examples of commonly available fixed doses)

• Indapamide SR 1.5 mg + Amlodipine 5 mg — one tablet once daily.
• Titration/alternative strengths: If additional BP lowering needed, increase amlodipine to 10 mg daily (if available and tolerated) or add other agents per guidelines; do not double daily tablets to catch up missed doses.

Elderly

• Start at the lower recommended dose (e.g., indapamide 1.5 mg + amlodipine 5 mg once daily) and titrate cautiously. Monitor orthostatic hypotension, renal function, and electrolytes.

Renal impairment

• Mild–moderate (CrCl ≥30 mL/min): no routine dose adjustment; monitor renal function and electrolytes.
• Severe (CrCl <30 mL/min) or anuria: indapamide is generally contraindicated or should be used with extreme caution; consider alternative regimens. Amlodipine requires caution but may be used with monitoring. Consult local product monograph.

Hepatic impairment

• Mild–moderate hepatic impairment: use standard dose but monitor for increased exposure to amlodipine (amlodipine is extensively metabolized hepatic).
• Severe hepatic impairment: use with caution; consider dose reduction for amlodipine and close monitoring (risk of accumulation).

Pediatrics

• Safety and efficacy not established in children and adolescents — not recommended.

Missed dose

• If a dose is missed, take it as soon as remembered on the same day. Do not take two doses the same day to make up for a missed dose.

This fixed-dose combination produces complementary antihypertensive effects through two distinct mechanisms. Indapamide is a thiazide-like diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, promoting natriuresis and mild diuresis; it also exerts direct peripheral vasodilatory effects that reduce total peripheral resistance. Amlodipine is a long-acting dihydropyridine calcium-channel blocker that inhibits L-type calcium channels in vascular smooth muscle, producing arteriolar vasodilation and decreased peripheral vascular resistance. Together, the diuretic-mediated reduction in intravascular volume and the arterial vasodilation produce additive blood-pressure lowering with a lower dose requirement of each component than might be needed as monotherapy.

Indapamide

• Absorption: Well absorbed orally; sustained-release formulations provide prolonged plasma levels.
• Distribution: Moderately protein bound (~70–80%).
• Metabolism: Hepatic metabolism to inactive metabolites (predominantly non-CYP oxidative pathways).
• Elimination & half-life: Elimination mainly renal as metabolites; terminal half-life generally in the 14–25 hour range permitting once-daily dosing.

Amlodipine

• Absorption: Slowly and well absorbed (oral bioavailability ≈ 60–90%). Peak plasma concentrations occur ~6–12 hours post-dose.
• Distribution: Highly protein bound; large apparent volume of distribution.
• Metabolism: Extensively metabolized by hepatic CYP3A4 to inactive metabolites.
• Elimination & half-life: Long terminal elimination half-life (~30–50 hours), allowing once-daily dosing; excreted mainly as inactive metabolites in urine.

Combination considerations

• No clinically significant pharmacokinetic antagonism between the two agents; pharmacodynamic additivity is exploited therapeutically. Hepatic impairment may increase exposure to amlodipine; severe renal impairment affects indapamide handling.

• Pregnancy: Limited human data for the combination. Diuretics (including thiazide-like agents) may reduce plasma volume and placental perfusion; indapamide is generally avoided in pregnancy unless clearly necessary. Amlodipine data are limited; use only if potential benefits justify potential risks. Discuss risk vs benefit with the patient and consider alternative antihypertensives with more established pregnancy data when possible.
• Lactation: Both drugs may be excreted in breast milk in small amounts (indapamide and amlodipine metabolites may be present). Potential for adverse effects (electrolyte effects, hypotension) in nursing infants cannot be excluded. Consider discontinuing nursing or the drug depending on clinical need.

• Primary class: Antihypertensive fixed-dose combination.
• Components: Thiazide-like diuretic (indapamide) + Dihydropyridine calcium-channel blocker (amlodipine).
• Clinical role: Combination antihypertensive for improved BP control and adherence.

• Known hypersensitivity to indapamide, amlodipine, or any excipients.
• Severe hepatic impairment where amlodipine accumulation is hazardous (per local product guidance).
• Severe renal impairment for indapamide (anuria or CrCl < 30 mL/min) — check local labeling.
• Cardiogenic shock or unstable cardiac conditions where vasodilation could be harmful.
• Pregnancy and lactation: use only if clearly needed and after risk–benefit assessment.

• Volume depletion / electrolyte imbalance: Monitor for hyponatremia, hypokalemia, hypomagnesemia — especially in elderly, on concomitant diuretics, or with vomiting/diarrhea.
• Hypotension / orthostatic hypotension: Risk when initiating or increasing therapy; advise caution on standing and monitor blood pressure.
• Peripheral edema: Amlodipine commonly causes dose-related peripheral edema; may be reduced by combination with a diuretic.
• Exacerbation of angina: In patients with severe obstructive coronary disease, initiation may precipitate ischemia in rare cases — monitor carefully.
• Severe hepatic impairment: Amlodipine is metabolized in the liver; reduced clearance can increase exposure and adverse effects.
• Gout/ hyperuricemia: Indapamide may raise uric acid levels and precipitate gout.
• Diabetes & dyslipidemia: Indapamide can impair glucose tolerance and alter lipid profile; monitor glucose and lipids as indicated.
• Monitoring recommended: BP, renal function, electrolytes (K⁺, Na⁺), signs of edema, liver function tests in hepatic disease, and symptoms of hypotension.

Very common / common

• Peripheral edema (amlodipine)
• Dizziness, flushing
• Headache
• Fatigue
• Gastrointestinal disturbances (nausea, abdominal pain)
• Increased urination or mild diuresis (indapamide)

Less common / clinically important

• Hypotension, orthostatic dizziness
• Hypokalemia, hyponatremia, hypomagnesemia (indapamide) — may cause muscle cramps, weakness, arrhythmia risk.
• Palpitations, tachycardia (occasionally)
• Gout attacks due to hyperuricemia (indapamide)
• Gingival hyperplasia (rare, amlodipine)
• Hepatic enzyme elevations (rare)
• Allergic reactions, rash, photosensitivity (rare)

Timing & dose-dependence

• Amlodipine-related peripheral edema and flushing often occur early and are dose-related; indapamide metabolic changes (electrolytes) commonly appear within the first 1–2 weeks of therapy.

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, certain antivirals): May increase amlodipine plasma concentrations → enhanced hypotensive effects; monitor and consider dose reduction of amlodipine.
• CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine): May reduce amlodipine exposure → reduced efficacy.
• Other antihypertensives / vasodilators: Additive blood-pressure lowering → increased risk of symptomatic hypotension.
• Lithium: Indapamide may reduce renal lithium clearance → lithium toxicity; monitor serum lithium if co-administered.
• Digitalis glycosides / antiarrhythmics / QT-prolonging drugs: Hypokalemia from indapamide increases risk of arrhythmias and digitalis toxicity.
• NSAIDs / COX-2 inhibitors: May blunt antihypertensive effect of diuretics and impair renal function.
• Alcohol: May potentiate orthostatic hypotension.
• Drugs that lower potassium (e.g., loop/thiazide diuretics, corticosteroids, amphotericin): Additive hypokalemia risk; monitor electrolytes.
• Grapefruit juice: Not a major interaction for amlodipine but large amounts may affect CYP3A4—exercise caution.

• Guideline trend: Contemporary hypertension guidelines increasingly support initial combination therapy (two complementary agents) for patients with BP substantially above target and for improved early control; combinations such as diuretic + CCB are classically recommended for many patient phenotypes (including elderly and isolated systolic hypertension).
• Fixed-dose combos: Emphasis on fixed-dose single-tablet regimens to enhance adherence and simplify therapy.
• Safety: No major global class-wide safety restrictions specific to this combination in recent years; monitoring for standard class warnings (electrolytes, edema, hepatic function) remains recommended. Always consult the most recent local product monograph and national guidelines for region-specific recommendations or label changes.

• Store at controlled room temperature, typically 20°C to 25°C (allowed range commonly 15°C to 30°C) — follow local product label for exact permitted range.
• Protect from moisture and light; keep in original blister or container until use.
• Do not store in the bathroom or other high-humidity areas.
• Keep out of reach of children.
• Do not refrigerate or freeze. Discard after expiry date.