“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Sunday, July 27, 2025

Indapamide


International Nonproprietary Name (INN): Indapamide
Drug Class: Thiazide-like diuretic; antihypertensive
Pharmacological Group: Sulfonamide derivative
ATC Code: C03BA11
Legal Status: Prescription-only medication
Common Brand Names: Natrilix, Lozol, Tertensif, Natrilix SR, Fludex

Mechanism of Action

Indapamide is a thiazide-like diuretic and antihypertensive that works through dual mechanisms:

  1. Renal Diuretic Action:
    It inhibits sodium and chloride reabsorption at the cortical diluting segment of the distal convoluted tubule in the nephron. This action leads to increased urinary excretion of sodium and water, resulting in reduced plasma volume and lower blood pressure. It also promotes mild potassium and magnesium loss while increasing calcium reabsorption.

  2. Vasodilatory (Antihypertensive) Action:
    Beyond its diuretic effects, indapamide directly affects vascular smooth muscle by enhancing nitric oxide-mediated vasodilation and reducing peripheral vascular resistance. This vasodilatory effect is independent of its diuretic properties and contributes significantly to its antihypertensive efficacy.

Therapeutic Indications

  1. Essential Hypertension (Primary):
    Indicated for the management of mild to moderate hypertension, either as monotherapy or in combination with other antihypertensives.

  2. Chronic Heart Failure (CHF):
    Used as an adjunct in the management of congestive heart failure to reduce preload through fluid reduction.

  3. Edematous Conditions (off-label use):
    Occasionally used for edema associated with renal or hepatic disorders, though not a first-line agent for this purpose.

  4. Nephrolithiasis due to Hypercalciuria (off-label):
    Occasionally used to reduce urinary calcium excretion.

Formulations and Dosage

Available Forms:

  • Immediate-release tablets: 2.5 mg

  • Sustained-release tablets: 1.5 mg (indapamide SR or indapamide retard)

Recommended Adult Dosing:

  • Hypertension:

    • Standard release: 2.5 mg orally once daily in the morning

    • Sustained release: 1.5 mg once daily

    • Titrate according to blood pressure response; max effect often seen within 1–2 weeks

  • Heart failure (adjunctive):

    • Standard: 2.5 mg daily

    • Use with caution and under specialist supervision

Elderly:
No special dosage adjustment required; monitor renal function and electrolyte balance closely.

Pediatric use:
Not recommended; safety and efficacy not established in children.

Pharmacokinetics

  • Absorption: Rapid and nearly complete after oral administration

  • Bioavailability: Approximately 93% (immediate-release)

  • Peak Plasma Concentration:

    • IR: ~1–2 hours

    • SR: 8–12 hours

  • Protein Binding: ~79%

  • Metabolism: Extensively hepatic (mainly via oxidation and hydrolysis)

  • Elimination Half-life:

    • IR: ~14–18 hours

    • SR: ~18–25 hours

  • Excretion:

    • 60–70% via urine (mainly as metabolites)

    • 20–30% via feces

Contraindications

  • Hypersensitivity to indapamide, sulfonamides, or any excipients

  • Severe renal impairment (creatinine clearance <30 mL/min)

  • Hepatic encephalopathy or severe liver disease

  • Hypokalemia

  • Lactation

  • Pregnancy (especially second and third trimesters, unless clearly necessary)

Warnings and Precautions

  1. Electrolyte Imbalances:

    • Hypokalemia is the most significant concern; monitor serum potassium regularly.

    • Hyponatremia and hypomagnesemia may also occur.

    • Risk is higher in the elderly, those on concomitant diuretics, or with vomiting/diarrhea.

  2. Volume Depletion and Hypotension:

    • May cause postural hypotension, especially in volume-depleted patients.

    • Titrate dosage carefully and monitor for dizziness or syncope.

  3. Gout:

    • May increase serum uric acid levels and precipitate gout attacks.

  4. Diabetes Mellitus:

    • May worsen glycemic control in susceptible individuals; monitor blood glucose levels.

  5. Lipid Metabolism:

    • Mild increase in cholesterol and triglycerides can occur, but clinical significance is debated.

  6. Renal Function:

    • Requires close monitoring in patients with renal insufficiency.

    • Discontinue if there is a significant decline in renal function.

  7. Photosensitivity:

    • Risk of skin photosensitivity reactions; patients should be advised to use sunscreen.

  8. Hepatic Impairment:

    • Risk of hepatic encephalopathy due to electrolyte disturbances; contraindicated in severe hepatic disease.

Adverse Effects

Common (>1%):

  • Hypokalemia

  • Fatigue

  • Headache

  • Dizziness

  • Muscle cramps

  • Nausea

  • Polyuria (initial phase)

Uncommon to Rare:

  • Hyponatremia

  • Hypercalcemia

  • Hypomagnesemia

  • Hyperuricemia

  • Skin rash, pruritus, or urticaria

  • Increased blood glucose

  • Arrhythmias (due to electrolyte disturbances)

  • Pancreatitis (very rare)

  • Thrombocytopenia or agranulocytosis (very rare)

  • Photosensitivity reactions

Drug Interactions

1. Potassium-lowering drugs:

  • Increases risk of hypokalemia when combined with corticosteroids, amphotericin B, β2-agonists, or laxatives.

2. Potassium-sparing diuretics or potassium supplements:

  • May balance potassium levels, but monitor closely to avoid hyperkalemia.

3. ACE inhibitors / ARBs:

  • Increased risk of hypotension and renal impairment; especially in volume-depleted patients.

  • Start with low doses and correct electrolyte imbalances before initiation.

4. NSAIDs:

  • Reduce diuretic and antihypertensive effect; increase nephrotoxicity risk.

  • Use lowest effective NSAID dose for shortest duration.

5. Lithium:

  • Indapamide reduces lithium clearance → risk of lithium toxicity.

  • Avoid combination or monitor lithium serum levels closely.

6. Antidiabetic drugs (e.g., insulin, sulfonylureas):

  • May blunt glucose-lowering effect; monitor blood glucose.

7. Digitalis glycosides (e.g., digoxin):

  • Hypokalemia increases digoxin toxicity risk; monitor potassium and digoxin levels.

8. Alcohol:

  • Potentiates orthostatic hypotension

Monitoring Parameters

  • Blood pressure (baseline and periodically)

  • Serum electrolytes: potassium, sodium, magnesium, calcium

  • Renal function: creatinine, urea

  • Blood glucose and uric acid (especially in diabetics or those with gout)

  • Lipid profile (if used long-term)

Pregnancy and Lactation

  • Pregnancy:

    • Not recommended; may impair fetal perfusion.

    • Use only if clearly needed under medical supervision.

  • Lactation:

    • Contraindicated; indapamide is excreted in breast milk and may suppress lactation or pose risk to infant.

Toxicity and Overdose

Symptoms of Overdose:

  • Nausea, vomiting

  • Electrolyte imbalance (especially hypokalemia)

  • Hypotension

  • Dehydration

  • CNS effects: drowsiness, confusion

  • Muscle weakness or cramps

Management:

  • Supportive therapy

  • Rehydration with isotonic saline

  • Correction of electrolyte disturbances

  • Monitor ECG and vital signs

  • Dialysis is not significantly effective due to high protein binding

Clinical Trials and Evidence

  1. HYVET Study (Hypertension in the Very Elderly Trial):

    • Indapamide (SR) significantly reduced stroke risk, all-cause mortality, and cardiovascular mortality in patients aged ≥80 with systolic hypertension.

  2. ADVANCE Trial (Action in Diabetes and Vascular Disease):

    • Indapamide plus perindopril combination reduced major cardiovascular events in patients with type 2 diabetes, regardless of baseline BP.

  3. PATS Study (Post-Stroke Antihypertensive Treatment Study):

    • Demonstrated reduction in stroke recurrence with indapamide treatment in Chinese patients.

Storage and Stability

  • Store at room temperature (15–25°C)

  • Protect from moisture and light

  • Keep out of reach of children

Comparison with Related Diuretics

Vs. Hydrochlorothiazide (HCTZ):

  • Indapamide has longer duration of action (once daily)

  • More potent antihypertensive effect at lower doses

  • Less metabolic disturbance (lipids, glucose)

Vs. Chlorthalidone:

  • Comparable efficacy in blood pressure lowering

  • Indapamide has less risk of hypokalemia and glucose intolerance

Vs. Loop diuretics (e.g., furosemide):

  • Indapamide is preferred in hypertension, whereas loop diuretics are used in volume overload states

Patient Counseling Points

  • Take dose in the morning to reduce nocturia

  • Report signs of dizziness, fainting, or irregular heartbeat

  • Avoid excessive sun exposure or use sunscreen (photosensitivity risk)

  • Maintain adequate hydration, especially during hot weather

  • Adhere to scheduled laboratory monitoring

  • Avoid high-sodium diet or potassium supplements unless advised

  • Inform healthcare providers about all medications to avoid interactions




on
Labels:

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)