Indapamide is a thiazide diuretic that is used in the treatment of mild to moderate hypertension as monotherapy or in combination with other drugs.

Indapamide Uses:

• Heart failure:

  • Treatment of edema in heart failure

• Hypertension:

  • Management of mild to moderate hypertension

Guideline recommendations:

• • • The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends if monotherapy is warranted, in the absence of comorbidities (eg, cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc), that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke).
    • ACE inhibitors and ARBs are also acceptable for monotherapy.
    • Combination therapy may be required to achieve blood pressure goals and is initially preferred in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk ≥10%).

• Off Label Use of Indapamide in Adults:

  • Calcium nephrolithiasis

Indapamide dose in adults:

Indapamide Dose in the treatment of Calcium nephrolithiasis (off-label):

• Oral: 2.5 mg once daily.

Indapamide Dose in the treatment of Edema:

• Oral: Initial: at 2.5 mg daily;
• if the inadequate response after 1 week, may increase the dose to 5 mg daily.

Note:

• There is little therapeutic benefit to increasing the dose >5 mg daily; there is, however, an increased risk of electrolyte disturbances.

Indapamide dose in the treatment of Hypertension:

• Oral: Initial: at 1.25 mg once daily;
• titrate as needed every 4 weeks up to 5 mg once daily.
• Usual dosage range:
  • 1.25 to 2.5 mg once daily.

Pregnancy Risk Factor B

• In animal reproduction studies, adverse events were not seen.
• The placenta is crossed by diuretics and they are found in cord blood. Use by mothers may lead to neonatal or fetal jaundice, thrombocytopenia, or other adverse reactions in adults.
• Normal pregnancies are not a good time to use diuretics.
• Use may be considered if edema is caused by pathologic reasons (as in the patient is not pregnant).

Indapamide use during breastfeeding:

• It is unknown if breast milk contains indapamide.
• The manufacturer suggests that breastfeeding should be stopped if therapy is required.

Indapamide Dose in Kidney Disease:

• There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended:

  • GFR 10 to 50 mL/minute:

    • 1.25 to 2.5 mg once daily.

  • GFR <10 mL/minute:

    • 1.25 to 2.5 mg once daily (limited data).

  • Hemodialysis:

    • 1.25 to 2.5 mg once daily (limited data);
    • not dialyzable.

Indapamide Dose in Liver disease:

• There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Common Side Effects of Indapamide:

• Central nervous system:

  • Agitation
  • Anxiety
  • Dizziness
  • Fatigue
  • Headache
  • Irritability
  • Lethargy
  • Malaise
  • Nervousness (dose-dependent)
  • Pain
  • Paresthesia
  • Tension

• Endocrine & metabolic:

  • Hypokalemia

• Infection:

  • Infection

• Neuromuscular & skeletal:

  • Back pain
  • Muscle cramps
  • Muscle spasm
  • Weakness

• Respiratory:

  • Rhinitis

Less Common Side Effects of Indapamide:

• Cardiovascular:

  • Cardiac Arrhythmia
  • Chest Pain
  • Flushing
  • Orthostatic Hypotension
  • Palpitations
  • Peripheral Edema
  • Vasculitis
  • Ventricular Premature Contractions

• Central Nervous System:

  • Depression
  • Drowsiness
  • Hypertonia
  • Insomnia
  • Vertigo

• Dermatologic:

  • Pruritus
  • Skin Rash
  • Urticaria

• Endocrine & Metabolic:

  • Decreased Libido
  • Glycosuria
  • Hyperglycemia
  • Hyperuricemia
  • Hypochloremia
  • Hyponatremia
  • Weight Loss

• Gastrointestinal:

  • Abdominal Cramps
  • Abdominal Pain
  • Anorexia
  • Constipation
  • Diarrhea
  • Dyspepsia
  • Gastric Irritation
  • Nausea
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Nocturia

• Ophthalmic:

  • Blurred Vision
  • Conjunctivitis

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine
  • Polyuria

• Respiratory:

  • Cough
  • Flu-Like Symptoms
  • Pharyngitis
  • Rhinorrhea
  • Sinusitis

Contraindications to Indapamide:

• Hypersensitivity/hyperresponsiveness to indapamide or any component of the formulation or sulfonamide-derived drugs; anuria

Notice:

• Although the FDA-approved product labeling states that this medication is contraindicated with other sulfonamide-containing drug groups, the scientific basis of this statement has been challenged.

Canadian labeling: Additional contraindications not in US labeling

• Severe renal failure (CrCl <30 mL/minute);
• Hepatic Encephalopathy
• Grave hepatic impairment
• Hypokalemia
• Use of antiarrhythmic drugs in conjunction with torsade des pointes
• pregnancy;
• Breast-feeding
• Galactose intolerance is a hereditary problem
• glucose-galactose malabsorption,
• or Lapp lactase deficiency

Warnings and precautions

• Electrolyte disturbances:

  • At recommended doses, severe hyponatremia and hypokalemia have been reported (especially in elderly women).
  • Dose-dependent risk means that you should use the lowest dose.
  • Hypochloremic alkalosis can also be caused by hypomagnesemia or hypercalcemia.
  • During therapy, monitor your electrolytes regularly.

• Photosensitivity

  • Photosensitization can occur.

• Allergy to sulfonamide ("sulfa")

  • FDA-approved product labels for medications that contain a sulfonamide chemical group include a wide contraindication for patients who have had an allergic reaction to sulfonamides in the past.
  • Cross-reactivity is possible between members of one class (e.g., two antibiotics sulfonamides).
  • Crossreactivity concerns have been raised for all compounds with the sulfonamide structure.
  • A deeper understanding of allergic mechanisms suggests that cross-reactivity between nonantibiotic and antibiotic sulfonamides is unlikely.
  • Nonantibiotic sulfonamides are not likely to cause anaphylaxis (a mechanism of antibody production causing cross-reaction).
  • The T-cell-mediated type IV reactions (eg, maculopapular skin rash) are less understood.
  • It is difficult to exclude this possibility based on current knowledge. 
  • Some clinicians avoid these classes in cases of severe reactions (Stevens-Johnson syndrome/TEN).

• Insufficiency of the adrenal glands:

  • Patients with primary adrenal disease (Addison disease) should not be treated with diuretics to lower blood pressure.
  • Adjustment of glucocorticoid/mineralocorticoid therapy and/or the use of other antihypertensive agents is preferred to treat hypertension.

• Bariatric surgery

  • Dehydration
    • Do not take diuretics during the first 24 hours after bariatric surgery.
    • Electrolyte disturbances or dehydration can occur.
  • If necessary, diuretics can be resumed if oral fluid intake goals have been met.

• Diabetes:

  • Patients with diabetes mellitus or prediabetes should be cautious.
  • You may experience a change in their glucose control.

• Gout

  • Gout can occur in certain patients who have a history of gout or are suffering from chronic renal failure.

• Hepatic impairment

  • Patients with severe hepatic dysfunction should be cautious; avoid acid/base and electrolyte imbalances in cirrhosis as they could lead to hepatic neuropathy.

• Hypercholesterolemia:

  • Patients with high or moderate cholesterol levels should be cautious.
  • Thiazide diuretics can increase cholesterol concentrations.
  • However, Indapamide (a diuretic-like thiazide) has not been shown adversely to affect lipids.

• Hypokalemia

  • Hypokalemia patients should be treated with caution.

• Renal impairment

  • For severe renal disease, use caution.

• Systemic lupus erythematosus (SLE):

  • It can trigger or exacerbate SLE.

Indapamide: Drug Interaction

Monitoring parameters:

• Blood pressure (both standing and sitting/supine);
• serum electrolytes,
• hepatic function,
• renal function, uric acid;
• assess weight,
• intake and output (I and O) reports daily to determine fluid loss

Hypertension:

• The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known cardiovascular disease or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%:

• Target blood pressure <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased ASCVD risk:

• Target blood pressure <130/80 mm Hg may be reasonable.

Diabetes and hypertension:

The American Diabetes Association (ADA) guidelines (ADA 2019):

• Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%:

  • Target blood pressure <140/90 mm Hg is recommended

• Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk >15%:

  • Target blood pressure <130/80 mm Hg may be appropriate if it can be safely attained

• Patients >65 years of age (healthy or complex/intermediate health):

  • Target blood pressure <140/90 mm Hg is recommended

• Patients >65 years of age (very complex/poor health):

  • Target blood pressure <150/90 mm Hg is recommended

How to administer Indapamide?

• Oral: May be administered without regard to meals.
• however, administration with food or milk may decrease GI adverse effects.
• Administer early in the day to avoid nocturia.

Mechanism of action of Indapamide:

• The diuretic effect of diuretics is located at the distal tubule's proximal segment.
• Like other diuretics, it does not seem to have any significant effect on renal blood flow or glomerular filter rate.
• It increases sodium, chloride, and water excretion by interfering in the transport of sodium ions across the renal tubular epithelium.

Absorption:

• Rapid and complete

Plasma Protein binding:

• 71% to 79%

Metabolism:

• Extensively hepatic

Bioavailability:

• 93%.

Half-life elimination:

• Biphasic: 14 and 25 hours

Time to peak:

• 2 hours

Excretion:

• Urine (~70%; 7% as unchanged drug within 48 hours); feces (23%)

International Brands of Indapamide:

• APO-Indapamide
• DOM-Indapamide
• Indapamide 1.25
• JAMP-Indapamide
• Lozide
• MYLANIndapamide
• PHL-Indapamide
• PMS-Indapamide
• PRO-Indapamide
• RIVAIndapamide
• TEVA-Indapamide
• TRIA-Indapamide
• Aldapres
• Alvonamid
• Amoron
• Apadex
• Arifon
• Damide
• Dapa
• Dapa-tabs
• Dapalix
• Dapamax
• Depermide
• Dipam
• Diuremid CR
• Diuremid SR
• Diurex
• Dixamid
• Extur
• Fludex
• Fludex SR
• Flux
• Frumeron
• Heimdall Diurex
• Hemidol
• Hidromax SR
• Hydroless
• Hypotense
• Icorvida SR
• Inco SR
• Indalix
• Indamax
• Indanorm
• Indap
• Indapamide-Eurogenerics
• Indapamide-Generics
• Indapen
• Indapress
• Indelix SR
• Indicontin Continus
• Inditor-SR
• Inpamide
• Insig
• Intril SR
• Ipamix
• Lorvas
• Lorvas SR
• Magniton-R
• Millibar
• Napamide
• Natrilex SR
• Natrilix
• Natrilix AP
• Natrilix Retard
• Natrilix SR
• Natrix
• Natrix SR
• Noranat
• Noranat SR
• Pamid
• Pretanix
• Rawel SR
• Rinalix
• Sicco
• Tandix
• Tertensif
• Tertensif SR
• Vazamide SR
• Xelix SR
• Zytrilix

Indapamide Brand Names in Pakistan: