Indapamide is an oral antihypertensive/diuretic medication used primarily to treat high blood pressure (hypertension) and edema (fluid retention). It belongs to a class of drugs known as thiazide-like diuretics, though it's structurally different from true thiazide diuretics.

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:

• In the absence of comorbidities (such as cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc.), the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High
• Blood Pressure in Adults suggests that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferable options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke).
• ARBs and ACE inhibitors are also suitable for monotherapy.
• Combination therapy is initially favoured in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk 10%) and may be necessary to reach blood pressure objectives.

Off Label Use of Indapamide in Adults:

• Calcium nephrolithiasis

Indapamide Dose in adults:

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

• Indapamide is sometimes used to treat calcium kidney stones, even though that's not its main purpose (off-label use).
• The suggested dose for this is 2.5 mg taken by mouth once a day.
• This recommendation comes from the American Urological Association (AUA) as of 2014.

Indapamide Dose in the treatment of Edema:

For treating swelling (edema) with Indapamide:

• Start with 2.5 mg taken by mouth once a day.
• If after a week there's no improvement, the dose can be raised to 5 mg a day.
• But, it's not recommended to go over 5 mg a day. Higher doses don't add much benefit and can lead to issues with the body's salt balance.

Indapamide dose in the treatment of Hypertension:

For treating high blood pressure with Indapamide:

• Start with 1.25 mg taken by mouth once a day.
• If needed, the dose can be increased every 4 weeks, but not more than 5 mg a day.
• Typically, most people take between 1.25 to 2.5 mg a day, as suggested by the ACC/AHA in 2017.

Pregnancy Risk Factor B

• Animal studies didn't show any harmful effects on pregnancy.
• However, diuretics like Indapamide do reach the baby inside the womb.
• If a pregnant woman takes them, the baby could face issues like yellowing of the skin (jaundice), low platelet count, or other side effects that adults experience.
• It's not a good idea to use diuretics during a regular pregnancy. But, if there's swelling due to medical problems, it might be considered.
• If used during pregnancy, the baby needs close monitoring.

Indapamide use during breastfeeding:

• We don't know if Indapamide gets into breast milk.
• If someone needs to take this medicine, the company that makes it suggests stopping breastfeeding.

Indapamide Dose in Kidney Disease:

For people with different kidney functions, the suggested doses of Indapamide are:

• If the kidneys filter at a rate of 10 to 50 mL/minute: Take 1.25 to 2.5 mg once a day.
• If the kidneys filter at a rate less than 10 mL/minute: The same dose (1.25 to 2.5 mg once a day) is suggested, but there's not much data to fully support this.
• For people on hemodialysis (a kidney treatment): The suggested dose is 1.25 to 2.5 mg once a day. Again, there isn't a lot of data, and the medicine doesn't get removed during dialysis.

Indapamide Dose in Liver disease:

• The company that makes the medicine hasn't given specific dosage changes for people with liver problems.
• So, if someone has liver issues, they should be extra careful when using this medicine.

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:

People shouldn't take this medicine if they:

• Are allergic to indapamide, its ingredients, or drugs made from sulfonamides.
• Cannot produce urine (anuria).

However, while the official US guidelines warn about allergies to other sulfonamide drugs, some experts disagree with this. There's more detail on this in the "Warnings/Precautions" section.

In Canada, they also say not to use the medicine if:

• Kidneys function very poorly (filtering less than 30 mL/minute).
• Having serious liver problems or liver-related brain issues.
• Having very low potassium levels.
• Taking certain heart drugs that might lead to dangerous heart rhythms.
• Pregnant or breastfeeding.
• Having rare genetic issues related to digesting certain sugars (like lactose).

Warnings and precautions

Electrolyte disturbances:

• There have been cases of very low sodium and potassium levels, especially in older women, even when taking the suggested dose.
• The chance of this happening might increase with higher doses, so it's best to use the smallest effective dose.
• Imbalances like low chlorine levels leading to an overly alkaline blood, low magnesium, or high calcium can also happen.
• It's important to check the levels of these electrolytes from time to time while on the medication.

Photosensitivity

• Taking this medicine might make you more sensitive to sunlight.
• This means you could get sunburned more easily.

Allergy to sulfonamide ("sulfa")

• Many medicines that have a "sulfonamide" structure come with a warning that they shouldn't be used by people who've had allergic reactions to "sulfa" drugs.
• It was believed that if you're allergic to one type of sulfonamide drug, you might react to others too.
• But recent understanding shows that allergic reactions across different sulfonamide drugs are rare or might not happen at all.
• Allergic reactions due to the body producing antibodies (like anaphylaxis) are unlikely with non-antibiotic sulfonamides.
• However, other types of reactions (like certain rashes) aren't fully understood, so we can't say for sure if they'll happen or not.
• If someone had a severe reaction to a sulfonamide drug before (like Stevens-Johnson syndrome), some doctors prefer to avoid giving any drug with a sulfonamide structure.

Insufficiency of the adrenal glands:

• If someone has adrenal insufficiency, a condition where the adrenal glands don't produce enough hormones (known as Addison's disease), they shouldn't use diuretics like Indapamide to treat high blood pressure.
• Instead, adjusting their hormone treatments or using other blood pressure medicines is a better option.

Bariatric surgery

• After weight loss (bariatric) surgery, patients should not use diuretics like Indapamide right away.
• These medicines could cause dehydration and imbalances in body salts.
• However, once patients can drink enough fluids, these medicines might be used again if needed.

Diabetes:

• People with diabetes or those close to developing it should be careful when using this medicine.
• It might affect their blood sugar levels.

Gout

• People with a history of gout, a family tendency for gout, or long-term kidney problems might get gout attacks when using this medicine.

Hepatic impairment

• People with serious liver problems should be careful when using this medicine.
• Especially in patients with a condition called cirrhosis, because the medicine might cause imbalances in body salts and acids which can lead to brain problems related to the liver.

Hypercholesterolemia:

• For people with moderate to high cholesterol levels, be careful when using this medicine.
• While some similar medicines (thiazide diuretics) can raise cholesterol levels, indapamide, which is similar but a bit different, hasn't been shown to negatively impact cholesterol.

Hypokalemia

• People with low potassium levels should be cautious when using this medicine.
• They should get their potassium levels back to normal before starting the medication.

Renal impairment

• People with serious kidney problems should be careful when using this medicine.

Systemic lupus erythematosus (SLE):

• This medicine might make the symptoms of Systemic Lupus Erythematosus (SLE), a type of autoimmune disease, worse or even trigger it in some people.

Indapamide: Drug Interaction

Risk Factor C (Monitor therapy)
Ajmaline	Sulfonamides might make ajmaline more harmful or poisonous. In particular, there may be an elevated risk for cholestasis.
Alcohol (Ethyl)	Increases the effectiveness of thiazide and thiazide-like diuretics in lowering orthostatic blood pressure.
Alfuzosin	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Allopurinol	The possibility of allergic or hypersensitive reactions to allopurinol may be increased by thiazide and thiazide-like diuretics. The serum concentration of Allopurinol may rise in response to thiazides and thiazide-like diuretics. In particular, Thiazide Diuretics may raise Oxypurinol's levels, an active metabolite of Allopurinol.
Aminolevulinic Acid (Topical)	Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Topical).
Amphetamines	May lessen the effectiveness of antihypertensive agents.
Angiotensin-Converting Enzyme Inhibitors	Angiotensin-Converting Enzyme Inhibitors' hypotensive effects may be enhanced by thiazide and thiazide-like diuretics. Angiotensin-Converting Enzyme Inhibitors' nephrotoxic effects may be increased by thiazide and thiazide-like diuretics.
Anticholinergic Agents	May raise the levels of thiazide and thiazide-like diuretics in the blood.
Antidiabetic Agents	The therapeutic value of anti-diabetic agents may be diminished by thiazide and thiazide-like diuretics.
Antidiabetic Agents	The therapeutic benefit of anti-diabetic agents may be reduced by hyperglycemia-associated agents.
Antipsychotic Agents (Second Generation [Atypical])	Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]).
Barbiturates	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Benperidol	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Beta2-Agonists	Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact.
Brigatinib	May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents.
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Calcium Salts	The excretion of calcium salts may be decreased by thiazide and thiazide-like diuretics. Metabolic alkalosis can also be brought on by continued concurrent usage.
CarBAMazepine	Thiazide and Thiazide-Like Diuretics may intensify CarBAMazepine's negative/toxic effects. Particularly, there could be a higher risk of hyponatremia.
Cardiac Glycosides	Cardiac Glycosides may have an increased negative or toxic effect when used with thiazide and thiazide-Like Diuretics. Particularly, the hypokalemic and hypomagnesemic effects of thiazide diuretics may worsen cardiac glycoside toxicity.
Corticosteroids (Orally Inhaled)	Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact.
Corticosteroids (Systemic)	Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact.
Cyclophosphamide	Thiazide and Thiazide-Like Diuretics may intensify Cyclophosphamide's harmful or hazardous effects. Particularly, granulocytopenia could be worsened.
Dexketoprofen	Sulfonamides' harmful or poisonous effects could be amplified.
Dexmethylphenidate	Can lessen an antihypertensive drug's therapeutic impact.
Diacerein	Could make diuretics' therapeutic effects stronger. Particularly, there may be a higher chance of hypokalemia or dehydration.
Diazoxide	Thiazide and Thiazide-Like Diuretics may intensify Diazoxide's harmful or toxic effects.
Diazoxide	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Dichlorphenamide	The hypokalemic impact of dichlorphenamide may be enhanced by thiazide and thiazide-like diuretics.
DULoxetine	The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications.
Herbs (Hypertensive Properties)	May lessen the effectiveness of antihypertensive agents.
Herbs (Hypotensive Properties)	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Hypotension-Associated Agents	The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications.
Ipragliflozin	The toxic and harmful effects of thiazide and thiazide-like diuretics may be increased. In particular, there may be an elevated risk for intravascular volume depletion.
Ivabradine	The arrhythmogenic impact of ivabradine may be enhanced by thiazide and thiazide-like diuretics.
Levodopa-Containing Products	Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications.
Licorice	Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact.
Lormetazepam	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Methenamine	The therapeutic effects of methenamine may be diminished by thiazide and thiazide-like diuretics.
Methylphenidate	May lessen the effectiveness of antihypertensive agents.
Molsidomine	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Multivitamins/Fluoride (with ADE)	May intensify the effects of thiazide and thiazide-like diuretics on hypercalcemia.
Multivitamins/Minerals (with ADEK, Folate, Iron)	The effect of multivitamins and minerals on hypercalcemia may be enhanced by thiazide and thiazide-like diuretics (with ADEK, Folate, Iron).
Multivitamins/Minerals (with AE, No Iron)	The serum concentration of multiple vitamins and minerals may rise after taking thiazide and thiazide-like diuretics (with AE, No Iron). Particularly, thiazide diuretics may reduce calcium excretion, and long-term concurrent usage may result in metabolic alkalosis.
Naftopidil	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Neuromuscular-Blocking Agents (Nondepolarizing)	The neuromuscular-blocking action of neuromuscular-blocking agents may be enhanced by thiazide and thiazide-like diuretics (Nondepolarizing).
Nicergoline	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Nicorandil	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Nitroprusside	Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications.
Nonsteroidal Anti-Inflammatory Agents	Nonsteroidal Anti-Inflammatory Agents' nephrotoxic effects may be intensified by thiazide and thiazide-like diuretics. Thiazide and Thiazide-Like Diuretics may have less of a therapeutic impact when used with nonsteroidal anti-inflammatory drugs.
Opioid Agonists	Could make diuretics' harmful or toxic effects worse. Opioid antagonists may reduce diuretics' therapeutic benefit.
Oxcarbazepine	Thiazide and Thiazide-Like Diuretics may intensify OXcarbazepine's negative/toxic effects. Particularly, there could be a higher risk of hyponatremia.
Pentoxifylline	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Pholcodine	Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications.
Phosphodiesterase 5 Inhibitors	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Porfimer	The photosensitizing effect of Porfimer may be strengthened by photosensitizing agents.
Prostacyclin Analogues	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Quinagolide	The hypotensive effects of blood pressure-lowering medications may be strengthened.
Reboxetine	Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact.
Selective Serotonin Reuptake Inhibitors	The hyponatremic effects of thiazide and thiazide-like diuretics may be enhanced.
Toremifene	Toremifene's hypercalcemic impact may be enhanced by thiazide and thiazide-like diuretics.
Verteporfin	Verteporfin's photosensitizing effect may be strengthened by photosensitizing agents.
Vitamin D Analogs	The hypercalcemic impact of vitamin D analogues may be enhanced by thiazides and thiazide-like diuretics.
Yohimbine	May lessen the effectiveness of antihypertensive agents.
Risk Factor D (Consider therapy modification)
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.
Bile Acid Sequestrants	The absorption of thiazide and thiazide-like diuretics may be reduced. Also reduced is the diuretic reaction.
Dofetilide	The QTc-prolonging action of dofetilide may be enhanced by thiazide and thiazide-like diuretics. The blood concentration of Dofetilide may rise in response to thiazide and thiazide-like diuretics. Management: Despite the fact that hydrochlorothiazide is clearly listed as being contraindicated, the risk certainly applies to all thiazide and thiazide-like diuretics and may even be larger when using chlorthalidone or bendroflumethiazide. When feasible, take into account alternatives.
Lithium	The excretion of lithium may be reduced by thiazide and thiazide-like diuretics.
Obinutuzumab	May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.
Sodium Phosphates	Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status.
Topiramate	The hypokalemic impact of topiramate may be enhanced by thiazide and thiazide-like diuretics. The blood concentration of topiramate may rise in response to thiazide and thiazide-like diuretics. When using a thiazide diuretic, monitor for elevated topiramate levels and any negative consequences (such as hypokalemia). Serum potassium levels should be closely watched when receiving concurrent treatment. There may be a need to lower topiramate dosage.
Risk Factor X (Avoid combination)
Aminolevulinic Acid (Systemic)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).
Bromperidol	Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.
Fexinidazole [INT]	Fexinidazole [INTability ]'s to induce arrhythmias may be enhanced by the use of thiazide and thiazide-like diuretics.
Levosulpiride	Thiazide and Thiazide-Like Diuretics may intensify Levosulpiride's negative/toxic effects.
Mecamylamine	Sulfonamides may intensify Mecamylamine's harmful or hazardous effects.
Promazine	Promazine's ability to prolong QTc may be enhanced by thiazide and thiazide-like diuretics.

Monitoring parameters:

Blood Pressure: Check it while standing and sitting.

Blood Tests: Look at:

• Electrolytes (like potassium and sodium)
• Liver function
• Kidney function
• Uric acid levels

Daily Checks:

• Weight
• Amount of fluids taken in and out (I and O) to see how much fluid is lost.

Guidelines for High Blood Pressure (Hypertension):

• ACC/AHA Guidelines (2017):
  • If you have confirmed high blood pressure AND heart disease or a high 10-year risk of heart-related issues:
    • Aim for a blood pressure below 130/80 mm Hg.
  • If you have high blood pressure BUT no high risk of heart-related issues:
    • A blood pressure below 130/80 mm Hg is still a good target.

For People with Diabetes and High Blood Pressure:

• American Diabetes Association (ADA) Guidelines (2019):
  • Age 18-65 without heart disease and low 10-year heart disease risk:
    • Aim for a blood pressure below 140/90 mm Hg.
  • Age 18-65 with heart disease or high 10-year heart disease risk:
    • A blood pressure below 130/80 mm Hg might be good, but only if safe.
  • Age over 65 and in good or moderate health:
    • Aim for a blood pressure below 140/90 mm Hg.
  • Age over 65 and in poor health:
    • Aim for a blood pressure below 150/90 mm Hg.

How to administer Indapamide?

• You can take it with or without food.
• If it upsets your stomach, taking it with food or milk might help.
• It's best to take it earlier in the day to avoid needing to go to the bathroom at night.

Mechanism of action of Indapamide:

• Its main action is in a specific part of the kidney called the proximal segment of the distal tubule.
• It doesn't really change the speed at which the kidneys filter blood or the blood flow within the kidneys.
• Like other water pills, it helps the body get rid of salt (sodium and chloride) and water by affecting how salt moves in the kidney.

Absorption:

• It's quickly and fully absorbed into the body.

Distribution:

• The volume it spreads across in the body is 25 liters.

Protein Binding:

• Between 71% to 79% of the drug binds to proteins in the blood.

Metabolism:

• The liver breaks it down a lot.

Bioavailability:

• 93% of the drug is available in the body after taking it.

Half-life:

• It has two stages of elimination - 14 hours and 25 hours.

Peak Time:

• It reaches its highest level in the blood in about 2 hours.

Excretion:

• About 70% is removed through urine (with 7% unchanged in the first 48 hours) and 23% is removed through feces.

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:

Indapamide 2.5 mg Tablets
Baplow	Tagma Pharma (Pvt) Ltd.
Hypomide	Don Valley Pharmaceuticals (Pvt) Ltd.
Indurin	Paramount Pharmaceuticals
Natrilix	Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd.

Indapamide 1.5 mg Tablets
Hypomide	Don Valley Pharmaceuticals (Pvt) Ltd.
Natrilix	Servier Research & Pharmaceuticals Pakistan (Pvt) Ltd.