Schedule H

Oral

• Tablets: 25 mg, 50 mg, 100 mg

Fixed-Dose Combinations (FDCs) Available:

• Losartan + Hydrochlorothiazide (50/12.5 mg, 100/12.5 mg, 100/25 mg)

• Losartan + Amlodipine (50/5 mg, 50/2.5 mg)

• Losartan + Atenolol

• Losartan + Chlorthalidone

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension (Essential or Secondary)

Parameter Dose

Starting dose 50 mg orally once daily

Titration Increase after 2–4 weeks based on BP response

Usual maintenance dose 50–100 mg once daily (may be given in divided doses)

Maximum dose 100 mg/day

For Volume-Depleted Patients (on diuretics, salt restriction, diarrhoea):

Parameter Dose

Starting dose 25 mg orally once daily

Titration Increase gradually after correcting volume status

Usual maintenance dose 50–100 mg once daily

Maximum dose 100 mg/day

Clinical Notes:

• First-line option per ICMR Hypertension Guidelines 2020 (along with CCBs, ACE inhibitors, thiazides)

• Can be taken with or without food; no significant food interaction

• May be combined with thiazide diuretics, CCBs, or beta-blockers for improved BP control

• Active metabolite (E-3174) contributes significantly to antihypertensive effect; formed via CYP2C9

• BP lowering effect evident within 1 week; maximum effect at 3–6 weeks

1. Diabetic Nephropathy in Type 2 Diabetes Mellitus (with Proteinuria and Hypertension)

Parameter Dose

Starting dose 50 mg orally once daily

Titration Increase to 100 mg once daily based on BP response and tolerability

Usual maintenance dose 100 mg once daily

Maximum dose 100 mg/day

Clinical Notes:

• Evidence-based renoprotective effect: delays progression to ESRD (RENAAL trial)

• Target dose of 100 mg/day recommended for maximal nephroprotection

• Reduces proteinuria independent of BP lowering effect

• Monitor serum creatinine and potassium closely (especially in first 1–3 months)

• Acceptable up to 30% rise in creatinine from baseline if stabilises

• May be combined with dihydropyridine CCB for additional BP control; avoid combining with ACE inhibitor routinely

1. Heart Failure with Reduced Ejection Fraction (HFrEF) — When ACE Inhibitor Not Tolerated

Parameter Dose

Starting dose 12.5–25 mg orally once daily

Titration Double dose every 1–2 weeks as tolerated based on BP, renal function, and potassium

Usual maintenance dose 50–100 mg once daily (or in divided doses)

Maximum dose 150 mg/day (some guidelines); typically 100 mg/day in Indian practice

Clinical Notes:

• Use as alternative to ACE inhibitor when ACE inhibitor-induced cough or angioedema occurs

• Combine with beta-blocker and diuretics per heart failure protocols

• Not to be combined with ACE inhibitor and mineralocorticoid receptor antagonist together (triple RAAS blockade contraindicated)

• Evidence from ELITE II and HEAAL trials

• Monitor for symptomatic hypotension, worsening renal function, and hyperkalaemia

Secondary Indications – Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Left Ventricular Hypertrophy (LVH) Regression with Hypertension (OFF-LABEL as specific indication) 50–100 mg once daily Long-term Not required LIFE trial: losartan superior to atenolol for LVH regression and stroke prevention; Indian cardiology practice

Post-Myocardial Infarction (if ACE Inhibitor Not Tolerated) (OFF-LABEL) Starting: 25–50 mg once daily; Target: 50–100 mg once daily Long-term Cardiology supervision recommended OPTIMAAL trial; Indian specialist practice; alternative to captopril/ramipril in ACE-intolerant patients

Stroke Prevention in High CV Risk Patients with Hypertension (OFF-LABEL) 50–100 mg once daily Long-term Not required LIFE trial: superior to atenolol for stroke prevention; some Indian cardiology protocols

Marfan Syndrome — Aortic Root Dilation Prevention (OFF-LABEL) 25 mg once daily; titrate to 50–100 mg once daily Long-term Specialist only (Cardiology/Genetics) Limited RCT data; used in some Indian centres; alternative or adjunct to beta-blockers

Hyperuricaemia Associated with Hypertension (OFF-LABEL) 50–100 mg once daily Long-term Not required Losartan uniquely promotes uric acid excretion among ARBs; may be preferred in hypertensive patients with gout/hyperuricaemia

PAEDIATRIC DOSING (Specialist Only)

⚠️ Not recommended in children below 6 years of age. Safety and efficacy not established below this age.

Primary Indication: Hypertension in Children (≥6 years)

Weight-Based Dosing:

Weight Starting Dose Titration Maximum Dose

20–50 kg 0.7 mg/kg once daily (approximately 25 mg) Adjust based on BP response every 2–4 weeks 1.4 mg/kg/day OR 50 mg/day (whichever is lower)

50 kg 50 mg once daily Increase to 100 mg if needed after 2–4 weeks 100 mg/day

Parameter Dose

Starting dose 0.7 mg/kg/day once daily (maximum initial dose: 50 mg)

Titration Increase based on BP response every 2–4 weeks

Usual maintenance dose 0.7–1.4 mg/kg/day once daily

Maximum dose 1.4 mg/kg/day OR 100 mg/day (whichever is lower)

Safety Monitoring:

• Serum creatinine and potassium at baseline, 1–2 weeks after initiation, and periodically thereafter

• Blood pressure at each visit

• Monitor for symptomatic hypotension (dizziness, fatigue)

• Growth and development parameters

Clinical Notes:

• Tablets may be crushed and mixed with water for administration if child cannot swallow whole tablets

• Use with caution in children with renal impairment

• Paediatric nephrology or cardiology supervision recommended

Secondary Indications – Paediatrics (Off-label)

Indication Age Dose Duration Supervision Evidence Basis

Chronic Kidney Disease with Proteinuria (OFF-LABEL) ≥6 years 0.7–1.4 mg/kg/day once daily; Maximum: 100 mg/day Long-term Specialist only (Paediatric Nephrology) Extrapolated from adult data; IAP nephrology practice

Alport Syndrome — Renoprotection (OFF-LABEL) ≥6 years 0.7–1.4 mg/kg/day once daily Long-term Specialist only (Paediatric Nephrology) Limited evidence; used in some Indian paediatric nephrology centres

Age Restrictions:

• Not recommended below 6 years of age

• Use in younger children only in exceptional circumstances under paediatric nephrology or cardiology supervision

• Contraindicated in neonates due to risk of severe hypotension and renal failure

Additional Notes:

• Up to 30% rise in serum creatinine from baseline is acceptable if it stabilises; do not discontinue for modest creatinine rise unless progressive

• Monitor potassium closely — hyperkalaemia risk increases with declining renal function

• Not removed by haemodialysis (highly protein-bound); no supplemental dose required

• Avoid combination with other RAAS blockers (ACE inhibitors, aliskiren) in patients with eGFR <60

• Known hypersensitivity to losartan or any ARB

• Pregnancy (especially 2nd and 3rd trimesters — fetotoxic; causes oligohydramnios, fetal renal failure, neonatal death)

• Bilateral renal artery stenosis (or stenosis in solitary kidney)

• Co-administration with aliskiren in patients with diabetes mellitus or eGFR <60 mL/min/1.73 m²

• History of angioedema with ARB or ACE inhibitor use

• Severe hepatic impairment without specialist supervision

• Volume depletion or dehydration (risk of symptomatic first-dose hypotension) — correct volume status before initiation

• Unilateral renal artery stenosis — may precipitate acute renal failure

• Chronic kidney disease (eGFR <60) — requires close monitoring of creatinine and potassium

• Hyperkalaemia risk — avoid or use cautiously with potassium supplements, potassium-sparing diuretics, or aldosterone antagonists

• Aortic stenosis or hypertrophic obstructive cardiomyopathy — may cause excessive hypotension

• Elderly patients — more sensitive to hypotensive effects; start low

• Concurrent NSAIDs — may reduce antihypertensive efficacy and worsen renal function

• Concurrent lithium — increases lithium toxicity risk

• Primary hyperaldosteronism — poor response expected

• Black patients — may have reduced antihypertensive response (consider combination therapy)

Parameter Information

Overall Safety Contraindicated — especially in 2nd and 3rd trimesters; fetotoxic

Risk Fetal renal dysgenesis, oligohydramnios, anuria, pulmonary hypoplasia, skeletal deformities, neonatal hypotension, neonatal death

First Trimester Avoid; if inadvertent exposure occurs, discontinue immediately and switch to safer alternative; fetal anomaly scan recommended

Preferred Alternatives Labetalol (first-line for chronic hypertension in pregnancy); Nifedipine ER; Methyldopa

Monitoring (if exposure occurred) Detailed fetal anomaly scan; amniotic fluid index; fetal renal function assessment; neonatal renal function and BP after delivery

Parameter Information

Compatibility Insufficient data; avoid if possible during breastfeeding

Expected Drug Level in Milk Unknown; likely low based on high protein binding

Preferred Alternatives Enalapril (more breastfeeding data); Amlodipine; Nifedipine ER; Labetalol

Infant Monitoring If exposure occurs: monitor for poor feeding, lethargy, hypotension (theoretical risks)

Recommendation Use alternative antihypertensive with better lactation data; if essential, monitor infant closely

Parameter Recommendation

Starting dose 25 mg orally once daily

Titration Increase gradually every 2–4 weeks based on BP response and tolerability

Maximum recommended 100 mg/day

Increased Risks First-dose hypotension (especially if volume-depleted); falls; acute kidney injury; hyperkalaemia

Additional Precautions Assess renal function and volume status before initiation; check electrolytes and creatinine within 1–2 weeks of starting; use with caution in those on multiple antihypertensives or diuretics

Interacting Drug Mechanism Effect Management

Aliskiren (in diabetics or CKD) Dual RAAS blockade Increased risk of hyperkalaemia, hypotension, and acute kidney injury Contraindicated in diabetic patients or those with eGFR <60

ACE Inhibitors (dual RAAS blockade) Additive RAAS inhibition Increased risk of hyperkalaemia, hypotension, and renal dysfunction without significant additional benefit Avoid combination routinely; use only in specific heart failure situations under specialist supervision

Potassium supplements / Potassium-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene) Additive potassium retention Hyperkalaemia (potentially life-threatening) Avoid combination if possible; if essential, monitor potassium frequently; reduce or stop potassium supplements

Lithium Reduced renal lithium excretion Lithium toxicity (tremor, ataxia, confusion, seizures) Monitor lithium levels closely; may need lithium dose reduction; avoid if possible

NSAIDs (chronic use) — ibuprofen, diclofenac, naproxen Inhibit prostaglandin-mediated renal vasodilation Reduced antihypertensive efficacy; increased risk of acute kidney injury and hyperkalaemia Avoid chronic NSAID use; if essential, monitor BP, renal function, and potassium

Interacting Drug Effect Management

Thiazide / Loop Diuretics Additive hypotension (especially first-dose); beneficial for BP control Start losartan at lower dose (25 mg) if already on diuretic; monitor for symptomatic hypotension

Rifampicin CYP2C9 induction; reduced conversion to active metabolite; decreased antihypertensive efficacy Monitor BP; may need higher losartan dose or alternative antihypertensive

Fluconazole CYP2C9 inhibition; increased losartan and active metabolite levels Monitor BP and for adverse effects; usually clinically manageable

Warfarin Minor interaction; both metabolised by CYP2C9 Monitor INR when initiating or adjusting losartan; usually no significant change

Trimethoprim Additive hyperkalaemia risk Monitor potassium, especially in elderly or those with renal impairment

Antidiabetic Agents (insulin, sulfonylureas) Potential enhanced hypoglycaemic effect Monitor blood glucose, especially when initiating ARB

Digoxin No significant pharmacokinetic interaction No adjustment needed; safe combination

• Dizziness, lightheadedness

• Fatigue, asthenia

• Hyperkalaemia (especially with CKD or concurrent potassium-elevating drugs)

• Mild creatinine elevation (usually transient)

• Headache

• Upper respiratory tract infection

• Cough (less common than with ACE inhibitors; <1%)

• Diarrhoea

• Back pain, muscle cramps

Adverse Effect Clinical Action

Angioedema (rare but potentially life-threatening; involves face, lips, tongue, larynx) Discontinue immediately; emergency airway management if needed; do not rechallenge with any ARB or ACE inhibitor

Severe Hyperkalaemia (>6.0 mEq/L) Discontinue or reduce dose; ECG monitoring; treat hyperkalaemia urgently; identify contributing factors

Acute Kidney Injury (especially in bilateral renal artery stenosis, severe heart failure, or volume depletion) Discontinue or reduce dose; IV fluids if volume-depleted; investigate cause

Severe Hypotension (especially first-dose) Supportive care (supine position, IV fluids); reduce dose or discontinue temporarily

Hepatotoxicity (rare; transaminase elevation) Monitor LFTs if symptoms; discontinue if significant elevation

Rhabdomyolysis (very rare) Discontinue; check CK; supportive care

1–2 weeks after initiation or dose increase Serum creatinine, potassium; blood pressure

First 3 months Creatinine and potassium monthly if high-risk (CKD, elderly, concurrent diuretics/potassium-sparing agents)

Long-term (every 3–6 months) Serum creatinine, potassium, blood pressure; annual urine protein if diabetic nephropathy

Special Situations More frequent monitoring in elderly, CKD, concurrent NSAIDs, diuretics, or potassium-affecting drugs

Monotherapy:

• Losar™ (Unichem) — 25 mg, 50 mg, 100 mg

• Repace™ (Torrent) — 25 mg, 50 mg, 100 mg

• Cosart™ (Cipla) — 25 mg, 50 mg, 100 mg

• Losacar™ (Cadila) — 25 mg, 50 mg

• Losartan™ (Various generics) — 25 mg, 50 mg, 100 mg

• Angizaar™ (Micro Labs) — 25 mg, 50 mg

• Lorsave™ (Alkem) — 50 mg

Fixed-Dose Combinations (Examples):

• Arbitel-L™ (Losartan + Amlodipine)

• Repace-AM™ (Losartan + Amlodipine)

Regulatory: Listed under NLEM 2022 (50 mg tablet); NPPA price controlled for scheduled strengths; widely available in government supply

1. Preferred ARB in diabetic nephropathy — Losartan (at 100 mg/day target dose) has the strongest evidence base for renoprotection in Type 2 DM with proteinuria (RENAAL trial); use full dose for maximal nephroprotective benefit

1. Unique uricosuric effect — Unlike other ARBs, losartan promotes uric acid excretion; preferred choice in hypertensive patients with concurrent gout or hyperuricaemia

1. Cough advantage over ACE inhibitors — Cough incidence <1% compared to 5–15% with ACE inhibitors; excellent alternative in patients with ACE inhibitor-induced cough

1. First-dose hypotension prevention — In volume-depleted patients or those on high-dose diuretics, start at 25 mg to avoid symptomatic hypotension; correct volume depletion before initiating

1. Avoid dual RAAS blockade — Do not routinely combine losartan with ACE inhibitors or aliskiren; increases hyperkalaemia and AKI risk without mortality benefit (ONTARGET trial)

1. CYP2C9 metaboliser considerations — Losartan is a prodrug; poor CYP2C9 metabolisers may have reduced response; rifampicin reduces efficacy; fluconazole may increase levels

hypertension; ARB; angiotensin-receptor-blocker; diabetic-nephropathy; heart-failure; renoprotection; pregnancy-contraindicated; NLEM-India; uricosuric; CKD-safe; Schedule-H

RxIndia v1.0 — 26 Apr 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Hypertension 2020

• AIIMS Antihypertensive Treatment Protocols

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• RENAAL Trial (diabetic nephropathy evidence)

• LIFE Trial (LVH regression and stroke prevention evidence)

• ELITE II, HEAAL Trials (heart failure evidence)

• ONTARGET Trial (dual RAAS blockade evidence)

• IAP Guidelines (paediatric dosing support)

• WHO Essential Medicines List (paediatric supportive reference)