Schedule H

Oral

• Saroglitazar 4 mg tablet

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 2 Diabetes Mellitus with Diabetic Dyslipidaemia / Hypertriglyceridaemia

Approved by CDSCO (2013) as adjunct therapy in patients inadequately controlled on statins

Parameter Recommendation

Starting dose 4 mg once daily orally

Titration Not required

Usual maintenance dose 4 mg once daily

Maximum dose 4 mg once daily

Clinical Notes:

• Administer once daily, with or without food

• Indicated when statin monotherapy provides inadequate lipid control

• Improves both glycaemic parameters (HbA1c, FBG) and lipid profile (triglycerides, HDL-C)

• Evaluate lipid profile and glycaemic control at 8–12 weeks

1. Non-Alcoholic Fatty Liver Disease (NAFLD) / Non-Alcoholic Steatohepatitis (NASH)

Approved by DCGI (2020) — World's first approved drug for NASH indication; based on EVIDENCES-IV trial

Parameter Recommendation

Starting dose 4 mg once daily orally

Titration Not required

Usual maintenance dose 4 mg once daily

Maximum dose 4 mg once daily

Clinical Notes:

• Demonstrated improvement in ALT levels, hepatic steatosis on imaging, and metabolic parameters

• Reassess ALT and hepatic steatosis (via ultrasound/FibroScan) at 12–16 weeks

• Concomitant improvement in glycaemic and lipid parameters observed

• Duration of therapy: Based on clinical and biochemical response; long-term use may be required

Secondary Indications — Adults (Off-label, if any)

Indication Dose Duration Notes

Diabetic dyslipidaemia without overt hyperglycaemia 4 mg once daily Ongoing OFF-LABEL; Specialist only; Based on Indian specialist experience and metabolic clinic protocols

Advanced NASH with fibrosis (F2–F3) 4 mg once daily Ongoing OFF-LABEL; Hepatology input required; Based on institutional liver protocols (AIIMS, ILBS)

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable.

• Saroglitazar is NOT approved for use in individuals below 18 years of age in India

• Safety and efficacy data in children and adolescents are not available

Secondary Indications — Paediatric doses (Off-label, if any)

Not applicable. No documented off-label paediatric use in Indian practice.

Statement: Not recommended in children or adolescents under 18 years. Use only in clinical trial settings or under paediatric gastroenterology/endocrinology specialist supervision.

Clinical Notes:

• No dose adjustment required in mild to moderate renal impairment

• Limited pharmacokinetic data in severe renal impairment or dialysis-dependent patients

Note: Although used for NAFLD/NASH, baseline hepatic function must be assessed. Drug is intended for metabolic liver disease, not decompensated cirrhosis.

• Known hypersensitivity to Saroglitazar or any excipient in the formulation

• Severe hepatic impairment (Child-Pugh C) or decompensated cirrhosis

• Active bladder cancer or history of bladder cancer (class-related precaution from glitazone/glitazar class)

• Pregnancy

• Lactation

• NYHA Class III–IV heart failure (due to fluid retention risk)

• Fluid retention: PPAR-γ activity may cause peripheral oedema and exacerbate heart failure — avoid in NYHA Class III–IV; use cautiously in Class I–II

• Hepatotoxicity: Monitor LFTs regularly; discontinue if ALT >3× ULN persists or if accompanied by symptoms (jaundice, nausea, fatigue)

• Weight gain: Class effect; monitor weight at each visit

• Macular oedema: Pre-existing macular oedema or diabetic retinopathy — periodic ophthalmologic evaluation recommended

• Fracture risk: Use cautiously in postmenopausal women and elderly at risk for osteoporotic fractures (class effect)

• Bladder symptoms: Advise patients to report haematuria or dysuria

Parameter Details

Overall safety Not recommended; insufficient human data; animal studies do not indicate direct teratogenicity

Recommendation Contraindicated during pregnancy

Preferred alternatives Insulin for glycaemic control; statins are also contraindicated in pregnancy

If used (emergency only) Only under specialist supervision if no alternative exists

Monitoring Maternal glucose, fetal growth surveillance if inadvertent exposure

Parameter Details

Compatibility Not recommended — avoid use during breastfeeding

Excretion in milk Unknown; theoretical risk due to PPAR-γ activity

Preferred alternatives Insulin for diabetes; lifestyle modification for dyslipidaemia

Infant monitoring (if used) Feeding difficulties, weight gain, signs of hypoglycaemia

Parameter Recommendation

Starting dose 4 mg once daily (same as adults)

Titration Not required

Special considerations Assess renal and hepatic function before initiation

Additional risks Increased susceptibility to oedema, heart failure exacerbation, fractures, and weight gain

Clinical Note: Use cautiously in elderly patients with pre-existing cardiac disease or osteoporosis risk.

Interacting Drug Effect Management

Pioglitazone / Rosiglitazone Additive PPAR-γ effects; ↑ risk of oedema, weight gain, heart failure Avoid combination

Fenofibrate ↑ Risk of hepatic enzyme elevation and potential hepatotoxicity Avoid combination unless strongly indicated; monitor LFTs closely

Gemfibrozil May increase Saroglitazar exposure; ↑ risk of myopathy Avoid combination

High-dose statins (Atorvastatin >40 mg, Rosuvastatin >20 mg) Potential for increased myopathy risk due to hepatic metabolism overlap Monitor for muscle symptoms; check CK if myalgia develops

Interacting Drug Effect Management

Sulfonylureas ↑ Risk of hypoglycaemia Consider reducing SU dose by 20–30%; monitor glucose

Insulin ↑ Risk of hypoglycaemia and fluid retention Reduce insulin dose; monitor for oedema

Warfarin Potential alteration in INR Monitor INR during initiation or dose changes

Beta-blockers May mask hypoglycaemia symptoms Counsel patient on atypical hypoglycaemia symptoms

CYP3A4 inducers (Rifampicin, Phenytoin, Carbamazepine) May reduce Saroglitazar efficacy (mechanism not fully characterised) Monitor glycaemic and lipid control

• Upper abdominal discomfort

• Bloating / flatulence

• Elevated transaminases (ALT, AST)

• Peripheral oedema

• Weight gain

• Headache

• Myalgia

• Asthenia

Adverse Effect Notes

Hepatotoxicity Monitor LFTs monthly for first 3 months; discontinue if ALT >3× ULN with symptoms

Congestive heart failure exacerbation Due to fluid retention (PPAR-γ effect); avoid in NYHA III–IV

Rhabdomyolysis Rare; especially with high-dose statin combination — discontinue if myopathy suspected

Bladder malignancy Class effect (glitazar/glitazone); not observed in Saroglitazar trials; remain vigilant

Macular oedema Report visual changes; ophthalmology referral if suspected

Bone fractures Increased risk in postmenopausal women (class effect)

After initiation (1 month) LFTs, weight, oedema assessment

3 months LFTs, HbA1c, lipid profile

6 months LFTs, HbA1c, lipid profile, hepatic imaging (if NAFLD/NASH)

Long-term LFTs every 3–6 months; lipid profile and HbA1c every 3–6 months; weight and oedema assessment at each visit

Single-ingredient (Saroglitazar 4 mg):

• Lipaglyn® (Zydus Lifesciences) — Innovator brand; most commonly prescribed

Note: No generic versions currently available. Lipaglyn remains the sole marketed brand in India as of 2025.

Note: Not listed under NLEM (2022); prices not NPPA-controlled. May be available at lower cost through government procurement in some state formularies.

1. Unique dual indication: Saroglitazar is the only drug approved in India (and globally) for both diabetic dyslipidaemia and NAFLD/NASH — consider in patients with overlapping metabolic liver disease and diabetes.

1. Not a statin substitute: Saroglitazar is intended as adjunctive therapy to statins in dyslipidaemia, not as a replacement; ensure statin is optimised before adding Saroglitazar.

1. Hepatic enzyme monitoring is critical: Despite being used for fatty liver disease, transaminases must be monitored closely — transient elevations are expected but persistent elevation >3× ULN warrants discontinuation.

1. Avoid in heart failure: Fluid retention risk (PPAR-γ effect) makes Saroglitazar unsuitable for patients with NYHA Class III–IV heart failure.

1. Weight monitoring: Counsel patients regarding potential weight gain; reinforce lifestyle measures.

1. Reassess at 3–6 months: If no significant improvement in ALT, lipid profile, or hepatic steatosis on imaging, reconsider continuation of therapy.

saroglitazar; PPAR agonist; glitazar; type 2 diabetes; diabetic dyslipidaemia; NAFLD; NASH; fatty liver; hypertriglyceridaemia; India-approved; hepatic monitoring; Lipaglyn

RxIndia v1.0 — 01 Jun 2025

• CDSCO approved prescribing information (Saroglitazar)

• Indian Pharmacopoeia / National Formulary of India

• NLEM 2022 — Not listed

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 2 Diabetes (2018)

• AIIMS Internal Protocols for NAFLD/NASH management

• EVIDENCES-IV Trial (Indian Journal of Gastroenterology, 2020)

• EVIDENCES-II Trial (Lipids in Health and Disease, 2014)

• Zydus Lifesciences product monograph

• Indian Association for Study of Liver (INASL) NAFLD guidelines (2022)