Schedule H

Oral

• Tablet: 2 mg

• Tablet: 4 mg

Note: Plain rosiglitazone has very limited standalone availability in India. Most commonly available as fixed-dose combinations (FDCs) with metformin or glimepiride.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus (in adults) — adjunct to diet and exercise

Used when metformin or sulfonylurea monotherapy provides insufficient glycaemic control. May be used as monotherapy, dual therapy, or triple therapy.

Parameter Recommendation

Starting dose 4 mg once daily (may be given as single dose or divided into 2 mg twice daily)

Titration If glycaemic response inadequate after 8–12 weeks, increase to 8 mg/day

Usual maintenance dose 4–8 mg/day in single or divided doses

Maximum dose 8 mg/day

Clinical notes Risk of fluid retention and heart failure increases with higher doses; onset of action is gradual (2–4 weeks for initial effect, maximal effect at 8–12 weeks); not suitable for rapid glycaemic correction

When used with Metformin (FDC):

• Starting dose: Rosiglitazone 2 mg + Metformin 500 mg twice daily

• Titration: Increase based on glycaemic response after 8–12 weeks

• Maximum: Rosiglitazone 8 mg/day component

When used with Sulfonylurea:

• Starting dose: Rosiglitazone 4 mg once daily

• Consider reducing sulfonylurea dose if hypoglycaemia occurs

• Maximum: Rosiglitazone 8 mg/day

Secondary Indications — Adults (Off-label)

Indication Status

Polycystic Ovary Syndrome (PCOS) NOT AVAILABLE — Limited evidence; not recommended in Indian specialist practice due to cardiovascular concerns; metformin preferred

Non-alcoholic Steatohepatitis (NASH) NOT AVAILABLE — Insufficient Indian practice data; pioglitazone preferred if TZD required

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable — Rosiglitazone is NOT approved for use in children or adolescents below 18 years of age.

Safety and efficacy have not been established in the paediatric population.

Secondary Indications — Paediatrics (Off-label)

Not applicable — No established off-label paediatric indications.

Age Restriction: Not recommended below 18 years of age. Use only in exceptional research settings under paediatric endocrinologist supervision with institutional ethics approval.

30 No dose adjustment required for rosiglitazone alone

<30 Use with caution; limited data available; avoid FDC with metformin (metformin contraindicated in severe renal impairment)

Haemodialysis Not dialyzable; no utility in dialysis-dependent patients

Peritoneal dialysis Limited data; avoid use

• NYHA Class III or IV heart failure

• Active liver disease or baseline ALT >2.5× upper limit of normal (ULN)

• Known hypersensitivity to rosiglitazone or any excipient

• Diabetic ketoacidosis (DKA)

• Type 1 diabetes mellitus

• Pregnancy

• Lactation

• Concurrent use with insulin (increased risk of heart failure and fluid retention)

• NYHA Class I–II heart failure — increased risk of fluid retention and worsening cardiac status

• Ischaemic heart disease or history of myocardial infarction — controversial cardiovascular risk data

• Pre-existing oedema or conditions predisposing to fluid retention

• Postmenopausal women — increased risk of bone fractures (distal limb fractures)

• Anaemia or haemoglobin decline during therapy

• Macular oedema — may worsen; report visual symptoms promptly

• Combination with sulfonylureas — risk of hypoglycaemia

• Patients at risk of bladder cancer (class concern, though more established for pioglitazone)

Parameter Recommendation

Risk category Not recommended during pregnancy; limited human data; animal studies showed developmental toxicity

Preferred alternatives Insulin (human regular, NPH, or analogues as per specialist guidance); metformin may be considered under specialist supervision

When it may be used Only if no suitable alternatives and potential benefit clearly outweighs fetal risk — requires specialist diabetologist/obstetrician input

What to monitor Maternal glycaemic control, fetal growth via ultrasound, signs of macrosomia or fetal distress

Parameter Recommendation

Compatibility Not compatible with breastfeeding — unknown excretion in human milk; potential risk to infant

Expected drug levels in milk Unknown

Preferred alternatives Insulin (no systemic absorption in infant); metformin (low milk levels, generally acceptable)

What to monitor in infant If inadvertent exposure occurs: monitor for hypoglycaemia, feeding difficulties, weight gain patterns

Parameter Recommendation

Starting dose 4 mg once daily

Titration Slower titration recommended; reassess after 12 weeks before dose escalation

Key risks Heart failure, fluid retention, oedema, fractures (especially in postmenopausal women), hypoglycaemia when combined with sulfonylureas

Monitoring Baseline and periodic assessment for signs of heart failure (weight gain, dyspnoea, peripheral oedema); LFTs; bone health

Interacting Drug Mechanism / Effect Action

Insulin Additive fluid retention; significantly increased risk of heart failure Avoid combination — contraindicated per CDSCO guidelines

Gemfibrozil Inhibits CYP2C8 metabolism of rosiglitazone; markedly increases plasma levels Avoid combination or reduce rosiglitazone dose to 4 mg/day maximum; monitor closely for adverse effects

Rifampicin Induces CYP2C8; substantially reduces rosiglitazone plasma levels May lead to loss of glycaemic control; consider alternative antidiabetic or increased monitoring; dose adjustment may be needed

Nitrates Combined use may worsen cardiac symptoms in patients with underlying heart disease Use with caution; monitor for worsening heart failure

Interacting Drug Mechanism / Effect Action

Sulfonylureas (glimepiride, gliclazide) Additive hypoglycaemic effect Monitor blood glucose; may need to reduce sulfonylurea dose

Trimethoprim Inhibits CYP2C8; may modestly increase rosiglitazone levels Monitor for adverse effects; usually can continue with monitoring

Fluconazole Moderate CYP2C8/CYP2C9 inhibitor; may increase rosiglitazone levels Monitor glycaemic control and adverse effects

Glucocorticoids (prednisolone, dexamethasone) Antagonize hypoglycaemic effect Monitor blood glucose; may need to increase antidiabetic dosage

Statins (especially simvastatin, atorvastatin) Potential CYP-mediated interactions Monitor lipid profile and glycaemic response

Ketoconazole CYP2C8 inhibition; modest increase in rosiglitazone exposure Monitor; usually can continue with caution

• Weight gain (dose-related; may be significant)

• Peripheral oedema (especially lower limbs)

• Headache

• Anaemia (haemodilutional)

• Myalgia / arthralgia

• Upper respiratory tract infections

• Fatigue

• Hypoglycaemia (when combined with sulfonylureas)

Adverse Effect Clinical Significance

Congestive heart failure May develop or worsen; requires immediate discontinuation and cardiology referral if symptomatic CHF occurs

Hepatotoxicity Monitor LFTs; discontinue if ALT exceeds 3× ULN or if jaundice develops

Bone fractures Increased risk of distal limb fractures (hand, foot, wrist) especially in postmenopausal women; consider bone health monitoring

Macular oedema May cause or worsen visual impairment; refer to ophthalmology if visual symptoms reported

Cardiovascular events Controversial data on increased MI/stroke risk (RECORD, ROSIGLITAZONE meta-analyses); individual benefit-risk assessment essential

Long-term maintenance HbA1c every 3 months initially, then every 6 months if stable; LFTs every 6–12 months; weight at each visit; annual assessment for heart failure symptoms, fracture risk, and macular oedema symptoms

Additional Report any visual disturbances promptly; periodic cardiac evaluation in high-risk patients

Monotherapy (Limited Availability):

• Rosicon

• Rosizone

Fixed-Dose Combinations (More Commonly Available):

• Rosicon MF (Rosiglitazone + Metformin)

• Roseday M (Rosiglitazone + Metformin)

• Rosimet (Rosiglitazone + Metformin)

• Windose RG (Rosiglitazone + Glimepiride)

Note: Plain rosiglitazone monotherapy tablets are increasingly difficult to source in India; FDCs with metformin are more widely available.

NPPA Status: FDCs containing metformin may fall under DPCO price control; verify current NPPA ceiling prices.

• Not a first-line agent — Reserve for patients inadequately controlled on metformin or sulfonylurea, or those intolerant to first-line agents; pioglitazone often preferred within the TZD class due to better cardiovascular profile

• Avoid in any patient with cardiac history — NYHA Class III/IV heart failure is an absolute contraindication; Class I/II requires careful benefit-risk assessment

• Gradual onset of action — Full glycaemic effect takes 8–12 weeks; not suitable for rapid glucose lowering

• Monitor weight and oedema early — Weight gain and peripheral oedema may precede overt heart failure; discontinue if CHF symptoms develop

• Fracture risk counselling — Important to counsel postmenopausal women; consider bone density monitoring in long-term users

• LFT monitoring mandatory — Check at baseline, at 4–8 weeks, then periodically; discontinue if ALT >3× ULN

Rosiglitazone; thiazolidinedione; TZD; PPAR-gamma; type 2 diabetes; insulin sensitizer; fluid retention; heart failure risk; hepatic monitoring; fracture risk; Schedule H

RxIndia v1.0 — 09 Apr 2025

• CDSCO — Approved drug information

• Indian Pharmacopoeia / National Formulary of India

• NLEM 2022

• API Textbook of Medicine

• RSSDI Clinical Practice Guidelines for Management of Type 2 Diabetes

• AIIMS Rational Use of Medicine Guidelines

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian product inserts (Rosicon, Roseday M)