Schedule H

Oral

• Fenofibrate tablets: 67 mg, 160 mg, 200 mg

• Fenofibrate micronized tablets: 54 mg, 67 mg, 145 mg, 160 mg

• Fenofibrate nanocrystal tablets: 145 mg

• Fixed-dose combinations with statins (Atorvastatin, Rosuvastatin) — use with caution

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertriglyceridemia (Fredrickson Type IV and Type V Hyperlipidemia)

Parameter Standard Fenofibrate Micronized Fenofibrate

Starting dose 160 mg once daily with meals 145 mg once daily with meals

Titration Generally not required if tolerated Adjust based on triglyceride response at 8 weeks

Usual maintenance dose 160 mg once daily 145 mg once daily

Maximum dose 200 mg/day 145 mg/day

Key Clinical Notes:

• Administer with food to enhance absorption (bioavailability increases by approximately 35%)

• Assess fasting triglycerides at baseline and 8–12 weeks after initiation

• If triglycerides remain >500 mg/dL despite therapy, re-evaluate diet compliance and consider combination therapy

• Discontinue if no adequate response after 2–3 months of adherent therapy

1. Mixed Dyslipidemia (Elevated Triglycerides with Low HDL-C)

Parameter Recommendation

Starting dose 160 mg once daily (standard) OR 145 mg once daily (micronized)

Titration Based on lipid profile response at 8–12 weeks

Usual maintenance dose 160 mg once daily OR 145 mg once daily

Maximum dose 200 mg/day (standard)

Key Clinical Notes:

• Evaluate complete lipid profile (TC, TG, LDL-C, HDL-C) at 8–12 weeks

• More effective for lowering triglycerides than for raising HDL-C or lowering LDL-C

• May be added to statin therapy in high cardiovascular risk patients under specialist supervision only

• Fenofibrate preferred over gemfibrozil when statin combination is required

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes

Diabetic Retinopathy (progression reduction in Type 2 DM) 160 mg once daily Long-term OFF-LABEL — Specialist only. Based on FIELD and ACCORD-Eye studies showing reduced progression of diabetic retinopathy. Consider in T2DM patients with persistent microvascular risk despite glycaemic control

Hyperuricemia associated with dyslipidemia 160 mg once daily As clinically indicated OFF-LABEL — Fenofibrate has uricosuric effect; may reduce serum uric acid by 20–25%. Based on Indian specialist practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — Fenofibrate is NOT approved for use in children <18 years in India.

Secondary Indications — Paediatric (Off-label)

Indication Age Dose Duration Notes

Severe Familial Hypertriglyceridemia ≥10 years 3–5 mg/kg/day (max: 160 mg/day) Long-term OFF-LABEL — Specialist only (Paediatric Endocrinologist/Lipidologist). Based on limited international data and Indian specialist practice

Safety Monitoring:

• LFTs every 3 months for first year, then every 6 months

• Fasting lipid profile at baseline, 8 weeks, then every 3–6 months

• Renal function monitoring

• CK if muscle symptoms develop

• Monitor growth parameters

Statement: Fenofibrate is NOT recommended in children <10 years. Use in adolescents (10–18 years) is strictly off-label and requires specialist supervision with documented severe familial hypertriglyceridemia.

Additional Notes:

• Assess renal function before initiation and periodically during therapy

• Risk of accumulation and myopathy increases with declining renal function

Additional Notes:

• Discontinue if ALT/AST persistently >3× ULN

• Fenofibrate is hepatically metabolised and excreted via glucuronidation

• Severe renal impairment (eGFR <30 mL/min/1.73m²)

• Active liver disease or persistent unexplained transaminase elevation (>3× ULN)

• Pre-existing gallbladder disease (cholelithiasis, cholecystitis)

• Known hypersensitivity to fenofibrate or fenofibric acid

• Chronic or acute pancreatitis (except pancreatitis secondary to severe hypertriglyceridemia)

• Concurrent use with other fibrates (e.g., gemfibrozil)

• Pregnancy and lactation

• Photoallergic or phototoxic reaction to fibrates previously

• History of myopathy or rhabdomyolysis (especially with prior statin use)

• Concurrent statin therapy — increased risk of myopathy/rhabdomyolysis; use with careful monitoring

• Uncorrected hypothyroidism — correct thyroid function before initiation (increases myopathy risk)

• Elderly patients — reduced renal reserve; require dose adjustment and close monitoring

• History of gallstones or biliary tract disease

• Patients on oral anticoagulants — requires frequent INR monitoring

• Diabetes mellitus — monitor blood glucose (may potentiate hypoglycaemia with sulfonylureas)

• Heavy alcohol consumption — increases triglycerides and pancreatitis risk

Aspect Recommendation

Risk category Contraindicated (Animal studies show embryotoxicity)

Safety statement No adequate human data; avoid use during pregnancy

Preferred alternatives Dietary modification; Omega-3 fatty acids (fish oil) under specialist guidance if severely elevated TG

When may be used Not recommended — avoid unless life-threatening hypertriglyceridemia with pancreatitis risk (specialist decision only)

Monitoring Not applicable — drug should not be used

Aspect Recommendation

Compatibility Not compatible with breastfeeding

Excretion in milk Unknown; assumed to be excreted based on lipophilicity

Preferred alternatives Dietary intervention; defer pharmacotherapy until breastfeeding completed

Infant monitoring If inadvertent exposure — monitor for GI disturbances, poor weight gain, feeding difficulties

Aspect Recommendation

Starting dose 67 mg once daily

Titration Slow; assess renal function and tolerability before dose escalation

Maximum dose Generally limit to 145 mg/day unless renal function preserved

Special considerations Increased myopathy risk; assess baseline renal function; avoid statin combination unless essential; monitor for signs of rhabdomyolysis

Interacting Drug Effect Recommendation

HMG-CoA reductase inhibitors (Statins) — especially simvastatin Increased risk of myopathy and rhabdomyolysis Avoid simvastatin combination; if statin required, use rosuvastatin or atorvastatin at lowest effective dose; monitor CK and muscle symptoms

Gemfibrozil Additive myotoxicity; pharmacokinetic interaction Contraindicated — do not co-prescribe fibrates

Oral anticoagulants (Warfarin, Acenocoumarol) Displaces warfarin from protein binding; enhanced anticoagulant effect Reduce anticoagulant dose by 30–50% initially; monitor INR frequently (every 3–5 days initially, then weekly)

Ciclosporin Increased nephrotoxicity; possible reduced ciclosporin levels Avoid combination; if unavoidable, monitor renal function closely and ciclosporin levels

Colchicine Additive myotoxicity risk Avoid combination; if essential, monitor CK and muscle symptoms closely

Bile acid sequestrants (Cholestyramine, Colesevelam) Reduced fenofibrate absorption Administer fenofibrate ≥1 hour before OR 4–6 hours after bile acid sequestrant

Interacting Drug Effect Recommendation

Sulfonylureas (Glimepiride, Glipizide) Potentiation of hypoglycaemic effect Monitor blood glucose closely; may need sulfonylurea dose reduction

Repaglinide Increased repaglinide exposure (via CYP2C8 inhibition) Use with caution; monitor for hypoglycaemia

Ezetimibe Increased cholesterol excretion into bile; potential cholelithiasis risk Monitor for gallstone symptoms

Rifampicin Induces fenofibrate metabolism Monitor lipid response; may need dose adjustment

Tacrolimus Potential additive nephrotoxicity Monitor renal function if concurrent use essential

• Dyspepsia, nausea, abdominal discomfort

• Diarrhoea or constipation

• Elevated hepatic transaminases (ALT, AST) — usually transient

• Myalgia (muscle pain without CK elevation)

• Headache

• Fatigue

• Elevated serum creatinine (usually reversible)

• Increased homocysteine levels

Adverse Effect Clinical Notes

Rhabdomyolysis Rare; higher risk with statin combination, renal impairment, or hypothyroidism; presents with severe muscle pain, weakness, dark urine; CK >10× ULN — STOP drug immediately; requires hospitalisation

Cholelithiasis (Gallstones) Fibrates increase biliary cholesterol saturation; monitor for biliary symptoms (RUQ pain, jaundice)

Pancreatitis Rare; discontinue if suspected; differentiate from hypertriglyceridemia-induced pancreatitis

Hepatotoxicity Persistent ALT/AST >3× ULN — discontinue therapy

Pulmonary embolism Rare; reported in post-marketing surveillance

Severe skin reactions Very rare — Stevens-Johnson syndrome, toxic epidermal necrolysis; discontinue immediately

Paradoxical severe HDL decrease Very rare; discontinue if significant unexplained HDL reduction

8–12 weeks after initiation Fasting lipid profile, LFTs, renal function

If muscle symptoms develop CK immediately; if >5× ULN, discontinue

Long-term (stable therapy) LFTs every 6 months for first year, then annually; lipid profile every 6–12 months; renal function annually; CK if symptomatic

If on anticoagulants INR every 3–5 days initially, then weekly until stable

Lipicard USV 67 mg, 145 mg, 160 mg tablets

Fenolip Zydus Cadila 145 mg, 160 mg tablets

Fibator Micro Labs 145 mg, 160 mg tablets

Lipikind Mankind 145 mg, 160 mg tablets

Fenoglide Lupin 54 mg, 160 mg tablets

Fibrasure Cipla 145 mg, 160 mg tablets

Fixed-Dose Combinations:

• Note: FDC with statin requires careful patient selection due to myopathy risk

Note: Fenofibrate is included in NLEM 2022 (160 mg tablet); NPPA price ceiling applicable for scheduled formulations. Prices vary by brand and region.

1. Fenofibrate is the fibrate of choice when combination with a statin is necessary — lower myopathy risk compared to gemfibrozil due to different pharmacokinetic interaction profile.

1. Not effective as primary therapy for hypercholesterolemia — use statins first-line for elevated LDL-C; fenofibrate is primarily for triglyceride reduction.

1. Always take with food — bioavailability significantly improved; ensures consistent drug absorption.

1. Transient creatinine elevation is expected — usually 10–15% increase; reversible on discontinuation; does not indicate true nephrotoxicity but represents altered creatinine production.

1. Discontinue if no response in 2–3 months — if triglycerides remain elevated despite adherent therapy and lifestyle modification, reassess diagnosis and consider alternative agents.

1. Unique microvascular benefit in diabetes — consider for diabetic patients with dyslipidemia who may benefit from retinopathy progression reduction (FIELD study evidence), though this remains off-label in India.

hypertriglyceridemia; fibrate; dyslipidemia; mixed-hyperlipidemia; statin-combination-caution; renal-adjustment; myopathy-risk; gallstone-risk; NLEM-India; diabetic-retinopathy-off-label

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• NLEM 2022

• API Textbook of Medicine

• AIIMS Drug Formulary

• Lipid Association of India Guidelines

• Goodman and Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• FIELD Study (Lancet 2005) — for diabetic retinopathy off-label indication

• ACCORD-Eye Study (NEJM 2010) — for diabetic retinopathy off-label indication

• Indian manufacturer product inserts (USV, Zydus, Cipla)