Schedule H

Oral

• Tablets: 10 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Primary Hypercholesterolaemia (Familial and Non-Familial)

As monotherapy in statin-intolerant patients or as add-on therapy with statins for enhanced LDL-C reduction.

Parameter Recommendation

Starting dose 10 mg once daily

Titration Not applicable (single fixed dose)

Usual maintenance dose 10 mg once daily

Maximum dose 10 mg once daily

Clinical Notes:

• Can be administered with or without food, at any time of day

• Monotherapy reduces LDL-C by approximately 15–20%

• When combined with statins, provides additional 20–25% LDL-C reduction beyond statin alone

• Monitor lipid profile after 4–6 weeks of therapy

• Preferred option in statin-intolerant patients

1. Homozygous Sitosterolaemia (Phytosterolaemia)

Rare inherited disorder with elevated plant sterol levels.

Parameter Recommendation

Starting dose 10 mg once daily

Titration Not applicable

Usual maintenance dose 10 mg once daily

Maximum dose 10 mg once daily

Clinical Notes:

• Adjunct to dietary restriction of plant sterols

• Specialist supervision required (rare indication)

1. Mixed Dyslipidaemia (Fredrickson Type IIa and IIb)

In combination with statins for patients not achieving lipid targets on statin alone.

Parameter Recommendation

Starting dose 10 mg once daily (added to existing statin therapy)

Titration Not applicable

Usual maintenance dose 10 mg once daily with statin

Maximum dose 10 mg once daily

Clinical Notes:

• Statin dose should be optimised before adding ezetimibe

• Monitor LFTs when used in combination with statins

• Not effective for isolated hypertriglyceridaemia

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

Indication Dose Duration Notes

Cardiovascular Risk Reduction Post-ACS 10 mg once daily with moderate-to-high intensity statin Long-term OFF-LABEL in India; Specialist only; Evidence: IMPROVE-IT trial demonstrated reduced cardiovascular events when added to simvastatin post-ACS

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Familial Hypercholesterolaemia (Heterozygous or Homozygous) — Age ≥10 Years

10–17 years 10 mg once daily Not applicable 10 mg once daily 10 mg once daily

Clinical Notes:

• Use as monotherapy or in combination with age-appropriate statin therapy

• Lipid profile monitoring every 3–6 months

• LFT monitoring when combined with statin

• Minimum age for use: 10 years

• Diet and lifestyle modifications should accompany pharmacotherapy

Secondary Indications – Paediatrics (Off-label, if any)

Not applicable.

• Not recommended below age 10 years except under specialist supervision in tertiary centres

• Limited safety and efficacy data in children below 10 years

No dose adjustment required.

• Safe to use across all stages of renal impairment including dialysis-dependent patients

• Ezetimibe and its active metabolite are not significantly removed by haemodialysis

• Severe hepatic impairment (Child-Pugh C)

• Active liver disease or unexplained persistent elevations in serum transaminases (when used with statin)

• Known hypersensitivity to ezetimibe or any excipient

• Pregnancy and lactation when used in combination with statins

• Concurrent use with statins in patients with active liver disease

• Pre-existing mild to moderate hepatic impairment — requires LFT monitoring, especially with statin combination

• Myopathy risk increases when combined with statins — counsel patients to report unexplained muscle pain

• Concurrent use with fibrates (gemfibrozil, fenofibrate) — increased risk of cholelithiasis and myopathy; specialist supervision advised

• Secondary causes of hyperlipidaemia (hypothyroidism, nephrotic syndrome, obstructive liver disease, diabetes) should be excluded or treated before initiating therapy

• Patients on cyclosporine — monitor drug levels and LFTs

Parameter Details

Risk Category Limited human data; not recommended

Monotherapy Avoid unless potential benefit clearly outweighs risk; defer lipid-lowering in pregnancy unless compelling indication

With Statin Contraindicated — statins are teratogenic

Preferred Alternatives Bile acid sequestrants (cholestyramine, colesevelam) in 2nd/3rd trimester if essential

Monitoring If inadvertent exposure occurs, assess fetal development; specialist obstetric input required

Parameter Details

Compatibility Not recommended during breastfeeding

Drug Levels in Milk Unknown; animal studies show excretion in milk

With Statin Contraindicated — statins are not safe in lactation

Preferred Alternatives Bile acid sequestrants (cholestyramine) if lipid-lowering essential postpartum

Infant Monitoring If inadvertent exposure, monitor infant growth and feeding

Parameter Recommendation

Starting dose 10 mg once daily (no adjustment required)

Titration Not applicable

Special Considerations Monitor hepatic function when combined with statins; increased vigilance for myopathy in elderly on multiple medications

Extra Risks Polypharmacy interactions; cumulative myopathy risk with statins

Interacting Drug Mechanism / Effect Recommendation

Cyclosporine Increases ezetimibe plasma concentration (up to 12-fold); cyclosporine levels may also increase Monitor cyclosporine levels and LFTs; consider risk-benefit carefully

Fibrates (Gemfibrozil) Increased risk of cholelithiasis and myopathy Avoid combination; if unavoidable, specialist supervision only

Bile Acid Sequestrants (cholestyramine, colesevelam) Reduce ezetimibe absorption Administer ezetimibe at least 2 hours before OR 4 hours after bile acid sequestrant

Statins (all) Additive risk of hepatotoxicity and myopathy Monitor LFTs at baseline and 6 weeks; counsel for myopathy symptoms

Interacting Drug Mechanism / Effect Recommendation

Warfarin Slight variability in INR reported Monitor INR more frequently when initiating or changing ezetimibe dose

Fenofibrate Less interaction than gemfibrozil but still increased gallstone and myopathy risk Use with caution; monitor for cholelithiasis symptoms

Antacids (aluminium/magnesium hydroxide) Minor reduction in ezetimibe bioavailability Stagger administration if clinically feasible

Rifampicin Induction of glucuronidation may reduce ezetimibe levels Monitor lipid response; may need clinical adjustment

• Headache

• Abdominal pain

• Diarrhoea

• Flatulence

• Myalgia (especially when combined with statin)

• Fatigue

• Upper respiratory tract infection

• Arthralgia

Adverse Effect Clinical Action

Hepatitis / Elevated Transaminases Discontinue if ALT/AST >3× ULN persists; more common with statin combination

Myopathy / Rhabdomyolysis Discontinue immediately; check CK levels; higher risk with statin or fibrate co-administration

Cholestatic Jaundice (rare) Discontinue; specialist hepatology review

Thrombocytopenia (rare) Investigate if unexplained bruising/bleeding; discontinue if confirmed

Pancreatitis (rare) Discontinue; supportive management

Angioedema (rare) Discontinue immediately; supportive care

4–6 weeks after initiation Lipid profile to assess response

6 weeks (if on statin combination) LFTs

Long-term Lipid profile every 3–6 months; LFTs periodically when on combination therapy; monitor for myopathy symptoms

Monotherapy:

• Ezentia (Sun Pharma)

• Ezedoc (Lupin)

• Ezetrol (Organon)

• Ezemate (Zydus)

• Lipisure (Macleods)

• Ezetimibe (Various generics)

Fixed-Dose Combinations (FDCs):

• With Atorvastatin: Atozet, Ezator

• With Rosuvastatin: Rosuez, Rozat-EZ

• With Simvastatin: Ezentia-S

• Not included in NLEM; pricing not NPPA-controlled

• Cost varies across brands and regions

• FDCs generally more expensive than individual components

• Ezetimibe is the preferred add-on agent when statin alone does not achieve LDL-C targets — provides additional 20–25% LDL-C reduction

• First-line monotherapy option in patients with documented statin intolerance (particularly statin-associated myopathy)

• Not effective for primary hypertriglyceridaemia — avoid as first-line in isolated triglyceride elevation

• Always separate dosing from bile acid sequestrants by at least 2 hours before or 4 hours after to ensure adequate absorption

• IMPROVE-IT trial demonstrated cardiovascular benefit when ezetimibe added to simvastatin post-ACS — consider in high-risk patients not meeting targets

• Monitor LFTs when combining with statins; muscle symptoms warrant CK check and potential discontinuation

Ezetimibe; hypercholesterolaemia; LDL-lowering; cholesterol absorption inhibitor; statin add-on; statin-intolerant; sitosterolaemia; renal-safe; hepatic-caution; Schedule H

RxIndia v1.0 — 10 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI) 2021

• API Textbook of Medicine — Dyslipidaemia chapter

• ICMR Guidelines on Dyslipidaemia Management

• AIIMS Drug Formulary 2023

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

• IMPROVE-IT Trial (for off-label cardiovascular risk reduction indication)

• Manufacturer product inserts (India)