Schedule H

Oral

• Tablets: 5 mg, 10 mg, 20 mg, 40 mg, 80 mg

Fixed-Dose Combinations (FDCs) Available:

• Atorvastatin + Ezetimibe (10/10 mg, 20/10 mg, 40/10 mg)

• Atorvastatin + Aspirin (10/75 mg, 20/75 mg)

• Atorvastatin + Fenofibrate (10/145 mg, 10/160 mg)

• Atorvastatin + Clopidogrel (10/75 mg, 20/75 mg)

• Atorvastatin + Amlodipine (5/5 mg, 10/5 mg)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Primary Hypercholesterolaemia and Mixed Dyslipidaemia

Parameter Dose

Starting dose 10–20 mg orally once daily

Titration Adjust at 4-week intervals based on LDL-C response

Usual maintenance dose 10–40 mg once daily

Maximum dose 80 mg once daily

Clinical Notes:

• Can be taken at any time of day (unlike simvastatin); no significant food interaction

• More potent LDL-C reduction per mg compared to simvastatin, pravastatin, or lovastatin

• 10 mg atorvastatin ≈ 20–40 mg simvastatin in LDL-lowering efficacy

• Assess baseline lipid panel; repeat at 4–6 weeks after dose adjustment

1. Heterozygous Familial Hypercholesterolaemia

Parameter Dose

Starting dose 10–20 mg orally once daily

Titration Increase at 4-week intervals based on LDL-C response

Usual maintenance dose 40–80 mg once daily

Maximum dose 80 mg once daily

Clinical Notes:

• Higher doses often required to achieve LDL-C targets

• May be combined with ezetimibe or PCSK9 inhibitors if target not met

• Family screening recommended

1. Homozygous Familial Hypercholesterolaemia

Parameter Dose

Starting dose 10–20 mg orally once daily

Titration Increase based on LDL-C response

Usual maintenance dose 40–80 mg once daily

Maximum dose 80 mg once daily

Clinical Notes:

• Adjunct to other lipid-lowering therapies (apheresis, ezetimibe, PCSK9 inhibitors)

• Response variable due to residual LDL receptor activity

• Specialist (lipidologist/cardiologist) supervision recommended

1. Primary Prevention of Cardiovascular Disease (CVD) in High-Risk Patients

Parameter Dose

Starting dose 10–20 mg orally once daily

Titration Adjust based on LDL-C target and CV risk

Usual maintenance dose 10–40 mg once daily

Maximum dose 80 mg once daily

Clinical Notes:

• Indicated in patients without prior CVD but with diabetes, hypertension, smoking, elevated LDL-C, or 10-year CV risk >10%

• Use risk calculators (QRISK, Framingham, ICMR charts) to guide initiation

• Target LDL-C depends on overall CV risk (typically <100 mg/dL or ≥50% reduction)

1. Secondary Prevention of Atherosclerotic Cardiovascular Disease (ASCVD)

(Post-MI, Post-Stroke, Peripheral Arterial Disease, Revascularization)

Parameter Dose

Starting dose 40–80 mg orally once daily (high-intensity therapy)

Titration Not applicable — start at high intensity

Usual maintenance dose 40–80 mg once daily

Maximum dose 80 mg once daily

Clinical Notes:

• High-intensity statin therapy (atorvastatin 40–80 mg) should be initiated promptly in all patients with ASCVD unless contraindicated

• In acute coronary syndrome (ACS): start atorvastatin 80 mg within 24–96 hours of presentation

• Target LDL-C: <70 mg/dL or ≥50% reduction from baseline

• Continue indefinitely for secondary prevention

Secondary Indications – Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Non-Alcoholic Fatty Liver Disease (NAFLD) with Dyslipidaemia (OFF-LABEL) 10–40 mg once daily Long-term Specialist recommended (Hepatology/Gastroenterology) Cohort studies showing ALT improvement and CV risk reduction; Indian hepatology practice consensus; statins safe in NAFLD/NASH without decompensated cirrhosis

Chronic Kidney Disease (CKD) Stages 3–5 (Non-Dialysis) (OFF-LABEL) 10–20 mg once daily Long-term Nephrology supervision recommended SHARP trial; KDIGO guidelines; reduces CV events in CKD; Indian nephrology practice

Post-Renal Transplant Dyslipidaemia (OFF-LABEL) 10 mg once daily initially; titrate cautiously Long-term Specialist only (Nephrology/Transplant) Drug interaction with cyclosporine/tacrolimus; start low; monitor for myopathy

Stroke Prevention (High-Risk Patients) (OFF-LABEL as primary indication) 40–80 mg once daily Long-term Not required SPARCL trial; reduces recurrent stroke in patients with prior stroke/TIA and no known CAD

PAEDIATRIC DOSING (Specialist Only)

⚠️ Not recommended in children below 10 years of age except under specialist lipidology supervision.

Primary Indication: Heterozygous Familial Hypercholesterolaemia (Children ≥10 years)

Parameter Dose

Starting dose 10 mg orally once daily

Titration Increase at 4-week intervals based on LDL-C response

Usual maintenance dose 10–20 mg once daily

Maximum dose 20 mg once daily

Eligibility Criteria:

• Age ≥10 years (post-pubertal; Tanner stage II or above)

• Confirmed diagnosis of heterozygous familial hypercholesterolaemia (clinical criteria + family history ± genetic testing)

• LDL-C persistently elevated despite 6–12 months of dietary intervention

Safety Monitoring:

• Lipid profile at baseline, 4 weeks, and every 3–6 months

• Liver function tests (ALT, AST) at baseline and periodically

• Creatine kinase (CK) if muscle symptoms develop

• Growth and pubertal development assessment annually

• Screen for diabetes risk factors

Clinical Notes:

• Treatment should be supervised by paediatric lipidologist, cardiologist, or endocrinologist

• Diet and lifestyle modification remain cornerstone of therapy

• Goal: LDL-C reduction of ≥50% or LDL-C <130 mg/dL

Secondary Indications – Paediatrics (Off-label)

Indication Age Dose Duration Supervision Evidence Basis

Homozygous Familial Hypercholesterolaemia (OFF-LABEL) ≥10 years Starting: 10–20 mg once daily; Maximum: 40–80 mg once daily based on response Long-term Specialist only (Paediatric Lipidology) Extrapolated from adult data; Indian tertiary care practice; adjunct to apheresis/other therapies

Age Restrictions:

• Not recommended below 10 years of age

• Use in children 6–10 years only in exceptional circumstances (severe familial hypercholesterolaemia) under specialist supervision

• Safety and efficacy not established below 6 years

Additional Notes:

• Atorvastatin is primarily hepatically metabolised (<2% excreted renally)

• Use with caution in severe renal impairment — increased risk of myopathy

• Consider lower starting dose (10 mg) and careful monitoring in CKD Stage 4–5

Active Liver Disease Contraindicated

Note: Atorvastatin is extensively hepatically metabolised. Contraindicated if ALT/AST persistently >3× ULN without explanation.

• Known hypersensitivity to atorvastatin or any excipients

• Active liver disease or unexplained persistent elevation of serum transaminases (>3× ULN)

• Pregnancy (teratogenic — disrupts fetal cholesterol synthesis)

• Breastfeeding

• Concurrent use with strong CYP3A4 inhibitors (itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, telithromycin) at high statin doses

• Concurrent use with cyclosporine (unless closely monitored with atorvastatin ≤10 mg)

• Concurrent use with gemfibrozil

• History of hepatic disease or heavy alcohol use — increased hepatotoxicity risk

• History of statin-associated myopathy or myalgia

• Predisposing factors for myopathy/rhabdomyolysis:

• Advanced age (≥65 years)

• Renal impairment

• Untreated hypothyroidism

• Concurrent fibrates (fenofibrate preferred over gemfibrozil)

• Concurrent niacin (≥1 g/day)

• Concurrent CYP3A4 inhibitors

• Asian ethnicity (may require lower doses)

• Low body weight

• Personal or family history of hereditary muscular disorders

• Interacting medications (see Drug Interactions)

• Diabetes risk — statins may slightly increase HbA1c and fasting glucose

Parameter Information

Overall Safety Contraindicated — Category X equivalent; evidence of fetal harm

Risk Statins inhibit cholesterol synthesis essential for fetal development; case reports of congenital anomalies (CNS, limb defects)

Preferred Alternatives Bile acid sequestrants (cholestyramine, colesevelam) if lipid lowering essential during pregnancy

When Use May Be Justified Never justified — must be discontinued immediately if pregnancy occurs

Women of Childbearing Potential Ensure reliable contraception during therapy; discontinue atorvastatin at least 1–3 months before planned conception

Monitoring Pregnancy test before initiation in women of childbearing potential

Parameter Information

Compatibility Contraindicated — avoid breastfeeding during atorvastatin therapy

Expected Drug Level in Milk Unknown; likely excreted based on pharmacokinetic properties

Risk to Infant Potential disruption of infant lipid metabolism; theoretical risk of adverse effects

Preferred Alternatives If lipid-lowering essential during lactation: bile acid sequestrants (not absorbed systemically)

Recommendation Either avoid breastfeeding or discontinue atorvastatin; consult cardiologist/lipidologist

Parameter Recommendation

Starting dose 10 mg orally once daily

Titration Increase cautiously at 4–6 week intervals; use lowest effective dose

Maximum recommended 40–80 mg (same as adults); individualize based on comorbidities

Increased Risks Myopathy, rhabdomyolysis (especially with polypharmacy, renal impairment, or hypothyroidism); new-onset diabetes

Additional Precautions Check renal function and thyroid status before initiation; assess for drug interactions; monitor for muscle symptoms; CK if symptoms develop

Interacting Drug Mechanism Effect Management

Cyclosporine Inhibits OATP1B1/OATP1B3 transport and CYP3A4 7–10 fold increase in atorvastatin exposure; high myopathy/rhabdomyolysis risk Avoid if possible; if essential, limit atorvastatin to ≤10 mg and monitor closely

Strong CYP3A4 Inhibitors (itraconazole, ketoconazole, posaconazole, clarithromycin, telithromycin, HIV protease inhibitors) CYP3A4 inhibition Significantly increased atorvastatin levels; myopathy risk Avoid combination or use lowest atorvastatin dose (10 mg); suspend statin temporarily during short-term azole/antibiotic course

Gemfibrozil Inhibits glucuronidation and OATP transport 2–3 fold increase in statin exposure; high rhabdomyolysis risk Avoid combination — use fenofibrate instead if fibrate needed

Niacin (≥1 g/day) Additive myotoxicity Increased myopathy risk Use with caution; monitor CK and muscle symptoms

Fusidic Acid (systemic) Unknown mechanism Case reports of rhabdomyolysis Suspend statin during fusidic acid treatment; resume 7 days after last fusidic acid dose

Colchicine Additive myotoxicity; possible transport inhibition Increased myopathy/rhabdomyolysis risk Use with caution; avoid in renal impairment; monitor for muscle symptoms

Grapefruit Juice (>1.2 L/day) CYP3A4 inhibition in gut wall Increased atorvastatin absorption and levels Avoid large quantities (>1 glass/day)

Diltiazem, Verapamil Moderate CYP3A4 inhibition; 2–4 fold increase in atorvastatin levels Limit atorvastatin to ≤20 mg; monitor for myopathy

Amlodipine Mild CYP3A4 inhibition Limit atorvastatin to ≤40 mg; generally safe combination

Erythromycin Moderate CYP3A4 inhibition Limit atorvastatin to ≤20 mg; monitor CK if concurrent use necessary

Fenofibrate Additive myopathy risk (less than gemfibrozil) Preferred fibrate for combination; monitor for myopathy; avoid in renal impairment

Rifampicin CYP3A4 induction Reduced atorvastatin levels and efficacy

Warfarin Possible modest increase in INR Monitor INR when starting, stopping, or changing atorvastatin dose; adjust warfarin if needed

Digoxin Possible modest increase in digoxin levels Monitor digoxin levels; usually clinically insignificant

Oral Contraceptives Increased ethinyl estradiol and norethindrone exposure Consider when selecting contraceptive dose

Antacids (aluminium/magnesium) May reduce atorvastatin absorption (modest) Separate administration by 2 hours if possible; usually not clinically significant

• Headache

• Myalgia (muscle aches without CK elevation; 5–10%)

• Nasopharyngitis, pharyngolaryngeal pain

• Arthralgia

• Diarrhoea, constipation

• Dyspepsia, nausea

• Flatulence

• Mild transaminase elevation (usually transient)

• Insomnia

Adverse Effect Clinical Action

Myopathy (CK >10× ULN with muscle symptoms) Discontinue immediately; check renal function (myoglobin); supportive care; rule out contributing factors

Rhabdomyolysis (muscle breakdown, CK markedly elevated, myoglobinuria, acute kidney injury) Discontinue immediately; hospitalisation; aggressive IV hydration; monitor renal function; may require dialysis

Hepatotoxicity (ALT/AST persistently >3× ULN) Discontinue; investigate other causes; usually reversible; rechallenge not recommended

Immune-Mediated Necrotising Myopathy (IMNM) (rare autoimmune myopathy; persists after statin discontinuation) Discontinue; immunosuppressive therapy may be needed; rheumatology/neurology referral

New-Onset Diabetes Mellitus (dose-related; more common at 80 mg) Continue statin (CV benefit outweighs diabetes risk); manage diabetes with lifestyle/pharmacotherapy

Interstitial Lung Disease (very rare) Discontinue; respiratory evaluation; usually reversible

Hypersensitivity Reactions (angioedema, rash, anaphylaxis — rare) Discontinue permanently; supportive care

4–12 weeks after initiation or dose change Fasting lipid profile (to assess response and adjust dose); LFTs (once at 6–12 weeks; routine monitoring not required unless symptoms)

Long-term (every 6–12 months) Lipid profile annually; LFTs not required routinely unless high dose, FDC, or symptoms suggestive of hepatotoxicity; fasting glucose/HbA1c periodically (diabetes surveillance); CK only if muscle symptoms develop

If muscle symptoms develop Check CK; discontinue if CK >10× ULN or if CK elevated with symptoms; if CK normal but symptoms tolerable, may continue with close monitoring

Monotherapy:

• Atorlip™ (Cipla) — 5 mg, 10 mg, 20 mg, 40 mg, 80 mg

• Lipitor™ (Pfizer) — 10 mg, 20 mg, 40 mg, 80 mg

• Storvas™ (Sun Pharma/Ranbaxy) — 5 mg, 10 mg, 20 mg, 40 mg, 80 mg

• Atorva™ (Zydus) — 5 mg, 10 mg, 20 mg, 40 mg

• Lipvas™ (Cipla) — 10 mg, 20 mg

• Atocor™ (Dr. Reddy's) — 10 mg, 20 mg, 40 mg

• Aztor™ (USV) — 10 mg, 20 mg, 40 mg, 80 mg

Fixed-Dose Combinations (Examples):

Regulatory: Listed under NLEM 2022 (10 mg, 20 mg tablets); NPPA price controlled for scheduled strengths; available through Jan Aushadhi at lower prices; widely available in government supply

1. High-intensity statin in ASCVD — In all patients with established atherosclerotic cardiovascular disease (post-MI, stroke, PAD), start atorvastatin 40–80 mg unless contraindicated; do not wait for lipid panel results in ACS

1. Atorvastatin vs Simvastatin — Atorvastatin has longer half-life (can be taken any time of day), more potent LDL-lowering, and fewer drug interactions (simvastatin has significant interaction with amlodipine requiring dose cap)

1. Myalgia without CK elevation — Common (5–10%); often tolerable; if bothersome, try temporary discontinuation, rechallenge, dose reduction, alternate-day dosing, or switch to rosuvastatin or pravastatin

1. CK monitoring strategy — Do not routinely monitor CK; check only if muscle symptoms develop; do not discontinue for asymptomatic mild CK elevation (<5× ULN); discontinue if CK >10× ULN or if CK elevated with symptoms

1. Statin-associated diabetes — High-intensity statins (80 mg) slightly increase diabetes risk; CV benefit far outweighs this risk; continue statin and manage diabetes appropriately

1. Perioperative management — May continue atorvastatin through most surgeries; if NPO for extended period, omitting a few doses is acceptable; resume as soon as oral intake possible

statin; hyperlipidaemia; dyslipidaemia; cardiovascular-prevention; ASCVD; familial-hypercholesterolaemia; CYP3A4; myopathy-risk; pregnancy-contraindicated; NLEM-India; hepatic-monitoring; Schedule-H

RxIndia v1.0 — 06 Apr 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Dyslipidaemia

• AIIMS Cardiovascular Drug Formulary

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• IAP Guidelines (paediatric familial hypercholesterolaemia)

• SPARCL Trial (stroke prevention evidence)

• SHARP Trial (CKD evidence)

• CARDS, ASCOT-LLA, TNT Trials (primary and secondary prevention evidence)

• Indian specialist practice consensus (NAFLD/statin safety)