Schedule H

Oral

• Tablets: 5 mg, 10 mg, 20 mg, 40 mg

• Fixed-dose combinations: Rosuvastatin + Ezetimibe, Rosuvastatin + Fenofibrate, Rosuvastatin + Clopidogrel, Rosuvastatin + Aspirin (various strengths)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Primary Hypercholesterolaemia and Mixed Dyslipidaemia

Parameter Details

Starting dose 5–10 mg once daily (preferably at bedtime)

Titration Reassess lipid profile at 4 weeks; increase by 5–10 mg increments if LDL-C target not achieved

Usual maintenance dose 10–20 mg once daily

Maximum dose 40 mg once daily (reserved for severe hypercholesterolaemia; specialist supervision)

Clinical Notes:

• Initiate at 5 mg in patients of Asian ethnicity, elderly (>70 years), or those with renal/hepatic impairment

• Can be taken at any time of day, but consistency preferred

• LDL-C reduction of approximately 45–55% expected at 10–20 mg dose

1. Primary and Secondary Prevention of Cardiovascular Events

Parameter Details

Starting dose 10 mg once daily

Titration Based on LDL-C response and cardiovascular risk category

Usual maintenance dose 10–20 mg once daily

Maximum dose 40 mg once daily (very high-risk cases; specialist decision)

Clinical Notes:

• For secondary prevention (post-MI, ACS, stroke), aim for LDL-C <70 mg/dL or ≥50% reduction

• Primary prevention in high-risk individuals (diabetes, CKD, high ASCVD risk score)

• Often combined with antiplatelet therapy

1. Homozygous Familial Hypercholesterolaemia

Parameter Details

Starting dose 20 mg once daily

Titration May increase to maximum dose after 4 weeks if tolerated

Usual maintenance dose 20–40 mg once daily

Maximum dose 40 mg once daily

Clinical Notes:

• Usually requires combination therapy (ezetimibe, PCSK9 inhibitors, LDL apheresis)

• Specialist lipidologist supervision mandatory

• Limited response expected as monotherapy

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Notes

Non-alcoholic Fatty Liver Disease (NAFLD) with dyslipidaemia 10–20 mg once daily Long-term OFF-LABEL; Specialist only (Hepatologist/Gastroenterologist); Evidence: Limited Indian data; observational studies suggest benefit in NAFLD with elevated cardiovascular risk

Chronic Kidney Disease (cardiovascular risk reduction) 10 mg once daily Long-term OFF-LABEL; Evidence: AURORA and SHARP trials; benefit primarily in non-dialysis CKD

PAEDIATRIC DOSING (Specialist Only)

Important: Rosuvastatin use in children is restricted to specialist supervision (Paediatric Cardiologist or Lipidologist) only.

Primary Indications

Heterozygous Familial Hypercholesterolaemia (Children ≥10 years)

10–17 years 5 mg once daily Increase at 4-week intervals based on LDL-C response 20 mg once daily

Clinical Notes:

• Requires confirmed diagnosis of familial hypercholesterolaemia

• Initiate only after 6–12 months of dietary intervention has failed

• Monitor growth parameters and pubertal development during long-term therapy

Safety Monitoring:

• Baseline: Lipid profile, LFTs (ALT, AST), CPK, renal function

• Follow-up: LFTs at 4 weeks, then every 3–6 months; lipid profile every 3 months initially

• CPK if myalgia develops

• Monitor height, weight, and Tanner staging annually

Age Restriction: NOT RECOMMENDED below 10 years except in homozygous familial hypercholesterolaemia under specialist lipidologist supervision in tertiary care settings.

Secondary Indications – Paediatrics (Off-label)

Indication Dose Notes

Homozygous Familial Hypercholesterolaemia (<10 years) 5–20 mg once daily OFF-LABEL; Specialist only; requires combination therapy; extremely limited Indian data

Key Point: Rosuvastatin is minimally metabolised by CYP450; renal excretion accounts for ~10% of elimination, but exposure increases significantly in severe renal impairment.

Caution: Active liver disease with unexplained persistent transaminase elevation (>3× ULN) is a contraindication to initiation.

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

• Pregnancy (confirmed or planned)

• Lactation

• Hypersensitivity to rosuvastatin or any excipient

• Concomitant use with ciclosporin (markedly increases rosuvastatin exposure)

• Severe hepatic impairment (Child-Pugh C)

• Myopathy or history of statin-induced myopathy

• History of liver disease or significant alcohol consumption

• Renal impairment (dose adjustment required)

• Asian ethnicity — higher systemic exposure; start at lower dose

• Hypothyroidism — increased risk of myopathy; ensure euthyroid state before initiating

• Diabetes mellitus or prediabetes — small increased risk of new-onset diabetes

• Elderly (>70 years) — higher risk of myopathy; start low

• Concomitant use with fibrates, niacin, or other myopathy-inducing drugs

• Personal or family history of hereditary muscular disorders

• Previous intolerance to other statins

Aspect Details

Overall safety Contraindicated; cholesterol and its derivatives are essential for fetal development

Preferred alternatives Discontinue statin therapy during pregnancy; lipid-lowering generally not required

Pre-conception advice Discontinue rosuvastatin at least 1 month before planned conception

If exposure occurs Counsel patient regarding potential risks; fetal anomaly scan recommended

Monitoring Not applicable — drug should not be used

Aspect Details

Compatibility Not compatible with breastfeeding

Expected levels in milk Unknown; likely excreted based on lipophilicity

Preferred alternatives Defer pharmacological lipid-lowering therapy until cessation of breastfeeding; dietary measures only

If use unavoidable Advise against breastfeeding during therapy

Aspect Recommendation

Starting dose 5 mg once daily

Titration Slow; reassess at 6–8 weeks rather than 4 weeks

Maximum dose 20 mg once daily preferred; avoid 40 mg in patients >70 years

Additional risks Increased risk of myopathy, cognitive effects, falls (if dizziness occurs), reduced renal reserve

Monitoring More frequent CPK monitoring if muscle symptoms; baseline and periodic renal function assessment

Interacting Drug Effect Recommendation

Ciclosporin Increases rosuvastatin AUC by ~7-fold Contraindicated — do not co-administer

Gemfibrozil Increases rosuvastatin levels 2-fold; significantly increased myopathy risk Avoid combination; if fibrate needed, use fenofibrate instead

Atazanavir, Lopinavir/ritonavir, Darunavir (HIV protease inhibitors) Marked increase in rosuvastatin exposure (OATP1B1 inhibition) Avoid or limit rosuvastatin to 5–10 mg/day maximum

Regorafenib, Eltrombopag Increased rosuvastatin levels Avoid or use lowest effective dose

Warfarin Enhanced anticoagulant effect; increased INR Monitor INR closely at initiation and dose changes; adjust warfarin as needed

Interacting Drug Effect Recommendation

Fenofibrate Additive myopathy risk (lower than gemfibrozil) May co-prescribe with monitoring; check CPK if muscle symptoms develop

Niacin (>1 g/day) Additive myopathy and hepatotoxicity risk Use with caution; limit rosuvastatin to 20 mg/day

Erythromycin, Clarithromycin Modest increase in rosuvastatin levels Monitor for muscle symptoms

Aluminium/Magnesium antacids Reduce rosuvastatin absorption by ~50% Administer rosuvastatin at least 2 hours before antacids

Colchicine Additive myopathy risk Use with caution; monitor for muscle symptoms

Rifampicin May alter rosuvastatin levels (OATP1B1 effect) Monitor lipid response; may need dose adjustment

Ezetimibe Additive LDL-lowering; generally safe combination Monitor LFTs; no major interaction

Oral contraceptives (ethinylestradiol, norgestrel) Increased levels of contraceptive hormones Generally clinically insignificant; no dose adjustment needed

• Myalgia and muscle weakness

• Headache

• Dizziness

• Nausea, abdominal pain

• Constipation

• Asthenia (fatigue)

• Elevated liver transaminases (usually transient, <3× ULN)

• Proteinuria (usually transient, tubular origin)

Adverse Effect Action Required

Rhabdomyolysis (CPK >10× ULN with muscle symptoms ± renal impairment) Rare but potentially fatal; discontinue immediately; hospitalisation for IV fluids and monitoring of renal function

Myopathy (CPK >5× ULN with symptoms) Discontinue; evaluate for secondary causes; symptoms usually resolve within weeks

Immune-mediated necrotising myopathy (IMNM) Rare autoimmune condition; may persist after discontinuation; requires immunosuppressive therapy

Hepatotoxicity (ALT/AST >3× ULN persistent) Discontinue; evaluate for other causes; rechallenge not recommended

New-onset diabetes mellitus Small increased risk; does not outweigh cardiovascular benefit in high-risk patients

Stevens-Johnson syndrome / TEN Extremely rare; immediate discontinuation and dermatology referral

Interstitial lung disease Rare; discontinue and evaluate

Phase Parameters Frequency

Baseline Lipid profile (fasting), LFTs (ALT, AST), serum creatinine, eGFR, fasting glucose/HbA1c, TSH, CPK (if high myopathy risk) Before initiation

After initiation / dose change Lipid profile 4–8 weeks

After initiation / dose change LFTs 6–12 weeks

Stable long-term therapy Lipid profile Every 6–12 months

Stable long-term therapy LFTs Annually

As needed CPK Only if unexplained muscle pain, tenderness, or weakness develops

High-risk patients Fasting glucose or HbA1c Annually (monitor for new-onset diabetes)

• Crestor (AstraZeneca)

• Rozavel (Sun Pharma)

• Rosuvas (Sun Pharma)

• Rosumac (Macleods)

• Rozucor (Torrent)

• Rosulip (Cipla)

• Novostat (Lupin)

• Arvast (Intas)

Fixed-Dose Combinations:

Note: Rosuvastatin 10 mg is included in NLEM 2022; NPPA price-controlled formulation available.

1. Potency advantage: Rosuvastatin is the most potent statin per milligram — 10 mg rosuvastatin provides LDL-C reduction equivalent to approximately 20–40 mg atorvastatin.

1. Asian ethnicity dosing: Indian patients may have higher systemic exposure; always initiate at 5 mg in treatment-naïve patients, especially elderly or those with comorbidities.

1. Myopathy screening: Consider baseline CPK in patients with hypothyroidism, renal impairment, elderly, high alcohol intake, or personal/family history of muscle disorders before initiating therapy.

1. Timing flexibility: Unlike simvastatin, rosuvastatin does not require evening dosing due to its long half-life (~19 hours); can be taken at any consistent time.

1. Statin intolerance management: If myalgia occurs, rule out hypothyroidism and vitamin D deficiency; consider rechallenge with lower dose or alternate-day dosing after symptom resolution.

1. Antacid separation: Counsel patients taking antacids to take rosuvastatin at least 2 hours before antacid administration to avoid reduced absorption.

statin; hyperlipidaemia; LDL-lowering; cardiovascular prevention; dyslipidaemia; NLEM India; myopathy-risk; pregnancy-contraindicated; renal-caution; Asian-dosing

RxIndia v1.0 — 25 Jan 2025

• CDSCO Product Database

• Indian Pharmacopoeia (latest edition)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• AIIMS Drug Formulary

• ICMR Guidelines on Dyslipidaemia Management (2023)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian specialist prescribing practices (Lipid Association of India recommendations)

• JUPITER, METEOR, AURORA trials (for evidence basis)