Simvastatin and Ezetimibe
Hypolipidaemic/Anti-atheroma · Cholesterol absorption inhibitor/HMG-CoA reductase inhibitor
Indications
Primary hypercholesterolaemia or mixed hyperlipidaemia not controlled by a statin alone or when patient is already treated with a statin and ezetimibe. Homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatment.
Dosage
Adults: Hypercholesterolaemia: Usually 1 tab of 10/20 mg as single dose in evening. Adjust at minimum 4 wk intervals according to response; max 10 mg ezetimibe and 80 mg simvastatin daily. Homozygous familial hypercholesterolaemia: 10 mg ezetimibe and 40 mg simvastatin or 10 mg ezetimibe and 80 mg simvastatin as a single dose in evening. Children: Not recommended.
Adverse Effects
Headache, flatulence, myalgia, abdominal pain, diarrhoea, fatigue, raised serum transaminase and creatine kinase. Reports of immune-mediated necrotising myopathy.
Risk Factor (Pregnancy/Lactation)
Pregnancy: Contraindicated in pregnancy. Lactation: Contraindicated or not recommended. Contraindications: Active liver disease, moderate or severe liver impairment. Precautions: Severe renal impairment. Perform liver function tests before and during treatment, withdraw if ALT or AST >3 x ULN. History of liver disease. Advise patients to report unexplained muscle weakness or pain; monitor creatine kinase levels, withdraw if >5 x ULN. Renal impairment, hypothyroidism, history of muscle toxicity, family or personal history of muscle disorders, alcohol abuse, elderly (>70 years). Risk of interstitial lung disease; advise patients to report symptoms. Risk factors for diabetes; monitor patients with risk factors, incl hypertension, raised triglycerides, BMI >30kg/m2 and fasting blood glucose 5.6-6.9mmol/L. Asian patients. Surgery.
Interactions
Digoxin, coumarin anticoagulants, cyclosporin, gemfibrozil and other fibrates, nicotinic acid, erythromycin, clarithromycin, macrolide antibiotics, azole antifungals, other CYP3A4 inhibitors, immunosuppressants, nefazodone, protease inhibitors, grapefruit juice, danazol, amiodarone, calcium-channel blockers, QATP1B inhibitors, BCRP inhibitors (e.g., elbasvir, grazoprevir), rifampicin, colchicine, cobicistat, lomitapide, with or within 7 days of systemic fusidic acid, bile acid sequestrants.
Advice to Patient
Take with or without meals in evening. Avoid high intake of grapefruit juice (>1 L per day).
Pharmacokinetics
SIMVASTATIN: Onset of action: > 3days. Peak effect: 2 wks. LDL-C reduction: 20-40 mg/day: 35%-41%. Average HDL-C increase: 5%-15%. Average triglyceride reduction: 7%-30%. Absorption: 85%. <5% reaches the systemic circulation. Metabolism: Hepatic; extensive first-pass effect. Bioavailability: <5%. Half-life elimination: Unknown. Time to peak: 1.3-2.4 hrs. Excretion: Faeces (60%). Urine (13%). EZETIMIBE: Onset of action: Within 1 wk. Max effect: 2-4 wks. Metabolism: Small intestine and liver. Bioavailability: Variable. Hepatic impairment: Moderate hepatic impairment (Child-Pugh score 7-9): AUC increased 3-4 times. Severe hepatic impairment (Child-Pugh 10-15): AUC increased 5-6 times. Renal impairment: Severe renal dysfunction (CrCl <30 mL/min/1.73 m2): AUC increased 1.5 times. Half-life elimination: 22 hrs (ezetimibe and metabolite).
Brands with this active ingredient
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