Simvastatin

Source: UK SPC (eMC) for Simvastatin 10 mg film-coated tablets, §4.2 (https://www.medicines.org.uk/emc/product/10665/smpc). ELDERLY (the focus of this page): §4.2 'Use in the elderly — No dosage adjustment is necessary.' However the US label §8.5 (PD-Rx simvastatin, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4bbbb5c9-6c29-bc3b-e063-6294a90a6cce) records that in a clinical study of simvastatin 80 mg daily, patients ≥65 years had an increased risk of myopathy including rhabdomyolysis compared with patients <65 years, and a pharmacokinetic study found mean plasma levels of total inhibitors approximately 45% higher in patients aged 70–78 years than in those aged 18–30; US §5.1 lists age 65 years or greater as a myopathy risk factor. TITRATION: adjustments, if required, should be made at intervals of not less than 4 weeks, up to a maximum of 80 mg/day as a single evening dose. HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA: recommended starting dose 40 mg/day in the evening, used as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or where such treatments are unavailable; with concomitant lomitapide the simvastatin dose must not exceed 40 mg/day. DIET: the patient should be placed on a standard cholesterol-lowering diet and continue it during treatment. DOSE CAPS WITH CONCOMITANT THERAPY (§4.2): with fibrates other than gemfibrozil (contraindicated) or fenofibrate, simvastatin must not exceed 10 mg/day; with amiodarone, amlodipine, verapamil, diltiazem, or products containing elbasvir or grazoprevir, simvastatin must not exceed 20 mg/day; dosing with a bile acid sequestrant should occur either more than 2 hours before or more than 4 hours after the sequestrant. MYOPATHY RISK (§4.4): the risk of myopathy/rhabdomyolysis is dose related — incidence was approximately 0.03%, 0.08% and 0.61% at 20, 40 and 80 mg/day respectively in the trial database, and approximately 1.0% at 80 mg/day versus 0.02% at 20 mg/day in post-myocardial-infarction patients; the risk of myopathy is greater with simvastatin 80 mg than with other statins of similar LDL-C-lowering efficacy. If an interacting agent is needed in a patient taking 80 mg, use a lower simvastatin dose or an alternative statin regimen. DIABETES (§4.4): statins as a class raise blood glucose and may produce hyperglycaemia requiring formal diabetes care in some at-risk patients, but this risk is outweighed by the vascular risk reduction and is not a reason to stop treatment; monitor at-risk patients (fasting glucose 5.6–6.9 mmol/L, BMI >30 kg/m2, raised triglycerides, hypertension) clinically and biochemically per national guidelines. PAEDIATRIC (stated as fixed mg doses, not per kg, hence paedDose is null): for children and adolescents with heterozygous familial hypercholesterolaemia (boys Tanner Stage II and above and girls at least one year post-menarche, 10–17 years of age), the recommended usual starting dose is 10 mg once a day in the evening, dosing range 10–40 mg/day with a maximum recommended dose of 40 mg/day, adjusted at intervals of 4 weeks or more after a standard cholesterol-lowering diet has been started; experience in pre-pubertal children is limited. Verify any under-18 use against a children's formulary. METHOD: oral administration, as a single dose in the evening. NOTE ON SOURCES: §4.5 was not retrieved in this bundle — the interactions below come from UK §4.2/§4.3 plus §7 of the US label. §4.4 and §4.8 were truncated at the fetch limit.