simvastatin

CLINICAL USE

HMG CoA reductase inhibitor:Primary hypercholesterolaemia

DOSE IN NORMAL RENAL FUNCTION

10–80 mg at night

PHARMACOKINETICS

Molecular weight :418.6

%Protein binding :>95

%Excreted unchanged in urine : 13

Volume of distribution (L/kg) :54

half-life – normal/ESRD (hrs) :1.9/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 :

10 to 20 : mg daily. In severe renal impairment doses above 10 mg should be used with caution (doses up to 40 mg have been used)

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unlikely to be dialysed. Dose as in GFR <10 mL/min

HD :Unlikely to be dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Anti-arrhythmics: increased risk of myopathy with amiodarone – do not exceed 20 mg of simvastatin.1

Antibacterials: increased risk of myopathy with clarithromycin, daptomycin, telithromycin and erythromycin – avoid concomitant use; increased risk of myopathy with fusidic acid

Anticoagulants: effects of coumarins enhanced

Antifungals: increased risk of myopathy with itraconazole, posaconazole or ketoconazole and possibly miconazole – avoid concomitant use; possibly increased risk of myopathy with imidazoles and triazoles

Antivirals: increased risk of myopathy with atazanavir, indinavir, nelfinavir, ritonavir or saquinavir and possibly amprenavir or lopinavir – avoid concomitant use; concentration reduced by efavirenz

Calcium-channel blockers: increased risk of myopathy with verapamil and possibly diltiazem – do not exceed 20 mg of simvastatin with verapamil or 40 mg with diltiazem.1

Ciclosporin: increased risk of myopathy – do not exceed 10 mg of simvastatin.1Grapefruit: increased risk of myopathy – avoid concomitant useHormone antagonists: possibly increased risk of myopathy with danazol – do not exceed 10 mg of simvastatin.1Lipid-lowering agents: increased risk of myopathy with fibrates – do not exceed 10 mg of simvastatin except with fenofibrate;1 gemfibrozil –avoid; and nicotinic acid

ADMINISTRATION

Reconstition

–

Route

Oral

Rate of Administration

–

Comments

–

OTHER INFORMATION

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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