CLINICAL USE


HMG CoA reductase inhibitor:Primary hypercholesterolaemia

DOSE IN NORMAL RENAL FUNCTION

10–80 mg at night

PHARMACOKINETICS

  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :418.6
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :>95
  • %Excreted unchanged in urine &nbsp &nbsp : 13
  • Volume of distribution (L/kg) &nbsp &nbsp &nbsp :54
  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :1.9/–

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50 &nbsp &nbsp : Dose as in normal renal function
  • 10 to 20 &nbsp &nbsp : Dose as in normal renal function
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp :
  • 10 to 20 &nbsp &nbsp : 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 &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Unlikely to be dialysed. Dose as in GFR <10 mL/min

  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Unlikely to be dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux &nbsp :Unknown dialysability. Dose as in GFR <10 mL/min
  • CAV/VVHD &nbsp &nbsp &nbsp: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