Simvastatin
Mechanism :
Simvastatin is a potent inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the b-hydroxy acid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin.
Indication :
- Hypercholesterolemia
- Familial hypercholesterolemia
Contraindications :
Contraindicated in active liver disease, renal impairment, unexplained increase in transaminases and in hypersensitivity to simvastatin. Liver function tests should be carried out.
Dosing :
<10 years:
Safety and efficacy not established. An initial dose of 5 mg PO once daily titrated up to 10 to 20 mg PO once daily has been used in small studies.
>10 years:
10 mg oral daily evening dose; maximum: 40 mg/day.
Recommended dose:
10-40 mg/day; dose adjustment at 4 weeks or more.
Adverse Effect :
Reversible increases in liver enzymes and creatinine kinase, nausea, diarrhea, constipation, skin rash, peripheral neuropathy, rarely rhabdomyolysis.
Interaction :
Immunosuppressive therapy including Cyclosporin and Prednisolone: May increase plasma statin concentration and the risk of muscle toxicity.
Fibrates/or Nicotinic Acid, Erythromycin, Clarithromycin: May also be associated with an increased risk of serious myopathy.
Itraconazole and Ketoconazole: Increase risk of myopathy with simvastatin.
Warfarin: Anticoagulant effects of warfarin increased by simvastatin.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | 10–20 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 |
Hepatic Dose :
If there is active hepatic disease or persistent raised liver aminotransaminases, then administration of simvastatin is contraindicated.