Rationale:
- Coadministration with diltiazem may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and potentiate the risk of statin-induced myopathy.
- Proposed mechanism is diltiazem inhibition of simvastatin metabolism via intestinal and hepatic CYP450 3A4
- The authors suggest that coadministration of simvastatin with diltiazem was roughly equivalent in therapeutic potency to doubling the dosage of simvastatin
- Simvastatin dosage should not exceed 10 mg daily when used in combination with diltiazem.
- benefits of this combination should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis
- Fluvastatin, pravastatin, and rosuvastatin are probably safer alternatives in patients receiving diltiazem, since they are not metabolized by CYP450 3A4
- MHRA August 2012 does issue do not exceed 20mg simvastatin in combination with diltiazem
- Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine.
- Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.
- http://www.drugs.com/drug-interactions/diltiazem-hydrochloride-sr-with-simvastatin-890-2667-2067-0.html?professional=1
- http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm
- Simvastatin Patient Information Leaflet
- http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?nidchk=1&cs=&s=PL&pt=2&segment=4421&dd=280606
- Simvastain MHRA safety update - Aug 2012
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