Wednesday, December 9, 2015

Simvastatin – Diltiazem Interaction

Interaction: MAJOR
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
Management:
  • 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
Monitoring:
  • 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.
References:
  1. http://www.drugs.com/drug-interactions/diltiazem-hydrochloride-sr-with-simvastatin-890-2667-2067-0.html?professional=1
  2. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm
  3. Simvastatin Patient Information Leaflet
  4. http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?nidchk=1&cs=&s=PL&pt=2&segment=4421&dd=280606
  5. Simvastain MHRA safety update - Aug 2012

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