ASK DIS: 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:

ASK DIS