[Interaction risk with statin switch].
BACKGROUND
The article is based upon two adverse drug reaction reports after switch from atorvastatin to simvastatin. Simvastatin interactions with warfarin and the cytochrome P450-3A4 inhibitor diltiazem were suspected as possible causes of the events (fatal intracranial haemorrhage with INR > 8 and myopathy). Relevant literature was examined to evaluate potential differences in atorvastatin and simvastatin interaction profiles.


METHODS
Relevant interaction studies were identified through searches in the databases PubMed and ISI Web of Knowledge. Interaction databases referring to primary sources and product monographs were also examined.


RESULTS
One interaction study was found for the warfarin-atorvastatin combination, but this showed no relevant changes in prothrombin time. Three interaction studies were identified for the combination warfarin-simvastatin and these showed consistently increased INR and/or reduced dose requirements for warfarin (10-30%) after starting treatment with simvastatin. Three studies had investigated the degree to which simvastatin and atorvastatin interact with a CYP3A4 inhibitor in the same population. In these studies, plasma concentrations of both statins increased, but the increases were several times greater for simvastatin than for atorvastatin.


CONCLUSIONS
Interaction studies show that atorvastatin and simvastatin display differences in interaction potential toward warfarin and drugs inhibiting CYP3A4 metabolism. It is important to consider the risk of interactions when switching to or starting simvastatin treatment.
Molden
Espen
E
Farmasøytisk institutt, Universitetet i Oslo.
Westergren
Tone
T
D000924:Anticholesteremic Agents / Q000009:adverse effects*; D000925:Anticoagulants / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000069059:Atorvastatin; D004110:Diltiazem / Q000009:adverse effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D009135:Muscular Diseases / Q000139:chemically induced; D011758:Pyrroles / Q000009:adverse effects*; D012307:Risk Factors; D019821:Simvastatin / Q000009:adverse effects*; D014859:Warfarin / Q000009:adverse effects
D000924:Anticholesteremic Agents; D000925:Anticoagulants; D000959:Antihypertensive Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014859:Warfarin; D000069059:Atorvastatin; D019821:Simvastatin; D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human; D004110:Diltiazem