Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature.
A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient's goal INR. The literature supports a drug interaction between warfarin and fluvastatin due to the strong affinity of fluvastatin for the cytochrome P450 enzyme 2D6. This interaction has not been seen with atorvastatin. Lovastatin also reportedly has caused increases in INR when coadministered with warfarin. It is unclear whether simvastatin interacts with warfarin, but it may increase INRs slightly or increase serum simvastatin levels. One case report describes an interaction between simvastatin and the anticoagulant acenocoumarol, which resulted in an elevated INR. Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione. Thus, until more definitive data are available, clinicians should monitor the INR closely after starting statin therapy in any patient receiving anticoagulation therapy.
Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA.
Miranda R
MR
Andrus
D000074:Acenocoumarol / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D000069059:Atorvastatin; D004347:Drug Interactions; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D006949:Hyperlipidemias / Q000188:drug therapy; D007211:Indoles / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D019934:International Normalized Ratio / Q000009:adverse effects; D008297:Male; D010349:Patient Compliance; D011758:Pyrroles / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D020246:Venous Thrombosis / Q000188:drug therapy; D014859:Warfarin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D000925:Anticoagulants; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077340:Fluvastatin; D014859:Warfarin; D000069059:Atorvastatin; D019821:Simvastatin; D000074:Acenocoumarol