OBJECT DRUGS

Anticoagulants, Oral:

• Acenocoumarol
• Warfarin (Coumadin, etc.)

PRECIPITANT DRUGS

Antidepressants:

• Fluoxetine (Prozac, etc.)
• Fluvoxamine (Luvox, etc.)

Comment:

CYP2C9 inhibitors increase S-warfarin concentrations; the onset of increased anticoagulant effect is usually gradual (over 7-10 days). Most studies involve warfarin, but assume that acenocoumarol interacts similarly until proved otherwise. Phenprocoumon is metabolized primarily by glucuronidation and theoretically would be unlikely to interact with CYP2C9 inhibitors. Also, SSRIs as a class may increase the risk of bleeding in patients receiving oral anticoagulants, even in the absence of a pharmacokinetic interaction.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Other SSRIs such as citalopram (Celexa), escitalopram (Lexapro), desvenlafaxine (Pristiq), venlafaxine (Effexor), paroxetine (Paxil) or sertraline (Zoloft) may be less likely to increase the hypoprothrombinemic response to warfarin, but SSRIs may increase bleeding risk even in the absence of increased INR response due to their antiplatelet effects.
• Monitor: Monitor for altered anticoagulant effect if fluvoxamine or fluoxetine is initiated, discontinued, or changed in dosage.