Warfarin Institute of America

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ESCITAPROLAM INTERACTION WITH WARFARIN 

Brand Name: Lexapro

There is no established interaction between Coumadin (warfarin) and Lexapro (escitaprolam); however, Lexapro, a selective serotonin reuptake inhibitor (SSRI), may enhance the anticoagulant effect of warfarin.  Several reports are published regarding the impact of SSRI and oral anticoagulants.  Most pharmacokinetic reports describe little to no apparent effect of SSRI on warfarin serum concentration^1,2. One report describes a 65% increase in serum warfarin concentration in normal subjects when co-administered with fluvoxamine⁴. However, several cases of increasing in INR with associated bleeding with fluoxetine and paroxetine have been reported^2,3,5.  The mechanism of the interaction is unclear.  It may be related to of cytochrome P450 isoenzymes. Warfarin is mainly metabolized by CYP1A2, CYP2C9, and CYP3A4.  Most of the SSRIs inhibit at least one of those pathways. Escitaprolam only appears to weakly inhibit CYP2D6.  Hence, it is the least likely drug to have the interaction with warfarin, but careful warfarin management is necessary to avoid any adverse events.   

It is recommended that the level of warfarin should be monitored closely if a SSRI is initiated, increased/decreased in dose, or discontinued.  Another reason to monitor INR closely in these patients is that there may be an increase in patients’ daily activity when SSRI is working in those patients.  Patients tend to be more active when they are less depressed, so they may metabolize the drug faster.

 References:

1. Lemberger L et al. Fluoxetine: Clinical Pharmacology and Physiologic Disposition. J Clin Psychiatry. 1985, 46(3): 14-9
2. Ford MA et al. Lack of Effect of Fluoxetine on the Hypoprothrombinemic Response of Warfarin. J Clin Psychopharmacol. 1997, 17:110-2
3. Bannister SJ et al. Evaluation of the Potential Interactions of Paroxetine with Diazepam, Cimetidine, Warfarin, and Digoxin. Acta Psychiatr Scand. 1989, 80:102-6
4. Benfield P and Ward A. Fluvoxamine, A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Efficiency in Depressive Illness. Drugs. 1986, 32:313-34 
5. Sayal KS et al. Psychotropic Interactions with Warfarin. Acta Psychiatr Scand 2000: 102: 250-55

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Last updated February 6, 2005