Published: 5 March 2015

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Check INR after starting Roxithromycin for Patients on Warfarin

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Prescriber Update 36(1): 3
March 2015

Some antibiotics can interact with warfarin which can increase the international normalised ratio (INR) and cause severe bleeding.

Roxithromycin was recently associated with a bleeding episode in a patient taking warfarin for atrial fibrillation. The patient (whose INR had been between 2 and 3) complained of abdominal pain three days after starting roxithromycin. An abdominal bleed was diagnosed and the INR was found to be greater than 7.

In the reports received by the Centre for Adverse Reactions Monitoring (CARM), roxithromycin accounted for 44% of the adverse event reports of increased INR in patients taking antibiotics and warfarin. The occurrence of an increased INR in association with the roxithromycin-warfarin combination was noted in a previous article of Prescriber Update (www.medsafe.govt.nz/profs/PUArticles/watchingbriefsMay08.htm#Roxithromycin).

In a recent observational study, 3.2% of patients taking warfarin and an antibiotic experienced an INR of 5.0 or more. ¹

In contrast, rifampicin markedly reduces the anticoagulant effect of warfarin.²

Prescribers should monitor the INR three days after (on day three)³ starting the following antibiotics:

• macrolides (erythromycin, azithromycin, clarithromycin, roxithromycin)
• fluoroquinolones (nalidixic acid and ciprofloxacin)
• selected cephalosporins (eg, cefamandole)
• co-trimoxazole

The mechanism of the interaction is not fully understood but may include inhibition of cytochrome P450, displacement of protein-bound warfarin, interference with platelet function, and the elimination of vitamin-K producing bacteria from the intestine. Fever itself may increase the catabolism of clotting factors and exaggerate a potential antibacterial-warfarin interaction.^{1, 4}

Please report all suspicions of medicine interactions to CARM.

References

1. Clark NP, Delate T, Riggs CS, et al. Warfarin-Associated Research Projects and Other Endeavors Consortium. 2014. Warfarin interactions with antibiotics in the ambulatory care setting. JAMA Internal Medicine. 174(3): 409-16.
2. Stockley IH. 2002. Stockley's Drug Interactions. London: Pharmaceutical Press.
3. Bryant L, Fishman T, et al. 2009. Drug interactions that matter and how to manage them. Journal of Primary Health Care. 1(2).
4. Sweetman SC (ed) 2011. Martindale: The Complete Drug Reference (37th Ed). Great Britain: Pharmaceutical Press. Warfarin. 1563-1572.