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Br J Clin Pharmacol. 2010 Dec;70(6):834-43. doi: 10.1111/j.1365-2125.2010.03780.x.

Effect of oseltamivir treatment on anticoagulation: a cross-over study in warfarinized patients.

Author information

1
Hoffmann-La Roche Inc., Nutley, NJ, USA. brian.davies@roche.com

Abstract

AIM:

To investigate whether oseltamivir enhances the anticoagulant effect of warfarin and to evaluate any pharmacokinetic (PK) interaction between the agents.

METHODS:

Twenty volunteers (mean age 62 years) receiving daily warfarin and with INR values of 2.0-3.5 during the previous 2 weeks were randomized to concomitant oseltamivir 75 mg twice daily for 4.5 days or warfarin alone in a two-way cross-over design with a 4-8 day wash-out. Anticoagulant effects were assessed by calculating overall [AUEC(0,96 h)] and observed maximum effect (E(max) ) increase from baseline in INR, decrease from baseline in factor VIIa, and change in vitamin K₁ concentrations. Plasma pharmacokinetics of (R)- and (S)-warfarin and oseltamivir were also assessed.

RESULTS:

For both treatments, changes in INR and factor VIIa during treatment were small; for net AUEC(0,96 h), least square mean values were -9.53 (oseltamivir + warfarin) and -1.69 h (warfarin alone) for INR (difference -7.84 h, 90% CI -18.86, 3.17 h), and 1.56 and 0.54 kIU l⁻¹ h, respectively, for factor VIIa (difference, 1.01 kIU l⁻¹ h; 90% CI -1.18, 3.21). Differences between the treatments in E(max) increase from baseline for INR, decrease from baseline for factor VIIa and change from baseline in vitamin K₁ concentration were not statistically significant. Oseltamivir did not alter warfarin pharmacokinetics. Oseltamivir was well tolerated in this study with no clinically significant adverse safety findings.

CONCLUSION:

Concomitant administration of oseltamivir for 4.5 days to volunteers on daily warfarin had little or no effect on warfarin pharmacokinetics and no effect on pharmacodynamics.

PMID:
21175439
PMCID:
PMC3014067
DOI:
10.1111/j.1365-2125.2010.03780.x
[Indexed for MEDLINE]
Free PMC Article

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