Stereoselective interaction between piroxicam and acenocoumarol

Bonnabry, Pascal; Desmeules, Jules Alexandre; Rudaz, Serge; Leemann, T.; Veuthey, Jean‐Luc; Dayer, P.

doi:10.1046/j.1365-2125.1996.03558.x

Cited by 13 publications

(3 citation statements)

References 7 publications

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“…Other NSAIDs such as diclofenac and naproxen are reported to increase the risk of bleeding, but no evidence of a pharmacokinetic interaction with coumarins has been reported (4,5). No effect of piroxicam, nabumetone or lornoxicam on acenocoumarol pharmacokinetics or INR levels has been found (27)(28)(29). Warfarin drug interactions with NSAIDs have been described more frequently, possibly due to the fact that warfarin is the oral anticoagulant most widely used worldwide.…”

Section: Discussionmentioning

confidence: 99%

Potential interaction between acenocoumarol and diclofenac, naproxen and ibuprofen and role of CYP2C9 genotype

Dijk¹,

Plat²,

Dijk³

et al. 2004

Thromb Haemost

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NSAIDs are reported to increase the risk of bleeding in coumarin users. The mechanism underlying this risk is inhibition of platelet aggregation, however a pharmacokinetic mechanism resulting in an increased International Normalised Ratio (INR) was proposed in some case reports in warfarin treated patients. In this retrospective cohort study the influence of diclofenac, naproxen and ibuprofen on the INR of outpatients stabilised on acenocoumarol therapy was investigated. We also determined the role of cytochrome P450 2C9 (CYP2C9) polymorphism on coumarin dosage and INR in NSAID users. The study was carried out at the Groningen Outpatient Thrombosis Service. A retrospective cohort study among patients who received both acenocoumarol and one of the NSAIDs under study was performed. Patients whose INR rose above the upper level of the therapeutic range (INR above 3.5 or 4.0) after an NSAID under study was added to the acenocoumarol therapy, were compared with patients who did not show such an elevation. A two-sample t-test (average acenocoumarol dosage, age), and chi-square tests (sex, therapeutic range, type of NSAID) were used to test for differences. Genotyping was carried out by analysing blood samples for the relevant CYP2C9 alleles. The study population consisted of 112 patients on stable acenocoumarol therapy, of which 52 (46%) showed an elevation of the INR above the desired therapeutic level (INR 3.5 and 4.0 respectively) after the start of an NSAID under study. In 12 patients, the INR increased above 6. The INR of the other 60 patients (54%) remained constant after the start of one of the NSAIDs under study. There were no statistically significant differences between patients with increased INR and patients without increased INR with regard to age, sex, therapeutic range and average acenocoumarol dosage. Eighty patients, of whom 36 showed an increased INR as a result of a potential acenocoumarol-NSAID drug interaction, were included in the genotyping study. No association between CYP2C9 genotype and an increased INR as a result of the drug-drug interaction was found. In nearly half of a cohort of elderly patients, the INR increased beyond the therapeutic range (INR 3.5 or 4.0) as a result of a potential pharmacokinetic drug-drug interaction between acenocoumarol and diclofenac, naproxen and ibuprofen. The average increase in INR was between 1 and 4. Polymorphism of CYP2C9 does not seem to be a relevant risk factor for the NSAID-acenocoumarol interaction.

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Section: Discussionmentioning

confidence: 99%

Potential interaction between acenocoumarol and diclofenac, naproxen and ibuprofen and role of CYP2C9 genotype

Dijk¹,

Plat²,

Dijk³

et al. 2004

Thromb Haemost

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“…This enabled the evaluation of both pharmacokinetic and pharmacodynamic interactions between tamsulosin and acenocoumarol without the risk of chronic anticoagulation. This approach has also been used extensively for screening for interactions with anticoagulants [2–4]. The study population of healthy young volunteers is appropriate given the higher risk of cerebral haemorrhage in elderly subjects.…”

Section: Discussionmentioning

confidence: 99%

A placebo‐controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol

Rolan¹,

Terpstra²,

Clarke³

et al. 2003

Brit J Clinical Pharma

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Aim To evaluate pharmacokinetic and pharmacodynamic interactions between tamsulosin and acenocoumarol. Methods Twelve healthy volunteers received tamsulosin 0.4 mg or placebo once daily for 9 days in a double-blind, cross-over study. On day 5 of each study period, a single 10-mg oral dose of racemic acenocoumarol was administered. Results The ratios (point estimates (90% confidence intervals)) of values in the presence and absence of tamsulosin were: AUC PT 1.01 (0.98, 1.03); maximum prothrombin time (Pt max ) 0.99 (0.94, 1.05); AUC (R)-acenocoumarol 1.02 (0.90, 1.16), and AUC (S)-acenocoumarol 1.03 (0.89, 1.20). Both combinations, tamsulosin and placebo with acenocoumarol, were well-tolerated. Conclusions Multiple doses of tamsulosin had no effect on the pharmacokinetics or pharmacodynamics of a single high dose of acenocoumarol.

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“…The pharmacokinetics of acenocoumarol has been reported 17 , 18 , 23 , 24 , 25 . The CYP genotypes of the volunteers participating in those studies were not established.…”

Section: Discussionmentioning

confidence: 99%

Altered pharmacokinetics of R - and S -acenocoumarol in a subject heterozygous for CYP2C9*3

Thijssen

Drittij

Vervoort

et al. 2001

Clinical Pharmacology & Therapeutics

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Stereoselective interaction between piroxicam and acenocoumarol

Cited by 13 publications

References 7 publications

Potential interaction between acenocoumarol and diclofenac, naproxen and ibuprofen and role of CYP2C9 genotype

Potential interaction between acenocoumarol and diclofenac, naproxen and ibuprofen and role of CYP2C9 genotype

A placebo‐controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol

Altered pharmacokinetics of R - and S -acenocoumarol in a subject heterozygous for CYP2C9*3

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