Prolonged induction of warfarin metabolism and a paradoxical INR response in a mitral valve replacement patient receiving rifampicin for infective endocarditis

Dawson, Jessica L; Dedigama, Maneesha; Elliot, David J.; Sorich, Michael J.; Mangoni, Arduino A.; Rowland, Andrew

doi:10.15761/brcp.1000112

Cited by 6 publications

(8 citation statements)

References 9 publications

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“…Then INR dropped to below the desired 7–14 days from the combination. In the case reported by Dawson et al 34 , it took 17 days for the interaction to become apparent. These reports, aligned with our report, indicate that the time-course to rifampin CYP2C9 induction is more than 14 days.…”

Section: Discussionmentioning

confidence: 92%

Genetic Polymorphism Effect on Warfarin–Rifampin Interaction: A Case Report and Review of Literature

Salem

Eljilany

El-Bardissy

et al. 2021

PGPM

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Warfarin–rifampin interaction has been reported since the 1970s. Due to rifampin’s strong induction of CYP2C9 , most cases could not attain the target international normalized ratio (INR) despite warfarin dose escalation. Genetic polymorphisms determine up to 50% of warfarin dose variability. A 38-year-old woman was started on warfarin and rifampin for cerebral venous sinus thrombosis and pulmonary tuberculosis. Over six weeks, the daily warfarin dose was increased from 3 to 10 mg to attain three consecutive in-clinic therapeutic INRs. She completed three complications-free months of warfarin treatment with time in therapeutic range (TTR) of 46%. We performed retrospective genetic testing to determine the patient’s CYP2C9, CYP4F2 , and VKORC1 genotypes and whether they had affected the interaction outcome. The analysis revealed that the subject carries CYP2C9*3*3 and VKORC1-1639 (GA) mutations, classifying her as a slow metabolizer and, hence, highly warfarin-sensitive. This was reflected on how the case responded to a relatively lower dose than previously reported cases that did not achieve the target on warfarin daily doses up to 35 mg. This is the first report addressing the genotype effect on this interaction. Patients with genetic variants requiring low warfarin doses are more likely to respond at a feasible dose while on rifampin. Future studies to evaluate warfarin–rifampin-gene interaction are warranted.

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Section: Discussionmentioning

confidence: 92%

Genetic Polymorphism Effect on Warfarin–Rifampin Interaction: A Case Report and Review of Literature

Salem

Eljilany

El-Bardissy

et al. 2021

PGPM

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“…In contrast, where the increase in CYP3A4 activity is due to induction of CYP3A4 expression, a single dose of modafinil would be unlikely to increase CYP3A4‐mediated oestrogen clearance to a significant extent, but the interaction would persist for a prolonged period upon complete removal of modafinil from the body. Indeed, we and others have demonstrated previously that induction of CYP3A4 activity by alternate inducers persists for up to 3 weeks following cessation of the induction perpetrator. The clinical consequence of this time course is that co‐administration of a single dose of modafinil with the contraceptive pill would be unlikely to place a female at increased risk of unplanned pregnancy.…”

Section: Discussionmentioning

confidence: 59%

“…The clinical consequence of this time course is that co‐administration of a single dose of modafinil with the contraceptive pill would be unlikely to place a female at increased risk of unplanned pregnancy. However, a female may be at increased risk of unplanned pregnancy for a prolonged time (based on the turnover of this enzyme potentially up to 2 weeks) following cessation of steady state dosing of modafinil.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of modafinil as a perpetrator of metabolic drug–drug interactions using a model informed cocktail reaction phenotyping trial protocol

Rowland

Dyk

Warncken

et al. 2018

Brit J Clinical Pharma

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“…This indicates that a dose reduction of warfarin may not be required within the first week of stopping rifampicin but frequent INR monitoring is required. Jessica Dawson (2016) also reported a drop of INR from 2.50 to 1.50 with empirically dose reduction of 14% (from 35 mg per day to 30 mg per day) after five days discontinuation of rifampicin [11].…”

Section: Discussionmentioning

confidence: 97%

Time course of enzyme induction in rifampicin-warfarin interaction: A case report

Hon¹,

Purnata²,

Ching³

2018

Int J Case Rep Images

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Introduction: Concomitant administration of rifampicin and warfarin poses a challenge in achieving stable therapeutic international normalised ratio (INR). There is no published case report in Singapore to show the time course for enzyme induction and de-induction in Asian patient. Case Report: A 90-year-old man was on a stable warfarin dose of 1.5 mg daily for stroke prevention in atrial fibrillation with therapeutic INR before switching to rivaroxaban and subsequently apixaban. He was initiated with a 9-month course of rifampicin, isoniazid, pyridoxine and ethambutol for treatment of pulmonary tuberculosis. Hence, apixaban was switched back to warfarin. Therapeutic INR was first achieved 20 days after a dose increment of 166% in warfarin from 1.5 mg daily to 4 mg daily. The INR subsequently decreased again and warfarin dose was increased to 4.5 mg daily. A 2-fold increment in warfarin dose was required to reach the second therapeutic INR at week-7. INR was stable in therapeutic range with 4.5 mg daily and patient was followed up every 2 to 4 weeks. Time in therapeutic range (TTR) was 74% over the course of nine months. After five days of discontinuing rifampicin, INR decreased to 1.70 despite maintaining the same dose of warfarin. Conclusion: The total time course of enzyme induction takes about six to seven weeks to reach a steady state. The

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Prolonged induction of warfarin metabolism and a paradoxical INR response in a mitral valve replacement patient receiving rifampicin for infective endocarditis

Cited by 6 publications

References 9 publications

Genetic Polymorphism Effect on Warfarin–Rifampin Interaction: A Case Report and Review of Literature

Genetic Polymorphism Effect on Warfarin–Rifampin Interaction: A Case Report and Review of Literature

Evaluation of modafinil as a perpetrator of metabolic drug–drug interactions using a model informed cocktail reaction phenotyping trial protocol

Time course of enzyme induction in rifampicin-warfarin interaction: A case report

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