Probable drug–drug interaction between dabigatran and quinidine resulting in thrombin time rebound despite multiple idarucizumab doses

George, Stephy; Taburyanskaya, Margarita; Lewis, Vicky

doi:10.1097/mbc.0000000000000782

Cited by 8 publications

(3 citation statements)

References 21 publications

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“…Interacting drug (bleeding outcomes) Ritonavir [38,39] Strong CYP3A4 inhibitor/P-gp inhibitor Amiodarone [35,[40][41][42] Weak CYP3A4 inhibitor/P-gp inhibitor Clarithromycin [43] Strong CYP3A4/P-gp inhibitor Miconazole (topical) [44] Mechanism unclear Loperamide [45] Mechanism unclear Quinidine [46] Moderate P-gp inhibitor Fluconazole [35] Moderate CYP3A4 inhibitor Cyclosporine [35] Weak CYP3A4/P-gp inhibitor Phenytoin [35,42,47] Mechanism unclear Diltiazem [36,48] Moderate CYP3A4/P-gp inhibitor Verpamil [36] Moderate CYP3A4/P-gp inhibitor…”

Section: Mechanism Of Interaction a [37]mentioning

confidence: 99%

Drug-drug interactions with direct oral anticoagulants associated with adverse events in the real world: A systematic review

Crowther

et al. 2020

Thrombosis Research

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Background Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous thrombosis. Due to their novelty, pharmacokinetic DOAC drug-drug interactions (DDIs) that result in clinical adverse events have not been well-documented. Objective This study aims to systematically review reported pharmacokinetic DDIs resulting in clinical adverse events through documented observational evidence to better inform clinicians in clinical practice. Methods A comprehensive literature review of EMBASE, MEDLINE, and Ovid HealthStar was conducted through March 10th, 2020. Two independent reviewers screened and extracted data from eligible articles according to pre-established inclusion and exclusion criteria. Articles reporting bleeding or thrombotic outcomes in non-controlled (observational) settings resulting from suggested pharmacokinetic DOAC DDIs were included. Results A total of 5567 citations were reviewed, of which 24 were included following data extraction. The majority were case reports ( n = 21) documenting a single adverse event resulting from a suspected DOAC DDI, while the remaining papers were a case series ( n = 1) and cohort studies ( n = 2). The most commonly reported interacting drugs were amiodarone and ritonavir (bleeding), and phenobarbital, phenytoin, and carbamazepine (thrombosis). Bleeding events more often resulted from a combined mechanism (P-glycoprotein AND CYP3A4 inhibition), whereas thrombotic events resulted from either combined OR single P-glycoprotein/CYP3A4 induction. Conclusion Current literature evaluating the real-world risk of DOAC DDIs is limited to few case reports and retrospective observational analyses. Clinicians are encouraged to continue to report suspected drug interactions resulting in adverse events.

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Section: Mechanism Of Interaction a [37]mentioning

confidence: 99%

Drug-drug interactions with direct oral anticoagulants associated with adverse events in the real world: A systematic review

Crowther

et al. 2020

Thrombosis Research

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“…Apixaban: no anticipated drug interaction 15. Dabigatran: dabigatran 150 mg bid + dextromethorphan 20 mg/quinidine 10 mg bid resulting in lower GIB in a patient with acute kidney injury and ↑ thrombin time despite several doses of idarucizumab (1 case report 25 ); ↑ in AUC by 53%—product monograph recommends separating administration of dabigatran by at least 2 hours before quinidine 4 16. Edoxaban: single dose of edoxaban 60 mg and quinidine 300 mg × 2 days, ↑ in AUC by 77% and C max by 85% (clinical trial in 42 healthy volunteers 22 ) 17.…”

Section: Development Of the Practice Toolmentioning

confidence: 99%

“… 15. Dabigatran: dabigatran 150 mg bid + dextromethorphan 20 mg/quinidine 10 mg bid resulting in lower GIB in a patient with acute kidney injury and ↑ thrombin time despite several doses of idarucizumab (1 case report 25 ); ↑ in AUC by 53%—product monograph recommends separating administration of dabigatran by at least 2 hours before quinidine 4 …”

Section: Development Of the Practice Toolmentioning

confidence: 99%