Lesson of the month 2: Pulmonary embolism in a patient on rivaroxaban and concurrent carbamazepine

Burden, Thomas J.; Thompson, Charlotte; Bonanos, Efstathios; Medford, Andrew R L

doi:10.7861/clinmedicine.18-1-103

Cited by 20 publications

(17 citation statements)

References 4 publications

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“…Presented to the Emergency department with acute onset shortness of breath, chest pain and palpitations, computed tomographic pulmonary angiography (CTPA) revealed multiple bilateral pulmonary emboli. Carbamazepine was hypothesized to be responsible of the DOAC inefficacy as the anti Xa activity was reduced in both cases (71).…”

Section: Case Reportsmentioning

confidence: 99%

Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs

et al. 2018

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Direct oral anticoagulants (DOACs), namely apixaban, dabigatran, edoxaban, and rivaroxaban are being increasingly prescribed among the general population, as they are considered to be associated to lower bleeding risk than classical anticoagulants, and do not require coagulation monitoring. Likewise, DOACs are increasingly concomitantly prescribed in patients with epilepsy taking, therefore, antiepileptic drugs (AEDs), above all among the elderly. As a result, potential interactions may cause an increased risk of DOAC-related bleeding or a reduced antithrombotic efficacy. The objective of the present review is to describe the pharmacokinetic interactions between AEDs and DOACs of clinical relevance. We observed that there are only few clinical reports in which such interactions have been described in patients. More data are available on the pharmacokinetics of both drugs classes which allow speculating on their potential interactions. Older AEDs, acting on cytochrome P450 isoenzymes, and especially on CYP3A4, such as phenobarbital, phenytoin, and carbamazepine are more likely to significantly reduce the anticoagulant effect of DOACs (especially rivaroxaban, apixaban, and edoxaban). Newer AEDs not affecting significantly CYP or P-gp, such as lamotrigine, or pregabalin are not likely to affect DOACs efficacy. Zonisamide and lacosamide, which do not affect significantly CYP activity in vitro, might have a quite safe profile, even though their effects on P-gp are not well-known, yet. Levetiracetam exerts only a potential effect on P-gp activity, and thus it might be safe, as well. In conclusion, there are only few case reports and limited evidence on interactions between DOACs and AEDs in patients. However, the overall evidence suggests that the interaction between these drug classes might be of high clinical relevance and therefore further studies in larger patients' cohorts are warranted for the future in order to better clarify their pharmacokinetic and define the most appropriate clinical behavior.

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Section: Case Reportsmentioning

confidence: 99%

Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs

et al. 2018

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“…Coadministration of RIV and CBZ or PHT is commonly prescribed to post-stroke seizure or post-stroke epilepsy patients. Drug interactions have been reported in some case studies with decreased RIV exposures, resulting in adverse effects, including an increased risk of bleeding or pulmonary embolisms [28][29][30]38,39]. However, there have been no studies performed in animals or humans to investigate potential effects of CBZ/PHT on both PK and PD of RIV.…”

Section: Discussionmentioning

confidence: 99%

Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban

et al. 2020

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Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have been reported in several previous studies when they are coadministered, there are no studies of the interactions between these drugs. Therefore, our study was conducted to solve this lack of information. The potential effects of CBZ/PHT were investigated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RIV between the control group (RIV alone) and the test groups (RIV administered with CBZ/PHT) in rats using the noncompartmental analysis (NCA) and the compartmental model approach. The NCA results indicate that AUCt of RIV decreased by 57.9% or 89.7% and Cmax of RIV decreased by 43.3% or 70.0% after administration of CBZ/PHT, respectively. In addition, both CBZ and PHT generally reduced the effects of RIV on the prothrombin times of the blood samples. PK profiles of RIV were most properly described by a two-compartment disposition model with a mixed first- and zero-order absorption kinetics and a first-order elimination kinetics. The compartmental model approach showed that a 211% or 1030% increase in CL/F of RIV and a 33.9% or 43.4% increase in D2 of RIV were observed in the test groups by the effects of CBZ/PHT, respectively. In conclusion, CBZ and PHT significantly reduced RIV exposure and therefore reduced the therapeutic effects of RIV. Consequently, this might result in adverse events due to insufficient RIV concentration to attain its therapeutic effects. Further studies are needed to validate this finding.

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“…Editor -We read with interest the article by Burden et al on pulmonary embolism in a patient on rivaroxaban and concurrent carbamazepine. 1 While the authors highlight the interaction between rivaroxaban and carbamazepine, one should be mindful of other risk factors that might reduce the therapeutic efficacy of a direct oral anticoagulant (DOAC), namely severe obesity, possibly due to suboptimal dosing regime in such patients.…”

Section: Beware Of Thromboembolic Risk In Obese Patients On Direct Ormentioning

confidence: 99%

“…Editor -I read with interest the informative review by Tidswell and Singer regarding the definition, pathophysiology, diagnosis and management of sepsis. 1 The article correctly highlights that the issue of fluid choice for patients with sepsis is a key dilemma for both researchers and clinicians. The authors suggest that there is little to recommend one crystalloid over another as first-line resuscitation fluid.…”

Section: Which Crystalloid? Does Fluid Choice Influence Patient Outcomentioning

confidence: 99%

Beware of thromboembolic risk in obese patients on direct oral anticoagulants (DOACs)

2018

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Lesson of the month 2: Pulmonary embolism in a patient on rivaroxaban and concurrent carbamazepine

Cited by 20 publications

References 4 publications

Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs

Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs

Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban

Beware of thromboembolic risk in obese patients on direct oral anticoagulants (DOACs)

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