Interaction between warfarin and short-term intravenous amiodarone in intensive care unit patients after cardiac surgery

Takase, Tomoki; Ikesue, Hiroaki; Tohi, Makiko; Ueta, Hiroshi; Mima, Hiroyuki; Koyama, Tadaaki; Hashida, Tohru

doi:10.1186/s40780-018-0110-6

Cited by 7 publications

(5 citation statements)

References 24 publications

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“…32 The first patient was also initiated on amiodarone before adding rifampin, 32 which is known to inhibit warfarin metabolism and reduce warfarin dose requirement. 45 Interestingly, in consistence with most of the previously reported cases, our data showed that the mean required warfarin dose to attain the target INR in the responders group was 10.4 mg.…”

Section: Discussionsupporting

confidence: 85%

“…Another recent case series showed successful target attainment at a median of 30 days following rifampin addition to warfarin by 6 out of 7 patients at daily doses of 5.5, 9.5, 12.5, 16, 20, and 33 mg; which were increased from baseline requirements of 3.5, 3, 3, 8.5, 10.7, and 8.4 mg, respectively 32 . The first patient was also initiated on amiodarone before adding rifampin, 32 which is known to inhibit warfarin metabolism and reduce warfarin dose requirement 45 . Interestingly, in consistence with most of the previously reported cases, our data showed that the mean required warfarin dose to attain the target INR in the responders group was 10.4 mg.…”

Section: Discussionmentioning

confidence: 99%

“…We also compared the mean geneticbased calculated daily doses, estimated by the Gage algorithm with an additional 30% dose reduction for each CYP2C9 *8 or *11 allele, 5 in the warfarin-responders and nonresponders. Additionally, we compared the percentage time in therapeutic range (TTR), calculated by the Rosendaal method, 43 as well as the warfarin sensitivity index (WSI), 44,45 defined as the average INR divided by the corresponding maintenance dose or maximum-tried dose, in the carriers and the noncarriers of warfarinsensitizing CYP2C9/VKORC1 genotypes. In addition, we investigated the WSI correlation with the genetic-based calculated dose requirements.…”

Section: Methodsmentioning

confidence: 99%

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Warfarin‐Rifampin‐Gene (WARIF‐G) Interaction: A Retrospective, Genetic, Case–Control Study

Salem

El-Bardissy

Elshafei

et al. 2023

Clin Pharma and Therapeutics

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Warfarin is extensively metabolized by cytochrome P450 2C9 (CYP2C9). Concomitant use with the potent CYP2C9 inducer, rifampin, requires close monitoring and dosage adjustments. Although, in theory, warfarin dose increase should overcome this interaction, most reported cases over the last 50 years have not responded even to high warfarin doses, but some have responded to modest doses. To investigate the genetic polymorphisms' impact on this unexplained interpatient variability, we performed genotyping of CYP2C9, VKORC1, and CYP4F2 for warfarin and rifampin concomitant receivers from 2016 to 2022 at Hamad Medical Corporation, Doha, Qatar. We identified and included 36 patients: 22 responders and 14 nonresponders. Warfarin-responders were significantly more likely to have one or more warfarin-sensitizing CYP2C9/VKORC1 alleles than nonresponders (odds ratio = 23.2, 95% confidence interval = 3.2-195.6; P = 0.0001). The mean genetic-based pre-interaction calculated dose was significantly lower for responders than for nonresponders (P < 0.001); and was negatively correlated with warfarin sensitivity index (WSI) (r = −0.58; P = 0.0002). The median percentage time in therapeutic range and mean WSI were significantly higher in the warfarin-sensitizing CYP2C9/VKORC1 alleles carriers than noncarriers (P = 0.017 and 0.0004, respectively). Whereas the warfarin-sensitizing CYP2C9/VKORC1 genotypes were associated with modest onrifampin warfarin dose requirements, the noncarriers would have required more than double these doses to respond. Warfarin-sensitizing CYP2C9/VKORC1 genotypes and low genetic-based warfarin calculated doses were associated with higher warfarin sensitivity and better anticoagulation quality in patients receiving rifampin concomitantly.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Warfarin‐Rifampin‐Gene (WARIF‐G) Interaction: A Retrospective, Genetic, Case–Control Study

Salem

El-Bardissy

Elshafei

et al. 2023

Clin Pharma and Therapeutics

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“…For warfarin combined with amiodarone, several studies demonstrate that amiodarone has a significant effect on the anticoagulant effect of warfarin 31 , 32 . In this study, it shows that when patients are combined with amiodarone, the EC50 value of the anticoagulant effect will decrease by 0.602 mg/L.…”

Section: Discussionmentioning

confidence: 99%

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method

Xia,

Cai,

Chen

et al. 2024

Sci Rep

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The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

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“…The patient underwent emergency surgery for a partial small intestine resection and colostomy with a diagnosis of nonocclusive mesenteric ischemia. A PT-INR/dose of WF ratio 13) was used to rule out dose-dependent changes in anticoagulant effects and to confirm effects on metabolic processes. This work was approved the University of the Ryukyus Ethics Review Committee (Approval No.…”

Section: Introductionmentioning

confidence: 99%

Warfarin Drug-Drug Interactions with Amiodarone and Tramadol in a Patient with Paroxysmal Atrial Fibrillation: A Case Report

et al. 2023

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Amiodarone and tramadol are known to have drug-drug interactions that potentiate the effects of the anticoagulant warfarin. Herein we report a case which suggests increasing prothrombin time-international normalized ratio (PT-INR) and PT-INR/dose ratio due to the concomitant administration of warfarin, amiodarone (a cytochrome P450 2C9 inhibitor) and tramadol (an enhancer of anticoagulant effects of warfarin). A 72-yearold woman underwent emergency surgery following a suspected non-obstructive mesenteric ischemia, and diagnosis was confirmed. After surgery, the patient was given 2 mg/day of WF, and tramadol/acetaminophen, followed by amiodarone. After the concomitant dose of the triple combination, the PT-INR increased to over 7.02 (above the upper limit of the laboratory). The physician consulted the pharmacist for dose adjustment, and the pharmacist recommended a reduction in the dose to 0.5 mg. After restarting warfarin, PT-INR was controlled to 1.66-2.02. However, the PT-INR/dose ratio increased from 1.22 to 3.32-4.04 compared to the initial dose. The results suggest that these enhanced anticoagulant effects may be due to the inhibition of WF metabolism. Although the patient underwent resection of the small intestine, the effects of oral vitamin K1 were observed one day after administration. In conclusion, frequent PT-INR monitoring, and pharmacist intervention such as the assessment and dose adjustment in this report should be beneficial during anticoagulation therapy when multiple concomitant medications with suspected drug-drug interactions are present.

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Interaction between warfarin and short-term intravenous amiodarone in intensive care unit patients after cardiac surgery

Cited by 7 publications

References 24 publications

Warfarin‐Rifampin‐Gene (WARIF‐G) Interaction: A Retrospective, Genetic, Case–Control Study

Warfarin‐Rifampin‐Gene (WARIF‐G) Interaction: A Retrospective, Genetic, Case–Control Study

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method

Warfarin Drug-Drug Interactions with Amiodarone and Tramadol in a Patient with Paroxysmal Atrial Fibrillation: A Case Report

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