Inability to Attain Oral Anticoagulation

Casner, Paul R.

doi:10.1097/00007611-199612000-00014

Cited by 21 publications

(15 citation statements)

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“…Since the World Health Organization (WHO) adopted INR in the 1980s, 28 more than nineteen cases of warfarin-rifampin interaction have been reported. 14,[29][30][31][32][33][34][35][36] Despite extensive warfarin dose escalation over a prolonged time, the majority could not attain target INR while on the combination. 14,[29][30][31][32][34][35][36] Cases are summarized in [Table 1].…”

Section: Discussionmentioning

confidence: 99%

“…14,[29][30][31][32][33][34][35][36] Despite extensive warfarin dose escalation over a prolonged time, the majority could not attain target INR while on the combination. 14,[29][30][31][32][34][35][36] Cases are summarized in [Table 1]. Excessive warfarin exposure and hemorrhage after rifampin discontinuation have been reported, implying the importance of close monitoring and careful dose de-escalation after rifampin stoppage.…”

Section: Discussionmentioning

confidence: 99%

“…Comparable patterns have been observed in other cases when the commencement sequence was a few days apart or when rifampin was added to chronic warfarin. In 1996, Casner 29 reported a patient who had one therapeutic INR after 13 rifampin days, which declined to subtherapeutic until ten days after the rifampin stoppage. The case reported by Kim et al 31 had one in-target INR after warfarin 20 mg, which dropped then increased back to target for a week after escalation to 25 mg on rifampin days 25 and 33.…”

Section: Discussionmentioning

confidence: 99%

“…[25][26][27] After the INR test was universally adopted, 28 several reports demonstrated that most patients who required the anti-infective along with anticoagulation were unable to maintain target INR. 14,[29][30][31][32][33][34][35][36] This report aims to describe a case who received warfarin and rifampin concomitantly and the interaction outcome, and to perform genetic testing to determine the patient's CYP2C9, VKORC1, CALU, and CYP4F2 genotypes and whether they could explain the response to warfarin dose escalation.…”

Section: Introductionmentioning

confidence: 99%

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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: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…During the 1970s to 1980s, studies have shown that rifampin reduced warfarin's area under the curve (AUC) and effect by up to 85%, and several reports showed a significant warfarin dose requirements increase 17–22 . After INR was adopted during the 1980s, 23 more than 30 cases have been reported 24–34 . Most could not attain target INR while on the combination despite extensive escalations up to 30 mg per day 24–30 .…”

mentioning

confidence: 99%

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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Rifamycin Antibacterial Agents

2012

Antibacterial Agents

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Inability to Attain Oral Anticoagulation

Cited by 21 publications

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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

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

Rifamycin Antibacterial Agents

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