Potential Drug Interaction between Warfarin and Linezolid

Sakai, Yoshiro; Naito, Takaki; Arima, Chiyoko; Miura, Miho; Qin, Liang; Hidaka, Hidenobu; Masunaga, Kenji; Kakuma, Tatsuyuki; Watanabe, Hiroshi

doi:10.2169/internalmedicine.54.3146

Cited by 16 publications

(6 citation statements)

References 11 publications

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“…As cytochrome P450 enzymes do not play a significant role in linezolid metabolism, major pharmacokinetic drug-drug interactions with these drugs are not expected. Nevertheless, few case reports have demonstrated interactions between rifampicin, levothyroxine or warfarin leading to drug underexposure [93][94][95].…”

Section: Linezolid Drug Interactionsmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

2017

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Oxazolidinones are a class of synthetic antimicrobial agents with potent activity against a wide range of multidrug-resistant Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Oxazolidinones exhibit their antibacterial effects by inhibiting protein synthesis acting on the ribosomal 50S subunit of the bacteria and thus preventing formation of a functional 70S initiation complex. Currently, two oxazolidinones have been approved by the US Food and Drug Administration: linezolid and more recently tedizolid. Other oxazolidinones are currently under investigation in clinical trials. These antimicrobial agents exhibit a favourable pharmacokinetic profile with an excellent bioavailability and a good tissue and organ penetration. In-vitro susceptibility studies have shown that oxazolidinones are bacteriostatic against enterococci and staphylococci, and bactericidal for the majority of strains of streptococci. In the context of emergence of resistance to glycopeptides, oxazolidinones have become an effective alternative to vancomycin treatment frequently associated with nephrotoxicity. However, oxazolidinones, and linezolid in particular, are associated with significant adverse events, myelosuppression representing the main unfavourable side effect. More recently, tedizolid has been shown to effectively treat acute bacterial skin and skin structure infections. This newer oxazolidinone offers the advantages of once-daily dosing and a better safety profile in healthy volunteer studies (fewer gastrointestinal and haematological side effects). The potential use of tedizolid for other infections that could require longer therapy warrants further studies for positioning this new oxazolidinone in the available antimicrobial armamentarium. Moreover, other oxazolidinones are currently under active investigation.

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Section: Linezolid Drug Interactionsmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

2017

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“… 152 , 153 Disruption of intestinal flora synthesizing vitamin K and inhibition of cytochrome P450 enzymes involved in the metabolism of warfarin are proposed to be the major mechanisms involved in the drug interaction between antibiotics such as fluoroquinolones, amoxicillin-clavulanate and linezolid with warfarin resulting in increased risk of bleeding. 154 – 156 Concurrent use of amikacin and indomethacin with ibuprofen may result in increased amikacin exposure. Changes in renal blood flow is postulated to be the mechanism involved in explaining the DDI between NSAIDs and aminoglycosides.…”

Section: Discussionmentioning

confidence: 99%

Prediction of potential drug interactions between repurposed COVID-19 and antitubercular drugs: an integrational approach of drug information software and computational techniques data

Thomas

Birangal

Ray

et al. 2021

Therapeutic Advances in Drug Safety

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Introduction: Tuberculosis is a major respiratory disease globally with a higher prevalence in Asian and African countries than rest of the world. With a larger population of tuberculosis patients anticipated to be co-infected with COVID-19 infection, an ongoing pandemic, identifying, preventing and managing drug–drug interactions is inevitable for maximizing patient benefits for the current repurposed COVID-19 and antitubercular drugs. Methods: We assessed the potential drug–drug interactions between repurposed COVID-19 drugs and antitubercular drugs using the drug interaction checker of IBM Micromedex®. Extensive computational studies were performed at a molecular level to validate and understand the drug–drug interactions found from the Micromedex drug interaction checker database at a molecular level. The integrated knowledge derived from Micromedex and computational data was collated and curated for predicting potential drug–drug interactions between repurposed COVID-19 and antitubercular drugs. Results: A total of 91 potential drug–drug interactions along with their severity and level of documentation were identified from Micromedex between repurposed COVID-19 drugs and antitubercular drugs. We identified 47 pharmacodynamic, 42 pharmacokinetic and 2 unknown DDIs. The majority of our molecular modelling results were in line with drug–drug interaction data obtained from the drug information software. QT prolongation was identified as the most common type of pharmacodynamic drug–drug interaction, whereas drug–drug interactions associated with cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibition and induction were identified as the frequent pharmacokinetic drug–drug interactions. The results suggest antitubercular drugs, particularly rifampin and second-line agents, warrant high alert and monitoring while prescribing with the repurposed COVID-19 drugs. Conclusion: Predicting these potential drug–drug interactions, particularly related to CYP3A4, P-gp and the human Ether-à-go-go-Related Gene proteins, could be used in clinical settings for screening and management of drug–drug interactions for delivering safer chemotherapeutic tuberculosis and COVID-19 care. The current study provides an initial propulsion for further well-designed pharmacokinetic-pharmacodynamic-based drug–drug interaction studies. Plain Language Summary Introduction: Tuberculosis is a major respiratory disease globally with a higher prevalence in Asian and African countries than rest of the world. With a larger population of tuberculosis patients predicted to be infected with COVID-19 during this period, there is a higher risk for the occurrence of medication interactions between the medicines used for COVID-19 and tuberculosis. Hence, identifying and managing these interactions is vital to ensure the safety of patients undergoing COVID-19 and tuberculosis treatment simultaneously. Methods: We studied the major medication interactions that could likely happen between the various medicines that are currently given for COVID-19 and tuberculosis treatment using the medication interaction checker of a drug information software (Micromedex®). In addition, thorough molecular modelling was done to confirm and understand the interactions found from the medication interaction checker database using specific docking software. Molecular docking is a method that predicts the preferred orientation of one medicine molecule to a second molecule, when bound to each other to form a stable complex. Knowledge of the preferred orientation may be used to determine the strength of association or binding affinity between two medicines using scoring functions to determine the extent of the interactions between medicines. The combined knowledge from Micromedex and molecular modelling data was used to properly predict the potential medicine interactions between currently used COVID-19 and antitubercular medicines. Results: We found a total of 91 medication interactions from Micromedex. Majority of our molecular modelling findings matched with the interaction information obtained from the drug information software. QT prolongation, an abnormal heartbeat, was identified as one of the most common interactions. Our findings suggest that antitubercular medicines, mainly rifampin and second-line agents, suggest high alert and scrutiny while prescribing with the repurposed COVID-19 medicines. Conclusion: Our current study highlights the need for further well-designed studies confirming the current information for recommending safe prescribing in patients with both infections.

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“…Initial reports of the potential interaction between warfarin and linezolid surfaced in 2015 [7]. Linezolid can have the antimicrobial activity against Bifidobacterium, hence compromising the vitamin K production in the gut [7]. It is hypothesized that linezolid can decrease vitamin K production and potentiate the warfarin toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…It is generally well tolerated, but can have serious adverse e ects including myelosuppression [2], thrombocytopenia [3], serotonin syndrome [4], neuropathy [5], liver dysfunction [6], hypoglycemia, and lactic acidosis. However, rare but potential warfarin interaction leading to hypercoaguable state has been reported [7].…”

Section: Introductionmentioning

confidence: 99%

A Case of Linezolid Toxicity Presenting as a Sepsis Mimic

Mishra

Patel

Goel

et al. 2019

Case Reports in Critical Care

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Linezolid is an efficacious and well tolerated antimicrobial but can have serious adverse effects including myelo-suppression, serotonin syndrome, neuropathy, hypoglycemia, liver dysfunction, and lactic acidosis. The side effects are generally duration dependent; linezolid use is not recommended for more than 28 days. Case. A 59-year-old female presented with malaise, loss of appetite, and altered mentation. She had multiple medical comorbidities and required long-term anticoagulation with warfarin for venous thromboembolism. She had multiple medication allergies. Prior to admission, she was on linezolid for cellulitis of foot due to Methicillin-resistant Staphylococcus aureus (MRSA). On physical exam, she was drowsy and required endotracheal intubation for airway protection. Initial laboratory parameters showed lactic acidosis, thrombocytopenia, supra-therapeutic coagulation profile, low blood glucose, and transaminitis. Her altered mentation was due to hypoglycemia. The interaction with warfarin led to altered coagulation profile. She developed shock and vasopressors were initiated. Given her presentation, she was managed as severe sepsis. There were no active infectious foci attributing to decline of her clinical status. Linezolid was discontinued and she was managed with intravenous polymyxin B, aztreonam, and vancomycin. Her hemodynamic status improved within one day. She was extubated on Day 5 of her presentation. Her laboratory parameters showed gradual improvement over 12 days after discontinuation of linezolid. Retrospective evaluation revealed linezolid toxicity as possible cause of presentation. Linezolid toxicity can present as sepsis mimic and should be considered as a differential diagnosis while managing sepsis with other antimicrobial agents.

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Potential Drug Interaction between Warfarin and Linezolid

Cited by 16 publications

References 11 publications

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

Prediction of potential drug interactions between repurposed COVID-19 and antitubercular drugs: an integrational approach of drug information software and computational techniques data

A Case of Linezolid Toxicity Presenting as a Sepsis Mimic

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