Warfarin with Telithromycin Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Telithromycin
- Ketek®
- Telithromycin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Telithromycin is a strong CYP3A4 inhibitor and concomitant use with warfarin (a CYP3A4 substrate) may result in increased warfarin exposure and effect (ie, increased INR and risk for bleeding). Alternatively, the suggested mechanism of interaction is alteration in intestinal flora that synthesize vitamin K . Although, in an unpublished placebo-controlled study of healthy subjects, oral telithromycin did not alter the bioavailability of warfarin , a case report described excessive anticoagulation accompanied by hemoptysis and blood-tinged mucus in a 73-year-old man after receiving a course of telithromycin concurrently with a stable dose regimen of warfarin . Additionally, in a nested case-control study of continuous warfarin users aged 65 years or older, there was a 2-fold increase in risk of bleeding requiring hospitalization with exposure to any antibiotic therapy, including macrolides. When possible, substitute telithromycin with an antibiotic with a low-risk profile for bleeding. If telithromycin treatment is necessary in a patient who is taking warfarin, more frequent monitoring of prothrombin times/INR is recommended , especially during initiation and discontinuation of the antibiotic .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of telithromycin and warfarin should be approached with caution as this may result in increased INR and thereby increase the risk for bleeding. When possible, substitute telithromycin with an antibiotic with a low-risk profile for bleeding. If concomitant use of telithromycin and warfarin is required, more frequent monitoring of the patient's INR is recommended, especially during initiation and discontinuation of telithromycin . Adjustment of the warfarin dose may be necessary in order to maintain the desired level of anticoagulation.
Mechanism Of Interaction
Disruption of vitamin K synthesis; inhibition of CYP3A4-mediated warfarin metabolism
Literature Reports
A) Initiation of antibiotics in patients on continuous warfarin therapy resulted in a significantly increased risk of serious bleeding requiring hospitalization according to a nested case-control study of United States Medicare part D beneficiaries aged 65 years and older (n=38,762). Patients on warfarin who received any antibiotic were twice as likely to be hospitalized for bleeding compared with matched controls on warfarin who were not exposed to antibiotics (adjusted odds ratio (aOR), 2.01; 95% CI, 1.62 to 2.5). Additionally, continuous-warfarin users were twice as likely to have a bleeding event that required hospitalization within 60 days of antibiotic exposure compared with non-exposure. Antibiotic exposure greater than 60 days from the index bleed was not significantly associated with increased risk of bleeding. Specific antibiotics with the highest bleeding risk were azole antifungals (aOR, 4.57; 95% CI, 1.9 to 11.03), followed by cotrimoxazole (aOR, 2.7; 95% CI, 1.46 to 5.05), cephalosporins (aOR, 2.45; 95% CI, 1.52 to 3.95), penicillins (aOR, 1.92; 95% CI, 1.21 to 2.07), macrolides (aOR, 1.86; 95% CI, 1.08 to 3.21), and quinolones (aOR, 1.69; 95% CI, 1.09 to 2.62) .
B) Excessive anticoagulation occurred in a 73-year-old man after receiving a course of telithromycin 800 mg daily concurrently with a stable dose regimen of warfarin. At the time of admission, the patient presented with an INR measurement of 11, accompanied by a 1-day history of hemoptysis, blood-tinged mucus, and dyspnea. Within 10 days prior to admission, he had been receiving warfarin 7.5 mg daily alternating with warfarin 6.25 mg daily, and a routine measurement of the INR showed a value of 3.1. Telithromycin was discontinued, warfarin was withheld for 4 days, and the patient received 2 units of fresh-frozen plasma, after which his INR declined to 2.5. Hemoptysis completely resolved and the patient resumed his prior warfarin regimen. The authors assign a Naranjo rating of 'probable' to the interaction reported .
C) In an unpublished placebo-controlled study of healthy subjects, oral telithromycin did not alter the bioavailability of warfarin. Subjects received a single dose of warfarin (25 mg) given on day 4 of telithromycin administration (800 mg daily for 7 days); prothrombin time data were presented. Studies employing multiple doses of warfarin in patients with infection, with prothrombin time assessments, are needed to further clarify the potential for interaction .
Warfarin Overview
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Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.
Telithromycin Overview
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Telithromycin is used to treat certain types of pneumonia (an infection of the lungs) that is caused by bacteria. Telithromycin is in a class of medications called ketolide antibiotics. It works by killing bacteria.
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Antibiotics such as telithromycin not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.