Gefitinib with Warfarin Interaction Details
Brand Names Associated with Gefitinib
- Gefitinib
- Iressa®
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 27, 2023
Interaction Effect
Increased prothrombin time and INR values and an increased risk of bleeding
Interaction Summary
Concomitant use of gefitinib and warfarin has resulted in bleeding events and INR elevations in some patients. In a retrospective study, 6 of 12 patients experienced prothrombin time (PT) and INR elevation following concomitant gefitinib and warfarin use . Therefore, If gefitinib and warfarin are coadministered, the patient should be monitored regularly for changes in PT or INR , especially during the first 2 weeks following warfarin initiation. If PT or INR values become elevated, a warfarin dose adjustment may be needed .
Severity
Moderate
Onset
Unspecified
Evidence
Established
How To Manage Interaction
If gefitinib and warfarin are coadministered, monitor the patient regularly for changes in prothrombin time (PT) or INR, especially during the first 2 weeks following warfarin initiation. If PT or INR values increase, a warfarin dose adjustment may be needed . Concomitant use of gefitinib and warfarin has resulted in bleeding events and INR elevations in some patients .
Mechanism Of Interaction
Unknown
Literature Reports
A) Prothrombin time (PT) and INR elevations were reported in 6 of 12 patients within 2 weeks of receiving gefitinib and warfarin concomitantly in a retrospective study of patients with non-small cell lung cancer in a hospital in Japan. Of the 12 patients, 2 (16.7%) had liver metastases. According to inpatient and outpatient database records, 296 patients received at least one gefitinib prescription between September 1, 2002 and January 31, 2007. Among the 296 patients, 12 (4.1%) had also received a warfarin prescription at the same time and were included in the study. None of the 6 patients with elevated PT and INR experienced a bleeding event. A warfarin dose adjustment was required in all 6 patients. Of the 7 factors evaluated for a possible association with the elevated PT and INR values (age, gender, smoking status, liver metastasis, performance status, liver dysfunction, and response to treatment), liver dysfunction was the only factor associated with increased PT and INR values (p=0.01). Authors postulate that competition between the R(+) enantiomer of warfarin and gefitinib for CYP3A4 inhibition or the inhibition of warfarin metabolism, also a CYP3A4 substrate, by gefitinib may be responsible for this interaction. Gefitinib also extensively binds (approximately 97%) to human plasma protein and warfarin is also highly (97% to 99%) but reversibly bound to albumin binding site I. As a result, the coadministration of gefitinib may cause displacement of the binding site, thereby increasing the unbound fraction of warfarin. The increased concentration of unbound warfarin may cause hypoprothrombinemia, which could result in a PT and INR elevation .
Gefitinib Overview
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Gefitinib is used to treat non-small cell lung cancer that has spread to other parts of the body in people with certain types of tumors. Gefitinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
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.
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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.