Methotrexate with Flurbiprofen Interaction Details
Brand Names Associated with Methotrexate
- Amethopterin
- Methotrexate
- MTX
- Rheumatrex®
- Trexall®
Brand Names Associated with Flurbiprofen
- Ansaid®
- Flurbiprofen
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 17, 2023
Interaction Effect
Methotrexate toxicity (leukopenia, thrombocytopenia, anemia, nephrotoxicity, mucosal ulceration)
Interaction Summary
Use of NSAIDs with methotrexate has been shown in several case reports to increase methotrexate levels and cause toxicity resulting in deaths from severe hematologic and gastrointestinal toxicity ; however, flurbiprofen was used concurrently with methotrexate in 2 pharmacokinetic studies in rheumatoid arthritis patients, and it did not affect methotrexate disposition .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
In general, do not administer NSAIDs within 10 days of high-dose methotrexate (ie, doses used in cancer therapy). If concomitant administration is necessary, monitor closely for toxicity, especially myelosuppression and gastrointestinal toxicity. Concomitant administration of low-dose methotrexate (ie, doses used for arthritis, 7.5 to 15 mg per week) and NSAIDs has been well tolerated in many patients; however, caution is advised. The safety of higher doses of methotrexate, such as those used in psoriasis, in combination with NSAIDs has not been fully evaluated.
Mechanism Of Interaction
Decreased methotrexate clearance
Literature Reports
A) The potential for interaction between low dose methotrexate and ibuprofen or flurbiprofen was investigated in 6 patients with rheumatoid arthritis . There was no observable interaction between methotrexate and either ibuprofen or flurbiprofen, with respect to area under the curve, maximum plasma concentration, maximum concentration per dose, time to reach maximum concentration or serum half-life. The format used was a 6-way, crossover design with patients taking methotrexate in one of the following manners: having taken no nonsteroidal antiinflammatory agents for 48 hours prior to the methotrexate, having taken ibuprofen for at least 6 days prior to the methotrexate, or having taken flurbiprofen at least 6 days prior. Each patient had previously been maintained at a steady dosage of methotrexate and continued to receive the same dosage during the study. All patients had normal renal function, had received previous gold therapy, and none were receiving corticosteroids. Both oral and intramuscular preparations of methotrexate were used and exhibited comparable bioavailability. The dose of ibuprofen used was 800 mg 3 times a day and flurbiprofen was 100 mg 3 times a day each for 7 consecutive days.
B) A pharmacokinetic study was conducted in 10 rheumatoid arthritis patients who had been maintained on methotrexate for at least 3 months . Flurbiprofen 3 mg/kg/d was given for at least 6 days prior to the patients' usual weekly methotrexate dose; no significant effect was observed in methotrexate oral clearance, renal clearance, unbound fraction in plasma, or the amount that was excreted unchanged.
C) A 74-year-old woman was being treated with methotrexate 2.5 mg three times a week for 3 years for rheumatoid arthritis. Flurbiprofen 100 mg per day was then added to her treatment regimen. One to two weeks later, the patient was hospitalized for a one-week period with hematemesis, diarrhea with melena, nausea, and weakness. Other medications at the time of admission included folic acid, digoxin, gemfibrozil, iron supplements, and dipyridamole. Acute gastrointestinal bleeding was discovered. In addition, the patient was diagnosed with anemia, neutropenia, and thrombocytopenia secondary to methotrexate therapy .
Methotrexate Overview
-
Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments. Methotrexate is also used along with rest, physical therapy, and sometimes other medications to treat severe active rheumatoid arthritis (RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) that cannot be controlled by certain other medications. Methotrexate is also used to treat certain types of cancer including cancers that begin in the tissues that form around a fertilized egg in the uterus, breast cancer, lung cancer, certain cancers of the head and neck, certain types of lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from forming. Methotrexate may treat rheumatoid arthritis by decreasing the activity of the immune system.
Flurbiprofen Overview
-
Flurbiprofen is used to relieve pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of the lining of the joints). Flurbiprofen is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.