From the Guidelines
Using celecoxib with methotrexate requires caution and medical supervision due to the potential increased risk of methotrexate toxicity and liver or kidney problems. These medications can generally be used together, but the combination may increase the risk of methotrexate toxicity and liver or kidney problems, as noted in guidelines for the management of psoriasis and psoriatic arthritis 1. Celecoxib (a nonsteroidal anti-inflammatory drug or NSAID) can reduce kidney function, potentially leading to higher methotrexate levels in the blood since methotrexate is primarily eliminated through the kidneys, as indicated by the American Heart Association's update on the use of nonsteroidal antiinflammatory drugs 1. Some key points to consider when using these medications together include:
- Monitoring kidney function and liver enzymes regularly
- Reporting any unusual symptoms promptly, such as unusual fatigue, yellowing of skin or eyes, dark urine, easy bruising or bleeding, or severe stomach pain
- Staying well-hydrated to minimize the risk of kidney problems
- Avoiding adjustments to the dosage of either medication without consulting a healthcare provider first, as emphasized in the guidelines for the management of psoriasis and psoriatic arthritis 1. Additionally, the use of celecoxib may increase the risk of cardiovascular events, as noted by the American Heart Association 1, and therefore, patients with a history of cardiovascular disease should be closely monitored. Overall, the decision to use celecoxib with methotrexate should be made on a case-by-case basis, taking into account the individual patient's medical history and the potential risks and benefits of the combination, as recommended by the American Heart Association 1.
From the FDA Drug Label
Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). During concomitant use of celecoxib capsules and methotrexate, monitor patients for methotrexate toxicity.
The use of celecoxib with methotrexate may increase the risk of methotrexate toxicity. To minimize this risk, patients should be monitored for signs of methotrexate toxicity, such as neutropenia, thrombocytopenia, and renal dysfunction, when using these medications together 2.
From the Research
Drug Interactions
- Celecoxib does not appear to interact with methotrexate, according to a study on the clinical pharmacokinetics and pharmacodynamics of celecoxib 3.
- However, it is essential to note that celecoxib is metabolised by the cytochrome P450 (CYP) 2C9 isoenzyme, and increased clinical vigilance is required during the coadministration of other substrates or inhibitors of this enzyme 3.
Methotrexate Toxicity
- Methotrexate (MTX) is eliminated via the kidneys, and higher doses can produce toxicity and side effects such as bone marrow suppression, pulmonary toxicity, nephrotoxicity, hematologic toxicity, and an increased risk of infections 4.
- The treatment of severe MTX toxicity has three main goals: clearance of MTX from the bloodstream, folinic acid therapy, and organ treatment 4.
Considerations for Concomitant Use
- There is no direct evidence to suggest that concomitant use of celecoxib and methotrexate is contraindicated, but it is crucial to monitor patients for potential interactions and adjust dosages accordingly 3, 4.
- Patients with renal deficiency may require a lower initial dose of methotrexate, and a more gradual dosage increase and a lower weekly maximum should be considered regarding their general health situation 4.