Methotrexate Management

Introduction to Methotrexate and Infection Risk

Low-dose methotrexate (MTX) is associated with an increased risk of infection, particularly pneumonia, skin/soft tissue infections, and urinary tract infections, in the general population, according to the British Journal of Dermatology guidelines 1
The immunosuppressive effects of MTX can impair the body's ability to fight infection, potentially prolong existing infections, and increase the risk of opportunistic infections, as noted by the British Journal of Dermatology 1

The American College of Rheumatology recommends temporarily withholding MTX regardless of COVID-19 or other infection severity, as stated in Arthritis and Rheumatology 2
For severe infections not responding to standard treatment, MTX discontinuation is especially important, according to the British Journal of Dermatology guidelines 1
If antibiotics are given for a severe infection, MTX should be stopped until the patient recovers and the antibiotic course is complete, as recommended by the British Journal of Dermatology 1
Temporarily withhold Methotrexate during active infection until the infection has cleared, as recommended by the British Journal of Dermatology and Arthritis and Rheumatology guidelines 1, 3

Certain antibiotics (particularly trimethoprim, co-trimoxazole, penicillins, sulfonamides) can increase MTX toxicity by reducing renal elimination or causing folate deficiency, as noted by the British Journal of Dermatology and Journal of the American Academy of Dermatology 1, 4
MTX should be permanently discontinued in patients who develop opportunistic infections, according to the British Journal of Dermatology guidelines 1
Failing to monitor for opportunistic infections may lead to delayed diagnosis and treatment, as emphasized by the British Journal of Dermatology and Arthritis and Rheumatology guidelines 1, 5

For uncomplicated infections, consider restarting MTX within 7-14 days after symptom resolution, as recommended by Arthritis and Rheumatology 2
For COVID-19, if asymptomatic but PCR positive, consider restarting 10-17 days after positive test, according to Arthritis and Rheumatology 2
For severe infections, decisions should be made on a case-by-case basis, as stated in Arthritis and Rheumatology 2
When restarting Methotrexate after infection resolution, ensure complete resolution of infection symptoms, consider baseline laboratory monitoring, and resume at the previous effective dose if the infection was uncomplicated, as recommended by the American Academy of Dermatology and Arthritis and Rheumatology guidelines 4, 3

Ignoring drug interactions between MTX and antibiotics may increase toxicity risk, as noted by the British Journal of Dermatology and Journal of the American Academy of Dermatology 1, 4
Continuing Methotrexate during active infection may prolong the infection and increase risk of complications, as warned by the American Academy of Dermatology and British Journal of Dermatology guidelines 4, 1
Abrupt permanent discontinuation of Methotrexate may lead to disease flares; temporary discontinuation with planned resumption is preferred, according to the Arthritis and Rheumatology guidelines 3