Can methotrexate (MTX) be continued in a patient with a current infection?

Management of Methotrexate During Active Infection

Methotrexate should be temporarily discontinued during active infection until the infection has resolved. 1

Rationale for Discontinuation

Low-dose methotrexate (MTX) is associated with an increased risk of infection, particularly:

• Pneumonia
• Skin/soft tissue infections
• Urinary tract infections 2

The immunosuppressive effects of MTX can:

• Impair the body's ability to fight infection
• Potentially prolong existing infections
• Increase the risk of opportunistic infections 1, 3

Evidence-Based Recommendations

During Active Infection

1. Temporarily withhold MTX regardless of COVID-19 or other infection severity 2, 1
2. For severe infections not responding to standard treatment, MTX discontinuation is especially important 2
3. If antibiotics are given for a severe infection, MTX should be stopped until the patient recovers and the antibiotic course is complete 2

Special Considerations

• Drug interactions: Certain antibiotics (particularly trimethoprim, co-trimoxazole) can increase MTX toxicity by reducing renal elimination or causing folate deficiency 2, 1
• Opportunistic infections: MTX should be permanently discontinued in patients who develop opportunistic infections 2
• FDA warning: "Methotrexate should be used with extreme caution in the presence of active infection, and is usually contraindicated in patients with overt or laboratory evidence of immunodeficiency syndromes" 3

When to Restart MTX After Infection

1. For uncomplicated infections: Consider restarting MTX within 7-14 days after symptom resolution 2
2. For COVID-19: If asymptomatic but PCR positive, consider restarting 10-17 days after positive test 2
3. For severe infections: Decisions should be made on a case-by-case basis 2

Potential Risks of MTX Discontinuation

• Disease flare risk increases with longer discontinuation periods
• 2-week discontinuation appears safe with minimal impact on disease activity
• 4-week discontinuation is associated with transient increase in disease flares 4

Common Pitfalls to Avoid

1. Continuing MTX during active infection - increases risk of infection complications and may delay recovery 1
2. Permanent discontinuation without plan to restart - may lead to unnecessary disease flares 1
3. Ignoring drug interactions between MTX and antibiotics - may increase toxicity risk 2, 1
4. Failing to monitor for opportunistic infections - may lead to delayed diagnosis and treatment 2, 1

In summary, while MTX is a cornerstone therapy for many rheumatologic and dermatologic conditions, the evidence clearly supports temporary discontinuation during active infection to prioritize patient safety and optimize infection resolution.