Is methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)) contraindicated during active infection?

Methotrexate Should Be Temporarily Discontinued During Active Infection

Methotrexate should be temporarily discontinued during active infection until the infection has resolved, as it is considered a relative contraindication that increases infection risk and may impair recovery. 1

Rationale for Discontinuation

Methotrexate (MTX) is an immunosuppressive agent that affects the immune system's ability to fight infections through several mechanisms:

• Low-dose MTX is associated with increased risk of infection, particularly pneumonia, skin/soft tissue infections, and urinary tract infections 1
• MTX can impair the normal immune response needed to clear infections
• The immunosuppressive effects may lead to opportunistic infections, which can occur at any time but particularly within the first 12 weeks of treatment 1

Guidelines for Management

During Active Infection:

• Temporarily withhold methotrexate during active infection until the infection has cleared 1
• Resume MTX only after the infection has completely resolved
• For severe infections not responding to standard treatment, MTX discontinuation is especially important 1

Types of Infections Requiring Caution:

• Respiratory tract infections (43% increased risk) 2
• Skin infections (119% increased risk) 2
• Opportunistic infections (including Pneumocystis pneumonia) 3
• Mycobacterial infections (including tuberculosis and non-tuberculous mycobacteria) 1, 4
• Viral infections (including herpes zoster) 2

Special Considerations

Infection Severity Assessment:

• For mild infections responding to standard treatment, temporary discontinuation may be sufficient
• For severe or opportunistic infections, longer discontinuation periods may be necessary
• For patients with non-tuberculous mycobacterial lung disease, conventional synthetic DMARDs are preferred over biologics or targeted synthetic DMARDs 1

Medication Interactions:

• Certain antibiotics (penicillins, sulfonamides, trimethoprim) may increase MTX levels by decreasing its binding to albumin or reducing renal elimination 1
• Ceftriaxone may compete with MTX for renal elimination, potentially leading to severe neutropenia 5
• These interactions can increase the risk of MTX toxicity during infection treatment

Resuming Treatment

When restarting MTX after infection resolution:

1. Ensure complete resolution of infection symptoms
2. Consider baseline laboratory monitoring (CBC, liver function, renal function)
3. Resume at the previous effective dose if the infection was uncomplicated
4. Consider a lower dose with gradual titration if the infection was severe or prolonged

Common Pitfalls to Avoid

1. Continuing MTX during active infection - this may prolong the infection and increase risk of complications
2. Abrupt permanent discontinuation - this may lead to disease flares; temporary discontinuation with planned resumption is preferred
3. Ignoring drug interactions - antibiotics used to treat infections may interact with MTX
4. Failing to monitor for opportunistic infections - MTX can mask symptoms of infection while simultaneously increasing risk

By temporarily discontinuing methotrexate during active infection, you can reduce the risk of infection-related complications while optimizing patient outcomes in terms of morbidity, mortality, and quality of life.