Should methotrexate be stopped in an inpatient setting?

Methotrexate Management in the Inpatient Setting

Methotrexate should be temporarily discontinued during inpatient hospitalization, particularly when patients have acute illness, infection, or are receiving medications that may interact with methotrexate. 1

Rationale for Stopping Methotrexate Inpatient

• Methotrexate is primarily eliminated via the kidneys, and acute illness or dehydration during hospitalization may impair renal function, potentially leading to drug accumulation and toxicity 2, 3

• Hospitalized patients often receive multiple medications that can interact with methotrexate, including antibiotics (particularly trimethoprim, co-trimoxazole, penicillins, tetracyclines), NSAIDs, and other medications that may increase methotrexate toxicity 1

• Acute infections, which are common reasons for hospitalization, can increase the risk of methotrexate toxicity, especially myelosuppression 1

Specific Clinical Scenarios Requiring Methotrexate Discontinuation

• Infection requiring antibiotics: Methotrexate should be stopped until the patient recovers and completes the antibiotic course 1

• Abnormal liver function: Methotrexate should be stopped if transaminases exceed twice the upper limit of normal 1, 2

• Renal impairment: Methotrexate elimination is compromised in patients with decreased renal function, increasing toxicity risk 2, 3

• Bone marrow suppression: If total white cells <3.5×10^9/L or neutrophils <2×10^9/L, methotrexate should be withheld until counts normalize 1

Monitoring During Hospitalization

• If methotrexate was recently administered before admission, monitor complete blood count, liver function tests, and renal function closely 1, 4

• Watch for signs of methotrexate toxicity including mucositis, fever, diarrhea, erythema, and ulceration 1

• If toxicity is suspected, measure serum methotrexate levels if available 2

Resuming Methotrexate After Hospitalization

• Methotrexate can be resumed upon discharge if:
  • The acute illness has resolved 1
  • Liver function tests have normalized if previously abnormal 1
  • Blood counts are adequate (white cells >3.5×10^9/L, neutrophils >2×10^9/L) 1
  • Renal function has returned to baseline 2
  • Interacting medications have been discontinued 1

Special Considerations

• Surgery: For elective orthopedic surgery, evidence suggests methotrexate can be safely continued perioperatively, but for major surgery with comorbidities like diabetes that increase infection risk, methotrexate should be temporarily discontinued 1

• Pregnancy: Methotrexate is teratogenic and should be stopped at least 3 months before planned pregnancy for both men and women 1, 4

• Long-term use: Despite temporary discontinuations, methotrexate has favorable long-term tolerability with >50% of patients continuing therapy after 12 years 5

Potential Pitfalls and Caveats

• Abrupt discontinuation of methotrexate may lead to disease flares in conditions like rheumatoid arthritis, but this risk is generally outweighed by the potential for serious toxicity during acute illness 1

• When restarting methotrexate after prolonged discontinuation, consider resuming at a lower dose with gradual escalation while monitoring for toxicity 1, 4

• Ensure patients understand the weekly dosing schedule when restarting to prevent dosing errors, which can lead to severe toxicity 4