Methotrexate Management in the Inpatient Setting

Rationale for Stopping Methotrexate Inpatient

• Methotrexate should be temporarily discontinued during inpatient hospitalization, particularly when patients have acute illness, infection, or are receiving medications that may interact with methotrexate, as recommended by the British Journal of Dermatology and Gut 1, 2
• Hospitalized patients often receive multiple medications that can interact with methotrexate, including antibiotics and NSAIDs, which may increase methotrexate toxicity, according to the British Journal of Dermatology 2
• Acute infections can increase the risk of methotrexate toxicity, especially myelosuppression, as reported by Gut and the British Journal of Dermatology 2, 3

Specific Clinical Scenarios Requiring Methotrexate Discontinuation

• Infection requiring antibiotics: Methotrexate should be stopped until the patient recovers and completes the antibiotic course, as recommended by the British Journal of Dermatology 2
• Abnormal liver function: Methotrexate should be stopped if transaminases exceed twice the upper limit of normal, according to Gut 1
• 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, as reported by Gut 3

Monitoring During Hospitalization

• If methotrexate was recently administered before admission, monitor complete blood count, liver function tests, and renal function closely, as recommended by Gut 4
• Watch for signs of methotrexate toxicity including mucositis, fever, diarrhea, erythema, and ulceration, according to the British Journal of Dermatology 2

Resuming Methotrexate After Hospitalization

• Methotrexate can be resumed upon discharge if the acute illness has resolved, liver function tests have normalized, blood counts are adequate, and interacting medications have been discontinued, as recommended by the British Journal of Dermatology and Gut 1, 2, 3

Special Considerations

• Surgery: For elective orthopedic surgery, evidence suggests methotrexate can be safely continued perioperatively, but for major surgery with comorbidities, methotrexate should be temporarily discontinued, as reported by the British Journal of Dermatology and Annals of the Rheumatic Diseases 2, 5
• Pregnancy: Methotrexate is teratogenic and should be stopped at least 3 months before planned pregnancy for both men and women, according to Gut and Annals of the Rheumatic Diseases 1, 6

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, as reported by Annals of the Rheumatic Diseases 5, 6
• When restarting methotrexate after prolonged discontinuation, consider resuming at a lower dose with gradual escalation while monitoring for toxicity, as recommended by Gut 4

Methotrexate Management in the Perioperative Period

Perioperative Considerations

• The British Journal of Dermatology recommends that methotrexate can generally be safely continued during the perioperative period for most patients undergoing surgery and anesthesia, as evidence suggests no increased risk of infection or surgical complications when maintained 7
• For elective orthopedic surgery, evidence from prospective randomized studies indicates that methotrexate can be safely continued without increased risk of infection or postoperative complications 7
• For patients with well-controlled skin disease, it is generally safe to continue methotrexate during the perioperative period 7

Renal Function and Medication Interactions

• Assess renal function with eGFR before anesthesia, as methotrexate is primarily excreted by the kidneys 8
• For patients with creatinine clearance <20 mL/min, methotrexate should be avoided 8
• For patients with creatinine clearance between 20-50 mL/min, the methotrexate dose should be reduced by half 8
• Impaired renal function significantly increases the risk of myelosuppression, which is the most important cause of methotrexate-associated death 8

Postoperative Management

• If antibiotics are required postoperatively for severe infection, consider temporarily stopping methotrexate until the patient recovers and completes the antibiotic course 7
• Be aware of potential drug interactions that may increase methotrexate toxicity, including many NSAIDs, salicylates, penicillin, proton pump inhibitors, and tetracyclines 7
• Consider urine alkalinization with sodium bicarbonate if there are concerns about methotrexate toxicity 7

Special Considerations

• The presence of interstitial lung disease is not an absolute contraindication for methotrexate use but requires careful monitoring, especially in the perioperative period 9
• For patients with diabetes or other comorbidities that increase infection risk, the decision to continue methotrexate must be made on a case-by-case basis, weighing the risk of disease flare against the potential for increased complications 7

Perioperative Methotrexate Management

Introduction to Methotrexate Continuation

• The American College of Rheumatology conditionally recommends continuing methotrexate through surgery for patients undergoing elective orthopedic procedures, based on moderate-quality evidence showing a decreased infection risk when methotrexate is continued 10

Disease-Specific Considerations

• For IBD patients, immunomodulators including methotrexate can be continued during the perioperative period without adversely affecting postoperative outcomes, as the elimination half-life is only 1-2 hours, so stopping immediately before surgery provides no measurable benefit 10

Post-operative Management

• Resume methotrexate immediately when oral intake recommences, according to the Journal of Crohn's and Colitis 10

Perioperative Management of Rheumatoid Arthritis Patients on Methotrexate and Glucocorticoids

Medication Management

• The American College of Rheumatology conditionally recommends continuing methotrexate at the usual dose through elective orthopedic surgery, based on low to moderate quality evidence, for patients with rheumatoid arthritis undergoing femoral neck fracture repair 11, 12
• Continuing methotrexate decreases infection risk (RR 0.39, 95% CI 0.17-0.91) and reduces the risk of disease flares (RR 0.06, 95% CI 0.0-1.10) in patients with rheumatoid arthritis undergoing surgery 13
• The American College of Rheumatology conditionally recommends continuing the current daily dose of glucocorticoids rather than administering supraphysiologic doses on the day of surgery for patients with rheumatoid arthritis undergoing femoral neck fracture repair 11, 12
• The traditional practice of stress-dose steroids lacks strong evidence and may increase perioperative complications without clear benefit in patients with rheumatoid arthritis undergoing surgery 12

Postoperative Care

• Resume methotrexate immediately when oral intake recommences after surgery, and continue deflazacort at the same alternate-day dosing postoperatively for patients with rheumatoid arthritis undergoing femoral neck fracture repair 11, 12
• If methotrexate was held for any reason perioperatively, restart once wound shows evidence of healing, sutures/staples are removed, there is no significant swelling/erythema/drainage, and no ongoing infection (typically ~14 days) for patients with rheumatoid arthritis undergoing surgery 11, 12

Special Considerations

• The American College of Rheumatology guidelines support medication continuation for patients with rheumatoid arthritis in clinical remission undergoing femoral neck fracture repair, but active disease or severe comorbidities might alter the risk-benefit calculation 11
• Fracture neck of femur repair follows the same perioperative medication principles as elective total hip arthroplasty per American College of Rheumatology guidelines for patients with rheumatoid arthritis 11, 12, 13