Methotrexate

Methotrexate is a cornerstone medication in the management of many musculoskeletal and inflammatory conditions due to its anti-metabolite and anti-inflammatory properties. However, its use requires careful monitoring and shared care between specialists and general practitioners (GPs) to ensure patient safety and optimal outcomes. This article provides comprehensive guidance for the use of methotrexate, emphasizing both specialist and primary care roles.
== Initiation ==
Methotrexate therapy must always be initiated by a specialist. Before starting treatment, a detailed safety evaluation is essential:
* Conduct baseline investigations, including a full blood count (FBC), liver function tests (LFTs), albumin, creatinine, and hepatitis B and C serology. If indicated, include a Quantiferon Gold test to assess latent tuberculosis (TB).
* Perform a chest X-ray if one has not been conducted within the past 12 months, particularly if there is a history of respiratory disease. For patients with significant respiratory conditions, consultation with a respiratory specialist is recommended.
* Assess alcohol consumption to ensure it is within safe limits (<14 units per week) to minimize hepatic risk.
Some specialists may consider a procollagen type 3 aminoterminal peptide (P3NP) assay for patients at risk of fibrosis. However, this test has limited utility in the context of inflammatory arthritis.
== Dosage and Administration ==
Methotrexate is administered either orally (2.5 to 25 mg weekly) or subcutaneously (10 to 25 mg weekly) on the same day each week. To mitigate adverse effects, folic acid supplementation is essential:
* Standard dose: 5 mg once weekly, typically 2 to 4 days post-methotrexate.
* Adjusted dose: Increased to 5 mg up to 6 times per week if side effects such as mouth ulcers occur.
Clinical improvement may be observed within 2 to 6 months of therapy initiation. Once the patient achieves stable disease control, annual specialist review is recommended.
== Monitoring ==
Regular laboratory testing includes:
* FBC, albumin, creatinine, bilirubin, GGT, ALP, AST, and ALT:
** For rheumatological and gastroenterological patients: Monthly testing for the first 3 months, then quarterly if stable.
** For dermatological patients: Weekly testing for the first 4 weeks, monthly for the next 3 months, and quarterly thereafter.
* P3NP levels every 6 months for dermatology patients to assess fibrosis risk, with a Fibroscan if P3NP is elevated.
== Identifying and Managing Adverse Effects ==
Remain vigilant for adverse effects and act promptly:
* Hematologic: Stop methotrexate and arrange urgent consultation if neutrophils <1 or platelets <50.
* Hepatic: Consider stopping therapy if ALT or AST exceed twice the upper limit of normal.
* Pulmonary: Discontinue methotrexate immediately for pneumonitis or unexplained respiratory symptoms.
* Other common side effects:
** For mouth ulcers, increase folic acid dosing.
** For nausea, consider splitting the dose, administering after meals, or changing the administration route.
== Drug Interactions and Contraindications ==
Methotrexate interacts with several drugs, including NSAIDs, penicillins, and trimethoprim. Caution is advised when using hepatotoxic agents, and live vaccines are contraindicated during therapy. Patients planning pregnancy must discontinue methotrexate at least 3 months prior, as the drug is teratogenic (Category X).
== Vaccination ==
Patients on methotrexate should receive annual influenza and pneumococcal vaccinations. The non-live Shingrix vaccine is preferred over Zostavax. Consult specialists for guidance on COVID-19 vaccinations, as temporary discontinuation of methotrexate may be required post-vaccination.
== Resources ==
Category:Pharmacology