Methotrexate Shortage: What Providers and Prescribers Need to Know in 2026

Methotrexate injection has been on the FDA Drug Shortage Database since March 13, 2023, and continues to affect clinical practice in 2026. This guide is designed to help rheumatologists, oncologists, dermatologists, and primary care providers navigate current availability, make evidence-based substitution decisions, and support patients through access challenges.

Current Shortage Status and Manufacturer Availability

The shortage primarily affects injectable methotrexate (25 mg/mL) in all vial sizes. Oral tablets (2.5 mg) remain more broadly available. Current manufacturer status as of 2026:

Fresenius Kabi: Available — all vial sizes (2 mL, 10 mL, 40 mL preservative-free)

Hikma: Available

Pfizer: Available, periodic allocation

Accord Healthcare: Resumed production late 2023; 40 mL vials were on back order; check current ASHP bulletins for latest status

Teva: On allocation due to increased demand; availability varies

Consult the ASHP Drug Shortage Bulletins for the most current NDC-level availability. Your institution's pharmacy buyer should have real-time distributor access (AmerisourceBergen, McKesson, Cardinal Health).

Clinical Management Guidance by Indication

Rheumatoid Arthritis and Inflammatory Arthritis

For non-oncology indications, the ASHP recommendation is to use oral methotrexate whenever possible. Oral bioavailability averages approximately 60% at doses of 30 mg/m² or less, and many patients on subcutaneous MTX for RA can safely transition to oral dosing with comparable clinical outcomes.

If oral MTX is not appropriate or if the patient has prior GI intolerance, consider:

Leflunomide (Arava): 20 mg daily; comparable efficacy to MTX in RA trials; similar hepatotoxicity risk; absolute contraindication in pregnancy; long washout required

Hydroxychloroquine + sulfasalazine combination: Reasonable option for mild-moderate disease; triple DMARD therapy (MTX + HCQ + SSZ) can be replicated as double therapy in shortage

Biologic escalation: For moderate-to-severe disease with inadequate csDMARD response, biologics (adalimumab, etanercept, abatacept, tocilizumab) or JAK inhibitors (tofacitinib, upadacitinib) are appropriate. Insurance prior authorization processes will apply.

Oncology Applications

For cancer patients, substitution is indication-specific and protocol-dependent. ASHP guidelines recommend:

Reserve preservative-free MTX vials for intrathecal CNS prophylaxis and treatment (pediatric and adult ALL, CNS lymphoma)

Monitor institutional MTX supplies before initiating high-dose regimens; plan ahead for multiple cycles

ASHP cautions that methotrexate cannot be universally substituted — alternatives are highly patient- and tumor-specific. Consult Hematology/Oncology pharmacists for regimen modification guidance

Dermatology (Psoriasis and Psoriatic Arthritis)

Most dermatology patients are on oral methotrexate and are less directly affected by the injectable shortage. For patients requiring injectable MTX for psoriatic disease:

Trial oral MTX first; subcutaneous administration improves bioavailability only modestly at typical psoriasis doses

Apremilast (Otezla) is an oral alternative with no required lab monitoring

IL-17 inhibitors (secukinumab, ixekizumab) or IL-23 inhibitors (guselkumab, risankizumab) are highly effective for moderate-to-severe psoriasis refractory to conventional agents

Supporting Your Patients Through Access Challenges

Many patients will not know to call multiple pharmacies or to check hospital outpatient pharmacies. Proactive communication from your practice can prevent dangerous treatment gaps:

Advise patients to start searching for their next fill 2–3 weeks early

Have office staff ready to assist patients in contacting hospital pharmacies or specialty pharmacies

Consider prescribing a backup oral formulation for injectable RA patients in case injectable supply fails

Refer patients to pharmacy search services like medfinder that can call pharmacies on their behalf

For more on how to integrate pharmacy access support into your practice workflow, visit medfinder for providers or read our provider guide to helping patients find methotrexate.