Unavailability of high-dose methotrexate: recommendations for physician-specialists and (hospital) pharmacists

date: 19/07/2023

The stock of high-dose methotrexate, used in oncology, is currently limited worldwide. A task force therefore issues recommendations.

The company Teva Pharma Belgium, holder of the marketing authorisation for the medicinal products Emthexate 25 mg/ml (2ml, 20 ml and 40 ml) and Emthexate 100 mg/ml, has informed the FAMHP that supply problems may occur until the end of August 2023, and after that the supply will stay constrained.

The company Accord Healthcare, holder of the marketing authorisation for the medicinal products Methotrexate Accord Healthcare 25 mg/ml (2ml and 40 ml), has informed the FAMHP that supply problems may occur until the end of November 2023.

A short-term solution is importation of foreign packages for patients by the pharmacist until the high-dose methotrexate becomes available again in sufficient quantities. In addition, the government is currently investigating the possibility of procuring a strategic stock of high dose methotrexate.

The experts of the Unavailability Task Force issue the following recommendations to (hospital) pharmacists and physician specialists.

Prioritisation of indications

1.    The following indications have high priority

  • Acute lymphoblastic leukemia (ALL), in adults and children
  • High risk trophoblasts
  • Osteosarcoma, in adults and children
  • Medulloblastoma in small children
  • Lymphomas
    • Diffuse large B-cell lymphoma
    • Primary CNS-lymphomas
    • Secondary CNS-lymphomas
    • Burkitt lymphoma
    • NK cell lymphoma
    • Primary testicular B-cel lymphoma
    • Lymphoblastic lymphoma (LBL)
  • Cerebral tumors
    • Ependymoma
    • Glioma
  • Desmoid fibromatosis (schedule with MTX and vinblastine)
  • Cutaneous T-cell lymphoma (schedule with MTX in monotherapy)

2.    Other priority indications

  • Advanced breast cancer: priority if other options cannot be used
  • Advanced bladder cancer: should be considered a priority for the dose-dense MVAC if Cisplatine and Gemcitabine cannot be used
  • Ectopic pregnancy: priority if other options cannot be used
  • Anaplastic large-cell lymphoma (ALCL)
    • Primary cutaneous ALCL: Adcetris (Brentuximab vedotin) is reimbursable (in § 10300000). Failure of systemic treatment will need to be demonstrated against at least one other systemic treatment (for as long as the official unavailability of methotrexate applies)
    • Systemic ALCL: Adcetris (Brentuximab vedotin) is reimbursable in §§ 7280000 and 12030000

3.    The following indications have temporary alternative treatments

  • Prophylaxis CNS-lymphoma’s in high risk cases: a switch to low dose intrathecal methrotexate is possible.
  • Head and neck cancer, metastasised or recurrent: no use of high dose methotrexate for this indication; low dose methotrexate are still available if necessary.

Monitoring the situation
In the meantime, the FAMHP will closely monitor the situation, both at national and European level and is working together with the Belgian National Institute for Health and Disability Insurance (NIHDI) as well as the Federal Public Service Health, Federal Strategic Stock, to continue to seek additional solutions in the very short term.

Last updated on 19/07/2023