Caution when prescribing methotrexate has become more important since it became the most commonly used first-line therapy for rheumatoid arthritis. This indication, along with treatment of severe psoriasis and some cancers, generated the dispensing of 270,000 prescriptions under the Pharmaceutical Benefits Scheme in 2014.

Of 132 hepatobiliary adverse reactions reported to the Therapeutic Goods Administration (TGA) to date, two were related to the possible reactivation of hepatitis B. One of these cases, which was fatal, had previously demonstrated serological evidence of hepatitis B immunity and was reported in the Journal of Gastroenterology and Hepatology.

Although the TGA could not confirm methotrexate as the causative agent, the serious nature of this complication contributed to a decision to extend the warnings relating to potential hepatotoxicity in the product information by recommending thorough preliminary evaluation and ongoing monitoring of patients with a history of hepatitis B or hepatitis C infections.

High levels of hepatic enzymes and fluctuations in viral DNA levels indicate reactivation of hepatitis B, and may develop after methotrexate has been ceased.

Only the product information of Methoblastin® has incorporated the new precautions at this stage.


  1. Phillips T, Venugopol K, Kontorinis N. A case of fatal acute liver failure due to Hepatitis B reactivation in a patient on Methotrexate, despite prior serological evidence of hepatitis immunity. J Gastroen Hepatol. 2013; 28(S2):170.
  2. Therapeutic Goods Administration. Methotrexate and hepatitis B reactivation. Medicines Safety Update 2015; 6(3):1.

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