Trexject®, a subcutaneous formulation of methotrexate, is now available on the Pharmaceutical Benefits Scheme (PBS). Trexject® is currently listed for the treatment of severe psoriasis and severe active rheumatoid arthritis where an oral form of methotrexate is unsuitable.
Subcutaneous administration of methotrexate may provide therapeutic benefits for some patients. Oral bioavailability of low-dose methotrexate is around 70-80%. However, variability may increase with higher doses. A head-to-head study comparing oral and subcutaneous methotrexate suggests that there may not be an advantage in using oral doses greater than 15mg per week for some patients. The mean area under the curve was observed to plateau above this dose for oral preparations while continuing to increase in proportion to dose for subcutaneous formulations. Data from studies conducted in patients with rheumatoid arthritis also suggests that subcutaneous methotrexate has superior clinical efficacy and comparable tolerability to oral formulations.
The Australian Rheumatology Association describes methotrexate as the “gold standard” disease modifying anti-rheumatic drug (DMARD). However, methotrexate is associated with a number of serious adverse effects. Gastrointestinal adverse effects including diarrhoea, nausea, stomatitis, and anorexia are the most common, affecting 42% of clinical trial patients. Concomitant administration of folic acid at doses of at least 5mg per week may minimise these effects and reduce elevations of hepatic transaminases. To avoid major toxicity, patients must be educated on the appropriate administration of methotrexate, with particular emphasis given to the importance of weekly dosing.
- Bianchi G, Caporali R, Todoerti M, Mattana P. Methotrexate and rheumatoid arthritis: current evidence regarding subcutaneous versus oral routes of administration. Adv Ther. 2016; 33: 369-78.
- Parker S, Hanrahan P, Barrett C. Folate for therapy. Aust Prescr. 2013; 36: 52-5.
- Schiff MH, Jaffe JS, Freundlich B. Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration. Ann Rheum Dis. 2014; 73(8): 1549-51.
- Therapeutic Goods Administration. Australian Public Assessment Report for: Methotrexate. Proprietary product name: Trexject & Trexject IN. Commonwealth of Australia. Woden, 2017.
- Trexject® (methotrexate [as sodium] injection) Australian approved product information. Warriewood: Link Medical Products. Approved November 2015.