From the FDA Drug Label
The terminal half-life reported for methotrexate is approximately 3 to 10 hours for patients receiving treatment for psoriasis, or rheumatoid arthritis or low-dose antineoplastic therapy (less than 30 mg/m2). The half-life of methotrexate when administered subcutaneously is not explicitly stated in the provided drug labels. However, based on the information provided for other routes of administration, the terminal half-life of methotrexate is approximately 3 to 10 hours for patients receiving treatment for psoriasis, or rheumatoid arthritis or low-dose antineoplastic therapy (less than 30 mg/m2) 1.
- The half-life may vary depending on the dose, route of administration, and individual patient factors, such as renal function.
- It is essential to consult the specific drug label and clinical guidelines for the recommended dose and administration route of methotrexate for a particular condition.
- The provided information does not directly address the half-life of methotrexate when administered subcutaneously, and therefore, no conclusion can be drawn regarding the specific half-life for this route of administration.
From the Research
The half-life of subcutaneous (subQ) methotrexate is approximately 8-10 hours. When administered subcutaneously, methotrexate has better bioavailability compared to oral administration, typically around 76-90% 2. This route of administration bypasses first-pass metabolism in the liver, leading to more predictable drug levels in the bloodstream. The elimination of methotrexate occurs primarily through renal excretion, with approximately 80-90% of the drug excreted unchanged in the urine. Patients with impaired kidney function may experience prolonged half-life and potentially increased toxicity, so dosage adjustments are often necessary in these cases.
Some key points to consider when administering subcutaneous methotrexate include:
- The subcutaneous route is commonly used for higher doses of methotrexate in conditions like rheumatoid arthritis, psoriasis, and certain inflammatory conditions, as it provides more consistent absorption than oral dosing and may reduce gastrointestinal side effects 3.
- Therapeutic drug monitoring may be necessary for patients on high-dose methotrexate therapy to ensure appropriate clearance and minimize toxicity risks.
- The bioavailability of subcutaneous methotrexate is higher compared to oral administration, with a relative bioavailability of around 76-90% 2.
- Subcutaneous administration of methotrexate is well tolerated and well absorbed, and appears to overcome the problems associated with oral administration, including variable absorption and saturation of the absorption mechanism with increasing doses 4.
It's worth noting that the most recent study 5 does not provide information on the half-life of subcutaneous methotrexate, but rather focuses on the efficacy and safety of tocilizumab monotherapy or combined with methotrexate for rheumatoid arthritis. However, this study does highlight the importance of considering the route of administration and dosage of methotrexate in the treatment of rheumatoid arthritis.