At what interval is the methotrexate (MTX) dose repeated in the multi-dose protocol?

From the Guidelines

The methotrexate dose should be repeated every 48 hours in the multi-dose protocol. This dosing interval is based on the regimen outlined in the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of gestational trophoblastic disease, as published in the Annals of Oncology in 2013 1. According to this guideline, methotrexate is administered at a dose of 50 mg by intramuscular injection, repeated every 48 hours for a total of four doses.

• Key points to consider in this protocol include:
  • The use of calcium folinate (folinic acid) at a dose of 15 mg orally, 30 hours after each injection of methotrexate
  • Courses of methotrexate and folinic acid are repeated every 2 weeks
• It is essential to note that this protocol is specifically designed for low-risk patients, and the dosing interval may vary depending on the patient's response to treatment and their individual risk factors.
• The 48-hour interval between methotrexate doses allows for adequate monitoring of the patient's response to treatment, while also minimizing the risk of toxicity and side effects.

From the FDA Drug Label

1. Divided oral dosages of 2. 5 mg at 12 hour intervals for 3 doses given as a course once weekly.
2. Divided oral dose schedule: 2. 5 mg at 12 hour intervals for three doses.

The dose of methotrexate in the multi-dose protocol is repeated at 12 hour intervals for a total of 3 doses, given as a course once weekly 2.

From the Research

Methotrexate Dosing Interval in Multi-Dose Protocol

• The multi-dose protocol for methotrexate (MTX) treatment involves administering the drug on alternating days, with folinic acid rescue 3.
• The specific interval for repeating the MTX dose in the multi-dose protocol is not explicitly stated in the provided studies, but it can be inferred that the dose is repeated every other day, as indicated by the administration of MTX with folinic acid rescue on alternating days 3.
• In the study by 3, patients received multiple doses of MTX (1 mg/kg) with folinic acid rescue on alternating days, with a success rate of 88.5% in treating ectopic pregnancies with high initial β-hCG levels.
• Another study 4 compared the success rates of single-dose and multi-dose MTX protocols for unruptured ectopic pregnancies, with the multi-dose protocol involving 1 mg/kg MTX + 0.1 mg/kg folinic acid, but did not specify the exact interval for repeating the dose.

Factors Influencing Methotrexate Treatment Outcome

• The number of MTX injections, MTX dose, and follow-up period did not differ significantly between success and failure groups in the study by 3.
• Body mass index (BMI), MTX dose, number of MTX injections, and the decrement of β-hCG levels were found to be highly predictive for the success of MTX treatment in the study by 3.
• Other studies 4, 5 compared the effectiveness of single-dose and multi-dose MTX protocols for treating ectopic pregnancies, but did not provide specific information on the dosing interval for the multi-dose protocol.

Folinic Acid Rescue in Methotrexate Treatment

• Folinic acid rescue is an essential component of MTX treatment, and its dosing and frequency can impact treatment outcomes 6, 7.
• The study by 6 compared the outcomes of patients with low-risk gestational trophoblastic neoplasia treated with 8-day MTX and two different regimens of folinic acid, highlighting the importance of optimal folinic acid dosing in MTX treatment.
• The study by 7 provided recommendations for reversing high-dose MTX cytotoxicity with folinic acid, emphasizing the need for careful consideration of folinic acid dosing and frequency to avoid over-rescue and potential adverse effects.