What is the dose of methotrexate (MTX) for the treatment of an ectopic pregnancy?

From the Guidelines

The standard dose of methotrexate for treating ectopic pregnancy is 50 mg/m² of body surface area, administered as a single intramuscular or intravenous dose. This dosage is based on the most recent and highest quality evidence available, which prioritizes minimizing morbidity, mortality, and improving quality of life for patients with ectopic pregnancy 1. The decision to administer methotrexate is complex and should be made on a case-by-case basis, considering factors such as the patient's hemodynamic stability, the size and location of the ectopic pregnancy, and the presence of fetal cardiac activity.

Key considerations for methotrexate therapy include:

• The patient should be hemodynamically stable with an unruptured ectopic pregnancy
• The ectopic gestational sac should be smaller than 3.5 cm
• There should be no embryonic cardiac motion observed on ultrasound
• The patient's beta-hCG level should be typically below 5,000 mIU/mL
• Methotrexate is contraindicated in patients with certain medical conditions, such as alcoholism, immunodeficiency, peptic ulcer, or active disease of the lungs, liver, kidneys, or hematopoietic system

After administration of methotrexate, patients require close monitoring, including:

• Laboratory testing, including a CBC count with differential and platelet counts, hepatic enzyme level, and renal function tests
• Serial measurements of serum beta-hCG levels to assess treatment response
• Prompt evaluation for signs of rupture or treatment failure, such as increasing pain or hemodynamic instability

It is essential to note that methotrexate therapy may not be effective in all cases, and treatment failure can occur, leading to rupture of the ectopic pregnancy 1. Therefore, patients should be closely monitored and advised to seek immediate medical attention if they experience severe pain or signs of rupture.

From the Research

Dose of Methotrexate in Ectopic Pregnancy

• The dose of methotrexate used in the treatment of ectopic pregnancy varies across studies, with some using a fixed dose and others using a weight-based dosing protocol 2, 3, 4.
• A study published in 1997 used a dose of 50 mg/m2 of intramuscular methotrexate, with the dose repeated if the beta-hCG level did not drop by at least 15% between days 4 and 7 or if a plateau or rise was noted during weekly follow-up evaluation 2.
• Another study published in 1991 used a single dose of 50 mg/m2 of intramuscular methotrexate without citrovorum rescue, with all patients having a continued rise in hCG titer for at least 3 days after methotrexate injection, although all levels began to decline by day 7 3.
• A more recent study published in 2025 used a fixed dose of 90 mg of methotrexate, with an overall success rate of 81.1% 4.
• The use of methotrexate in the treatment of ectopic pregnancy is generally considered safe and effective, with a high success rate in selected patients who fulfill strict inclusion criteria, including compliance with follow-up evaluation 5, 6.

Factors Affecting Treatment Success

• Baseline human chorionic gonadotropin (hCG) levels have been shown to be associated with treatment success, with lower levels (less than 1000 mIU/ml) associated with a higher rate of treatment success 4, 6.
• Pretreatment values of progesterone have also been shown to be inversely related to medicamentous treatment success, with lower levels associated with a higher rate of treatment success 6.
• The initial level of hCG has been shown to be a predictor of treatment success, with higher levels associated with a lower rate of treatment success 6.