Ectopic Pregnancy Medication

Updated: Jun 23, 2022
  • Author: Vicken P Sepilian, MD, MSc; Chief Editor: Michel E Rivlin, MD  more...
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Medication Summary

The standard medical treatment for unruptured ectopic pregnancy is methotrexate therapy. Methotrexate is an antineoplastic agent that inhibits cell proliferation by destroying rapidly dividing cells. It acts as a folate antagonist. [71] The decision to use this agent should be made in conjunction with, if not by, the consulting obstetric specialist.

The ideal candidate for medical treatment should have the following:

  • Hemodynamic stability

  • No severe or persisting abdominal pain

  • The ability to follow up multiple times

  • Normal baseline liver and renal function test results.


Absolute contraindications to methotrexate therapy include the following:

  • Existence of an intrauterine pregnancy

  • Immunodeficiency

  • Moderate to severe anemia, leukopenia, or thrombocytopenia

  • Sensitivity to methotrexate

  • Active pulmonary or peptic ulcer disease

  • Clinically important hepatic or renal dysfunction

  • Breastfeeding

  • Evidence of tubal rupture

Relative contraindications that indicate likely failure of methotrexate therapy include the following:

  • Sonogram findings of an ectopic gestational sac greater than 4cm in size (or 3.5cm, if the ectopic pregnancy has fetal heart motion)

  • An initial beta–human chorionic gonadotropin (β-HCG) concentration of greater than 5000 mIU/mL

  • Significant free fluid

  • Fetal cardiac activity


The multiple-dose regimen for methotrexate consists of the administration of daily IM doses of 1 mg/kg, with leucovorin (folinic acid, which reduces side effects) given on alternating days, until there is a 15% decline in β-HCG over 2 days.

The single-dose regimen consists of 1 dose of methotrexate 50 mg/m2, followed by a repeat β-HCG measurement at day 4, and another dose of methotrexate 50 mg/m2 if the β-HCG has declined less than 15% between days 4 and 7.

Efficacy and adverse effects

Both treatment regimens show an efficacy similar to that of surgical management for unruptured ectopic pregnancies in the ideal patient population. Common side effects include an increase in abdominal girth, vaginal bleeding or spotting, abdominal pain, gastrointestinal (GI) symptoms, stomatitis, and dizziness. Rare side effects include severe neutropenia, reversible alopecia, and pneumonitis. [71]


Antineoplastics, Antimetabolite

Class Summary

Antimetabolite agents are used to terminate pregnancy.

Methotrexate (Trexall, Rheumatrex)

Methotrexate is used for the treatment of unruptured tubal pregnancy and for persistent disease after salpingostomy



Class Summary

Vitamins are used to correct folic acid deficiency resulting from use of folic acid antagonists.


Leucovorin is used with folic acid antagonists, such as methotrexate. It is a reduced form of folic acid that does not require enzymatic reduction reaction for activation. It allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis. It is an important cofactor for the enzymes used in production of red blood cells. Leucovorin (folinic acid, which reduces adverse effects) is given alternating with methotrexate days, until there is a 15% decline in β-HCG over 2 days.



Class Summary

Vasopressors are used for their alpha1 and beta1 properties and for stimulating vasoconstriction in peripheral circulation.

Vasopressin (Pitressin)

Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. In linear salpingostomy, the involved tube is identified and freed from surrounding structures. To minimize bleeding, a dilute solution containing 20 U of vasopressin in 20 mL of isotonic sodium chloride solution may be injected into the mesosalpinx just below the ectopic pregnancy. Make sure that the needle is not in a blood vessel by aspirating before injecting, because intravascular injection of vasopressin may precipitate acute arterial hypertension and bradycardia.