What is the Rush protocol for treating ectopic pregnancy with methotrexate (MTX)?

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Rush Protocol for Treating Ectopic Pregnancy with Methotrexate

The Rush protocol for treating ectopic pregnancy consists of a multiple-dose methotrexate regimen of 1 mg/kg intramuscularly, alternating with leucovorin (folinic acid) rescue at 0.1 mg/kg. 1

Patient Selection Criteria

  • Treatment is appropriate for hemodynamically stable patients with unruptured ectopic pregnancy ≤3.5 cm in greatest dimension 2
  • Ideal candidates have β-hCG levels ≤5,000 mIU/mL and no embryonic cardiac activity on ultrasound 2
  • Patients must be willing and able to comply with close follow-up monitoring 2
  • Contraindications include alcoholism, immunodeficiency, peptic ulcer disease, active disease of lungs, liver, kidneys, or hematopoietic system 2

Protocol Details

  • Pre-treatment laboratory testing required: complete blood count with differential and platelet counts, liver enzyme levels, and renal function tests 2
  • The Rush protocol consists of:
    • Methotrexate 1 mg/kg intramuscularly (day 1,3,5,7 as needed) 1
    • Leucovorin (folinic acid) 0.1 mg/kg intramuscularly (day 2,4,6,8 as needed) 1
  • Treatment continues until β-hCG levels decline appropriately 1
  • This differs from the single-dose protocol (50 mg/m²) which doesn't require leucovorin rescue 3

Monitoring and Follow-up

  • β-hCG levels are monitored frequently (typically three times in the first week, then weekly) 3
  • Treatment continues until β-hCG levels fall below 15 mIU/mL 3
  • Patients should be monitored for side effects including nausea, vomiting, stomatitis, and elevated liver enzymes 4

Important Precautions

  • Folic acid supplements should be avoided as they counteract methotrexate's mechanism of action 5
  • Aspirin and NSAIDs should be avoided due to potentially lethal interactions with methotrexate 5
  • For Rh-negative women, anti-D immunoglobulin should be administered due to risk of alloimmunization 2

Treatment Outcomes and Expectations

  • The success rate of the multiple-dose regimen appears more effective than single-dose protocols, though they have not been directly compared 4
  • Patients should be warned about potential rupture, which can occur even after treatment begins (median time to rupture is 14 days, maximum 32 days) 6
  • Warning signs requiring immediate medical attention include severe abdominal pain, signs of hemodynamic instability, heavy vaginal bleeding, and shoulder pain 2

Side Effects and Complications

  • Common side effects include nausea, vomiting, stomatitis, elevated liver function tests, anorexia, and diarrhea 4
  • The most serious complication is ruptured ectopic pregnancy, which requires immediate surgical intervention 2
  • Patients with higher β-hCG levels (>5,000 mIU/mL) or larger adnexal masses have higher failure rates and may require surgical intervention 6

References

Research

Conservative treatment of ectopic pregnancy with methotrexate.

American journal of obstetrics and gynecology, 1986

Guideline

Methotrexate Treatment for Unruptured Ectopic Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

The pharmacology of methotrexate.

Expert opinion on pharmacotherapy, 2001

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Care for a Patient with Unruptured Ectopic Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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