Leucovorin Dosing in Medical Management of Ectopic Pregnancy
Leucovorin (folinic acid) is NOT routinely recommended in the standard medical management of ectopic pregnancy with methotrexate, as the single-dose methotrexate protocol (50 mg/m² IM) without leucovorin rescue has become the preferred approach with lower toxicity and excellent efficacy. 1, 2
Standard Methotrexate Protocol (Without Leucovorin)
The current evidence-based approach for ectopic pregnancy does not include leucovorin:
- Single-dose methotrexate 50 mg/m² IM is the standard treatment, with repeat dosing on day 7 if β-hCG levels do not decrease appropriately 3, 1
- This protocol achieves success rates of 88.1% for single-dose regimens and 92.7% for multiple-dose regimens without leucovorin rescue 3
- The single-dose regimen without leucovorin has been associated with lower frequency of toxicity compared to multi-dose protocols that included leucovorin 2
Historical Multi-Dose Protocol (With Leucovorin)
When leucovorin was used historically, the dosing was:
- Leucovorin 0.1 mg/kg IM given after each methotrexate dose in older multi-dose protocols 4
- Alternatively, leucovorin 15 mg orally 30 hours after each methotrexate injection was used to reduce side effects 5
- This approach involved methotrexate 1.0 mg/kg IV followed by leucovorin rescue on alternate days 4
Why Leucovorin Is Not Used in Current Practice
The shift away from leucovorin in ectopic pregnancy management occurred because:
- Single-dose methotrexate without leucovorin is safer with fewer gastrointestinal side effects (stomatitis, gastritis) and hepatotoxicity 2
- Success rates remain excellent (71-95%) without leucovorin rescue 6
- The simpler protocol improves patient compliance and reduces treatment complexity 1
Important Clinical Caveat
Folic acid supplements must be avoided during methotrexate treatment as they counteract methotrexate's action, which is the opposite of what leucovorin would do 1, 5
When Leucovorin Might Be Considered
Leucovorin rescue is reserved for:
- Molar pregnancy treatment with intensive multi-dose methotrexate regimens (15 mg orally 30 hours after each methotrexate dose) 5
- High-risk gestational trophoblastic disease requiring EMA/CO chemotherapy protocols 5
- Cases of methotrexate toxicity requiring rescue therapy (not routine prophylaxis)
In summary, do not administer leucovorin for routine ectopic pregnancy management with methotrexate—use the standard single-dose protocol of 50 mg/m² IM without leucovorin rescue. 1, 2