The multidose regimen is outlined in Table 20.3. Patients receive 1 mg/kg of methotrexate intramuscularly on days 1, 3, 5, and 7 with leucovorin 0.1 mg/kg intramuscular administered on days 2, 4, 6, and 8. As a result of the repeat dosing of methotrexate, side effects are more common. The leucovorin helps reduce these side effects and increases patients’ tolerance of the treatment. A patient may not require all four doses of methotrexate and her β-hCG levels should be monitored on days 1, 3, 5, and 7. If the β-hCG level drops 15% between two measurements, the regimen can be stopped and weekly β-hCG monitoring initiated. If the methotrexate is discontinued early, the patient should receive leucovorin after her final dose of methotrexate to help reduce potential side effects. If a patient’s β-hCG level plateaus or increases, a second round of methotrexate and leucovorin can be given 1 week later. Earlier studies indicated approximately 19% will require all four doses, and 17% of women will require only one dose with this regimen (195,196). A more recent meta-analysis showed 10% of women require only one dose, while nearly 54% will require all four doses.
Methotrexate Single-Dose Regimens Single-dose regimens were designed to increase patient compliance and simplify the administration of methotrexate. This regimen is well studied and safe and effective in the treatment of ectopic pregnancies. The single-dose regimen is detailed in Table 20.3.
Approximately 15% to 20% of patients in the single-dose regimen will require a second dose of methotrexate due to persistent β-hCG levels (194,197). The β-hCG level at the time of treatment appears to predict the subsequent success rate of single-dose therapy. Patients with β-hCG levels greater than 5,000 mIU/mL have a 14.3% chance of treatment failure compared to only 3.7% for women with levels less than 5,000 mIU/mL (198).
Compared with the multidose protocol, single-dose methotrexate is less expensive, patient acceptance is greater because less monitoring is required during treatment, and the treatment results and prospects for future fertility are comparable (194).
Methotrexate Two-Dose Regimen The two-dose regimen was described as a cross between the single and multidose regimens. Because only 54% require all four doses of the multidose regimen, and 15% to 20% will require a second dose in the single-dose regimen, it is reasonable to consider a two-dose regimen of methotrexate. The protocol is outlined in Table 20.3 and involves
Table 20.4 Initiation of Methotrexate: Physician Checklist and Patient Instructions
Obtain hCG level.
Check CBC, liver function tests, creatinine, and blood type
Administer RhoGAM if patient is Rh-negative.
Identify unruptured ectopic pregnancy smaller than 3.5 cm (relative contraindication)
Prescribe FeSO4 325 mg PO bid if hematocrit is less than 30%.
Schedule follow-up appointment on days 4 and 7.
Refrain from alcohol use, multivitamins containing folic acid, NSAID use, and sexual intercourse until hCG level is negative.
Call your physician if:
You experience prolonged or heavy vaginal bleeding.
The pain is prolonged or severe (lower abdomen and pelvic pain is normal during the first 10–14 days of treatment).
You use oral contraception or barrier contraceptive methods.