Ectopic, Medical Therapy

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Methotrexate sodium formerly Amethopterin
Folic acid antagonist inhibits dihydrofolic acid reductase interfering with DNA synthesis, repair, and cellular replication.

Ectopic pregnancy is usually suspected when the hCG level exceeds 2000 mIU/ml and an intrauterine sac is not seen on transvaginal ultrasound. Abnormally rising beta-hCG levels also suggest an ectopic pregnancy. If an ectopic pregnancy is identified on ultrasound or beta-hCG levels are stable or continue to rise after dilatation and curettage medical management may be an option.

Indicated for the management of ectopic pregnancies meeting the following criteria[1]:

Contraindications [1]	Relative contraindications [1,2.3]
Breast feeding Known sensitivity to methotrexate Active pulmonary disease Alcoholism Liver disease Renal disease Peptic ulcer Immunodeficiency Hematologic disease including severe anemia, bone marrow hypolasia, leukopenia, and thrombocytopenia.	Gestational sac greater than 3.5 cm Embryonic cardiac motion* beta-hCG gretaer than 15,000 mIU/mL*

* Embryonic cardiacactivity noted on ultrasound or beta-hCG levels greater than 15,000mIU/mL have been significantly associated with failure of treatment [2,3] .

Methotrexate may be given in one dose at 50 mg/m² for the treatment of an ectopic. Methotrexate may also be given using a “multidose” regimen of 1 mg/kg intramuscularly, alternating with 0.1 mg/kg of leucovorin intramuscularly for up to four daily doses of each drug [2] .

Women treated with the single-dose regimen had significantly fewer side effects. However, The multidose regimen appears to be more effective effective [2]

The appropriate dose of methotrexate may be obtained using the calculator below:

Input Weight

lbs

Input Height

Body surface area (m²) =
Average BSA for women: 1.6 m²

"Single" Dose Protocol
Day 0	HCG, D&C, CBC,AST,serum creatinine, T&S,Rh
Day 1	Methotrexate 50 mg/m²= IM
Day 4	hCG
Day 7	hCG . Repeat methotrexate if drop in hCG is not > 15% between day 4-7 . hCG levels are then obtained weekly until they are undetectable. An additional dose of methotrexate may be given if there is less than a 15% decrease in hCG levels in subsequent weeks [4]. Exacerbation of pain during day 3-7 is common [4].

Multidose Dose Protocol**
Day 1	HCG, D&C, CBC,AST,serum creatinine, T&S,Rh Methotrexate 1mg/kg = IM
Day 2	hCG Leucovorin 0.1 mg/kg= IM
Day 3	hCG Methotrexate 1mg/kg = IM
Day 4	hCG Leucovorin 0.1 mg/kg= IM
Day 5	hCG Methotrexate 1mg/kg = IM
Day 6	hCG Leucovorin 0.1 mg/kg= IM
Day 7	hCG Methotrexate 1mg/kg = IM
Day 8	hCG Leucovorin 0.1 mg/kg= IM
**Continue protocol until 15% decrease in two consecutive hcg titers. Then weekly hCG until not detectable

Formula : BSA (m²) = ( [Height(cm) x Weight(kg) ]/ 3600 )^½ [5]

All calculations must be confirmed before use. The suggested results are not a substitute for clinical judgment. Neither perinatology.com nor any other party involved in the preparation or publication of this site shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.

Side effects include nausea, vomiting,gastritis, diarrhea, vomiting, mouth sores, pneumonitis, bone marrow suppression, and rarely neutropenia or alopecia. an increase in liver transaminases.

Patients should be advised to:

Avoid alcoholic beverages, vitamins containing folic acid, nonsteroidal drugs and sexual intercourse.

To contact the physician if they have severe abdominal pain, heavy vaginal bleeding, rapid heart rate, dizziness, or fainting.

(25 mg/mL, and 20 mg, 1 g powder for injection)

Methotrexate is associated with the aminopterin-methotrexate syndrome (IUGR, hypoplastic suporbital ridges, small lowset ears, micrognathia, limb abnormaliters, and occasional mental retardation) when used at 8 to 10 weeks after the first day of the LMP at a dose of 10 mg or more per week.[6]

REFERENCES:

1.ACOG practice bulletin. Medical management of tubal pregnancy. Number 3, December 1998. Clinical management guidelines for obstetrician-gynecologists. American College of Obstetricians and Gynecologists.1999;65(1):97-103. PMID:10390113
2. Barnhart KT, Gosman G, Ashby R, et al. The medical management of ectopic pregnancy: a meta-analysis comparing "single dose" and "multidose" regimens. Obstet Gynecol2003;101:778–784. Search date 2001; primary sources Medline, and manual search of references. PMID:12681886
3. Lipscomb GH, McCord ML, Stovall TG, Huff G, Portera SG, Ling FW. Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies. N Engl J Med 1999;341:1974–8 PMID:10607814
4. Stenchever MA, Droegemueller W, eds. Comprehensive Gynecology. 4th ed. St. Louis: Mosby, 2001p 462 to 470
5. Mosteller RD: Simplified Calculation of Body Surface Area. N Engl J Med 1987 Oct 22;317(17):1098 (letter) PMID:3657876
6. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 7th edition,Baltimore, MD: Williams & Wilkins, 2005 p 1037-1044.