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Methotrexate Pregnancy and Breastfeeding Warnings

Methotrexate is also known as: Folex PFS, Methotrexate LPF Sodium, Otrexup, Rasuvo, Rheumatrex Dose Pack, Trexall

Methotrexate Pregnancy Warnings

Anecdotal data have revealed the following MTX-induced congenital defects: absence of labdoid and coronal sutures, oxycphaly, absence of frontal bone, low set ears, hypertelorism, dextroposition of the heart, absence of digits, growth retardation, wide posterior fontanel, hypoplastic mandible, multiple anomalous ribs, depressed/wide nasal bridge, and long webbed fingers. Based on several instances of congenital abnormalities among infants whose conceptions were dated up to 7 months after their mothers had received MTX, some experts theorize the drug may persist in maternal tissues for prolonged periods of time. Data have revealed an association between the use of chemotherapy combinations that contain MTX during pregnancy and neonatal myelosuppression (anectdotal data), low birth weight (40% of infants), and persistent congenital chromosomal abnormalities (limited data). Retrospective analysis of 436 female cancer survivors who received chemotherapy which included MTX (average duration of chemotherapy was 4 months), of whom 187 (43%) had at least one live birth (average interval between MTX use and conception was 2.7 years), has revealed no statistically significant association between the use of MTX and congenital defects. Observed congenital abnormalities included anencephaly (2), spina bifida (1), tetralogy of Fallot (1), talipes equinovaus (1), collapsed lung (1), umbilical hernia (1), desquamative fibrosing alveolitis (1), asymptomatic heart murmur (1), mental retardation (1), and sudden infant death syndrome (1, at 4 weeks of age). One study reported the results of four patients who had received low dose weekly pulses of MTX inadvertently taken from up to one to six weeks gestation. One patient miscarried at week six while the other pregnancies ended with the delivery of healthy children.

Methotrexate (MTX) has been assigned to pregnancy category X by the FDA. MTX can cause fetal death or teratogenic effects when administered to a pregnant woman. Women of childbearing potential should not be started on MTX until pregnancy is excluded and should be fully counseled on the serious risk to the fetus should they become pregnant during treatment. Pregnancy should be avoided if either partner is receiving MTX, during and for a minimum of 3 months after therapy for male patients, and during and for at least 1 ovulatory cycle for female patients. This drug has been successfully used to terminate tubal pregnancy. MTX is contraindicated in pregnant patients with psoriasis or rheumatoid arthritis and should be used in the treatment of neoplastic diseases only when the potential benefit outweighs the risk to the fetus.

See references

Methotrexate Breastfeeding Warnings

Methotrexate (MTX) is excreted into human milk in low concentrations. Because of the potential for serious adverse reactions from MTX in breast-fed infants, it is contraindicated in nursing mothers. The American Academy of Pediatrics considers MTX to be contraindicated during breast-feeding because of several potential problems, including immune suppression, neutropenia, adverse effects on growth, and carcinogenesis.

MTX is excreted into human milk. In one case, peak milk MTX levels of 6 x 10-9 M, or 0.26 mcg/dL, were detected approximately 10 hours after dosing in a woman who was receiving 22.5 mg of MTX per day. The highest milk:plasma MTX ratio was 0.08:1. The cumulative excretion of MTX in milk within the first 12 hours after oral administration was 0.32 mcg. Although adverse effects were not reported in her nursing infant, and the milk MTX levels from this case represent nontoxic doses for infants, experts consider the use of MTX to be contraindicated during breast-feeding because of the unknown risk of this concentration of MTX to the nursing infant, the possibility of accumulation of the drug in neonatal tissues, and because of the known adverse effects of MTX in breast-fed infants.

See references

References for pregnancy information

  1. Ostensen M, Hartmann H, Salvesen K "Low dose weekly methotrexate in early pregnancy. A case series and review of the literature." J Rheumatol 27 (2000): 1872-5
  2. Sites CK "Treatment of ectopic pregnancy with single-dose methotrexate in a patient with an intrauterine device: a case report." J Reprod Med 40 (1995): 800-2
  3. Fernandez H, Pauthier S, Doumerc S, Lelaidier C, Olivennes F, Ville Y, Frydman R "Ultrasound-guided injection of methotrexate versus laparoscopic salpingotomy in ectopic pregnancy." Fertil Steril 63 (1995): 25-9
  4. Schaff EA, Eisinger SH, Franks P, Kim SS "Combined methotrexate and misoprostol for early induced abortion." Arch Fam Med 4 (1995): 774-9
  5. Briggs GG, Freeman RK, Yaffe SJ.. "Drugs in Pregnancy and Lactation. 5th ed." Baltimore, MD: Williams & Wilkins (1998):
  6. Mitchellbanks W "Effect of methotrexate on the fetus." Can Med Assoc J 152 (1995): 13
  7. "Product Information. Methotrexate and Methotrexate LPF (methotrexate)." Lederle Laboratories, Wayne, NJ.
  8. Feldkamp M, Carey JC "Clinical teratology counseling and consultation case report: low dose methotrexate exposure in the early weeks of pregnancy." Teratology 47 (1993): 533-9
  9. Ramsey-Goldman R, Mientus JM, Kutzer JE, Mulvihill JJ, Medsger TA, Jr "Pregnancy outcome in women with systemic lupus erythematosus treated with immunosuppressive drugs." J Rheumatol 20 (1993): 1152-7
  10. Donderwinkel PFJ, Vandermeer S, Dorr JPJ "Methotrexate in management of advanced ectopic pregnancy complicated by ovarian hyperstimulation syndrome." Acta Obstet Gynecol Scand 73 (1994): 753-4
  11. Floridon C, Thomsen SG "Methotrexate treatment of ectopic pregnancy." Acta Obstet Gynecol Scand 73 (1994): 746-52
  12. Fernandez H, Benifla JL, Lelaidier C, Baton C, Frydman R "Methotrexate treatment of ectopic pregnancy: 100 cases treated by primary transvaginal injection under sonographic control." Fertil Steril 59 (1993): 773-7
  13. Slaughter JL, Grimes DA "Methotrexate therapy - nonsurgical management of ectopic pregnancy." West J Med 162 (1995): 225-8
  14. Potts M "Non-surgical abortion: who's for methotrexate?" Lancet 346 (1995): 655-6
  15. Shalev E, Peleg D, Bustan M, Romano S, Tsabari A "Limited role for intratubal methotrexate treatment of ectopic pregnancy." Fertil Steril 63 (1995): 20-4
  16. Zohav E, Gemer O, Sassoon E, Segal S "Successful pregnancy following conservative treatment of cervical pregnancy with methotrexate." Int J Gynaecol Obstet 48 (1995): 97-8
  17. Hsu JJ, Chiu TH, Lai IM, Soong YK "Methotrexate treatment of cervical pregnancies with different clinical parameters: a report of three cases." J Reprod Med 40 (1995): 246-50
  18. Lindblom B, Bengtsson G, Bryman I, Thorburn J "Medical treatment of ectopic pregnancy." Eur J Obstet Gynecol Reprod Biol 49 (1993): 80-2
  19. Carson SA, Buster JE "Ectopic pregnancy." N Engl J Med 329 (1993): 1174-81
  20. Gross Z, Rodriguez JJ, Stalnaker BL "Ectopic pregnancy: nonsurgical, outpatient evaluation and single-dose methotrexate treatment." J Reprod Med 40 (1995): 371-4
  21. Morris LF, Harrod MJ, Menter MA, Silverman AK "Methotrexate and reproduction in men: case report and recommendations." J Am Acad Dermatol 29 (1993): 913-6

References for breastfeeding information

  1. Johns DG, Rutherford LD, Leighton PC, Vogel CL "Secretion of methotrexate into human milk." Am J Obstet Gynecol 112 (1972): 978-80
  2. Balis FM, Holcenberg JS, Bleyer WA "Clinical pharmacokinetics of commonly used anticancer drugs." Clin Pharmacokinet 8 (1983): 202-32
  3. Briggs GG, Freeman RK, Yaffe SJ.. "Drugs in Pregnancy and Lactation. 5th ed." Baltimore, MD: Williams & Wilkins (1998):
  4. "Product Information. Methotrexate and Methotrexate LPF (methotrexate)." Lederle Laboratories, Wayne, NJ.

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