AMPHOTERICIN B

Fetal Risk Summary

No reports linking the use of amphotericin B with congenital defects have been located. Reproduction studies of amphotericin B liposome were conducted with maternal non-toxic doses in rats (5 mg/kg; equivalent to 0.16 to 0.8 times the recommended human clinical dose [RHCD] range of 1 to 5 mg/kg based on body surface area) and rabbits (3 mg/kg; equivalent to 0.2 to 1 times the RHCD) (1). Rabbits administered doses equivalent to 0.5 to 2 times the RHCD had a higher rate of spontaneous abortions than did controls (1). No fetal harm was observed in reproduction studies of amphotericin B lipid complex in rats and rabbits at doses up to 0.64 the human dose (2).

The antibiotic crosses the placenta to the fetus with cord blood:maternal serum ratios ranging from 0.38–1.0 (3,4 and 5). In a term (42 weeks) infant whose mother was treated with amphotericin B 0.6 mg/kg every other day, cord and maternal blood levels at delivery were both 2.6 µg/mL, a cord blood:maternal serum ratio of 1.0 (3). Amniotic fluid concentration was 0.08 µg/mL at delivery. The time interval between the last dose and delivery was not specified. Concentrations in the cord blood and maternal serum of a woman treated with 16 mg of amphotericin B just before delivery (one fifth of a planned total dose of 80 mg had infused when delivery occurred) were 0.12 µg/mL and 0.32 µg/mL, respectively, a ratio of 0.38 (4). The woman's last dose before this time was 7 days previously when she had received 80 mg. In a third case, a mother was receiving 20 mg IV every other day (0.5 mg/kg) (5). The cord and maternal serum concentrations were 1.3 µg/mL and 1.9 µg/mL, respectively, a ratio of 0.68. The levels were determined 26 hours after her last dose.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 9 of whom had 1st trimester exposure to amphotericin B (6). Numerous other reports have also described the use of amphotericin B during various stages of pregnancy, including the 1st trimester (4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 and 22). No evidence of adverse fetal effects was found by these studies. Amphotericin B can be used during pregnancy in those patients who will clearly benefit from the drug.

Breast Feeding Summary

No data are available.

References

1. Product information. Ambisome. Fujisawa Healthcare, 2000.
2. Product information. Abelcet. Liposome, 2000.
3. McCoy MJ, Ellenberg JF, Killam AP. Coccidioidomycosis complicating pregnancy. Am J Obstet Gynecol 1980;137:739–40.
4. Ismail MA, Lerner SA. Disseminated blastomycosis in a pregnant woman. Review of amphotericin B usage during pregnancy. Am Rev Respir Dis 1982;126:350–3.
5. Hager H, Welt SI, Cardasis JP, Alvarez S. Disseminated blastomycosis in a pregnant woman successfully treated with amphotericin-B: a case report. J Reprod Med 1988;33:485–8.
6. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:297.
7. Neiberg AD, Maruomatis F, Dyke J, Fayyad A. Blastomyces dermatitidis treated during pregnancy. Am J Obstet Gynecol 1977;128:911–2.
8. Philpot CR, Lo D. Cryptococcal meningitis in pregnancy. Med J Aust 1972;2:1005–7.
9. Aitken GWE, Symonds EM. Cryptococcal meningitis in pregnancy treated with amphotericin. A case report. Br J Obstet Gynaecol 1962;69:677–9.
10. Feldman R. Cryptococcosis (torulosis) of the central nervous system treated with amphotericin B during pregnancy. South Med J 1959;52:1415–7.
11. Kuo D. A case of torulosis of the central nervous system during pregnancy. Med J Aust 1962;1: 558–60.
12. Crotty JM. Systemic mycotic infections in Northern territory aborigines. Med J Aust 1965;1:184.
13. Littman ML. Cryptococcosis (torulosis). Current concepts and therapy. Am J Med 1959;27:976–8.
14. Mick R, Muller-Tyl E, Neufeld T. Comparison of the effectiveness of Nystatin and amphotericin B in the therapy of female genital mycoses. Wien Med Wochenschr 1975:125:131–5.
15. Silberfarb PM, Sarois GA, Tosh FE. Cryptococcosis and pregnancy. Am J Obstet Gynecol 1972;112:714–20.
16. Curole DN. Cryptococcal meningitis in pregnancy. J Reprod Med 1981;26:317–9.
17. Sanford WG, Rasch JR, Stonehill RB. A therapeutic dilemma: the treatment of disseminated coccidioidomycosis with amphotericin B. Ann Intern Med 1962;56:553–63.
18. Harris RE. Coccidioidomycosis complicating pregnancy. Report of 3 cases and review of the literature. Obstet Gynecol 1966;28:401–5.
19. Smale LE, Waechter KG. Dissemination of coccidioidomycosis in pregnancy. Am J Obstet Gynecol 1970;107:356–9.
20. Hadsall FJ, Acquarelli MJ. Disseminated coccidioidomycosis presenting as facial granulomas in pregnancy: a report of two cases and a review of the literature. Laryngoscope 1973;83:51–8.
21. Daniel L, Salit IE. Blastomycosis during pregnancy. Can Med Assoc J 1984;131:759–61.
22. Peterson CW, Johnson SL, Kelly JV, Kelly PC. Coccidioidal meningitis and pregnancy: a case report. Obstet Gynecol 1989;73:835–6.