Drugs in Pregnancy and Lactation Name: TRETINOIN (SYSTEMIC)
Class: Antineoplastic/Vitamin
Risk Factor:    DM

Fetal Risk Summary

Tretinoin (all-trans retinoic acid; retinoic acid; vitamin A acid) is a retinoid and vitamin A (retinol) metabolite that is available both as a topical formulation (see Tretinoin [Topical]) and as an oral antineoplastic for the treatment of acute promyelocytic leukemia. Like other retinoids, all-trans retinoic acid is a potent teratogen when taken systemically during early pregnancy (see also Etretinate, Isotretinoin, and Vitamin A), producing a pattern of birth defects termed retinoic acid embryopathy (central nervous system, craniofacial, cardiovascular, and thymic anomalies). The teratogenic effect of all-trans retinoic acid is dose dependent because an endogenous supply of the vitamin is required for normal morphogenesis and differentiation of the embryo, including a role in physiologic developmental gene expression (1). Low serum concentrations or frank deficiency of vitamin A and all-trans retinoic acid is also teratogenic (see Tretinoin [Topical]).

The teratogenicity of all-trans retinoic acid in animals is summarized under the topical formulation, as is the reported human pregnancy experience following topical use.

A number of reports have described the use of systemic tretinoin (45 mg/m2/day in eight cases, 70 mg/day in one) for the treatment of acute promyelocytic leukemia during pregnancy (2,3,4,5,6,7,8,9 and 10). In one case treatment was started during the 6th week of gestation (about 36 days from the last menstruation) (2); in five cases (1 set of twins), treatment was started during the 2nd trimester (3,4,5,6 and 7); and in three cases, treatment was started during the 3rd trimester (8,9 and 10). No congenital abnormalities were observed in the 10 newborns, although 8 were delivered prematurely (4 by elective cesarean section at 32, 32, 32, and 30 weeks; and 4 [1 set of twins] by spontaneous vaginal delivery at 32, 32 and 33 weeks). The growth and development in eight of the infants (postnatal examinations not reported in two cases) were normal in the follow-up periods ranging up to 15 months.

Breast Feeding Summary

Vitamin A and, presumably, tretinoin (all-trans retinoic acid) are natural constituents of human milk. No data are available on the amount of all-trans retinoic acid excreted into breast milk following the doses used for the treatment of promyelocytic leukemia or the risk, if any, this may present to a nursing infant.

"Official medicines" is the best online drugstore.

World’s leading meds delivered to your door – and you don’t even need a prescription! Only certified, first class drugs on offer! Buy more and spend less with our great discount system.

References

  1. Morriss-Kay, G. Retinoic acid and development. Pathobiology 1992;60:264–70.
  2. Simone MD, Stasi R, Venditti A, Del Poeta G, Aronica G, Bruno A, Masi M, Tribalto M, Papa G, Amadori S. All-trans retinoic acid (ATRA) administration during pregnancy in relapsed acute promyelocytic leukemia. Leukemia 1995;9:1412–3.
  3. Stentoft J, Lanng Nielsen J, Hvidman LE. All-trans retinoic acid in acute promyelocytic leukemia in late pregnancy. Leukemia 1994;8(Suppl 2):S77–S80.
  4. Harrison P, Chipping P, Fothergill GA. Successful use of all-trans retinoic acid in acute promyelocytic leukaemia presenting during the second trimester of pregnancy. Br J Haematol 1994;86:681–2.
  5. Lin C-P, Huang M-J, Liu H-J, Chang IY, Tsai C-H. Successful treatment of acute promyelocytic leukemia in a pregnant Jehovah's Witness with all-trans retinoic acid, rhG-CSF, and erythropoietin. Am J Hematol 1996;51:251–2.
  6. Incerpi MH, Miller DA, Posen R, Byrne JD. All-trans retinoic acid for the treatment of acute promyelocytic leukemia in pregnancy. Obstet Gynecol 1997;89:826–8.
  7. Morton J, Taylor K, Wright S, Pitcher L, Wilson E, Tudehope D, Savage J, Williams B, Taylor D, Wiley J, Tsoris D, O'Donnell A. Successful maternal and fetal outcome following the use of ATRA for the induction APML late in the first trimester (abstract). Blood 1995;86(Suppl 1):772a.
  8. Watanabe R, Okamoto S, Moriki T, Kizaki M, Kawai Y, Ikeda Y. Treatment of acute promyelocytic leukemia with all-trans retinoic acid during the third trimester of pregnancy. Am J Hematol 1995;48:210–1.
  9. Nakamura K, Dan K, Iwakiri R, Gomi S, Nomura T. Successful treatment of acute promyelocytic leukemia in pregnancy with all-trans retinoic acid. Ann Hematol 1995;71:263–4.
  10. Lipovsky MM, Biesma DH, Christiaens GCML, Petersen EJ. Successful treatment of acute promyelocytic leukaemia with all-trans-retinoic-acid during late pregnancy. Br J Haematol 1996;94:699–701.

Index