Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Some small clinical studies suggest that desipramine and other tricyclic antidepressants may reduce libido and cause erectile and ejaculatory dysfunction in males. Other reports have also associated desipramine with testicular pain and swelling.

[REPROTOX® Database: Klasco RK: REPROTOX® Database. Truven Health Analytics, Greenwood Village, Colorado.]

Effects on developmental toxicity

Description of key information

Based on experimental animal studies and human experience with imipramine, desipramine is not expected to increase the risk of congenital malformations. Desipramine (Norpramin; Pertofrane) is an active metabolite of imipramine.

Neonatal complications have been reported in newborns who were exposed to desipramine in utero. The symptoms observed during the first neonatal month have included colic, cyanosis, rapid breathing, and irritability. The pediatrician can be advised in advance that the mother has been taking this drug. Also, nortriptyline, a congener of desipramine, was associated with urinary retention in one newborn.

[REPROTOX® Database: Klasco RK: REPROTOX® Database. Truven Health Analytics, Greenwood Village, Colorado.]

Toxicity to reproduction: other studies

Description of key information

Desipramine enters human milk. Maternal and infant serum levels of desipramine and its metabolite 2-hydroxydesipramine were measured in an exclusively breastfed infant after one week of maternal treatment with high-dose desipramine (300 mg/d). Neither desipramine nor its metabolite were detected using cutoffs of 1 ng/mL and 5 ng/mL respectively.  No signs of infant toxicity were observed during 3 weeks of maternal treatment.

Desipramine concentrations were reported as undetectable (<25 ng/mL) in 3 infants exposed during pregnancy and lactation to maternal doses of 150-200 mg/d, measured at 2.3-14.9 weeks of age.

An exclusively breastfed infant was exposed beginning at 16 weeks postpartum, for a total of 8 weeks, to maternal treatment with desipramine 100 mg/d.  Development was normal at 3 years of age. The clinical significance of low levels of desipramine in the breastfed newborn is not well defined, so observation for possible behavioral effects has been recommended.  The American Academy of Pediatrics categorized the effects of desipramine on the nursing infant to be "unknown but a possible cause for concern".  In contrast, however, the WHO Working Group on Human Lactation assessed the use of desipramine during lactation as "probably safe," although they noted the need for more data to delineate the range of drug concentrations that may be found in milk.

[REPROTOX® Database: Klasco RK: REPROTOX® Database. Truven Health Analytics, Greenwood Village, Colorado.]

Justification for classification or non-classification

Overall, available data are inconclusive for the classification of the substance.