Because of its sedating potential, active metabolite, presence in infant serum, two reports of adverse effects in breastfed infants, and only one report of use without apparent adverse reactions, doxepin is a poor choice and other agents may be preferred, especially while nursing a newborn or preterm infant. If doxepin is required by the mother of an older infant, it may not a reason to discontinue breastfeeding, but the infant should be monitored carefully for excessive sedation, and adequate weight gain.
Maternal use of topical doxepin cream is unlikely to pose a problem for a breastfed infant as long as it is applied away from the breasts so that the infant cannot ingest the drug directly.
Doxepin is metabolized to N-desmethyldoxepin which has antidepressant activity equal to that of doxepin.
In one patient taking doxepin 25 mg three times daily, milk doxepin levels ranged from 7 to 29 mcg/L at various times throughout the day, with peaks occurring at about 4 to 5 hours after the dose. N-desmethyldoxepin levels ranged from trace to 11 mcg/L.
A mother who was taking 150 mg daily at bedtime, had milk doxepin and metabolite levels measured 8 times before and after feeding her infant over a 92-day postpartum period at about 18 hours after her dose. Her doxepin plus N-desmethyldoxepin milk levels averaged 141 mcg/L prefeed and 214 mcg/L postfeed. The authors estimated that the infant received about 2.2% of the maternal weight-adjusted dosage.
A mother who was taking doxepin 35 mg daily had breastmilk doxepin and N-desmethyldoxepin measured 3 times 11 to 13 days postpartum from 13 to 15 hours after the dose. The combined milk levels were 60, 100 and 100 mcg/L.
An 8-week-old exclusively breastfed infant whose mother was taking doxepin 25 mg three times daily had serum levels of N-desmethyldoxepin of 58 and 66 mcg/L on 2 occasions that were almost as high as maternal serum. The infant's doxepin serum level was 3 mcg/L.
An infant whose mother was taking 150 mg of doxepin a bedtime daily had an undetectable (<5 mcg/L) serum doxepin level and 15 mcg/L of N-desmethyldoxepin at 43 days of age.
An 11-day-old infant whose mother was taking 35 mg daily of doxepin had combined doxepin plus N-desmethyldoxepin plasma levels that were undetectable (<40 mcg/L) and individual drug and metabolite levels that were undetectable (<10 mcg/L) 2 hours after feeding.
Effects in Breastfed Infants:
One infant was breastfed (extent not stated) over a 2-month period during maternal use of doxepin 150 mg at bedtime, beginning at 30 days postpartum. The infant experienced no apparent adverse reactions.
One infant had an adverse reaction that was probably caused by doxepin in breastmilk. An 8-week old breastfed infant was found pale, limp, somnolent and almost not breathing 4 days after the maternal dosage had been increased from 10 mg daily to 25 mg three times daily. The infant returned to normal 24 hours after discontinuing breastfeeding.
A 9-day-old breastfed infant had poor sucking and swallowing, hypotonia, vomiting, and weight loss. The reaction was probably caused by doxepin in breastmilk. The infant's mother was taking 35 mg of doxepin at bedtime daily.
Possible Effects on Lactation:
Relevant published information was not found as of the revision date.
1. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID:15169695 2. Matheson I, Pande H, Alertsen AR. Respiratory depression caused by N-desmethyldoxepin in breast milk. Lancet. 1985;326:1124. Letter. PMID:2865592 3. Kemp J, Ilett KF, Booth J et al. Excretion of doxepin and N-desmethyldoxepin in human milk. Br J Clin Pharmacol. 1985;20:497-9. PMID:4074620 4. Frey OR, Scheidt P, von Brenndorff AI. Adverse effects in a newborn infant breast-fed by a mother treated with doxepin. Ann Pharmacother. 1999;33:690-3. PMID:10410181
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