Is doxepin safe to use during pregnancy?

Doxepin Safety During Pregnancy

Doxepin should be avoided during pregnancy due to lack of established safety data and potential risks to the fetus. According to the FDA drug label, while animal studies showed no evidence of harm to animal fetuses, there is no experience in pregnant women who have received this drug, and therefore safety in pregnancy has not been established 1.

Evidence on Doxepin in Pregnancy

The FDA drug label for doxepin specifically states:

• "Reproduction studies have been performed in rats, rabbits, monkeys and dogs and there was no evidence of harm to the animal fetus. The relevance to humans is not known."
• "Since there is no experience in pregnant women who have received this drug, safety in pregnancy has not been established."
• There has been a report of apnea and drowsiness occurring in a nursing infant whose mother was taking doxepin 1.

Risk Assessment

When considering the use of any medication during pregnancy, several factors must be evaluated:

1. Established safety data: Doxepin lacks human pregnancy safety data
2. Potential risks: A case report indicates risk of apnea and drowsiness in nursing infants
3. Benefit-risk ratio: The potential benefits must be weighed against theoretical adverse effects on the fetus

Alternative Medications with Better Safety Profiles

If treatment is necessary during pregnancy, consider medications with more established safety profiles:

• For depression/anxiety treatment: The FDA label indicates that some medications have longer safety records during pregnancy 1
• For ADHD treatment: Atomoxetine does not seem to be associated with major congenital malformations or significant adverse obstetrical outcomes, although data are limited 2, 3
• For insomnia: If a benzodiazepine is needed, chlordiazepoxide appears to have a better safety profile during pregnancy than other options 4

Important Considerations for Medication Use During Pregnancy

If medication is absolutely necessary during pregnancy:

• Use drugs with established safety records at the lowest effective dosage for the shortest possible duration
• Avoid use during the first trimester when possible, as this is when risk of congenital malformations is greatest 2
• Avoid multidrug regimens, as combinations may increase risks (e.g., benzodiazepines with antidepressants showed increased risk of congenital malformations) 5
• Divide daily dosage into multiple doses to avoid high peak concentrations 4

Monitoring and Follow-up

If doxepin must be used during pregnancy despite these concerns:

• Closely monitor the pregnancy with more frequent prenatal visits
• Consider specialized fetal monitoring
• Be prepared to manage potential neonatal complications such as poor adaptation, respiratory depression, or withdrawal symptoms

Conclusion

Given the lack of established safety data in humans and the report of adverse effects in a nursing infant, doxepin should be avoided during pregnancy when possible. Alternative medications with better-established safety profiles should be considered when treatment is necessary.