Is tramadol (tramadol hydrochloride) safe to use during pregnancy?

Tramadol Use During Pregnancy

Tramadol should not be used during pregnancy due to risks of fetal toxicity, neonatal withdrawal syndrome, and potential congenital malformations. 1

Safety Profile & FDA Classification

Tramadol is classified as FDA Pregnancy Category C, indicating that:

• It has been shown to be embryotoxic and fetotoxic in animal studies at maternally toxic doses 1
• No adequate and well-controlled studies exist in pregnant women 1
• The drug crosses the placenta, with a mean ratio of 0.83 in umbilical veins compared to maternal veins 1

Risks to the Fetus and Newborn

First Trimester Exposure

• Potential teratogenic effects: A Swedish study found an adjusted odds ratio of 1.33 (95% CI 1.05-1.70) for relatively severe malformations, with significantly increased odds for cardiovascular defects (OR 1.56) and pes equinovarus (OR 3.63) 2
• However, a more recent Danish nationwide cohort study from 2022 found no significant association between tramadol exposure and major congenital malformations (RR 1.04,95% CI 0.87-1.24) 3

Throughout Pregnancy

• Risk of neonatal withdrawal syndrome: Case reports document neonatal abstinence syndrome requiring treatment with phenobarbital 4
• FDA labeling warns of neonatal seizures, withdrawal syndrome, fetal death, and stillbirth reported in post-marketing surveillance 1
• The drug should not be used prior to or during labor unless potential benefits outweigh risks 1

Late Pregnancy

• Chronic use during pregnancy may lead to physical dependence and post-partum withdrawal symptoms in the newborn 1
• Not recommended for obstetrical preoperative medication or post-delivery analgesia in nursing mothers 1

Alternative Pain Management Options During Pregnancy

For pain management during pregnancy, safer alternatives should be considered:

1. Non-pharmacological approaches should be first-line when possible
2. Acetaminophen is generally considered safer for pain management during pregnancy
3. If opioid analgesia is absolutely necessary, consultation with maternal-fetal medicine and pain specialists is essential to weigh risks and benefits

Monitoring Recommendations

If a pregnant woman has been exposed to tramadol:

• Detailed ultrasound examination to assess for potential congenital anomalies
• Close monitoring of fetal growth and development
• Preparation for potential neonatal withdrawal symptoms after delivery
• Plan for at least 72 hours of neonatal observation post-delivery

Clinical Decision Algorithm

1. Assess necessity: Is pain management absolutely required?
2. Consider non-pharmacological options first
3. If medication is needed: Use acetaminophen as first-line therapy
4. If stronger analgesia is required: Consult maternal-fetal medicine before considering any opioid
5. If tramadol exposure has already occurred: Implement close monitoring of fetal development and prepare for potential neonatal complications

Conclusion

The FDA clearly states that tramadol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 1. Given the availability of safer alternatives and the documented risks of neonatal withdrawal syndrome and potential congenital malformations, tramadol should be avoided during pregnancy whenever possible.