Is tramadol safe for use during pregnancy, especially in the first trimester?

Tramadol Should Be Avoided During Pregnancy

Tramadol is not safe for use during pregnancy and should be avoided, particularly in the first trimester, due to documented embryotoxic and fetotoxic effects, risk of neonatal withdrawal syndrome, and lack of established safety data. 1, 2

FDA Classification and Animal Studies

The FDA classifies tramadol as Pregnancy Category C, indicating significant concerns 1, 2:

• Embryotoxic and fetotoxic effects have been demonstrated in animal studies across multiple species (mice, rats, and rabbits) at maternally toxic doses 2
• Effects included decreased fetal weights, skeletal ossification delays, increased supernumerary ribs, and embryo/fetal lethality in rabbits 2
• The FDA explicitly states that "safe use in pregnancy has not been established" 1

Documented Neonatal Risks

Neonatal abstinence syndrome is a serious and well-documented complication when tramadol is used chronically during pregnancy 3, 4:

• Tramadol freely crosses the placenta due to its lipophilic characteristics 4
• Neonatal withdrawal symptoms typically develop 24-36 hours after delivery and require treatment with phenobarbital 4
• Post-marketing surveillance has reported neonatal seizures, neonatal withdrawal syndrome, fetal death, and stillbirth 2

Clinical Management If Tramadol Has Been Used

If a pregnant woman has already been using tramadol chronically 3:

• Do not abruptly discontinue due to risk of maternal and fetal withdrawal 3
• Access appropriate expertise for safe tapering 3
• Delivery must occur at a facility prepared to monitor, evaluate, and treat neonatal opioid withdrawal syndrome 3
• Neonates require observation for at least 3 days post-delivery for withdrawal symptoms 4

Alternative Analgesics

Alternative analgesics should be strongly prioritized over tramadol during pregnancy 3:

• Consider acetaminophen as first-line for mild to moderate pain
• NSAIDs may be used in the second trimester only (avoid in first and third trimesters)
• If opioids are absolutely necessary, other agents with better-established safety profiles should be considered, though all opioids carry risks

Breastfeeding Considerations

Tramadol use during breastfeeding also carries significant concerns 5, 1:

• The FDA issued a warning in April 2017 against taking tramadol while breastfeeding due to case reports of respiratory depression and death 5
• If used, it should be restricted to inpatient use with limited total dose 5
• Infants must be closely monitored for increased sleepiness, respiratory depression, sedation, and decreased alertness 5, 3
• Tramadol and its active metabolite O-desmethyltramadol are excreted into breast milk in clinically significant amounts 5, 6

Critical Caveat

Unlike medications with decades of safe use in pregnancy, tramadol lacks this safety profile and adequate well-controlled studies in pregnant women 1, 2. The medication should only be used during pregnancy if the potential benefit clearly justifies the substantial potential risk to the fetus, which is rarely the case given available alternatives 2.