Is tramadol (opioid analgesic) safe to use during pregnancy?

Tramadol Safety During Pregnancy

Tramadol should not be used during pregnancy due to significant risks of embryotoxicity, fetotoxicity, neonatal withdrawal syndrome, and lack of established safety, and should be avoided or used with extreme caution only when potential benefits clearly outweigh substantial fetal and neonatal risks. 1

FDA Classification and Primary Concerns

• Tramadol is FDA Pregnancy Category C, meaning animal studies have demonstrated embryotoxic and fetotoxic effects, and there are no adequate well-controlled studies in pregnant women 1
• The FDA label explicitly states tramadol "should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks" and that "safe use in pregnancy has not been established" 1
• Chronic use during pregnancy leads to physical dependence and post-partum withdrawal symptoms in newborns 1

Specific Risks to the Fetus and Neonate

Developmental Toxicity

• Animal studies demonstrate embryotoxicity and fetotoxicity in mice (at 120 mg/kg), rats (≥25 mg/kg), and rabbits (≥75 mg/kg) at maternally toxic doses, including decreased fetal weights, skeletal ossification delays, and increased supernumerary ribs 1
• Recent animal research confirms tramadol causes reduced live fetuses, decreased placental weights, reduced fetal length and weights, and structural abnormalities when administered during late pregnancy 2

Neonatal Complications

• Post-marketing reports document neonatal seizures, neonatal withdrawal syndrome, fetal death, and stillbirth 1
• Tramadol freely crosses the placenta with a mean umbilical vein to maternal vein ratio of 0.83, resulting in substantial fetal exposure 1, 3
• Neonatal abstinence syndrome typically develops 36 hours after delivery in infants exposed to chronic maternal tramadol use, requiring phenobarbital treatment and prolonged hospitalization 4

Clinical Management Considerations

If Tramadol Use Is Being Considered

• The decision requires weighing maternal pain control needs against documented fetal risks 1
• Alternative analgesics should be strongly prioritized over tramadol during pregnancy 5
• If tramadol has been used chronically, do not abruptly discontinue due to risk of maternal and fetal withdrawal; access appropriate expertise for tapering 5

If Chronic Use Has Occurred

• Delivery must occur at a facility prepared to monitor, evaluate, and treat neonatal opioid withdrawal syndrome 5
• Neonates require observation for at least 3 days post-delivery for withdrawal symptoms 4
• Monitor newborns for seizures, irritability, feeding difficulties, and other withdrawal signs 4

Breastfeeding Considerations

• Tramadol should be used with caution during breastfeeding, with close infant monitoring for drowsiness, respiratory depression, and decreased alertness 5, 6
• Breast milk excretion is documented at 0.1% of maternal dose after a single 100 mg IV dose, though concentrations increase with chronic use 1, 7
• Recent case reports show neonatal oral fluid concentrations can reach significant levels (1,011 ng/mL tramadol) with calculated absolute infant doses up to 294 μg/kg/day 7
• Infants must be monitored for increased sleepiness, difficulty breathing, decreased alertness, and feeding problems 6

Comparative Context

• Unlike inhaled asthma medications that have decades of safe use in pregnancy, tramadol lacks this safety profile 5
• The risk-benefit calculation differs substantially from conditions where untreated maternal disease poses clear fetal harm (such as severe asthma with maternal hypoxia) 5
• Codeine is contraindicated in breastfeeding, and tramadol carries similar concerns requiring heightened caution 5