What is the effect of tramadol (opioid analgesic) on breast milk?

Tramadol and Breastfeeding

Tramadol is not recommended for breastfeeding mothers because the FDA explicitly states its safety in infants and newborns has not been studied, and safer alternatives exist. 1

FDA Regulatory Position

The FDA drug label clearly states that tramadol hydrochloride is not recommended for post-delivery analgesia in nursing mothers due to lack of established safety data in infants and newborns. 1 Following a single 100 mg IV dose, tramadol is excreted into breast milk at approximately 0.1% of the maternal dose (100 μg tramadol and 27 μg of the M1 metabolite within 16 hours). 1

Transfer into Breast Milk

• Tramadol concentrates in breast milk with a milk-to-plasma ratio of 2.2 for tramadol and 2.8 for its active O-desmethyl metabolite at steady-state. 2
• The combined relative infant dose is approximately 2.88% of the weight-adjusted maternal dose, which is considered low by traditional standards. 2
• However, actual breast milk concentrations can vary significantly—one case report documented concentrations ranging from 63 ng/mL on day 12 to 1,254 ng/mL on day 20 postpartum, representing a 20-fold increase. 3
• The active metabolite (O-desmethyltramadol) was detected in neonatal oral fluid at concentrations almost four times higher than in breast milk, suggesting significant infant exposure and metabolism. 3

Risk Assessment Framework

All opioids carry risk during breastfeeding, and tramadol is no exception. The Association of Anaesthetists recommends caution with all opioids in breastfeeding women due to risks of infant sedation, respiratory depression, and decreased alertness. 4

Specific Concerns with Tramadol:

• Tramadol is metabolized by the polymorphic CYP2D6 enzyme system, similar to codeine, creating unpredictable variability in active metabolite production. 5
• Ultrarapid metabolizers (up to 28% in Middle Eastern/North African populations, up to 10% in Caucasians) could theoretically produce higher concentrations of the active O-desmethyl metabolite, though this has not been as extensively studied as with codeine. 6
• The manufacturer has not conducted safety studies in breastfed infants, making risk assessment inherently uncertain. 1

Monitoring Requirements If Tramadol Is Used

If tramadol has already been administered or alternative analgesics are unavailable, infants must be closely monitored for:

• Increased sleepiness or sedation 4
• Difficulty breathing or respiratory depression 4, 7
• Decreased alertness 4, 7
• Feeding problems or difficulty breastfeeding 4, 6

Preferred Alternatives

Consider safer analgesic options that have better-established safety profiles in breastfeeding:

• Ketorolac is considered safe for breastfeeding women and is recommended over opioids by the American Academy of Pediatrics. 4
• Dihydrocodeine may be preferred if a weak opioid is needed, due to its cleaner metabolism compared to codeine and tramadol. 4, 6
• Morphine is recommended as the opioid of choice if strong analgesia is required, as it has more predictable pharmacokinetics in this population. 6

Common Pitfalls

• Assuming low relative infant dose equals safety: While the 2.88% relative infant dose appears low, the case report showing 20-fold concentration increases and high metabolite levels in infant oral fluid demonstrates unpredictable exposure. 3, 2
• Failing to recognize genetic variability: Like codeine, tramadol's metabolism varies by CYP2D6 genotype, but genetic testing is not routinely available to identify high-risk mother-infant pairs. 6, 5
• Relying on short-term study data: The most cited study only evaluated tramadol use for 2-4 days postpartum during transitional milk production, not established lactation or longer-term use. 2