Is Tramadol safe while breastfeeding?

Effects on the breastfed infant

Seventy-five breastfed infants whose mothers were breastfeeding and taking tramadol 100 mg, every 6 hours following a cesarean section were compared to 75 matched infants at 2 to 4 days of age. Forty-nine percent of the mothers who were taking tramadol and all of the control mothers were taking other opiates (primarily oxycodone) and 61% of and 58%, respectively, also were taking a nonsteroidal anti-inflammatory agent (primarily diclofenac). Examination by a pediatrician revealed no difference between the groups using the Neurologic and Adaptive Capacity Score.[ 6 ] An 8-month-old infant was brought to an emergency department (ED) in Egypt with altered mental status, hypoxia, hypotension and a low hematocrit. In the ICU, the infant had a positive urine drug screen for tramadol and a negative urine test for cannabinoids and opiates. Two doses of naloxone improved her blood gases and 2 days later her mental status had improved. The infant s parents stated that they were addicted to tramadol, and the mother was breastfeeding the infant. The infant was discharged on day 3 after admission. Thirty-six hours later, the infant again presented to the ED with cardiopulmonary arrest, with a 4 on the Glasgow coma scale and generalized clonic-tonic seizures. The infant died from cardiac arrest 3 days after admission. The mother stated that she had breastfed the infant after the initial discharge from the hospital. The author speculates that mother or infant might be an ultra-rapid CYP2D6 metabolizer leading to high levels of the active metabolite, because this variant is relatively prevalent in those of Mediterranean origin. However, neither genetic testing nor measurement of tramadol in milk or the infant were performed.[ 9 ] This case cannot definitely be attributed to breastmilk exposure alone, because the sudden onset of the symptoms at 8-months of age seems implausible. It is somewhat more likely that the baby ingested the tramadol directly. A trial in women who received a

Effects on milk supply

Tramadol can increase serum prolactin.[ 13 ] Hyperprolactinemia and galactorrhea was reported in a woman who was abusing high doses of tramadol injection.[ 14 ] However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed. A randomized study compared tramadol and naproxen for post-cesarean section pain. Patients received the drugs either on a fixed schedule or as needed. No difference in breastfeeding rates were seen among the groups.[ 15 ] Similarly, a study compared a 100 mg tramadol rectal suppository to a 100 mg diclofenac rectal suppository for postpartum pain after closure of the surgical wound of a cesarean section. No difference in breastfeeding initiation rates within 2 hours were observed between the groups.[ 16 ] In a study in China, women with a scheduled cesarean section were randomized to receive intravenous patient-controlled analgesia with either sufentanil or tramadol. Postpartum prolactin levels were higher in the tramadol group (348 mcg/L) than in the sufentanil group (314 mcg/L). The onset of lactation was sooner in the tramadol group (21.4 hours) than in the sufentanil group (25.1 hours). Both of these difference were statistically significant.[ 17 ] Injectable tramadol is not available in the United States. A trial in women who received a cesarean section randomized participants to receive 2 tablets of acetaminophen 325 mg and tramadol 35.5 mg (Zaldiar, Gruenthal, Israel) every 6 hours as well as diclofenac 100 mg at 12, 24 and 48 hours after arrival in the maternity ward, either as a fixed dose or the same drugs on demand. Patients on the fixed dose regimen had more breastfeeds (23.8 vs 19.2) and fewer instances of formula (8.2 vs 11.9) than the on demand group.[ 10 ] A nonrandomized, nonblinded study in a Serbian hospital of women near term who underwent cesarean section compared general anesthesia (n = 284) to spinal or epidural anesthesia (n = 249). Spinal anesthesia consisted of hyperbaric bu

Levels in milk

In adults, tramadol has 70 to 100% oral bioavailability and is metabolized to the active O-desmethyltramadol (M1). Tramadol has a more potent monoamine reuptake inhibitory effect while M1 has a more potent opioid mu-agonist effect. M1 is about 10% as potent as morphine in mu-opiate binding, although some investigators have reported a 450-fold potency difference. Women who are extensive metabolizers of tramadol may have higher than expected serum levels of M1, potentially leading to higher levels of M1 in breastmilk. The capacity of preterm and newborn infants to metabolize tramadol to M1 is limited.[ 3 ] Maternal Levels. The manufacturer reports that in the 16 hours following a 100 mg intravenous dose of tramadol, the cumulative excretion into breastmilk was 100 mcg of tramadol and 27 mcg of M1. No further details are provided. Detectable levels ( 12 mcg/L) of tramadol were found in samples of breastmilk collected 10 hours after a 50 mg maternal dose of intravenous or oral tramadol.[ 4 ] No other clinical details or milk levels were reported. One mother was taking oral tramadol 300 mg daily during pregnancy and presumably the same dose postpartum for chronic back pain. On approximately day 3 postpartum (time not specified), the breastmilk concentration of tramadol was 1.8 mg/L.[ 5 ] Seventy-five mothers who were 2 to 4 days postpartum provided 3 milk samples from both breasts during the 6 hours following a dose of 100 mg of oral tramadol after taking at least 4 doses. The average milk concentration of tramadol was 748 mcg/L and of M1 was 203 mcg/L. These values translate to an average infant dosage of 112 and 30 mcg/kg daily of the drug and metabolite, respectively. An exclusively breastfed infant would receive maternal weight-adjusted dosages of 2.24% of tramadol and 0.64% of its metabolite.[ 6 ] Reanalysis of the above data using a pharmacokinetic model with first-pass conversion rates based on literature values and simulating a maternal dosage of 100 mg every 6 h

Alternatives LactMed lists

• Acetaminophen
• Butorphanol
• Fentanyl
• Hydromorphone
• Ibuprofen
• Morphine