Трамадола

A centrally-acting analgesic which has a weak opioid effect (1/6 to 1/10 that of morphine) and noradrenergic and serotonergic properties (AEMPS 2017). Indicated in the treatment of moderate to intense pain.
Intravenous and oral administration every 4 to 6 hours.
It is metabolized to the active metabolite, O-desmethyltramadol (M1), through the hepatic enzyme CYP2D6 (Reece 2017), which is deficient in the first 3 months of life (Palmer 2018). Tramadol causes sedation and its metabolite M1 causes sedation and respiratory depression (Palmer 2018).

Tramadol and M1 are excreted in breastmilk in clinically insignificant amounts (Gesseck 2021, AEMPS 2018, Actavis 2017, Reece 2017, FDA 2010, Hendrickson 2012, Hartenstein 2010, Ilett 2008, Kmetec 2003) even in cases of individuals with ultra-rapid metabolism (Salman 2011).

The dose received through breastmilk is much lower than the dose used in newborns and infants and no problems have been observed in infants whose mothers were taking it (Ilett 2008). The plasma levels of these infants were very low (Salman 2011).
Plasma levels of tramadol in a newborn on the third day of life whose mother took 300 mg daily of tramadol since pregnancy were 100 times lower than the therapeutic levels used in newborns and infants. According to their doctors, breastfeeding could have attenuated withdrawal symptoms (Hartenstein 2010).

Its use is authorized in pediatrics, even in newborns, in many countries (Palmer 2018, Alencar 2012).

A breastfed 8-month-old infant girl suffered fatal poisoning. Her mother and father were addicted to tramadol. It could not be established that the cause of her death was exposure to tramadol through breast milk (Hussien 2017).

With regard to sufentanil, tramadol increases prolactin levels and shortens the start time of breastfeeding (Chi 2017).

As with codeine (which is metabolized to morphine) there are ultra-fast metabolizers of tramadol that can accumulate a higher concentration of M1. For this reason, the FDA contraindicates codeine and also tramadol during breastfeeding (FDA 2017). But many experts consider tramadol safe or probably safe during breastfeeding (Palmer 2018, Reece 2017, Hale 2017 p 945, Bloor 2012, Salman 2011, Amir 2010, Ilett 2008), since:
- the metabolite of tramadol, M1, has a weak opioid effect, not like morphine, codeine metabolite.
- until two to three months of age the metabolism of tramadol to M1 is greatly diminished.
- Tramadol and M1 are excreted in very small amounts in breastmilk.
- no adverse effects have been reported in neonates or infants whose mothers were taking tramadol.

For these reasons, Palmer 2018 considers this contraindication of the FDA inappropriate.

A sufficient minimum dose should be used and signs of sedation or feeding difficulties should be monitored in the infant.

Postpartum pain, especially after an untreated caesarean section, makes it difficult to start breastfeeding (Carvalho 2013).
The use of non-steroidal anti-inflammatory drugs (NSAIDs) prescribed at fixed intervals can better control pain and have fewer side effects than tramadol (Worthington 2013, Sammour 2011).
The WHO’s guidelines for birth attendance should be followed, as well as decreasing the carrying out of caesarean sections and episiotomies, and therefore, the need to use analgesics in the first days.