Clinical pharmacology of methadone in neonates and in their mothers. A review

Abstract

The outstanding properties of methadone are its analgesic activity, its efficacy by oral route, its extended duration of action in suppressing of withdrawal symptoms in physically dependent individuals, and its tendency to show persistent effects with repeated administration. The analgesic activity of methadone, a racemate, is almost entirely the result of its R-methadone content. Respiratory depression is the chief hazard associated with methadone, and its peak respiratory depressant effects typically occur later, and persist for longer than its peak analgesic effect, particularly in the early dosing period. Methadone undergoes extensive metabolism in the liver and the major metabolic pathway is N-demethylation by CYP3A4 and CYP2B6. There is a remarkable interindividual variability in the rate of methadone metabolism. Mothers with opioid addiction are often placed on methadone before delivery in an attempt to reduce illicit opioid usage. Methadone is useful because it can be taken orally, only requires one or two daily doses and has a long-lasting effect. Weaning should not be attempted during pregnancy and, because of increased clearance, the dose of methadone may need to be increased in the last 3 months of pregnancy. Significant positive correlations were found for umbilical cord methadone concentrations, methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. In conclusion, umbilical cord methadone concentrations were correlated to methadone dose. A total of 55-94% of infants born to opioid-dependent mothers in US show signs of opioid withdrawal. Methadone is useful to avoid use of opioid illicit drugs.

Metabolism and pharmacokinetics of morphine in neonates: A review

“…Moreover, neonatal abstinence due to opiate withdrawal produces sleep/wake abnormalities, feeding difficulties, weight loss and seizures. An analysis of the management of morphine weaning has recently been presented elsewhere 4.…”

Paralytic ileus in the neonate as a rare complication of maternal methadone treatment—a case report

“…For more than 30 years, methadone has been used as a first-line medication for opioid substitution therapy during pregnancy [ 5 ]. Despite the strong evidence supporting the use of methadone in pregnancy, methadone use is not without risk or side effects [ 5 , 6 ]. Methadone does not only cross the placental barrier but is also retained by the placenta in a substantial amount [ 4 ].…”

“…Currently, the recommended pharmacotherapy for opioid dependency in the antenatal period is methadone, which was found to diminish illicit use [ 3–5 ]. The most common side effect of maternal methadone and opiate use is neonatal abstinence syndrome (NAS), a set of signs and symptoms related to nervous system dysfunction that increases morbidity and prolongs NICU stay [ 3 , 5 ]. In the available literature, we did not find reports describing early-onset gastrointestinal dysfunction in the neonates exposed to opiates and methadone in utero .…”