Is 1-Methyl-4-phenylisonipecotic acid, ethyl ester Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use 1-Methyl-4-phenylisonipecotic acid, ethyl ester? Is 1-Methyl-4-phenylisonipecotic acid, ethyl ester safe for nursing mother and child? Does 1-Methyl-4-phenylisonipecotic acid, ethyl ester extracts into breast milk? Does 1-Methyl-4-phenylisonipecotic acid, ethyl ester has any long term or short term side effects on infants? Can 1-Methyl-4-phenylisonipecotic acid, ethyl ester influence milk supply or can 1-Methyl-4-phenylisonipecotic acid, ethyl ester decrease milk supply in lactating mothers?

It is excreted in breast milk in very small quantities (Al-Tamimi 2011, Borgatta 1997, Quinn 1986, Peiker 1980) and, in general, no problems have been observed in infants whose mothers were taking it (Al-Tamimi 2011). After a caesarean section, newborns whose mothers were treated with pethidine to relieve pain showed greater signs of neurological depression during the first three days than those whose mothers were treated with morphine (Reynolds 2011, Wittels 1997 and 1990). Newborns whose mothers received pethidine, compared to mothers who received fentanyl, morphine or no analgesic drug, had more problems establishing breastfeeding in the first few days, less initial frequency of breastfeeding or greater early stopping of breastfeeding (Fleet 2016 and 2015, Wilson 2010, Yost 2004, Torvaldsen 2006, Ransjö 2001, Spigset 2000, Nissen 1997 and 1995, Lee 1993). The elimination of the metabolite norpethidine is slower, with a T½ of 20 hours (Lee 1993, Quinn 1986).Due to these considerations, although the American Academy of Pediatrics considered it to be a medication which was usually compatible with breastfeeding (AAP 2001), later it advised against its use (Sachs 2013) together with other scientific organizations (ABM Protocol # 15 2017 and 2012, ASGE 2012, Gastroenterology, 2012). Isolated doses for short procedures are unlikely to affect the infant (ABM Protocol # 15 2017 and 2012, WHO / UNICEF 2002).Avoid repeated doses. Monitor sedation and weak suction, especially in the neonatal period (WHO / UNICEF 2002).

Other agents are preferred over 1-Methyl-4-phenylisonipecotic acid, ethyl ester during breastfeeding.[1][2] Intravenous 1-Methyl-4-phenylisonipecotic acid, ethyl ester during labor can interfere with nursing and maternal use of 1-Methyl-4-phenylisonipecotic acid, ethyl ester during breastfeeding can sedate the infants. Patient-controlled epidural analgesia postpartum appears to be free from these effects. However, other agents, such as fentanyl, are preferred for intravenous or intramuscular use, especially while nursing a newborn or preterm infant.[3] Labor pain medication may delay the onset of lactation. A single dose for anesthesia or conscious sedation usually does not cause problems in older breastfed infants.[4][5] When a combination of anesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure. Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, central nervous system depression and even death. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of 1-Methyl-4-phenylisonipecotic acid, ethyl ester to a few days at a low dosage with close infant monitoring. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.

In 2 controlled studies, repeated maternal post-cesarean section 1-Methyl-4-phenylisonipecotic acid, ethyl ester doses, including patient-controlled analgesia, caused diminished alertness and orientation in 3- to 4-day old breastfed infants compared to equivalent doses of morphine.[10][13] Twenty breastfed (extent not stated) infants whose mothers had received patient-controlled epidural analgesia with 1-Methyl-4-phenylisonipecotic acid, ethyl ester for 48 to 72 hours postpartum. They were assessed with the Neurologic and Adaptive Capacity Score (NACS) at a median of 105 minutes after maternal 1-Methyl-4-phenylisonipecotic acid, ethyl ester cessation. The median NACS was 33.5 (range 24 to 38), which is similar to the average score of 35 in healthy infants with no drug effects.[12]

1-Methyl-4-phenylisonipecotic acid, ethyl ester can increase serum prolactin.[14] However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed. More importantly, 1-Methyl-4-phenylisonipecotic acid, ethyl ester is likely to interfere with infant nursing behavior when given during labor.[15][16][17] In one small study, women given promethazine with 1-Methyl-4-phenylisonipecotic acid, ethyl ester and secobarbital during labor, had the time to lactogenesis II prolonged by 14 hours. Women given 1-Methyl-4-phenylisonipecotic acid, ethyl ester or secobarbital without promethazine had lactogenesis II prolonged 7 hours compared to unmedicated women, but the difference was not statistically significant.[18] A randomized, multicenter trial compared the initiation rate and duration of breastfeeding in women who received high-dose epidural bupivacaine alone, or one of two low-dose combinations of bupivacaine plus fentanyl. A nonepidural matched control group, some of whom received systemic 1-Methyl-4-phenylisonipecotic acid, ethyl ester, was also compared. Women in the nonepidural group who received systemic 1-Methyl-4-phenylisonipecotic acid, ethyl ester had a lower breastfeeding initiation rate than in the epidural or unmedicated groups.[19] A national survey of women and their infants from late pregnancy through 12 months postpartum compared the time of lactogenesis II in mothers who did and did not receive pain medication during labor. Categories of medication were spinal or epidural only, spinal or epidural plus another medication, and other pain medication only. Women who received medications from any of the categories had about twice the risk of having delayed lactogenesis II (>72 hours) compared to women who received no labor pain medication.[20] A randomized, nonblinded study compared the use of intramuscular 1-Methyl-4-phenylisonipecotic acid, ethyl ester 100 mg to intranasal (mean dose 486 mcg) or subcutaneous (mean dose 300 mcg) fentanyl for labor analgesia. More women in the 1-Methyl-4-phenylisonipecotic acid, ethyl ester group had difficulty establishing lactation (79%) than in the intranasal (39%) or subcutaneous (44%) fentanyl groups. Mothers who received 1-Methyl-4-phenylisonipecotic acid, ethyl ester reported more sedation, had longer labors, and their infants were more likely to be admitted to the nursery.[21][22] Analysis of an Australian database of 1835 pregnant women found that the 285 women who received 1-Methyl-4-phenylisonipecotic acid, ethyl ester during labor were 41% more likely to have discontinued breastfeeding by 6 weeks of age.[23] A study of lactose, protein, sodium and potassium concentrations in the breastmilk found slightly higher lactose concentrations in the milk of mothers who delivered vaginally and received no 1-Methyl-4-phenylisonipecotic acid, ethyl ester compared to those who had a Cesarean section followed by patient-controlled analgesia with 1-Methyl-4-phenylisonipecotic acid, ethyl ester in the first 72 hours postpartum. Between 72 and 165 hours postpartum, vaginally delivered mothers without 1-Methyl-4-phenylisonipecotic acid, ethyl ester had lower sodium and protein content and higher potassium content in milk than those who received 1-Methyl-4-phenylisonipecotic acid, ethyl ester. However, by 72 hours postpartum, both groups had evidence of adequate secretory activation.[24] A retrospective case-control study conducted in two hospitals in central Iran compared breastfeeding behaviors in the first 2 hours postdelivery by infants of 4 groups of primiparous women with healthy, full-term singleton births who had vaginal deliveries. The groups were those who received no medications during labor, those who received oxytocin plus scopolamine, those who received oxytocin plus 1-Methyl-4-phenylisonipecotic acid, ethyl ester, and those who received oxytocin, scopolamine and 1-Methyl-4-phenylisonipecotic acid, ethyl ester. The infants in the no medication group performed better than those in all other groups, and the oxytocin plus scopolamine group performed better than the groups that had received 1-Methyl-4-phenylisonipecotic acid, ethyl ester.[25] Use of a combination of 1-Methyl-4-phenylisonipecotic acid, ethyl ester 50 mg and levallorphan 0.625 mg (Pethilorphan) per dose intramuscularly as a last resort for severe labor pain was studied retrospectively in a hospital in Japan that did not use epidural analgesia. It was often used with hydroizine 50 mg or promethazine 25 mg intramuscularly. Outcomes were compared to those of women who received no 1-Methyl-4-phenylisonipecotic acid, ethyl ester. Although women who received 1-Methyl-4-phenylisonipecotic acid, ethyl ester plus levallorphan had several indications of more difficult labor and delivery, there was no difference in the rates of suckling difficulties or breastfeeding rates at discharge or 1 month postpartum between the groups. No differences between dosages of 1-Methyl-4-phenylisonipecotic acid, ethyl ester received was found.[26]