毒理性
哺乳期间使用总结：哺乳期母亲口服麻醉剂可能会导致婴儿昏睡和严重的中枢神经系统抑制。母亲使用氧可酮时，婴儿镇静是常见且已有充分记录的。新生婴儿似乎对即使是小剂量的麻醉止痛剂都非常敏感。一旦母亲的乳汁开始分泌，最好使用非麻醉性止痛剂来控制疼痛，并将母亲口服氧可酮（及其组合药物）的时间限制在2到3天，特别是在门诊环境中。建议氧可酮的最大剂量为每日30毫克，尽管一些来源建议在哺乳期间避免使用氧可酮。每日30毫克的限制似乎为母亲提供与剖宫产后使用更高剂量相同的益处。年轻婴儿的氧可酮消除减少，个体间差异很大。密切监测婴儿的昏睡状态、适当的体重增长和发育里程碑，尤其是在较年轻、仅以母乳喂养的婴儿中。如果婴儿表现出比平时更嗜睡、哺乳困难、呼吸困难和无力，应立即联系医生。在哺乳期间，首选其他药物而不是氧可酮。
对哺乳婴儿的影响：一名10个月大、7.7公斤的婴儿，其母亲依赖处方药，在一段时间的昏睡、过度嗜睡和呼吸困难后死于心脏骤停。婴儿还有近期发热的历史。据报道，母亲在婴儿死亡前一天服用了180毫克的氧可酮以及肌肉松弛剂，并一直在哺乳婴儿3次/天。尸检时婴儿血液中氧可酮浓度为600微克/升。法医认为，婴儿血液中如此高的氧可酮水平不太可能仅仅是由于母亲报告的哺乳暴露所致，因此认为死亡是故意给婴儿直接服用氧可酮或通过母乳给予更高剂量氧可酮导致的他杀。
在一项对50位剖宫产后服用氧可酮的母亲的研究中，对50名新生儿进行了出生后48小时的镇静评估。没有一个严重镇静，不到4%的婴儿在1（完全清醒）到5（难以唤醒）的量表上出现3级镇静，没有超过3级的。由于这些婴儿出生后前3天，他们摄入的氧可酮剂量可能被限制在他们摄入的初乳的少量中。
一名母亲在服用氧可酮20毫克，每日3次、氟西汀40毫克/日和喹硫平400毫克/日的情况下生下了一名婴儿。婴儿每天哺乳6到7次，并接受每日3次，每次120微克的口服吗啡以治疗阿片类药物戒断。3个月大时检查，婴儿的体重降至年龄的第25百分位，而出生时为第50百分位。作者将体重下降归因于阿片类药物戒断。婴儿的丹佛发展评分等于其年龄。
一名妇女在完全哺乳她的婴儿时，每4到6小时服用5到10毫克的氧可酮以治疗会阴切开疼痛。她45天大的婴儿因体温98.4华氏度、心率每分钟154次、呼吸每分钟20次、血压71/52毫米汞柱、在室内空气中血氧饱和度为60%至69%而被带到急诊科。婴儿从出生起就一直便秘，每5到8天排便一次。婴儿的动作迟缓，呼吸浅而缓慢。她的瞳孔小，但反应灵敏。尿液中的氢吗啡酮水平升高。患者在持续两天全天候使用阿片类药物后拔管出院。婴儿的便秘、中枢神经系统和呼吸抑制可能是由母乳中的氧可酮引起的。
在一项回顾性研究中，通过电话联系了正在哺乳的母亲，她们在哺乳期间为了止痛而服用氧可酮、可待因或对乙酰氨基酚，以确定母亲感知到的中枢神经系统（CNS）抑制的程度。服用氧可酮的母亲报告说，她们的婴儿中有20%（28/139）表现出CNS抑制的迹象，而服用对乙酰氨基酚的母亲中只有0.5%（1/184）的婴儿出现CNS抑制。报告婴儿镇静的母亲服用的氧可酮剂量为每日0.4毫克/千克，而未受影响的母亲服用剂量为每日0.15毫克/千克。受影响的婴儿比未受影响的婴儿有更多的每日不间断睡眠时间，其中4名受影响的婴儿据报道有“呼吸不规则”。在39名母亲中，有38名报告说，随着母亲停止服用氧可酮，婴儿的镇静停止了。受影响婴儿的母亲也比未受影响婴儿的母亲更有可能经历嗜睡和其他副作用。服用可待因的母亲报告的婴儿镇静率与氧可酮相似（17%），但两组在产次和月经后年龄（PMA）上统计学上有差异，可待因组的PMA略高。
一名仅以母乳喂养的新生儿在2天大时被他的医生认为是健康的。在出生后3天，婴儿开始变得镇静并难以唤醒，并且不再从任一侧乳房吸奶。在4天大时，婴儿被带到急诊科，发现婴儿出现昏睡、低体温
◉ Summary of Use during Lactation:Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, and severe central nervous system depression. Infant sedation is common and well documented with maternal use of oxycodone. 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 oral oxycodone (and combinations) to a 2 to 3 days, especially in the outpatient setting. A maximum oxycodone dosage of 30 mg daily is suggested, although some sources recommend avoiding oxycodone during breastfeeding. A 30 mg daily limit appears to offer the same benefits to the mother as higher dosages for mothers after cesarean section. Oxycodone elimination is decreased in young infants with much inter-individual variability. Monitor the infant closely for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Other agents are preferred over oxycodone during breastfeeding.
◉ Effects in Breastfed Infants:A 10-month-old, 7.7 kg infant of a prescription drug-dependent mother died of cardiac arrest after a 12- to 24-hour period of lethargy, hypersomnolence and dyspnea. The infant also had a recent history of fever. The mother had reportedly been breastfeeding the infant 3 times a day for several weeks and had taken 180 mg of oxycodone, as well as muscle relaxants, the day prior to her infant's death. A blood oxycodone level of 600 mcg/L was measured on autopsy. The medical examiner considered it unlikely that such a high level of oxycodone in the infant's blood could be due to breastfeeding exposure as reported by the mother and thus considered the death a homicide resulting from either the intentional administration of oxycodone directly to the infant or from a higher dose of oxycodone in breastmilk than that reported by the mother.
In a study of 50 mothers taking oxycodone post-cesarean section, 50 neonates were evaluated for sedation over 48 hours after birth. None was severely sedated and less than 4% had sedation of 3 on a 1 (fully alert) to 5 (difficult to rouse) scale and none more sedated than 3 on the scale. Because these infants were in the first 3 days postpartum, their oxycodone dose was probably limited by the small volumes of colostrum they were ingesting.
An infant was born to a mother taking oxycodone 20 mg 3 times daily, fluoxetine 40 mg daily and quetiapine 400 mg daily. The infant was breastfed 6 to 7 times daily and was receiving 120 mcg of oral morphine 3 times daily for opiate withdrawal. Upon examination at 3 months of age, the infant's weight was at the 25th percentile for age, having been at the 50th percentile at birth. The authors attributed the weight loss to opiate withdrawal. The infant's Denver developmental score was equal to his chronological age.
A woman who was exclusively breastfeeding her infant was taking 5 to 10 mg of oxycodone every 4 to 6 hours for episiotomy pain. Her 45-day-old infant was brought to the emergency department with a temperature of 98.4 degrees F, a heart rate of 154 per minute, 20 breaths per minute, a blood pressure of 71/52, and an oxygen saturation of 60% to 69% on room air. The infant had been constipated since birth, passing one stool every 5 to 8 days. The infant had sluggish movements slow, shallow, and irregular breathing. Her pupils were small, but reactive. Hydromorphone levels in urine were elevated. The patient was intubated and given opiates around the clock for two days before being extubated and discharged. The infant's constipation, CNS and respiratory depression were probably caused by oxycodone in breastmilk.
In a retrospective study, nursing mothers who were taking either oxycodone, codeine or acetaminophen for pain while breastfeeding were contacted by telephone to ascertain the degree of maternally perceived central nervous system (CNS) depression. Mothers taking oxycodone reported signs of CNS depression in 20% (28/139) of their infants, while those taking acetaminophen reported infant CNS depression in only 0.5% (1/184) of their infants. Women who reported infant sedation were taking 0.4 mg/kg daily of oxycodone, and unaffected were taking 0.15 mg/kg daily. Affected infants had more hours of daily uninterrupted sleep than unaffected infants, and 4 of the affected infants reportedly had "irregular breathing". Thirty-eight of 39 mothers reported that infant sedation ceased with maternal oxycodone discontinuation. Mothers of affected infants were also more likely to experience lethargy and other side effects than mothers of unaffected infants. Mothers who took codeine reported a similar rate of infant sedation (17%) compared to oxycodone, but the groups were statistically different in parity and postmenstrual age (PMA), with the codeine group having a slightly higher PMA.
A newborn infant was exclusively breastfed and found to be well by his physician at 2 days of age. At 3 days postpartum, the infant began to be sedated and became difficult to arouse and did not feed from either breast. At 4 days of age, the infant was brought to the emergency department where the infant was found to have lethargy, hypothermia, pinpoint pupils, and a poor sucking reflex. The mother reported that her milk had come in the previous evening. She had taken 10 mg of oxycodone that evening and another 5 mg the next morning in the form of Percocet (oxycodone 5 mg plus acetaminophen 325 mg). The infant was given naloxone 0.34 mg intramuscularly and within 2 minutes, the baby's eyes opened and he drank 45 mL of formula. No further sedation was seen over the next 24 hours. The infant's sedation was probably caused by oxycodone in breastmilk.
A search was performed of the shared database of all U.S. poison control centers for the time period of 2001 to 2017 for calls regarding medications and breastfeeding. Of 2319 calls in which an infant was exposed to a substance via breastmilk, 7 were classified as resulting in a major adverse effect, and three of these involved oxycodone. A 16-day-old infant was exposed to cyclobenzaprine, acetaminophen and oxycodone in breastmilk. The infant was admitted to the hospital in a noncritical care unit for bradycardia, hypotension, and respiratory arrest. A 14-day-old infant was exposed to acetaminophen and oxycodone and developed cyanosis. The infant was treated and released. A one-month-old infant was exposed to fentanyl, morphine, oxycodone, and benzodiazepines. The infant was admitted to the intensive care unit and described as being agitated and irritable and having tachycardia, confusion, drowsiness, lethargy, miosis, respiratory depression, acidosis, and hyperglycemia. The dosages and extent of breastfeeding were not reported in any of the cases and the infants all survived.
A cross-sectional survey of mothers who had breastfed their infant in the past 12 months identified 142 mothers who had taken one or more medications while nursing. One of the mothers who was taking a combination product with oxycodone and naloxone reported that her infant developed drowsiness or sleepiness, which caused her to stop the drug.
In population study in the province of Ontario, Canada, 85,852 who filled an opioid prescription within seven days of discharge after delivery were matched to 538,815 did not. Compared with infants born to mothers who were not prescribed an opioid, those born to mothers prescribed an opioid were no more likely to be admitted to hospital in the 30 days after the index date. Infants born to mothers prescribed opioids after delivery were slightly more likely to be taken to the emergency department in the subsequent 30 days (hazard ratio 1.04). Forty-two percent of the mothers prescribed an opioid were prescribed oxycodone. No infant deaths occurred. Of note is that the median drug supply was for 3 days (IQR 2-4).
◉ Effects on Lactation and Breastmilk:Oxycodone can increase serum prolactin. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.
来源:Drugs and Lactation Database (LactMed)
