Current Management of Neonatal Abstinence Syndrome Secondary to Intrauterine Opioid Exposure

Wiles, Jason R.; Isemann, Barbara T.; Ward, Laura P.; Vinks, Alexander A.; Akinbi, Henry T.

doi:10.1016/j.jpeds.2014.05.010

Cited by 44 publications

(38 citation statements)

References 56 publications

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“…Morphine, a full μ‐opioid receptor agonist, is the first‐choice drug for treatment of NAS . Its pharmacokinetic properties are well studied in neonatology .…”

Section: Pharmacologic Managementmentioning

confidence: 99%

“…Oral methadone represents a valuable alternative to morphine . It is a synthetic full μ‐opioid agonist with a longer half‐life (about 26–30 hrs) and more stable plasma levels.…”

Section: Pharmacologic Managementmentioning

confidence: 99%

“…It is a synthetic full μ‐opioid agonist with a longer half‐life (about 26–30 hrs) and more stable plasma levels. On the other hand, significant variability in oral methadone pharmacokinetics has been shown both in adults and children, which becomes an issue of concern . At present, data on the potential superiority of methadone versus morphine for reducing the length of NAS treatment are conflicting and inconclusive .…”

Section: Pharmacologic Managementmentioning

confidence: 99%

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Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies

et al. 2017

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Substance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta. It usually requires prolonged hospitalization and may have long-term effects. The interplay of many factors contributes to its clinical heterogeneity, and its pathophysiology has not been fully unveiled. The first step in NAS management consists of nonpharmacologic interventions and includes promoting breastfeeding when not contraindicated. If withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring system supports care providers across the pharmacotherapy process from initiation through the monitoring phase, until weaning and discontinuation. However, a standardized approach to pharmacotherapy is still lacking. Morphine is usually the first-line agent to treat NAS. Methadone is a valid option, but its safety profile is not completely known. Phenobarbital, despite its lack of effect on gastrointestinal symptoms and unfavorable pharmacologic features, has been identified as a second-line agent to be used in infants unresponsive to opiates. Although buprenorphine and clonidine seem promising, their use requires further validation. Long-term developmental effects of NAS therapy call for more-comprehensive, longitudinal assessments. In this article, key points for use of recommended therapies are outlined, and directions for future research are suggested.

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“…Morphine, a full μ‐opioid receptor agonist, is the first‐choice drug for treatment of NAS . Its pharmacokinetic properties are well studied in neonatology .…”

Section: Pharmacologic Managementmentioning

confidence: 99%

“…Oral methadone represents a valuable alternative to morphine . It is a synthetic full μ‐opioid agonist with a longer half‐life (about 26–30 hrs) and more stable plasma levels.…”

Section: Pharmacologic Managementmentioning

confidence: 99%

Section: Pharmacologic Managementmentioning

confidence: 99%

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Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies

et al. 2017

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“…The phenomenon of neonatal opiate withdrawal after in utero exposure is referred to as Neonatal Abstinence Syndrome (NAS). NAS is a constellation of clinical symptoms that include neurologic excitability, gastrointestinal dysfunction, failure to thrive, and autonomic dysregulation [4, 5]. Moderate to severely affected neonates require pharmacologic treatment, the first line of which is opiate replacement with morphine [6].…”

Section: Introductionmentioning

confidence: 99%

The development of a high-performance liquid chromatography–tandem mass spectrometric method for simultaneous quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine in serum

Sartori

Lewis

Breaud

et al. 2015

Clinical Biochemistry

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Objectives Development and validation of a selective, robust high-performance liquid chromatography-tandem mass spectrometric (HPLC/MS-MS) method for the quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine in human serum. Design and methods Drug-free human serum samples spiked with morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine were prepared by protein precipitation using methanol containing the internal standards. Samples were injected onto a Thermo Scientific AccuCore PFP column for chromatographic separation. Detection was achieved using a Thermo Scientific TSQ Vantage mass spectrometer. Assay validation followed the new Clinical and Laboratory Standards Institute (CLSI) C62-A guidelines. Results The analytical measuring range for all analytes was determined to be 5 to 1,000 ng/mL. Intra- and inter-assay precision for three quality control levels were ≤ 7.0% and ≤ 13.5%, respectively. Carryover, stability, linearity, matrix effects, extraction and processing efficiency and method comparison characteristics were acceptable relative to the CLSI C62 guidelines. Conclusion The validation of this HPLC-MS/MS method demonstrated a robust and rapid assay for the quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine.

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“…NAS severe enough to require pharmacologic intervention most frequently occurs following opioid exposure. Chronic in utero exposure to opioids is a public health burden due to its increasing prevalence, frequent need for pharmacotherapy to mitigate signs of withdrawal, prolonged hospitalization and excessive cost 1–3 . Opioid use in the United States is highly prevalent 4,5 with a 5-fold increase during pregnancy over the last decade, affecting 5.6 per 1000 births 6,7 .…”

mentioning

confidence: 99%

Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study

Wiles

Isemann

Mizuno

et al. 2015

The Journal of Pediatrics

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Objective To characterize the population pharmacokinetic (PK) of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome (NAS) and to develop a PK model towards an evidence-based treatment protocol. Study design Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed via high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen. Results There was substantial inter-individual variability in methadone concentrations. Blood concentrations of methadone were best described by a one-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of NAS followed by an expedited weaning phase. Conclusions The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. Trial registration ClinicalTrials.gov: NCT01754324

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Current Management of Neonatal Abstinence Syndrome Secondary to Intrauterine Opioid Exposure

Cited by 44 publications

References 56 publications

Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies

Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies

The development of a high-performance liquid chromatography–tandem mass spectrometric method for simultaneous quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine in serum

Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study

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