Establishing Causality of CNS Depression in Breastfed Infants Following Maternal Codeine Use (original) (raw)

Background: We recently reported on a breastfed infant who succumbed to opioid toxicity following exposure Abstract to morphine, the active metabolite of codeine, which was prescribed to his mother who was a cytochrome P450 2D6 (CYP2D6) ultrarapid metabolizer. This report is believed to be the first case of neonatal fatality as a direct result of maternal drug excretion into breast milk and, therefore, it is critical to corroborate the causative relationship between maternal codeine use during breastfeeding and neonatal opioid toxicity with other existing evidence. Objective: To establish whether maternal use of codeine can be a cause of CNS depression in breastfed infants. Study design: A systematic review of the medical literature using several databases was conducted. The Naranjo Adverse Drug Reaction Probability Scale (NADRPS) was used to examine causality. Results: In addition to our case report, three abstracts and two full-length studies reported adverse drug reactions (ADRs) in infants exposed to codeine in breast milk. In total, 35 infants were identified. Specifically, ADRs were described as unexplained episodes of drowsiness, apnea, bradycardia, and cyanosis in suckling infants. Using the NADRPS, codeine was found to be a definite cause of CNS depression in breastfed infants. Conclusion: The use of codeine by breastfeeding mothers can cause adverse CNS events in breastfed infants. Physicians should recognize codeine use during breastfeeding as a cause of CNS depression in infants, and breastfeeding mothers should be educated on these adverse events before receiving codeine.

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A Clinical Tool for Reducing Central Nervous System Depression among Neonates Exposed to Codeine through Breast Milk

PLoS ONE, 2013

Background: Neonates are commonly exposed to maternal codeine through breast milk. Central Nervous System (CNS) depression has been reported in up to 24% of nurslings following codeine exposure. In 2009, we developed guidelines to improve the safety of codeine use during breastfeeding based on previously established pharmacogenetic and clinical risk factors. The primary objective of this study was to prospectively evaluate the effectiveness of these guidelines in ensuring neonatal safety.

When breastfeeding mothers need CNS-acting drugs

The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique, 2004

Breastfeeding is the ideal method of infant nutrition. However, if mothers need medications such as the central nervous system (CNS) acting drugs, infant safety concerns arise. Summarized information on infant exposure levels to drugs in milk and associated side effect profiles will help clinicians to rationalize and justify important drug therapy for a breastfeeding patient. Electronic searches of MEDLINE and PsycINFO from 1966-2003, and of EMBASE from 1980-2003, were conducted for studies on breastfeeding or breast milk and medications in the following categories: antidepressants, antipsychotics, antiepileptics (or anticonvulsants) and anxiolytics. The infant exposure level (%) was defined as follows: [Drug concentration in milk (mg/mL)] x [Daily milk intake (mL/kg/d)] x 100 / Maternal dose (mg/kg/d). A total of 129 papers were eligible for analyses. Our findings indicate that the majority of the CNS-acting drugs, if taken by nursing women, result in average exposure levels to the...

Pooled Analysis of Antidepressant Levels in Lactating Mothers, Breast Milk, and Nursing Infants

American Journal of Psychiatry, 2004

The available data on antidepressant levels in nursing infants were analyzed in order to calculate average infant drug levels and determine what factors influence plasma drug levels in breastfeeding infants of mothers treated with antidepressants. Method: Electronic searches of MEDLINE, PreMEDLINE, Current Contents, Biological Abstracts, and PsycINFO from 1966 through July 2002 followed by bibliographic searches identified 67 relevant studies (two unpublished). By consensus the authors identified 57 studies of maternal plasma, breast milk, and/or infant plasma antidepressant levels from nursing mother-infant pairs, measured by liquid chromatography. Results: Infants with recent prenatal exposure and symptomatic infants included in case reports were analyzed separately. Infant plasma levels were standardized against the average maternal level for each drug. The average infant-maternal plasma ratio was calculated for each drug, and correlations of infant plasma level to maternal dose, maternal plasma level, and breast milk level were calculated. Nortriptyline, paroxetine, and sertraline usually produce undetectable infant levels. Of drugs currently used, fluoxetine produces the highest proportion (22%) of infant levels that are elevated above 10% of the average maternal level. Based on smaller numbers, the data on citalopram indicate that it produces elevated levels in 17% of infants. The milk-to-plasma ratios for 11 antidepressants had a statistically significant negative association with the percentage of the drug bound to protein. Conclusions: Nortriptyline, paroxetine, and sertraline may be preferred choices in breast-feeding women. Minimizing the maternal dose may be helpful with citalopram. Current data do not support monitoring breast milk levels in individual patients. Future researchers should report maternal, breast milk, and infant antidepressant levels along with other appropriate variables.

Use of Antidepressants to Treat Postpartum Depression, During Breast Feeding

Journal of Depression and Anxiety, 2014

Postpartum depression affects approximately 14.5% of women and it can affect both mother and infant. Therefore, rapid attention and treatment are imperative. The pharmacological approach often represents one of the most realistic options of treatment. However, women may be reluctant to take antidepressants because of the fear of adverse effects for the infant, since that most drugs pass into breast milk. The use of pharmacotherapy has not been extensively documented in this population. The objective of this review is to evaluate the risk benefit of using antidepressants during breastfeeding to treat postpartum depression. An electronic search was performed by using PubMed database, from January 2001 through December 2010. The search was limited to articles in the English language and to articles that relate human's research. Manual searches of bibliographies were also conducted to identify additional pertinent studies. The use of antidepressants that do not appear in infants' plasma, for which use during breastfeeding is better documented and at standard therapeutic doses is recommended, such as sertraline and paroxetine. Fluoxetine has a long half-life which can lead to a long infant exposition through breast milk and citalopram can cause adverse effects in infants exposed through breast milk. Therefore, citalopram and fluoxetine should not be used as first-line treatments. More information is needed about the use of the other antidepressants referred in this study. This study aims to emphasize the importance of postpartum depression treatment, always considering its repercussions for the breastfed infants. Studies are needed with larger samples to properly evaluate the short and long-term effects of antidepressants on infants exposed through breast milk, so that clinicians can create standard decisions regarding the treatment of postpartum depression, without putting infants at risk.

Analgesics and Breast-Feeding Safety Considerations

2000

The issue of prescription of analgesics during lactation is clinically important but also complex. Most of the information available is based on single dose or short term studies, and for many drugs only a single or a few case reports have been published. As great methodological problems exist in the assessment of possible adverse drug reactions in neonates and infants,

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