Codeine Pregnancy and Breastfeeding Warnings
Codeine Pregnancy Warnings
Use is not recommended unless the benefit outweighs the risk to the fetus AU TGA pregnancy category: A US FDA pregnancy category: C Comments: Prolonged use of opioids during pregnancy can result in physical dependence in the neonate; women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available.
This drug has been shown to be embryolethal and fetotoxic in the hamster, rat, and mouse at doses of approximately 2 to 4 times the maximum recommended human dose. Maternally toxic doses(7 times the maximum recommended human dose) were associated with evidence of resorptions and incomplete ossification, including meningioencephalocele and cranioschisis. In the rabbit model, embryotoxicity and fetotoxicity were not observed. There are no adequate and well-controlled studies in pregnant women. AU TGA pregnancy category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Codeine Breastfeeding Warnings
UK: Use is contraindicated. AU: Use should be avoided. US: Benefit should outweigh risk; limit maternal intake Excreted into human milk: Yes Comments: -The American Academy of Pediatrics recommends that other agents are preferred over codeine during breastfeeding. -Both the European Medicine Agency and UK's Medicines and Healthcare Products Regulatory Agency recommend that codeine not be used in nursing mothers.
Codeine is present in breast milk and for women with normal codeine metabolism (normal CYP450 2D6 activity) the amount of codeine secreted is low and dose-dependent; however, in women who are ultra-rapid metabolizers of codeine (those with a specific CYP2D6 genotype) higher-than-expected serum levels of morphine, codeine's active metabolite, may be present in their breast milk which may lead to dangerously high serum morphine levels in their breastfed infants. In most cases, a person's specific CYP2D6 genotype is unknown. Several small series and 1 small retrospective study suggest that codeine may be causative in episodes of apnea, bradycardia, and cyanosis in the first week of life. A death of a breastfeed infant due to respiratory depression has been reported; the mother was found to be a CYP450 2D6 ultrarapid metabolizer. Once a mother's milk comes in, it is best to provide pain control with nonnarcotic analgesics; if codeine-containing drugs are prescribed, it is recommended that maternal intake of oral codeine be limited to 4 days at a low dose with close infant monitoring. If the baby shows signs of increased sleepiness, difficult breastfeeding, breathing difficulties, or limpness, medical care should be sought immediately. Excessive sedation in the mother often correlates with excess sedation in the breastfed infant. There is an FDA cleared test for determining a patient's CYP2D6 genotype. The test is not routinely used in clinical practice but is available through a number of different laboratories. The results of this test can predict those that convert codeine to morphine at a faster rate than average, resulting in higher morphine levels in the blood.
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