Codeine / promethazine Pregnancy and Breastfeeding Warnings
Medically reviewed on Jan 15, 2018
Codeine / promethazine Pregnancy Warnings
Benefit should outweigh risk
US FDA pregnancy category: C
Comment: 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.
Codeine has been shown to be embryolethal and fetotoxic in rats at maternally toxic doses. In rats and rabbits administered doses ranging from 5 to 120 mg/kg during the period of organogenesis, teratogenicity was not observed. Prolonged use of opioids during pregnancy has resulted in babies being born physically dependent. Opioids administered to mothers shortly before delivery may result in some degree of newborn respiratory depression, especially with higher doses. Rat feeding studies with promethazine at doses approximately 2.1 to 4.2 times (6.25 to 12.5 mg/kg) the recommended human daily dose have not shown teratogenicity. Intraperitoneal administration of daily doses of 25 mg/kg have been found to produce fetal mortality in rats. Administration of promethazine within 2 weeks of delivery may inhibit platelet aggregation in the newborn. There are no adequate and well-controlled studies in pregnant women.
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 / promethazine Breastfeeding Warnings
The US FDA recommends against use of prescription codeine pain and cough medicines in breastfeeding women. This is due to serious reactions in breastfed infants including excess sleepiness, difficultly breastfeeding, or serious breathing problems that could result in death.
Codeine is present in breast milk. 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 CYP450 2D6 genotype) higher-than-expected serum levels of morphine (codeine's active metabolite) may be present in breast milk which may lead to dangerously high serum morphine levels in their breastfed infants. In most cases, a person's specific CYP450 2D6 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. The anticholinergic effect of promethazine may suppress lactation
Use is not recommended
Excreted into human milk: Yes (codeine); Unknown (promethazine)
-Breastfeeding is not recommended when taking codeine due to the risk of serious adverse reactions in breastfed infants.
-If used, mother-infant pairs should be closely monitored; treating pediatricians should be advised about the use of codeine during breast-feeding.
References for pregnancy information
- "Product Information. Phenergan with Codeine (codeine-promethazine)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
References for breastfeeding information
- United States National Library of Medicine "Toxnet. Toxicology Data Network. Available from: URL: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT." ([cited 2013 -]):
- Seymour S "Joint Pulmonary-Allergy Drugs and Drug Safety and Risk Management Advisory Committee Meeting, FDA Introductory Remarks. Available from: URL: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/pulmonary-allergydrugsadvisorycom" ([2015, Dec 10]):
- US Food and Drug Administration (FDA) "FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. Available from: URL: https://www.fda.gov/Drugs/DrugSafety/ucm549679.h" ([2017, Apr 20]):
- "Product Information. Codeine Phosphate-Promethazine HCl (codeine-promethazine)." Par Pharmaceutical Inc (formerly Qualitest Pharmaceuticals Inc), Huntsville, AL.