Chlorpheniramine / codeine / pseudoephedrine Pregnancy and Breastfeeding Warnings
Chlorpheniramine / codeine / pseudoephedrine is also known as: Co-Histine DH, Codahistine-DH Elixir, Codehist DH, Decohistine DH, Dihistine DH, Novadyne DH, Phenylhistine DH, Phenylhistine DH Expectorant, Ryna-C, Tricode AR, Zodryl DAC
Chlorpheniramine / codeine / pseudoephedrine Pregnancy Warnings
Benefit should outweigh risk 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. -Pseudoephedrine use should be avoided during the first trimester.
Codeine has been shown to be embryolethal and fetotoxic in rats at maternally toxic doses. In the rabbit model, embryotoxicity and fetotoxicity were 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. Animal studies using chlorpheniramine at doses approximately 9 times the maximum recommended human daily dose have shown embryolethality. A small, but statistically significant association between maternal chlorpheniramine use and inguinal hernia and eye or ear anomalies in children was observed in a retrospective study, however, other studies have not shown this. In rabbits and rats, pseudoephedrine in doses of 35 and 50 times the human daily dose, respectively, have not produced teratogenic effects. Limited data in human pregnancy has shown an elevated risk of gastroschisis (defective closure of the abdominal wall) with first-trimester use; vascular disruption has been postulated as the aetiology. There are no adequate and well controlled studies in pregnant women.
Chlorpheniramine / codeine / pseudoephedrine 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. The US FDA is considering regulatory action for OTC combination cough and cold products containing codeine. 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 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 chlorpheniramine may suppress lactation if taken prior to nursing. Single doses of pseudoephedrine are unlikely to harm a nursing infant, but may cause irritability or disturbed sleep; repeated doses may interfere with lactation in mothers who are having difficulties producing sufficient milk or in those whose lactation is not well established.
Use is not recommended Comments: Breastfeeding is not recommended when taking codeine due to the risk of serious adverse reactions in breastfed infants.
References for pregnancy information
- Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
- "Product Information. Codeine Sulfate (codeine)." Roxane Laboratories Inc, Columbus, OH.
- Heinonen O, Slone D, Shapiro S; Kaufman DW ed. "Birth Defects and Drugs in Pregnancy." Littleton, MA: Publishing Sciences Group, Inc. (1977): 297
- Smith CV, Rayburn WF, Anderson JC, Duckworth AF, Appel LL "Effect of a single dose of oral pseudoephedrine on uterine and fetal Doppler blood flow." Obstet Gynecol 76 (1990): 803-6
- Werler MM, Mitchell AA, Shapiro S "First trimester maternal medication use in relation to gastroschisis." Teratology 45 (1992): 361-7
- "Product Information. Ryna-C Liquid (chlorpheniramine-pseudoephedrine)" Wallace Laboratories, Cranbury, NJ.
References for breastfeeding information
- 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]):
- 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 -]):
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