Codeine / guaifenesin / pseudoephedrine Pregnancy and Breastfeeding Warnings
Codeine / guaifenesin / pseudoephedrine is also known as: Ambifed CD, Ambifed CDX, Ambifed-G CD, Ambifed-G CDX, Cheratussin DAC, Co-Histine Expectorant, Decohistine Expectorant, Deproist with Codeine, Dihistine Expectorant with Codeine, Guaifen DAC, Lortuss EX, Maxifed CD, Maxifed CDX, Maxifed-G CD, Maxifed-G CDX, Medent C, Novahistine Expectorant, Nucofed Expectorant, Robitussin-DAC, Ryna-CX, Tricode GF, Tusnel C, Tussar-2, Virtussin DAC, Z-Tuss E
Codeine / guaifenesin / pseudoephedrine Pregnancy Warnings
Benefit should outweigh risk US FDA pregnancy category: Not formally assigned a pregnancy category 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 should be avoided during the first trimester.
In rats, codeine has been shown to be embryolethal and fetotoxic 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. Limited data is available on the oral use of phenylephrine in pregnancy. There are no adequate and well-controlled studies in pregnant women. 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 etiology. There are no adequate and well controlled studies in pregnant women.
Codeine / guaifenesin / 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 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. Pseudoephedrine may occasionally cause irritability in a nursing infant. A single dose has been shown to decrease milk production acutely while repeated use seems to interfere with lactation. This drug has been used to decrease milk supply. Mothers whose lactation is not established and mothers who are having difficulties producing sufficient milk should not take pseudoephedrine. The effect of guaifenesin on breastfed infant is unknown but not expected to be harmful. Alcohol may be present in cough and cold products and use of high alcohol containing products should be avoided while nursing.
Use is not recommended Excreted into human milk: Yes (codeine); Unknown (guaifenesin); Yes (pseudoephedrine) Comments: Breastfeeding is not recommended when taking codeine due to the risk of serious adverse reactions in breastfed infants.
References for pregnancy information
- "Product Information. Codeine Sulfate (codeine)." Roxane Laboratories Inc, Columbus, OH.
- 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. Robitussin-DAC Syrup (codeine/guaifenesin/PSE)" Whitehall-Robins, Madison, 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]):
- US Food and Drug Administration "FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Available from: URL: https://www.fda.gov/drugs/drugsafety/ucm518473.htm." ([2016, Aug 31]):
- 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 -]):
- 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]):
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