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Codeine / phenylephrine / promethazine Pregnancy and Breastfeeding Warnings

Medically reviewed by Last updated on Sep 22, 2022.

Codeine / phenylephrine / promethazine is also known as: M-Phen, Phenergan VC with Codeine, Promethazine VC with Codeine

Codeine / phenylephrine / promethazine Pregnancy Warnings

In rats, 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. Animal studies with promethazine in rat feeding studies 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. Administration of phenylephrine to rabbits during the first half of pregnancy resulted in a significant number of low birth weight litters; moderate exposure (3 mg/day) during the second half of pregnancy may have contributed to perinatal wastage, prematurity, premature labor, and possible fetal anomalies. In pregnant women, administration of phenylephrine late in pregnancy may cause fetal anoxia or bradycardia by increasing contractility of the uterus and decreasing uterine blood flow. 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.

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.

See references

Codeine / phenylephrine / promethazine Breastfeeding Warnings

Use is not recommended

Excreted into human milk: Yes (codeine); Unknown (phenylephrine); Unknown (promethazine)
Excreted into animal milk: Data not available; Yes (codeine); Data not available (phenylephrine); Data not available (promethazine)

Comments: Breastfeeding is not recommended when taking codeine due to the risk of serious adverse reactions in breastfed infants.

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.

See references

References for pregnancy information

  1. "Product Information. Codeine Phosphate/PE/Promethazine HCl (codeine/phenylephrine/promethazine)." Amneal Pharmaceuticals (2002):

References for breastfeeding information

  1. "Product Information. Codeine Phosphate/PE/Promethazine HCl (codeine/phenylephrine/promethazine)." Amneal Pharmaceuticals (2002):
  2. United States National Library of Medicine "Toxnet. Toxicology Data Network." (2013):
  3. Seymour S "Joint Pulmonary-Allergy Drugs and Drug Safety and Risk Management Advisory Committee Meeting, FDA Introductory Remarks." (2016):
  4. 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." (2017):

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.