Animal studies have not been conducted with this combination product, and there are no adequate and well-controlled studies in pregnant women.

Codeine: Animal studies administering approximately 20 times the maximum recommended human dose (MRHD) showed increased resorptions and decreased fetal weights, however these effects occurred in the presence of maternal toxicity. Other studies administering during organogenesis produced no adverse developmental effects at approximately 10 and 50 times the MRHD. Case control and observational studies of codeine use during pregnancy have inconsistent findings; some show increased overall congenital malformation risk, while others did not. An increase in specific malformations such as respiratory malformations, spina bifida, and congenital heart defects were reported with codeine use. Most of the studies (positive and negative) were limited by small sample size, recall bias, and lack of information regarding dose and timing of exposure. Chronic use of opioids, such as codeine, Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. Prolonged use of opioids during pregnancy has resulted in babies being born physically dependent. Opioids can prolong labor by temporarily reducing the strength, duration, and frequency of uterine contractions, however this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Chronic use of opioids may reduce fertility in males and females of reproductive potential; it is unknown if these effects are reversible.

Animal studies using chlorpheniramine during organogenesis at doses up to 35 to 45 times the MRHD showed no adverse developmental effects, however another study using doses 9 times the MRHD throughout pregnancy have shown embryolethality and decreased postnatal survival when dosing continued after parturition. Most studies looking at chlorpheniramine use during pregnancy did not see an increased risk of congenital anomalies, and in the few studies reporting an association, no consistent pattern of malformations was seen.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Use is not recommended, including during or immediately prior to labor

US FDA pregnancy category: Not assigned

Comment:
-Prolonged use of opioids during pregnancy may cause neonatal withdrawal syndrome and physical dependence in the neonate.
-Neonatal withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.
-The onset, duration, and severity of neonatal withdrawal syndrome vary with the specific opioid used, duration of use, timing and amount of last maternal use, and the newborn's rate of drug elimination.
-Observe newborns for symptoms of neonatal withdrawal syndrome and manage appropriately.
-An opioid antagonist (e.g. naloxone) should be available for reversal of opioid-induced respiratory depression in the neonate.
-Monitor neonates exposed to opioids during labor for excess sedation and respiratory depression.
-Advise women of the risk of neonatal withdrawal syndrome and ensure that appropriate treatment will be available.

See references

Use is not recommended

Excreted into human milk: Yes (chlorpheniramine); Yes (codeine)

Comments:
-Breastfeeding is not recommended due to the risk of serious adverse reactions including excess sedation, respiratory depression, and death in breastfed infants.
-At least one death in a nursing infant was reported when exposed to high morphine levels in breastmilk because the mother was an ultra-rapid metabolizer of codeine; breastfeeding is not recommended during treatment.
-Monitor infants exposed to this product for excess sedation and respiratory depression.
-Withdrawal symptoms may occur if maternal opioids are stopped or breastfeeding is stopped.

Codeine and its active metabolite morphine are present in breast milk. Studies and case reports have seen excess sedation, respiratory depression, and death (in one infant) in infants exposed to codeine via 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. There is no data on the effects of codeine on breast milk production.

Chlorpheniramine: Chlorpheniramine has not been reported to have effects on breast fed infants. The anticholinergic effect of chlorpheniramine may decrease milk production.

See references