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

US FDA pregnancy category: Not assigned

Comments:
-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.

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

Hydrocodone:
Animal studies with subcutaneous hydrocodone have shown teratogenicity when given during organogenesis at doses approximately 70 times the maximum recommended human dose (MRHD). Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. Babies born to mothers taking opioids regularly during pregnancy may become 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. Opioids given to mothers shortly before delivery may produce some degree of respiratory depression in the newborn, especially if high doses are used. Chronic use of opioids may reduce fertility in males and females of reproductive potential; it is unknown if these effects are reversible.

Guaifenesin:
Animal studies of oral guaifenesin given during organogenesis was embryolethal and induced hemorrhagic spots and decreased fetal weight and lengths of full body, skull, fore- and hind-limbs, and tail at 2 times the MRHD, and had teratogenicity (limb and tail defects, increased intercostal space, and improper development of limbs) at 3 times the MRHD.

Pseudoephedrine:
Animal studies with pseudoephedrine are not available. The majority of studies using pseudoephedrine during pregnancy did not see an increased risk of fetal abnormalities; some studies showed an increased risk of gastroschisis, however similar studies did not find a statistically significant association.



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.

See references

Hydrocodone and pseudoephedrine are excreted in human milk. No data is available on guaifenesin in milk or its effect on lactation.

Hydrocodone: Case reports have shown variable hydrocodone and hydromorphone (an active metabolite) levels in breast milk with use of immediate release hydrocodone to nursing mothers in the early postpartum period with relative infant doses of hydrocodone ranging between 1.4 and 3.7%. There are case reports of excessive sedation and respiratory depression in breastfed infants exposed to hydrocodone.

Pseudoephedrine: Pseudoephedrine has been reported to cause irritability in breastfed infants. A study of 8 lactating women, between 8 to 76 weeks postpartum, who received a single 60 mg dose of pseudoephedrine, showed a mean reduction in 24 hour milk production of 24%, and an estimated mean relative infant dose from breast milk (assuming mean milk consumption of 150 mL/kg/day and a maternal dosing regimen of 60 mg pseudoephedrine 4 times daily) was calculated to be 4.3% of the weight adjusted maternal dose.

Use is not recommended.

Excreted into human milk: Yes

Comments:
-Breastfed infants should be closely monitored for excess sedation, respiratory depression, and irritability.
-Withdrawal symptoms can occur in breastfed infants when maternal opioids are stopped or breastfeeding is stopped.

See references