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, Lortuss EX, Maxifed CD, Maxifed CDX, Maxifed-G CD, Maxifed-G CDX, Medent C, Novahistine Expectorant, Nucodine Expectorant, Nucofed Expectorant, Robitussin-DAC, Ryna-CX, Tricode GF, Tusnel C, Tussar-2, Virtussin DAC, Z-Tuss E
Codeine / guaifenesin / pseudoephedrine Pregnancy Warnings
Codeine/guaifenesin/pseudoephedrine has been assigned to pregnancy category C by the FDA. Codeine is the only narcotic analgesic which has shown a statistically significant association with teratogenicity (involving respiratory tract malformations) at the time of this writing. Like other narcotics, codeine rapidly crosses the placenta. Neonatal codeine withdrawal has occurred even in infants whose mothers were taking codeine at cough suppressant doses for as little as ten days prior to delivery. There are no controlled data in human pregnancy. Codeine/guaifenesin/pseudoephedrine is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk.
Codeine / guaifenesin / pseudoephedrine Breastfeeding Warnings
The FDA issued a Public Health Advisory regarding a very rare, but serious, side effect. This may occur in nursing infants whose mothers are taking codeine and are ultra-rapid metabolizers of codeine. When codeine enters the body and is metabolized, it changes to morphine, which relieves pain. Many factors affect codeine metabolism, including a person's genetic make-up. Some people have a variation in a liver enzyme and may change codeine to morphine more rapidly and completely than other people. Nursing mothers taking codeine may also have higher morphine levels in their breast milk. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. In most cases, it is not known if someone is an ultra-rapid metabolizer of codeine. When prescribing codeine-containing drugs to nursing mothers, it is recommended that the lowest effective dose be used for the shortest period of time. It is also recommended that the mother-infant pairs be closely monitored. There is an FDA cleared test for determining a patient's CYP450 2D6 genotype. The test is not routinely used in clinical practice but is available through a number of different laboratories. The results of this test predict that a person can convert codeine to morphine at a faster rate than average, resulting in higher morphine levels in the blood. When levels of morphine are too high, patients have an increased risk of adverse events.
Codeine is excreted into human milk in small amounts. The FDA issued a Public Health Advisory about a very rare, but serious, side effect in nursing infants whose mothers are taking codeine and are ultra-rapid metabolizers of codeine. Several small series and one small retrospective study suggest that codeine may be causative in episodes of apnea, bradycardia and cyanosis in the first week of life. Codeine is nevertheless considered compatible with breast-feeding by the American Academy of Pediatrics. There are no data on the excretion of guaifenesin into human milk. However, guaifenesin is generally accepted as compatible with breast-feeding. Pseudoephedrine is excreted into human milk. Three mothers given pseudoephedrine demonstrated milk concentrations consistently higher than plasma concentrations. Maximum milk concentrations were reached at 1 to 1.5 hours after dosing. In one woman, the milk:plasma concentration ratio at 1, 3, and 12 hours was 3.3, 3.9, and 2.6. The authors calculated that 1000 mL of breast milk consumed over 24 hours would provide an infant with 0.25 to 0.33 mg of pseudoephedrine, or 0.5% to 0.7% of the dose ingested by the mother. There are no reports of adverse effects in infants who were exposed to pseudoephedrine in breast milk. The American Academy of Pediatrics considers pseudoephedrine to be compatible with breast-feeding.
References for pregnancy information
- Koren G, Pastuszak A, Ito S "Drugs in pregnancy." N Engl J Med 338 (1998): 1128-37
- Mangurten HH, Benawra R "Neonatal codeine withdrawal in infants of nonaddicted mothers." Pediatrics 65 (1980): 159-60
- Bracken MB, Holford TR "Exposure to prescribed drugs in pregnancy and association with congenital malformations." Obstet Gynecol 58 (1981): 336-44
- 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. Robitussin-DAC Syrup (codeine/guaifenesin/PSE)" Whitehall-Robins, Madison, NJ.
- "Product Information. Humabid (guaifenesin)." Medeva Pharmaceuticals, Rochester, NY.
References for breastfeeding information
- Committee on Drugs, 1992 to 1993 "The transfer of drugs and other chemicals into human milk." Pediatrics 93 (1994): 137-50
- Roberts RJ, Blumer JL, Gorman RL, et al "American Academy of Pediatrics Committee on Drugs: Transfer of drugs and other chemicals into human milk." Pediatrics 84 (1989): 924-36
- Findlay JW, DeAngelis RL, Kearney MF, et al "Analgesic drugs in breast milk and plasma." Clin Pharmacol Ther 29 (1981): 625-33
- Findlay JW, Butz RF, Sailstad JM, Warren JT, Welch RM "Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers." Br J Clin Pharmacol 18 (1984): 901-6
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