Acetaminophen / propoxyphene Pregnancy and Breastfeeding Warnings
Acetaminophen / propoxyphene is also known as: Balacet, Darvocet A500, Darvocet-N 100, Darvocet-N 50, Propacet 100, Trycet, Wygesic
Acetaminophen / propoxyphene Pregnancy Warnings
Two cases of acetaminophen overdose in late pregnancy have been reported. In both cases neither the neonate nor the mother suffered hepatic toxicity.
Investigations have revealed conflicting results with regards to the pharmacokinetic disposition of acetaminophen in pregnant women. One study has suggested that the oral clearance of acetaminophen is 58% higher and the elimination half-life is 28% lower in pregnant women compared to non-pregnant women. Another study has suggested that the elimination half-life is not different in patients who are pregnant. That study also suggested that the volume of distribution of acetaminophen may be higher in pregnant women.
One study has suggested that acetaminophen in typical oral doses may result in a reduced production of prostacyclin in pregnant women. That study has also suggested that acetaminophen does not affect thromboxane production.
In most cases of congenital malformations in infants exposed to propoxyphene, other drugs were also used during pregnancy and a clear association between propoxyphene use and the malformations has not been established. Some of the specific malformations described in case reports of infants exposed to propoxyphene (and often other drugs) have included: prune perineum, Pierre Robin syndrome, arthrogryposis, severe caudal dysplasia, micrognathia, microcephaly, ductus arteriosus persistens, cataract, benign tumors, club foot, and limb reduction defects.
The Collaborative Perinatal Project identified 686 mother-child pairs with first trimester exposure to propoxyphene and observed 31 malformed children. (In that group, 34.4 malformed children were expected.)
A study of Michigan Medicaid patients identified 1029 neonates exposed in utero to propoxyphene and observed 41 malformed children (personal communication, Franz Rosa, MD, Food and Drug Administration, 1994). (In that group, 43 malformed children were expected.)
Neonatal propoxyphene withdrawal symptoms include irritability, hypertonicity, jitteriness, increased temperature, tremors, increased appetite, diarrhea and high-pitched cry.
Acetaminophen has not been formally assigned to a pregnancy category by the FDA. Acetaminophen is routinely used for short-term pain relief and as an antipyretic in all stages of pregnancy. Acetaminophen is believed to be safe in pregnancy when used intermittently for short durations. Acetaminophen should only be given during pregnancy when need has been clearly established.
Propoxyphene has not been formally assigned to a pregnancy category by the FDA. Several case reports have described infants exposed to propoxyphene in utero who were born with a variety of congenital malformations. Withdrawal symptoms have also been reported in neonates whose mothers took propoxyphene during pregnancy. There are no controlled data in human pregnancy. Propoxyphene is only recommended for use during pregnancy when benefit outweighs risk.
Acetaminophen / propoxyphene Breastfeeding Warnings
Acetaminophen is excreted into human milk in small concentrations. One case report of an adverse effect (involving a rash) has been reported in a nursing infant. Acetaminophen is considered compatible with breast-feeding by the American Academy of Pediatrics.
Propoxyphene and its active metabolite norpropoxyphene are excreted into human breast milk in small amounts. The clinical effects in breast-fed infants have not been described. Propoxyphene is considered compatible with breast-feeding by the American Academy of Pediatrics.
One small study has reported that following a 1000 mg dose of acetaminophen to nursing mothers, nursing infants receive less than 1.85% of the weight-adjusted maternal oral dose.
References for pregnancy information
- O'Brien WF, Krammer J, O'Leary TD, Mastrogiannis DS "The effect of acetaminophen on prostacyclin production in pregnant women." Am J Obstet Gynecol 168 (1993): 1164-9
- Ringrose CA "The hazard of neurotropic drugs in the fertile years." Can Med Assoc J 106 (1972): 1058
- "Product Information. Darvocet N-100 (acetaminophen-propoxyphene)." Lilly, Eli and Company, Indianapolis, IN.
- Galinsky RE, Levy G "Absorption and metabolism of acetaminophen shortly before parturition." Drug Intell Clin Pharm 18 (1984): 977-9
- Ente G, Mehra MC "Neonatal withdrawal from propoxyphene hydrochloride." N Y State J Med 78 (1978): 2084-5
- Williams DA, Weiss T, Wade E, Dignan P "Prune perineum syndrome: report of a second case." Teratology 28 (1983): 145-8
- Levy G, Garrettson LK, Soda DM "Evidence of placental transfer of acetaminophen." Pediatrics 55 (1975): 895
- Rayburn W, Shukla U, Stetson P, Piehl E "Acetaminophen pharmacokinetics: comparison between pregnant and nonpregnant women." Am J Obstet Gynecol 155 (1986): 1353-6
- Tyson HK "Neonatal withdrawal symptoms associated with maternal use of propoxyphene hydrochloride (Darvon)." J Pediatr 85 (1974): 684-5
- Klein RB, Blatman S, Little GA "Probable neonatal propoxyphene withdrawal: a case report." Pediatrics 55 (1975): 882-4
- Golden NL, King KC, Sokol RJ "Propoxyphene and acetaminophen. Possible effects on the fetus." Clin Pediatr (Phila) 21 (1982): 752-4
- Barrow MV, Souder DE "Propoxyphene and congenital malformations." JAMA 217 (1971): 1551-2
- Strode SW "Propoxyphene dependence and withdrawal." Am Fam Physician 32 (1985): 105-8
- Roberts I, Robinson MJ, Mughal MZ, Ratcliffe JG, Prescott LF "Paracetamol metabolites in the neonate following maternal overdose." Br J Clin Pharmacol 18 (1984): 201-6
- Miners JO, Robson RA, Birkett DJ "Paracetamol metabolism in pregnancy." Br J Clin Pharmacol 22 (1986): 359-62
- Heinonen O, Slone D, Shapiro S; Kaufman DW ed. "Birth Defects and Drugs in Pregnancy." Littleton, MA: Publishing Sciences Group, Inc. (1977): 297
- Quillian 2d, Dunn CA "Neonatal drug withdrawal from propoxyphene." JAMA 235 (1976): 2128
- Poskitt EM, Hensey OJ, Smith CS "Alcohol, other drugs and the fetus." Dev Med Child Neurol 24 (1982): 596-602
- Byer AJ, Traylor TR, Semmer JR "Acetaminophen overdose in the third trimester of pregnancy." JAMA 247 (1982): 3114-5
- Rudolph AM "Effects of aspirin and acetaminophen in pregnancy and in the newborn." Arch Intern Med 141 (1981): 358-63
References for breastfeeding information
- Notarianni LJ, Oldham HG, Bennett PN "Passage of paracetamol into breast milk and its subsequent metabolism by the neonate." Br J Clin Pharmacol 24 (1987): 63-7
- Kunka RL, Yong CL, Ladik CF, Bates TR "Liquid chromatographic determination of propoxyphene and norpropoxyphene in plasma and breast milk." J Pharm Sci 74 (1985): 103-4
- Findlay JW, DeAngelis RL, Kearney MF, et al "Analgesic drugs in breast milk and plasma." Clin Pharmacol Ther 29 (1981): 625-33
- Kunka RL, Venkataramanan R, Stern RM, Ladik CF "Excretion of propoxyphene and norpropoxyphene in breast milk." Clin Pharmacol Ther 35 (1984): 675-80
- 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
- Matheson I, Lunde PK, Notarianni L "Infant rash caused by paracetamol in breast milk." Pediatrics 76 (1985): 651-2