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Acetaminophen / butalbital / caffeine / codeine Pregnancy and Breastfeeding Warnings

Acetaminophen / butalbital / caffeine / codeine is also known as: Fioricet with Codeine, Floricet with Codeine, Phrenilin with Caffeine and Codeine

Acetaminophen / butalbital / caffeine / codeine Pregnancy Warnings

Acetaminophen-butalbital-caffeine-codeine has been assigned to pregnancy category C by the FDA. Animal reproduction studies have not been conducted on this combination product. There are no controlled data on this combination product in human pregnancy. Acetaminophen-butalbital-caffeine-codeine is only recommended for use during pregnancy when benefit outweighs risk.

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. 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 nonpregnant 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. Barbiturates in general have been reported to readily cross the placental barrier. Withdrawal seizures have been reported in a two day old infant whose mother had taken a butalbital containing drug during the last two months of pregnancy. Butalbital was found in the infant's serum. Both human and animal studies have failed to reveal evidence of significant mutagenic or carcinogenic effects. Caffeine crosses the placenta. Fetal blood and tissue levels in the fetus are similar to those in the mother. Caffeine has shown animal teratogenicity only with doses high enough to cause toxicity in the mother. In 1980, the Food and Drug Administration issued an advisory (based primarily on animal evidence) which stated that pregnant women should limit there intake of caffeine to a minimum. In a study of 2817 fertile women, no evidence of adverse effects from caffeine was found. The fecundability ratio (adjusted for known risk factors for time to conceive) was 1.03 between fertile women who consumed more than 7000 mg caffeine per month and those who consumed 500 mg or less per month. Furthermore, caffeine was not associated with infertility in 1818 infertile women and their primiparous controls. In another study (n=441) no evidence was found that moderate caffeine use increased the risk of spontaneous abortion, intrauterine growth retardation, or microcephaly. Codeine has shown a statistically significant association with teratogenicity involving respiratory tract malformations. 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.

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Acetaminophen / butalbital / caffeine / codeine Breastfeeding Warnings

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.

Acetaminophen is excreted into human milk in small concentrations. One case of a rash has been reported in a nursing infant. Acetaminophen is considered compatible with breast-feeding by the American Academy of Pediatrics. Barbiturates are excreted in breast milk in small amounts. The significance of the effects on nursing infants has not been reported. Because of the potential for serious adverse reactions in nursing infants from butalbital, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Caffeine is excreted into human milk in small amounts. Adverse effects in the nursing infant are unlikely. However, irritability and poor sleep patterns have been reported in nursing infants. The amount of caffeine generally found in caffeinated beverages is considered to usually be compatible with breast-feeding by the American Academy of Pediatrics. Because caffeine is excreted into human milk and because caffeine is metabolized slowly by nursing infants, consumption of more than moderate levels of caffeine by nursing mothers is not recommended. Codeine is excreted into human milk in small amounts. 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.

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References for pregnancy information

  1. Galinsky RE, Levy G "Absorption and metabolism of acetaminophen shortly before parturition." Drug Intell Clin Pharm 18 (1984): 977-9
  2. Joesoef MR, Beral V, Rolfs RT, Aral SO, Cramer DW "Are caffeinated beverages risk factors for delayed conception? [see comments." Lancet 335 (1990): 136-7
  3. Briggs GG, Freeman RK, Yaffe SJ.. "Drugs in Pregnancy and Lactation. 5th ed." Baltimore, MD: Williams & Wilkins (1998):
  4. Bracken MB, Holford TR "Exposure to prescribed drugs in pregnancy and association with congenital malformations." Obstet Gynecol 58 (1981): 336-44
  5. Rudolph AM "Effects of aspirin and acetaminophen in pregnancy and in the newborn." Arch Intern Med 141 (1981): 358-63
  6. Heinonen O, Slone D, Shapiro S; Kaufman DW ed. "Birth Defects and Drugs in Pregnancy." Littleton, MA: Publishing Sciences Group, Inc. (1977): 297
  7. Rayburn W, Shukla U, Stetson P, Piehl E "Acetaminophen pharmacokinetics: comparison between pregnant and nonpregnant women." Am J Obstet Gynecol 155 (1986): 1353-6
  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
  9. Byer AJ, Traylor TR, Semmer JR "Acetaminophen overdose in the third trimester of pregnancy." JAMA 247 (1982): 3114-5
  10. Mangurten HH, Benawra R "Neonatal codeine withdrawal in infants of nonaddicted mothers." Pediatrics 65 (1980): 159-60
  11. Eskenazi B "Caffeine during pregnancy: grounds for concern? [editorial; comment]." JAMA 270 (1993): 2973-4
  12. 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
  13. Miners JO, Robson RA, Birkett DJ "Paracetamol metabolism in pregnancy." Br J Clin Pharmacol 22 (1986): 359-62
  14. 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
  15. Mills JL, Holmes LB, Aarons JH, Simpson JL, Brown ZA, Jovanovic-Peterson LG, Conley MR, Graubard BI, Knopp RH, Metzger BE "Moderate caffeine use and the risk of spontaneous abortion and intrauterine growth retardation [see comments." JAMA 269 (1993): 593-7
  16. Levy G, Garrettson LK, Soda DM "Evidence of placental transfer of acetaminophen." Pediatrics 55 (1975): 895

References for breastfeeding information

  1. Rose JE, Behm FM "Psychophysiological interactions between caffeine and nicotine." Pharmacol Biochem Behav 38 (1991): 333-7
  2. Matheson I, Lunde PK, Notarianni L "Infant rash caused by paracetamol in breast milk." Pediatrics 76 (1985): 651-2
  3. 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
  4. Committee on Drugs, 1992 to 1993 "The transfer of drugs and other chemicals into human milk." Pediatrics 93 (1994): 137-50
  5. Findlay JW, DeAngelis RL, Kearney MF, et al "Analgesic drugs in breast milk and plasma." Clin Pharmacol Ther 29 (1981): 625-33
  6. Berlin CM Jr, Denson HM, Daniel CH, Ward RM "Disposition of dietary caffeine in milk, saliva, and plasma of lactating women." Pediatrics 73 (1984): 59-63

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