Risk Factor: C
Class: Central nervous system drugs/ Analgesics and antipyretics
Fetal Risk Summary
Because of its rare association with hemolytic anemia and agranulocytosis (1), antipyrine (phenazone), a prostaglandin synthesis inhibitor, is no longer available as a single agent. However, the drug is still available in some topical eardrops and in the prodrug, dichloralphenazone (see also Dichloralphenazone). This latter agent, a combination of chloral hydrate and antipyrine, is a component, along with isometheptene and acetaminophen, of several proprietary mixtures commonly used for tension and vascular (migraine) headaches (see also Isometheptene and Acetaminophen).
Although animal reproductive studies involving antipyrine have not been located, the drug has been used extensively in investigations of fetal metabolism in pregnant sheep as reviewed in a 1993 Reference (2). This latter investigation found that antipyrine did not affect umbilical metabolism, but did alter metabolism and blood flow distribution in the fetal lamb (2).
Eight cases of antipyrine exposure (presumably oral), among 27 women using a miscellaneous group of non-narcotic analgesics during the 1st trimester, were reported by the Collaborative Perinatal Project (3). From the 27 mother-child pairs, one infant had a congenital malformation (SRR 0.46), but the specific agent the mother had taken was not identified.
In a double-blind, randomized study of neonatal jaundice prophylaxis, either antipyrine (N=24), 300 mg/day, or placebo (N=24) was given from the 38th week of gestation until delivery (4). The average duration of treatment in both groups was 15.5 days. The mean bilirubin concentration in the infants 4 days after birth was 62.6 mol/L in those exposed to antipyrine compared with 111.5 mol/L in the placebo group (p
Breast Feeding Summary
Antipyrine (phenazone), a nonelectrolyte with a molecular weight less than 200, freely diffuses into the aqueous phase of milk with a milk:plasma ratio of approximately 1.0 (5,6). No reports of its use during lactation have been located.
- Swanson M, Cook R. Drugs Chemicals and Blood Dyscrasias. Hamilton, IL:Drug Intelligence Publications, 1977:889.
- Gull I, Charlton V. Effects of antipyrine on umbilical and regional metabolism in late gestation in the fetal lamb. Am J Obstet Gynecol 1993;168:70613.
- Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:287.
- Lewis PJ, Friedman LA. Prophylaxis of neonatal jaundice with maternal antipyrine treatment. Lancet 1979;1:3002.
- Hawkins DF. Drugs and Pregnancy. Human Teratogenesis and Related Problems. 2nd ed. New York, NY:Churchill Livingstone, 1987:312.
- McNamara PJ, Burgio D, Yoo SD. Pharmacokinetics of acetaminophen, antipyrine, and salicylic acid in the lactating and nursing rabbit, with model predictions of milk to serum concentration ratios and neonatal dose. Toxicol Appl Pharmacol 1991;109:14960.