Antigout (Uricosuric)
PREGNANCY RECOMMENDATION: Limited Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports linking the use of probenecid with congenital defects have been located. Probenecid has been used during pregnancy without producing adverse effects in the fetus or in the infant (1–7).
FETAL RISK SUMMARY
Probenecid is a uricosuric and renal tubular blocking agent. It is indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis. It also is indicated as an adjuvant to therapy with penicillin or with ampicillin, methicillin, ocacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given (8).
Animal reproduction studies have apparently not been conducted.
The manufacturer reports that the drug crosses the placenta and appears in cord blood (8). This is consistent with its relatively low molecular weight (about 285).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 339 newborns had been exposed to probenecid during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 17 (5.0%) major birth defects were observed (14 expected). Specific data were available for six defect categories, including (observed/expected) 5/3 cardiovascular defects, 1/1 oral clefts, 0/0 spina bifida, 1/1 polydactyly, 0/1 limb reduction defects, and 1/1 hypospadias. These data do not support an association between the drug and congenital defects.
BREASTFEEDING SUMMARY
Consistent with its molecular weight (about 285), probenecid is excreted into breast milk. A 30-year-old, penicillin-allergic, breastfeeding woman developed erysipelas/cellulitis in her breasts 9 days after a cesarean section (9). She was treated with IV cephalothin, 1 g every 6 hours for 3 days, then oral cephalexin and probenecid (both 500 mg 4 times daily). Severe diarrhea, discomfort, and crying was observed in the nursing infant during IV therapy and continued with oral therapy, but at a decreased level. The symptoms had nearly resolved after partial replacement of breast milk with goat’s milk for 7 days. Sixteen days after initiation of oral therapy, the woman collected 12 milk samples (6 pairs of fore- and hind-milk) by manual expression over a 16-hour interval. The average concentrations of probenecid and cephalexin were 964 and 745 mcg/L, respectively. The concentrations of the two substances in fore- and hind-milk were not significantly different. The infant doses, based on the milk AUC and an estimated intake of 150 mL/kg/day, of probenecid and cephalexin were 0.7% and 0.5%, respectively, of the mother’s weight-adjusted dose. Although these doses were thought to be low enough to exclude systemic effects, it was concluded that cephalexin was the most likely cause of the diarrhea (9).
References
1.Beidleman B. Treatment of chronic hypoparathyroidism with probenecid. Metabolism 1958;7:690–8.
2.Lee FI, Loeffler FE. Gout and pregnancy. J Obstet Gynaecol Br Commonw 1962;69:299.
3.Batt RE, Cirksena WJ, Lebhertz TB. Gout and salt-wasting renal disease during pregnancy. Diagnosis, management and follow-up. JAMA 1963;186:835–8.
4.Hayashi TT. The effect of Benemid on uric acid excretion in normal pregnancy and in pre-eclampsia. Am J Obstet Gynecol 1957;73:17–22.
5.Czaczkes WJ, Ullmann TD, Sadowsky E. Plasma uric acid levels, uric acid excretion, and response to probenecid in toxemia of pregnancy. J Lab Clin Med 1958;51:224–9.
6.Harris RE, Gilstrap LC III, Pretty A. Single-dose antimicrobial therapy for asymptomatic bacteriuria during pregnancy. Obstet Gynecol 1982;59:546–9.
7.Cavenee MR, Farris JR, Spalding TR, Barnes DL, Castaneda YS, Wendel GD Jr. Treatment of gonorrhea in pregnancy. Obstet Gynecol 1993;81:33–8.
8.Product information. Probenecid. Mylan Pharmaceuticals, 2006.
9.Ilett KF, Hackett LP, Ingle B, Bretz PJ. Transfer of probenecid and cephalexin into breast milk. Ann Pharmacother 2006;40:986–9.