Risk Factor: CM
Class: Anti-infectives/ Antituberculosis
Fetal Risk Summary
Para-aminosalicylic acid is a bacteriostatic agent used for the treatment of Mycobacterium tuberculosis. It is most frequently used in combination with other agents for the treatment of multi-drug resistant tuberculosis.
In reproduction studies with rats at doses within the human dose range, occipital malformations were observed (1). No adverse effects on the fetus were observed in rabbits treated with 5 mg/kg/day throughout gestation (1).
No reports describing the placental transfer of para-aminosalicylic acid have been located. The molecular weight (approximately 153) is low enough, however, that passage to the fetus should be expected.
The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 43 of whom had 1st trimester exposure to para-aminosalicylic acid (4-minosalicylic acid) (2). Congenital defects were found in five infants. This incidence (11.6%) was nearly twice the expected frequency. No major categories of malformations or individual defects were identified. An increased malformation rate for ear, limb, and hypospadias has been reported for 123 patients taking 714 g of para-aminosalicylic acid per day with other antitubercular drugs (3). An increased risk of congenital defects has not been found in other studies (4,5 and 6).
Breast Feeding Summary
Para-aminosalicylic acid is excreted into human breast milk. In one non-breast-feeding patient given an oral 4-g dose of the drug, a peak milk concentration of 1.1 g/mL was measured at 3 hours with an elimination half-life of 2.5 hours (7). The peak maternal plasma concentration, 70.1 g/mL, occurred at 2 hours.
- Product information. Paser. Jacobus Pharmaceutical, 2000.
- Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:299.
- Varpela E. On the effect exerted by first line tuberculosis medicines on the foetus. Acta Tuberc Scand 1964;35:5369.
- Lowe CR. Congenital defects among children born to women under supervision or treatment for pulmonary tuberculosis. Br J Prev Soc Med 1964;18:146.
- Wilson EA, Thelin TJ, Ditts PV. Tuberculosis complicated by pregnancy. Am J Obstet Gynecol 1973;115;5269.
- Scheinhorn DJ, Angelillo VA. Antituberculosis therapy in pregnancy. Risk to the fetus. West J Med 1977;127;1958.
- Holdiness MR. Antituberculosis drugs and breast-feeding. Arch Intern Med 1984;144:1888.