PENTOXIFYLLINE

Fetal Risk Summary

Pentoxifylline is a synthetic xanthine derivative used to lower blood viscosity in peripheral vascular and cerebrovascular diseases. No published reports of its use in human pregnancy have been located.

Reproduction studies in rats and rabbits at oral doses up to 4.2 and 3.5 times the maximum recommended human dose on a surface area basis revealed no evidence of teratogenicity (1). In rats, however, an increased incidence of resorptions was seen at the maximum dose (1).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 34 newborns had been exposed to pentoxifylline during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Five (14.7%) major birth defects were observed (one expected), including (observed/expected) 2/0 cardiovascular defects and 1/0 spina bifida. No anomalies were observed in four other defect categories (oral clefts, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. Although the number of exposures is small, the total number of defects and both specific defects are suggestive of possible associations, but other factors, including the mother's disease, concurrent drug use, and chance, may be involved.

Pentoxifylline causes a significant increase in sperm motility, but not concentration, and may be useful in patients with normogonadotrophic asthenozoospermia (2).

Breast Feeding Summary

Pentoxifylline is excreted into human milk. Five healthy women, who had been breast-feeding for at least 6 weeks, were given a single 400-mg sustained-release tablet of pentoxifylline (commercially available formulation) after a 4-hour fast (3). The mean milk:plasma ratio of unmetabolized pentoxifylline at 4 hours was 0.87. Mean milk:plasma ratios for the three major metabolites at 4 hours were 0.76, 0.54, and 1.13. Mean milk concentration of pentoxifylline at 2 hours (73.9 ng/mL) was approximately twice as much as that occurring at 4 hours (35.7 ng/mL) (3). Pentoxifylline and its metabolites are stable in breast milk for 3 weeks when stored at –15° C (4).

References

1. Product information. Trental. Hoechst Roussel Roussel, 2000.
2. Shen M-R, Chiang P-H, Yang R-C, Hong C-Y, Chen S-S. Pentoxifylline stimulates human sperm motility both in vitro and after oral therapy. Br J Clin Pharmacol 1991;31:711–4.
3. Witter FR, Smith RV. The excretion of pentoxifylline and its metabolites into human breast milk. Am J Obstet Gynecol 1985;151:1094–7.
4. Bauza MT, Smith RV, Knutson DE, Witter FR. Gas chromatographic determination of pentoxifylline and its major metabolites in human breast milk. J Chromatogr 1984;310:61–9.