Urinary Tract Agent (Analgesic)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Except for the one case (discussed below), no reports describing the use of pentosan in human pregnancy have been located. The animal data suggest low risk but the absence of human pregnancy experience prevents a more complete assessment. The drug does not appear to cross the placenta, at least in amounts that could affect fetal coagulation. The prevalence of interstitial cystitis in pregnancy is unknown. Studies have found that nearly one in four women in the general population has the disease (1). Thus, the prevalence in pregnancy may be higher than suggested by the lack of reported exposures. Based only on the animal data and the pharmacokinetics of the drug, inadvertent or planned exposure during gestation appears to represent a low risk to the embryo–fetus.
FETAL RISK SUMMARY
Pentosan polysulfate is an oral semi-synthetic heparin-like macromolecular carbohydrate derivative that chemically and structurally resembles glycosaminoglycans. It is a low-molecular-weight heparinoid compound with anticoagulant and fibrinolytic effects. Pentosan is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis. The oral absorption is low, about 3%, and drug reaching the systemic circulation is partly metabolized in the liver, spleen, and kidney. The elimination half-life from urine following oral administration is 4.8 hours (2).
Reproduction studies have been conducted in mice, rats, and rabbits. In mice and rats, daily IV doses 0.42 times the daily oral human dose based on BSA (DOHD) revealed no evidence of impaired fertility or fetal harm. A similar negative result was observed in rabbits given daily IV doses 0.14 times the DOHD. Bathing of in vitro–cultured mouse embryos with a concentration of 1 mg/mL caused reversible limb bud abnormalities (2). However, this finding has no clinical significance because the concentration was far in excess of the potential human embryo exposure.
Animal studies for carcinogenicity have not been conducted. However, assays for mutagenic and clastogenic effects were negative (2).
The high molecular weight (4000–6000) and low oral absorption suggest that pentosan does not reach the embryo or the fetus. A 1986 study found no evidence of placental transfer in eight women undergoing elective abortions between the 18th and 23rd week of gestation for chromosomal abnormalities (3). All women were given a single 50-mg IV dose of pentosan polysulfate. Blood samples drawn 30 minutes later showed a marked change in the mean activated partial thromboplastin time (APTT), which increased from 35 to 88 seconds, and factor V level, decreasing from 87% to 33%. Fetal samples, drawn from the umbilical cord before abortion in controls and at the same time as the maternal samples in exposed fetuses, showed no differences in these parameters (93 vs. 91 seconds and 42% vs. 48%, respectively) (3).
BREASTFEEDING SUMMARY
No reports describing the use of pentosan polysulfate during human lactation have been located. The high molecular weight (4000–6000) and low oral bioavailability suggest that the drug will not be detected in breast milk. Moreover, at least in adults, the oral absorption is only about 3%. Thus, the risk to a nursing infant from the drug probably is nil.
References
1.Rosenberg MT, Moldwin RM, Stanford EJ. Early diagnosis and management of interstitial cystitis. Women’s Health Primary Care 2004;7:456–63.
2.Product information. Elmiron. Ortho Women’s Health & Urology, Ortho-McNeil Pharmaceutical, 2006.
3.Forestier F, Fischer AM, Daffos F, Beguin S, Diner H. Absence of transplacental passage of pentosan polysulfate during mid-trimester of pregnancy. Thromb Haemost 1986;56:247–9.