FLAVOXATE

Fetal Risk Summary

Flavoxate is a tertiary amine that is a direct inhibitor of smooth muscle spasm of the urinary tract. The drug also possesses some antimuscarinic (i.e., atropine-like) activity. It is used for the symptomatic relief of urinary tract discomfort resulting from inflammatory conditions.

Reproduction studies in mice, rats, and rabbits at doses up to 34 times the human therapeutic dose found no evidence of impaired fertility or fetal harm (1,2 and 3). At doses approximately 40 times the therapeutic dose, cleft palate (not thought to be drug-induced) and fetal resorption occurred in mice, and intrauterine growth retardation was observed in fetal mice and rabbits (3).

No reports on the placental transfer of flavoxate have been located. The molecular weight (about 428 for the hydrochloride salt) is low enough, however, that passage to the fetus should be expected.

One presentation at a 1975 conference in Yugoslavia described the use of flavoxate during human pregnancy (4). Although specific obstetric data were not provided, IV flavoxate, often as a single dose in combination with antibiotics, was routinely used in pregnant women for the treatment of pyelonephritis. In addition, the effect of flavoxate on uterine contractions, using total IV doses ranging from 100 to 600 mg, was studied in 30 women at term and in 5 women with premature labor at 7–8 months. Uterine contractions were not modified in any of these patients and no fetal or newborn adverse effects were observed.

A 1984 source cited a 1972 study in which flavoxate, 100 mg IM 3 times daily followed by 400 mg/day by suppository, was used as a tocolytic in 66 women with premature labor (3). The 1984 source cited a second study that involved a reduction in the duration of labor in 120 women with a 100-mg IV dose of flavoxate (3). In neither of the cited studies were adverse effects noted in the mothers or fetuses.

In summary, the available human pregnancy data available for flavoxate are very limited and are completely lacking for 1st trimester exposure. Moreover, most of the treated women apparently received short-term therapy (i.e., no more than a few doses), and none involved the oral route with tablets, the only available form of the drug in the United States. The limitations also include a lack of information on the growth and development of the exposed infants. Although these uncertainties markedly limit the validity of any fetal safety assessment, the absence of reported toxicity in the fetus and newborn coupled with the lack of fetal toxicity in animals appear to indicate that the use of flavoxate during the second half of pregnancy presents a small, if any, risk to the fetus. The potential fetal effects of flavoxate exposure in the first half of pregnancy are unknown.

Breast Feeding Summary

No reports describing the use of flavoxate during lactation or measuring the amount excreted, if any, into human milk have been located. The molecular weight of the drug (about 428 for the hydrochloride salt) is low enough, however, that excretion into milk should be expected. The effect of this exposure on a nursing infant is unknown.

References

1. Product information. Urispas. SmithKline Beecham Pharmaceuticals, 1998.
2. Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY:Marcel Dekker, 1993:447.
3. Onnis A, Grella P. The Biochemical Effects of Drugs in Pregnancy. Volume 1. West Sussex, England:Ellis Norwood Limited, 1984:221–2.
4. Esposito A. Preliminary studies on the use of flavoxate in obstetrics and gynaecology. International Round Table Discussion on Flavoxate, Opatija, Yugoslavia, March 30, 1975:66–73 (translation provided by BA Wallin, Smith Kline & French Laboratories, 1987).