TROVAFLOXACIN

Fetal Risk Summary

Trovafloxacin is a synthetic, broad-spectrum, fluoroquinolone antibacterial agent. It is in the same anti-infective class as ciprofloxacin, enoxacin, gatifloxacin, lomefloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, and sparfloxacin. The injectable form of trovafloxacin is alatrofloxacin, the L-alanyl-L-alanyl prodrug that is rapidly hydrolyzed in vivo to trovafloxacin (1).

Neither trovafloxacin or alatrofloxacin affected the fertility of male and female rats at oral and IV doses that were approximately 2 times the maximum recommended human dose based on body surface area (MRHD) (1). At this dose some dams experienced uterine dystocia. At oral doses 6 times the MRHD, an increased incidence of preimplantation loss occurred. In addition, oral doses greater than about 0.14 times the MRHD were associated with prolonged gestation (1).

When an oral dose of trovafloxacin 2 times the MRHD was administered during organogenesis, an increase in skeletal variations was seen in rat fetuses, but not at 0.4 times the MRHD. (1). Other signs of fetal toxicity observed at the higher dose were increased perinatal mortality and decreased body weights. No increases in the incidence of skeletal variations or malformations were observed in pregnant rabbits at 2.7 times the MRHD (1). In contrast, an increase in skeletal variations and malformations were seen in rats with daily IV doses of alatrofloxacin at ³ 0.6 times the MRHD during organogenesis. Skeletal malformations were also seen in rabbits at an IV dose approximately equal to the MRHD during organogenesis. No skeletal variations or malformations were seen at IV doses that were 0.2 (rat) and 0.3 (rabbit) times, respectively, the MRHD.

It is not known if trovafloxacin crosses the human placenta. The molecular weight of about 512 is low enough that transfer to the fetus should be expected.

No reports describing the use of either the IV or oral forms of trovafloxacin during human pregnancy have been located. The animal toxicity observed at or near the maximum recommended human doses should be considered before this antiinfective is used in pregnant women. Moreover, because of severe hepatic toxicity in adults, trovafloxacin should not be used in any patient if safer alternatives will be effective (1). In addition, some reviewers have concluded that all fluoroquinolones should be considered contraindicated in pregnancy (e.g., Ciprofloxacin and Norfloxacin), because safer alternatives are usually available.

Breast Feeding Summary

Trovafloxacin is excreted into breast milk (1). The average milk concentration in three lactating women was 0.8 µg/mL (range 0.2–2.1 µg/mL) after a single IV alatrofloxacin dose (300 mg trovafloxacin equivalents) and repeated oral 200 mg doses (1). The effects of this exposure on a nursing infant are unknown. However, because of the potential for serious adverse effects in the infant, women taking this agent should probably not breast feed.

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