LOMEFLOXACIN

Fetal Risk Summary

Lomefloxacin is an oral, synthetic, broad-spectrum antibacterial agent. As a fluoroquinolone, it is the same class of agents as ciprofloxacin, enoxacin, levofloxacin, norfloxacin, ofloxacin, and sparfloxacin. Nalidixic acid is also a quinolone drug.

Reproductive studies have been conducted in rats, rabbits, and monkeys (1). No evidence of impaired fertility, in male or female rats, or fetal harm in pregnant rats was observed at doses up to 8 times the recommended human dose (RHD) based on a mg/m2 basis (34 times the RHD based on mg/kg). In rabbits, maternal and fetal toxicity was evident at a dose 2 times the RHD based on mg/m2, consisting of reduced placental weight and variations of the coccygeal vertebrae. Pregnant monkeys dosed at 3 to 6 times the RHD (mg/m2 basis) (6 to 12 times the RHD based on mg/kg) had an increased incidence of fetal loss, but no teratogenic effects were observed. As with other quinolones, multiple doses of lomefloxacin produced permanent lesions and erosion of cartilage in weight-bearing joints leading to lameness in immature rats and dogs (1).

It is not known whether lomefloxacin crosses the placenta to the human fetus, but the molecular weight (about 388) is low enough that transfer to the fetus should be expected. No reports describing the use of the antibacterial in human gestation have been located.

In a prospective follow-up study conducted by the European Network of Teratology Information Services (ENTIS), data on 549 pregnancies exposed to fluoroquinolones (none to lomefloxacin) were described in a 1996 Reference (2). Data on another 116 prospective and 25 retrospective pregnancy exposures to the antibacterials were also included. Of the 666 cases with known outcome, 32 (4.8%) of the embryos, fetuses, or newborns had congenital malformations. From previous epidemiologic data, the authors concluded that the 4.8% frequency of malformations did not exceed the background rate (2). Finally, 25 retrospective reports of infants with anomalies, who had been exposed in utero to fluoroquinolones, were analyzed, but no specific patterns of major congenital malformations were detected.

The authors of the above study concluded that pregnancy exposure to quinolones was not an indication for termination, but that this class of antibacterial agents should still be considered contraindicated in pregnant women. Moreover, this study did not address the issue of cartilage damage from quinolone exposure and the authors recognized the need for follow-up studies of this potential toxicity in children exposed in utero. Because of their own and previously published findings, they further recommended that the focus of future studies should be on malformations involving the abdominal wall and urogenital system and on limb reduction defects (2).

In summary, although no reports describing the use of lomefloxacin during human gestation have been located, the available evidence for other members of this class indicates that a causal relationship with birth defects cannot be excluded (see Ciprofloxacin, Norfloxacin, or Ofloxacin), although the lack of a pattern among the anomalies is reassuring. Because of these concerns and the available animal data, the use of lomefloxacin during pregnancy, especially during the 1st trimester, should be considered contraindicated. A 1993 review on the safety of fluoroquinolones concluded that these antibacterials should be avoided during pregnancy because of the difficulty in extrapolating animal mutagenicity results to humans and because interpretation of this toxicity is still controversial (3). The authors of this review were not convinced that fluoroquinolone-induced fetal cartilage damage and subsequent arthropathies were a major concern, even though this effect had been demonstrated in several animal species after administration to both pregnant and immature animals and in occasional human case reports involving children (3). Others have also concluded that fluoroquinolones should be contraindicated in pregnancy, because safer alternatives are usually available (2).

Breast Feeding Summary

The administration of lomefloxacin during breast feeding is not recommended because of the potential for arthropathy and other serious toxicity in the nursing infant (1). Phototoxicity has been observed when lomefloxacin was given chronically to mice, who were also exposed periodically to ultraviolet (UV) light (1). Moreover, most of the mice exposed to the combination of drug and UV light eventually developed well-differentiated squamous cell carcinoma of the skin (1). The tumors were not observed in mice exposed only to the drug.

No reports describing the use of lomefloxacin in human lactation have been located. Other quinolones are excreted into milk (see Ciprofloxacin and Ofloxacin) and, because of its relatively low molecular weight (about 388), the passage of lomefloxacin into milk should be expected. Because of the potential for toxicity, the drug should be avoided during breast feeding.

References

1. Product information. Maxaquin. G.D. Searle, 1997.
2. Schaefer C, Amoura-Elefant E, Vial T, Ornoy A, Garbis H, Robert E, Rodriguez-Pinilla E, Pexieder T, Prapas N, Merlob P. Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European Network of Teratology Information Services (ENTIS). Eur J Obstet Gynecol Reprod Bio 1996;69:83–9.
3. Norrby SR, Lietman PS. Safety and tolerability of fluoroquinolones. Drugs 1993;45(Suppl 3):59–64.