Risk Factor: CM
Class: Anti-infectives/ Quinolones
Fetal Risk Summary
Sparfloxacin is an oral, synthetic, broad-spectrum antibacterial agent. As a fluoroquinolone, it is in the same class of agents as ciprofloxacin, enoxacin, levofloxacin, lomefloxacin, norfloxacin, and ofloxacin. Nalidixic acid is also a quinolone drug.
Reproduction studies, conducted in male and female rats, found no evidence of impaired fertility or reproductive performance at oral doses approximately 15 times the maximum human dose on a mg/m2 basis (MHD) (1). No teratogenic effects were observed in rats, rabbits, and monkeys at oral doses approximately 6, 4, and 3 times, respectively, the MHD, although maternal toxicity was evident at these dose levels. When the dose was increased to about 9 times the MHD or higher in pregnant rats, a dose-dependent increase in the number of fetuses with ventricular septal defects was observed. This effect did not occur in rabbits or monkeys.
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 sparfloxacin) were described in a 1996 Reference (see also Ciprofloxacin) (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. Based on 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 antibacterials 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 sparfloxacin 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 sparfloxacin 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 considered contraindicated in pregnancy, because safer alternatives are usually available (2).
Breast Feeding Summary
The administration of sparfloxacin 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 with quinolones when exposure to excessive sunlight (i.e., ultraviolet [UV] light) has occurred (1). Well-differentiated squamous cell carcinomas of the skin has been produced in mice who were exposed chronically to some fluoroquinolones and periodic UV light (e.g., see Lomefloxacin), but studies to evaluate the carcinogenicity of sparfloxacin in this manner have not been conducted.
No reports describing the use of sparfloxacin in human lactation or measuring the amount of the antibacterial in breast milk have been located. The manufacturer states, however, that the antibacterial agent is excreted in human milk (1). Because of the potential for toxicity, sparfloxacin should be avoided during breast feeding.
- Product information. Zagam. Bertek Pharmaceuticals, 2000.
- 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;69:839.
- Norrby SR, Lietman PS. Safety and tolerability of fluoroquinolones. Drugs 1993;45(Suppl 3):5964.