Concomitant administration of 2 g of SOLOSEC with the combination OC resulted in no significant effect on mean Cmax and AUC of NE (increases of 13% and 16%, respectively). Administration of 2 g of SOLOSEC 1 day before combination OC administration also resulted in no significant effect on mean Cmax and AUC of NE. [see Drug Interactions (7.1)] 

 

Ethanol Metabolism 

 

In vitro studies showed that secnidazole had no effect on aldehyde dehydrogenase activity.

 

12.4 Microbiology

 

Mechanism of Action 

 

Secnidazole is a 5-nitroimidazole antimicrobial. 5-nitroimidazoles enter the bacterial cell as an inactive prodrug where the nitro group is reduced by bacterial enzymes to radical anions. It is believed that these radical anions interfere with bacterial DNA synthesis of susceptible isolates.

 

Resistance 

 

The development of resistance to secnidazole by bacteria associated with bacterial vaginosis was not examined. Bacterial isolates exhibiting reduced in vitro susceptibility to metronidazole also show reduced susceptibility to secnidazole. The clinical significance of such an effect is unknown.

 

Antibacterial Activity 

 

Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis [see Indications and Usage (1.2)]; standard methodology for the susceptibility testing of potential bacterial pathogens, Gardnerella vaginalis or Mobiluncus spp. has not been defined.

 

The following in vitro data are available but their clinical significance is unknown. Secnidazole is active in vitro against most isolates of the following organisms reported to be associated with bacterial vaginosis:

 

Bacteroides spp.

 

Gardnerella vaginalis 

 

Prevotella spp.

 

Mobiluncus spp.

 

Megasphaera-like type I/II

 

13 NONCLINICAL TOXICOLOGY 

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

 

Nitroimidazoles, which have similar chemical structures to secnidazole, have been associated with tumors affecting the liver, lungs, mammary, and lymphatic tissues in animals after lifetime exposures. It is unclear if these positive tumor findings in lifetime rodent studies of these nitroimidazoles indicate a risk to patients taking a single dose of secnidazole to treat bacterial vaginosis.

 

Secnidazole was positive in the bacterial reverse mutation assay, but was negative for the rat micronucleus test and mouse lymphoma test.

 

In a rat fertility study, females were dosed for two weeks prior to mating until Day 7 of gestation with males that were dosed for a minimum of 28 days before cohabitation. No parental toxicity or adverse effects on mating performance, estrous cycles, fertility or conception was observed at doses of up to the maximum tolerated dose (300 mg/kg/day, approximately 1.4 times the recommended dose based on AUC comparisons).

 

14 CLINICAL STUDIES