Difloxacin HCL

(difloxacin)

Brand

Dicural

Availability

Tablets: 11.4 mg, 45.4 mg, 136 mg
Oral suspension may be made from tablets

Pharmacology

Difloxacin is a second-generation 4-Fluoroquinolone, and like other fluoroquinolones is a broad-spectrum, concentration dependent, bactericidal antibiotic. It has activity against some Gram-positive aerobes such as staphylococci, and a wide range of Gram-negative bacilli and cocci, which include klebsiella spp., pasteurella spp., pseudomonas spp., salmonella, and other organisms such as mycoplasma, and chlamydia. The mechanism of action is to inhibit bacterial DNA-gyrase, prevent DNA synthesis, and disrupt bacterial cell duplication.

Difloxacin is well absorbed orally from the GI tract and documented as having a longer elimination half-life than other fluoroquinolones, staying in the body longer. It allows for once-daily application of the total daily dose , however it’s efficacy appears to be the same as that of enrofloxacin.

Some studies, in the rat, showed no significant reproductive effects; however, there is some indication of embryofetotoxicity at the high dose of 275 mg/kg.

In rats the excretion of the drug is primarily in feces.

It is known that the quinolone class of drugs have been shown to produce erosions of articular cartilage in weight bearing joints, as well as producing other signs of arthropathy in immature animals of various species, including juvenile rats (Kashida et al., 1997). However, evidence of cartilage abnormalities appear to be dose related (high dosages over extended period).

It is also important to note that although the use of fluoroquinolones have not been recommended for initial treatment in the pregnant and nursing doe or juvenile rats (under 4 months) due to the risks of cartilage abnormalities (Egerbacher et al., 2000), in cases where other antibiotics are not helping, or if the infection is deemed severe, the benefit of using fluoroquinolones (alone or in combination with other compatible antimicrobials) may, in fact, outweigh the risks.

Indications

Useful in: respiratory infection, urinary tract infections, soft tissue infection and soft tissue injury.

Drug Interactions or Contraindications

Concurrent administration of a quinolone, including difloxacin, with cation-containing GI products such as magnesium/aluminum antacids or sucralfate, or GI products containing calcium, iron, or zinc may reduce its absorption. It is suggested to separate dosing from any of these products by 2 hours.
Theophylline blood levels may be increased when used with difloxacin.
Probenecid blocks tubular secretion of difloxacin and may cause an increase in its blood level and half life.
Synergism can occur when aminoglycosides, cephalosporins, and extended-spectrum penicillins are used with fluorinated quinolones such as difloxacin.

Adverse Reactions

CNS: restlessness, may lower seizure threshold (increasing likelihood of seizure activity)

GI: decreased appetite, diarrhea

GU: crystaluria

Other: itching

Dosage Recommendations

4.5 mg/lb, PO, BID ³^, ¹²

*Note: see warning for young, pregnant or nursing rats in Pharmacology section above.

Considerations

Be sure to keep animals well hydrated in order to prevent crystalluria (formation of crystals in urine).
Difloxacin can be used simultaneously with doxycycline in the treatment of Mycoplasma.
Also, in treating suspected polymicrobial infections, where a broader coverage may be needed, synergistic or combination drugs may be used. The following drugs may be seen used simultaneously with difloxacin: aminoglycosides (e.g., amikacin or gentamicin), or aminopenicillins (e.g., amoxicillin or ampicillin), or third generation cephalosporins, or clindamycin, or metronidazole. ¹
Please note that it is imperative to discuss the changing, or adding of any medications during your rat’s treatment with your veterinarian, to prevent future resistance of microbes to the drugs prescribed.
Store tablets at room temperature in tight moist free container.
Reconstituted suspension from tablets should be kept refrigerated and has a 14 day expiration time.

Reference

Egerbacher, M., Seiberl, G., Wolfesberger, B., & Walter, I. (2000). Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro. Arch Toxicol, 73(10-11), 557-63. Retrieved December 20, 2008, from the PubMed database.
Pallo-Zimmerman, L., Byron, J., & Graves, T. (July 2010). Fluoroquinolones: Then and Now. Vetlearn.com. Retrieved April 25, 2011, from www.vetlearn.com/Portals/0/PV0710_zimmerman_CE.pdf
Kashida Y, Kato M. Toxic effects of quinolone antibacterial agents on the musculoskeletal system in juvenile rats. Toxicol Pathol 1997;25:635-43. Retrieved 2011.
Committee for Veterinary Medicinal Products. (1995). Difloxacin: Summary Report. European Medicines Agency. Retrieved September 10, 2020, from https://www.ema.europa.eu/en/documents/mrl-report/difloxacin-summary-report-committee-veterinary-medicinal-products_en.pdf