(ciprofloxacin) Otic Solution 0.2%
CETRAXAL (ciprofloxacin otic solution) 0.2% contains the synthetic antimicrobial agent ciprofloxacin hydrochloride. CETRAXAL (ciprofloxacin otic solution) is a sterile, preservative-free solution for otic use. Each single use container of CETRAXAL delivers 0.25 mL of solution equivalent to 0.5 mg of ciprofloxacin. The inactive ingredients are povidone, glycerin, and water for injection. Sodium hydroxide and/or lactic acid may be added to adjust pH.
Ciprofloxacin, a fluroquinolone is available as the monohydrochloride, monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its molecular formula is C17H18FN3O3•HCl•H2O, and molecular weight is 385.82.
The chemical structure of ciprofloxacin hydrochloride is:
DOSAGE AND ADMINISTRATION
The contents of one single use container (deliverable volume: 0.25 mL) should be instilled into the affected ear twice daily (approximately 12 hours apart) for 7 days.
Wash hands before use. The solution should be warmed, by holding the container in the hands for at least 1 minute, to minimize the dizziness that may result from the instillation of a cold solution into the ear canal. The patient should lie with the affected ear upward and then the solution should be instilled. This position should be maintained for at least 1 minute to facilitate penetration of the drops into the ear. Repeat, if necessary, for the opposite ear.
Dosage Forms And Strengths
CETRAXAL is a sterile, preservative-free, otic solution of ciprofloxacin hydrochloride quivalent to 0.2 % ciprofloxacin (0.5 mg in 0.25 mL) in each single use container.
Storage And Handling
CETRAXAL (ciprofloxacin otic solution) is a clear, colorless, sterile, preservative-free solution. CETRAXAL (ciprofloxacin otic solution) is supplied as a 0.2% otic solution in a low-density polyethylene (LDPE) single use container. Each single use container delivers 0.25 mL of solution equivalent to 0.5 mg of ciprofloxacin; 14 single use containers are packaged in a foil overwrap pouch in a carton (NDC 66992-450-14).
Store at 15°C to 25°C (59°F to 77°F). Discard used containers. Store unused containers in pouch to protect from light.
CETRAXAL (ciprofloxacin otic solution) is: Distributed by: WraSer Pharmaceuticals, Ridgeland, MS 39157. Manufactured by: The Ritedose Corporation, Columbia, SC 29203 USA.
Because clinical studies are conducted under widely varying conditions, adverse drug reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
In a randomized, active-controlled clinical trial, approximately 300 patients with clinical signs and symptoms of otitis externa were treated with CETRAXAL (ciprofloxacin otic solution) . The most frequently reported adverse reactions were application site pain, ear pruritus, fungal ear superinfection, and headache, each reported in approximately 2-3% of patients.
No information provided.
Included as part of the PRECAUTIONS section.
Otic Use Only
CETRAXAL (ciprofloxacin otic solution) is for otic use only. It should not be used for injection, for inhalation or for opical ophthalmic use.
CETRAXAL (ciprofloxacin otic solution) should be discontinued at the first appearance of a skin rash or any other ign of hypersensitivity.
Growth of Resistant Organisms with Prolonged Use
As with other anti-infectives, use of CETRAXAL (ciprofloxacin otic solution) may result in overgrowth of onsusceptible organisms, including yeast and fungi. If super-infection occurs, discontinue use and institute alternative therapy.
Lack of Clinical Response
If the infection is not improved after one week of therapy, cultures may help guide further treatment.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term carcinogenicity studies in mice and rats have been completed for ciprofloxacin. After daily oral doses of 750 mg/kg (mice) and 250 mg/kg (rats) were administered for up to 2 years, there was no evidence that ciprofloxacin had any carcinogenic or tumorigenic effects in these species. No long-term studies of CETRAXAL (ciprofloxacin otic solution) have been performed to evaluate carcinogenic potential.
Eight in vitro mutagenicity tests have been conducted with ciprofloxacin, and the test results are listed below:
- Salmonella/Microsome Test (Negative)
- Escherichia coli DNA Repair Assay (Negative)
- Mouse Lymphoma Cell Forward Mutation Assay (Positive)
- Chinese Hamster V79 Cell HGPRT Test (Negative)
- Syrian Hamster Embryo Cell Transformation Assay (Negative)
- Saccharomyces cerevisiae Point Mutation Assay (Negative)
- Saccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative)
- Rat Hepatocyte DNA Repair Assay (Positive).
Two of the 8 in vitro tests were positive, but results of the following 3 in vivo test systems gave negative results:
Fertility studies performed in rats at oral doses of ciprofloxacin up to 100 mg/kg/day revealed no evidence of impairment. This would be over 100 times the maximum recommended clinical dose of ototopical ciprofloxacin based upon body surface area, assuming total absorption of ciprofloxacin from the ear of a patient treated with CETRAXAL (ciprofloxacin otic solution) twice per day.
Use In Specific Populations
Pregnancy Category C.
Reproduction studies have been performed in rats and mice using oral doses of up to 100 mg/kg and intravenous (IV) doses up to 30 mg/kg and have revealed no evidence of harm to the fetus as a result of ciprofloxacin. In rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, but no teratogenicity was observed at either dose. After intravenous administration of doses up to 20 mg/kg, no maternal toxicity was produced in the rabbit, and no embryotoxicity or teratogenicity was observed.
Animal reproduction studies have not been conducted with CETRAXAL (ciprofloxacin otic solution) . No adequate and well-controlled studies have been performed in pregnant women. Caution should be exercised when CETRAXAL (ciprofloxacin otic solution) is used by a pregnant woman.
Ciprofloxacin is excreted in human milk with systemic use. It is not known whether ciprofloxacin is excreted in human milk following otic use. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of CETRAXAL (ciprofloxacin otic solution) in infants below one year of age have not been established. The efficacy of CETRAXAL (ciprofloxacin otic solution) in treating otitis externa in pediatric patients one year or older has been demonstrated in controlled clinical trials (see Clinical Studies).
There is no evidence that the otic administration of quinolones has any effect on weight bearing joints, even though systemic administration of some quinolones has been shown to cause arthropathy in immature animals.
No overall differences in safety and effectiveness have been observed between elderly and younger patients.
Mechanism of Action
Ciprofloxacin is a fluoroquinolone antimicrobial (see CLINICAL PHARMACOLOGY, Microbiology).
The plasma concentrations of ciprofloxacin were not measured following administration of 0.25 mL CETRAXAL (total dose: 0.5 mg ciprofloxacin). However, the maximum plasma concentration of ciprofloxacin is anticipated to be less than 5 ng/mL.
Bacterial resistance to quinolones can develop through chromosomally- or plasmidmediated mechanisms.
The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of macrolides. Therefore, ciprofloxacin may be active against pathogens that are resistant to these antibiotics, and these antibiotics may be active against pathogens that are resistant to ciprofloxacin. In vitro studies demonstrated cross-resistance between ciprofloxacin and some fluoroquinolones.
In a randomized, multi-center, evaluator-blinded study of patients with acute otitis externa, patients were treated with either CETRAXAL (ciprofloxacin otic solution) twice daily or neomycin and polymyxin B sulfates and hydrocortisone otic solution (PNH) three times daily for 7 days.
In the per protocol population, clinical cure was achieved at the end of a 7-day treatment in 70% (173/247) for the CETRAXAL (ciprofloxacin otic solution) treated group versus 60% (147/243) for the control treated group.
Directions for Use
Patients should be advised that CETRAXAL (ciprofloxacin otic solution) is for otic use only. It is not for ophthalmic or inhalation use. It is not for injection.
CETRAXAL (ciprofloxacin otic solution) should be given 2 times each day (about 12 hours apart) in each infected ear.
CETRAXAL (ciprofloxacin otic solution) should be used for as long as it is prescribed, even if the symptoms improve. The patient should be advised to follow these directions while on CETRAXAL (ciprofloxacin otic solution) :
- Wash their hands before use.
- Warm the container in their hands for at least one minute prior to use to minimize dizziness that may result from the instillation of a cold solution into the ear canal. Twist off and discard top of container.
- Lie with the affected ear upward and then instill the contents of one container into the ear. Maintain this position for at least one minute to facilitate penetration of the drops into the ear.
- Repeat, if necessary, for the opposite ear.
- Discard used container.
- Store unused containers in pouch to protect from light.
Patients should be advised to immediately discontinue CETRAXAL (ciprofloxacin otic solution) at the first appearance of a skin rash or any other sign of hypersensitivity [see WARNINGS AND PRECAUTIONS].
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.