Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Aspire Pharma Limited, Unit 4, Rotherbrook Court, Bedford Road, Petersfield, Hampshire, GU32 3QG, United Kingdom
Pharmacotherapeutic group: Otological preparations: corticosteroids and antiinfectives in combination
ATC Code: S02CA05
Fluocinolone acetonide is a synthetic fluorinated corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictive properties. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids.
As a fluoroquinolone antibacterial agent, the bactericidal action of ciprofloxacin results from the inhibition of both type II topoisomerase (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair and recombination.
The mutation in genes encoding ciprofloxacin targets (gyr A, gyrN, parC, parE) represent the main mechanism of ciprofloxacin resistance in P. aeruginosa. Another mechanism of resistance described is overexpression of the efflux pumps, in particular Mex (Multiple EffluX) gene. The single mutations do not necessarily result in clinical resistance, but multiple mutations generally result in clinical resistance.
For most topical agents there are limited pharmacological data and no data relating treatment to outcome. For this reason EUCAST proposes that epidemiological cut-off values (ECOFFs) are used to indicate susceptibility to topical agents.
EUCAST Clinical Breakpoint for ciprofloxacin (Table v. 7.1, valid from 2017-03-10):
| Microorganisms | Sensible (S) | Resistant ® |
|---|---|---|
| Staphylococcus species | S ≤1 mg/l | R >1 mg/l |
| Streptococcus pneumoniae | 2 mg/l* | 2 mg/l* |
| Haemophilus influenza | S ≤0.06 mg/l | R >0.06 mg/l |
| Moraxella catarrhalis | S ≤0.5 mg/l | R >0.5 mg/l |
| Pseudomonas species | S ≤0.5 mg/l | R >0.5 mg/l |
* Epidemiological cut-off value (ECOFF) for topical agents
Prevalence of resistance may vary according to geographical zone and weather for the selected microorganisms. Local information on resistance should be available, particularly in the case of serious infections. This information only provides an approximate orientation as to the probability of the microorganism being sensitive to this antibiotic.
The following tables show the cases whose resistance patterns are known to vary in the European Union:
Aerobic Gram-positive micro-organisms:
Staphylococcus aureus (methicillin-susceptible)
Streptococcus pneumoniae
Aerobic Gram negative micro organisms:
Haemophilus influenzae
Moraxella catarrhalis
Pseudomonas aeruginosa
Aerobic Gram-positive micro-organisms:
Staphylococcus aureus (methicillin-resistant)
Aerobic Gram-positive micro-organisms:
Staphylococcus aureus (methicillin-susceptible)
Aerobic Gram negative micro organisms:
Pseudomonas aeruginosa
Aerobic Gram-positive micro-organisms:
Staphylococcus aureus (methicillin-resistant)
Blood samples were taken in two studies of AOMT to determine the plasma levels of ciprofloxacin and/or fluocinolone acetonide. Pharmacokinetic analysis showed no or negligible plasma level of the active ingredients demonstrating that topical application of Cetraxal Plus in the ear is unlikely to result in pharmacokinetically or clinically relevant systemic levels of ciprofloxacin and/or fluocinolone acetonide.
The toxicity of ciprofloxacin has been deeply studied. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Adverse effects on the central nervous system and potential to damage cartilage as well as tendons have been described in human and preclinical studies. In juvenile and prenatal animals exposed to quinolones, effects on immature cartilage have been observed. However, these toxic effects have been observed after oral or IV administration at doses that cannot be achieved after otic administration.
Non-clinical data reveal low potential ototoxicity and systemic toxicity after intratympanic administration of the combination fluocinolone acetonide 0.025% plus ciprofloxacin 0.3%.
The ototopical use of this product should be considered safe and no risk for hearing loss should be expected with its clinical use.
Fluocinolone acetonide was not genotoxic in the usual battery of genotoxicity tests.
Long-term animal studies have not been performed to evaluate the carcinogenic potential of fluocinolone acetonide.
Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals but there are no adequate and well-controlled reproductive and developmental toxicity studies with fluocinolone acetonide.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
