CILOXAN 0,3 % Ophthalmic ointment Tube/3,5g

Ophthalmic ointment.
Tube containing 3,5 g, with nozzle and screw cap.

For 100 g:

Ciprofloxacin: 0,30 g
in the form of ciprofloxacin hydrochloride: 0,35 g

CILOXAN 0,3 %, ophthalmic ointment is indicated in adults and children from the age of 1 year.

Local antibacterial treatment of severe eye infections (severe conjunctivitis, keratitis, corneal ulcers and corneal abscesses) due to germs sensitive to ciprofloxacin.

Official recommendations concerning the appropriate use of antibacterial agents should be taken into account.

Dosage

Adults and children from the age of 1 year:

• Corneal abscesses : apply a ribbon of 1,25 cm into the conjunctival sac of the eye every 1 or 2 hours, including during the night, for 2 days, then every 4 hours for the following 12 days.
• Conjunctivitis, keratitis, corneal ulcers : apply a ribbon of 1,25 cm into the conjunctival sac three times a day for 2 days, then 2 times a day for the following 5 days.

The dosage regimens may be adjusted at the physician's discretion.

In elderly patients

No dosage adjustment is necessary.

Method of administration

Ophthalmic route

Hypersensitivity to the active substance, to another medicine of the quinolone family or to any of the excipients mentioned in section Composition.

Breast-feeding (see section Fertility, pregnancy and breastfeeding).

General:

For ophthalmic use only.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic shock), some occurring after administration of the first dose, have been observed in patients treated with systemic quinolones. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria and pruritus. Treatment must be discontinued at the first signs of skin rash or any other hypersensitivity reaction.

Serious acute hypersensitivity reactions to ciprofloxacin may require immediate emergency treatment. Oxygen therapy and respiratory support should be administered when clinically indicated.

As with all antibiotic pharmaceutical presentations, prolonged use may promote the emergence or selection of resistant bacteria or the development of fungi. In case of superinfection, appropriate treatment must be initiated.

Tendinitis and tendon rupture may occur with systemic fluoroquinolone treatment such as ciprofloxacin, particularly in elderly patients and in those concomitantly treated with corticosteroids. Therefore, CILOXAN must be discontinued at the first sign of tendinitis.

Related to the ointment:

The use of this ophthalmic ointment must take into account a risk of nasopharyngeal passage that may contribute to the emergence and spread of bacterial resistance.

Cross-resistance between quinolones may exist.

There is no clinical experience in children under 1 year.

The use of CILOXAN 0,3 %, ophthalmic ointment in newborns with neonatal conjunctivitis is not recommended because it has not been evaluated in these patients. These newborns should receive appropriate treatment.

Wearing contact lenses is not recommended during treatment of an eye infection. Therefore, patients should avoid wearing contact lenses during treatment with CILOXAN 0,3 %, ophthalmic ointment.

During application, do not touch the eye, eyelids or other surfaces with the tip of the tube.

In patients with corneal ulcer requiring frequent administration of CILOXAN, white precipitates (drug residues) have been observed, but these disappear with continued treatment with CILOXAN. The precipitate does not prevent continued use of CILOXAN and does not interfere with the clinical healing process.

No interaction studies have been performed.

Given the low systemic concentration of ciprofloxacin following topical ocular administration of the product, drug interactions are unlikely.

The effectiveness of an ophthalmic ointment may be disrupted by the concomitant instillation of an eye drop. In case of concomitant treatment with other topical ophthalmic products, wait 5 minutes before instilling them. The ophthalmic ointment should be applied last.

Pregnancy

There are little or no data on the use of CILOXAN in pregnant women. Animal studies with ciprofloxacin do not indicate direct harmful effects on reproduction.

Systemic exposure to ciprofloxacin following topical use is low. As a precaution, it is preferable to avoid using CILOXAN during pregnancy, unless the expected therapeutic benefit outweighs the potential risk to the foetus.

Breast-feeding

Ciprofloxacin is excreted in breast milk after oral administration. It is unknown whether ciprofloxacin is excreted in breast milk following topical ocular or otic administration. A risk to the breastfed child cannot be excluded.

Therefore, CILOXAN is contraindicated during breastfeeding.

Fertility

Studies to evaluate the effect of topical administration of ciprofloxacin on fertility have not been performed in humans. Oral administration in animals does not indicate direct harmful effects on fertility.

CILOXAN 0,3 %, ophthalmic ointment has no or negligible effect on the ability to drive vehicles and use machines.

Transient blurred vision or other visual disturbances may reduce the ability to drive vehicles or use machines. If blurred vision occurs upon instillation, the patient must wait until their vision returns to normal before driving a vehicle or using a machine.

Summary of the safety profile

In clinical trials, the most frequently reported adverse reactions were: ocular discomfort, dysgeusia and corneal deposits occurring in approximately 6 %, 3 % and 3 % of patients, respectively.

Tabulated list of adverse reactions

The following adverse reactions were reported in clinical trials with CILOXAN and are classified according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000). Within each frequency group, adverse reactions are presented in order of decreasing seriousness.

The following adverse reactions have been reported with ocular use of CILOXAN:

Other adverse effects identified from post-marketing surveillance are presented below. Frequencies cannot be estimated from the available data.

Description of certain adverse effects:

Local effects:

With locally administered fluoroquinolones, (generalised) skin rash, toxic epidermal necrolysis, exfoliative dermatitis, Stevens-Johnson syndrome and urticaria are very rarely observed. In isolated cases, blurred vision, decreased visual acuity, and drug residues have been observed with ophthalmic administration of ciprofloxacin.

Systemic effects:

Serious and sometimes fatal hypersensitivity reactions (anaphylactic shock), some occurring after the first dose, have been observed in patients treated with systemically administered quinolones. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, paraesthesia, pharyngeal or facial oedema, dyspnoea, urticaria and pruritus.

Ruptures of the tendons of the shoulder, hand, Achilles tendon, or other tendons requiring surgical intervention or resulting in prolonged disability have been reported in patients receiving systemic fluoroquinolones. Studies and post-marketing experience with systemic administration of fluoroquinolones indicate that the risk of such ruptures is increased in patients treated with corticosteroids, particularly in elderly patients, and where the tendon is subjected to high stress, including the Achilles tendon.

Severe to moderate phototoxicity has been observed in patients treated with systemically administered quinolones. However, phototoxic reactions to ciprofloxacin are uncommon.

Paediatric population

The safety and efficacy of CILOXAN 0,3 %, ophthalmic ointment have been evaluated in 103 children aged 1 to 12 years. No serious adverse reactions were observed in these patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr.

In case of excessive local application, rinse abundantly with lukewarm water.

Due to the characteristics of this preparation, no toxic effect is to be expected with ocular overdose of this product, nor in case of accidental ingestion of the contents of a vial.

Pharmacotherapeutic class: OTHER ANTI-INFECTIVES, ATC code: J01MA02.

Ciprofloxacin is a synthetic antibiotic belonging to the quinolone family, of the fluoroquinolone group. Its activity is strongly bactericidal through inhibition of bacterial DNA gyrase, preventing the synthesis of bacterial chromosomal DNA.

ANTIBACTERIAL ACTIVITY SPECTRUM

Critical concentrations separate susceptible strains from strains of intermediate susceptibility, and the latter from resistant ones:

S ≤ 1 mg/l and R > 2 mg/l.

The prevalence of acquired resistance can vary according to geography and time for certain species. It is therefore useful to have information on local resistance prevalence, especially for the treatment of severe infections. These data can only provide guidance on the probabilities of the susceptibility of a bacterial strain to this antibiotic.

Where the variability of resistance prevalence in Europe is known for a bacterial species, it is indicated in the table below:

* The frequency of methicillin resistance is approximately 30% to 50% of all staphylococci and is found mainly in hospital settings.

** Bacillus anthracis : a study conducted on an experimental infection model of anthrax, carried out by inhalation of spores of Bacillus anthracis in rhesus monkeys, shows that antibiotic therapy started early after exposure prevents the onset of the disease if treatment is continued until the number of spores persisting in the body falls below the infecting dose.

Atypical mycobacteria : ciprofloxacin has in vitro moderate activity on certain species of mycobacteria: Mycobacterium tuberculosis, Mycobacterium fortuitum, lesser activity on Mycobacterium kansasii, and even lesser activity on Mycobacterium avium.

Cross-resistance:

There is cross-resistance in vitro between ciprofloxacin and other fluoroquinolones. Given the mechanism of action, there is generally no cross-resistance between ciprofloxacin and other classes of antibacterials.

Remark : this spectrum corresponds to that of the systemic forms of ciprofloxacin. With local pharmaceutical presentations, the concentrations obtained in situ are much higher than plasma concentrations. Some uncertainties remain regarding the kinetics of the concentrations in situ, the local physicochemical conditions that may alter the activity of the antibiotic, and the stability of the product in situ.

According to data obtained after administration of ciprofloxacin in eye drop form

In men

Penetration into the cornea is around 5 μg/g after 1 drop/hour for 10 hours, and also increases strongly with multiplication of doses (173 μg/g after 1 drop every 15 minutes for 4 hours) and with corneal abrasion (900 μg/g).

Kinetics in tears show a level of 16 μg/mL 4 hours after 1 drop of this product in healthy volunteers.

Mean maximum serum concentrations are not higher (2,6 ng/mL) with intensive administration in corneal ulcers than with administration at the conjunctivitis dosage (2,4 ng/mL). These levels correspond to 1/1 000 of the serum levels after administration of a ciprofloxacin tablet at 500 mg.

No pharmacokinetic data are available in children.

Repeated-dose toxicity studies carried out in rats and monkeys, with a maximum duration of 13 and 26 weeks respectively, revealed typical changes in certain renal tubules caused by the presence of crystals. As these were observed in animals under maximised dose conditions and pH-specific conditions, the occurrence of renal damage is unlikely in humans under therapeutic conditions of use.

Non-clinical data from conventional studies of genotoxicity, carcinogenesis and teratogenesis did not reveal any particular risk.

In most species studied, ciprofloxacin and other quinolones administered orally caused arthropathies in young animals. The degree of impact on cartilage depended on age, species and dosage. At the dose of 30 mg/kg, the effect of ciprofloxacin on the joints was minimal.

A one-month study evaluating ocular administration of ciprofloxacin 3 mg/ml in young dogs showed no joint lesions. Therefore, there are no preclinical signs suggesting that the ophthalmic form could have effects on the joints.

No occurrence of cataract has been reported in the toxicological studies.

2 years

After first opening: 1 month

Store at a temperature not exceeding 25 °C.

Do not refrigerate. Do not freeze.

At the end of treatment, the remainder of the tube must be discarded and must not be kept for reuse.