EXOCINE 0,3 % Collyre Fl/5ml

Eye drops in solution.

Clear solution, slightly yellow-green in colour.

Ofloxacin........................................................................................................................................................ 0,3 g

for 100 ml.

Excipients with known effect: one ml of solution contains 0,05 mg of benzalkonium chloride.

Excipients:

EXOCINE is indicated in adults and children over one year of age for the local antibacterial treatment of severe eye infections (severe conjunctivitis; keratitis and corneal ulcers) due to germs sensitive to ofloxacin.

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

Data are insufficient to establish the efficacy and safety of use of ofloxacin eye drops at 0,3% in the treatment of conjunctivitis in newborns.

Dosage

The usual dosage is 2 drops 4 times a day into the affected eye or eyes.

Treatment lasting more than 15 days should require a new ophthalmological review.

Paediatric population

The safety and efficacy of EXOCINE in children aged 0 to 1 year have not been established.

Method of administration

Ophthalmic use.

FOR OCULAR INSTILLATION.

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

• Breastfeeding.

The eye drops must not be injected or swallowed.

The eye drops must not be used for peri- or intra-ocular injection.

After local administration, a small amount of ofloxacin may pass into the general circulation. Adverse effects reported after systemic use of ofloxacin may possibly occur with ophthalmic administration.

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, tingling, pharyngeal or facial oedema, dyspnoea, urticaria and itching. Only a few patients had a known history of hypersensitivity reactions.

Therefore, treatment with this medicine must be discontinued at the first signs of skin rash or any other hypersensitivity reaction.

The use of this eye drop solution must take into account a risk of nasopharyngeal passage that may contribute to the emergence and spread of bacterial resistance. As with all antibiotic pharmaceutical forms, prolonged use may promote the emergence of resistant bacteria.

If the infection worsens or if no clinical improvement is observed within a reasonable time, EXOCINE must be discontinued and another treatment must be initiated.

Cardiac disorders

The use of quinolones, including EXOCINE, should be undertaken with caution in patients with known risk factors for QT interval prolongation, such as:

• congenital long QT syndrome,

• concomitant use of medicinal products known to prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides and antipsychotics),

• uncontrolled electrolyte imbalance (e.g., hypokalaemia, hypomagnesaemia),

• heart disease (e.g., heart failure, myocardial infarction, bradycardia).

(See sections Interactions, Adverse effects and Overdose).

Elderly patients and women may be more sensitive to medicinal products that prolong the QT interval. Therefore, the use of fluoroquinolones, including EXOCINE, should be undertaken with caution in these populations.

Eye disorders

Non-clinical and clinical publications have reported the occurrence of corneal perforation in patients with corneal epithelial disorders or corneal ulcers following topical antibiotic treatment based on fluoroquinolone. However, significant confounding factors were identified in most of these cases, such as advanced age, the presence of multiple ulcers, associated ocular conditions (e.g., dry eye syndrome), inflammatory systemic diseases (e.g., rheumatoid arthritis), and concomitant use of ophthalmic steroids or non-steroidal anti-inflammatory drugs. Therefore, caution is recommended regarding the risk of corneal perforation when treating patients with corneal ulcer or corneal abscess with a fluoroquinolone.

Corneal deposits have been reported during ophthalmic treatment with ofloxacin. However, a causal relationship has not been established.

Exposure to sunlight or UV should be avoided during treatment with ofloxacin because of the potential risk of photosensitivity.

EXOCINE contains a preservative, benzalkonium chloride, which may cause eye irritation, symptoms of dry eye, and may damage the tear film and corneal surface. EXOCINE should be used with caution in patients with dry eye and in patients whose corneal condition may be damaged. Patients should be monitored in case of prolonged use.

Patients must remove contact lenses before instillation and wait at least 15 minutes before reinserting them. Benzalkonium chloride is known to discolour soft contact lenses.

Patients should be advised to wash their hands thoroughly before and after instillation, and during instillation not to touch the eye, eyelids or other surfaces with the tip of the bottle.

Elderly patients

No comparative data are available regarding the use of the topical form in elderly subjects versus other age groups.

Paediatric population

The safety and efficacy of EXOCINE in children aged 0 to 1 year have not been established.

Data are insufficient to establish the efficacy and safety of this ofloxacin 0,3% eye drop in the treatment of conjunctivitis in newborns.

In the absence of evaluation, the use of ofloxacin eye drops is not recommended in newborns with neonatal conjunctivitis due to Neisseria gonorrhoeae or due to Chlamydia trachomatis. These should receive appropriate treatment, such as systemic treatment of infections due to Neisseria gonorrhoeae or due to Chlamydia trachomatis.

No specific drug interaction study has been performed with topical ophthalmic ofloxacin.

The efficacy of an eye drop may be disrupted by the simultaneous instillation of another eye drop. In case of concomitant treatment with a second eye drop, an interval of 15 minutes should be observed before its instillation.

EXOCINE, like other medicinal products of the quinolone family, should be used with caution in patients receiving medicinal products known to prolong the QT interval (such as class IA and III antiarrhythmics, tricyclic antidepressants, macrolides and antipsychotics) (see section Warnings and precautions).

Pregnancy

Although animal studies have not shown a teratogenic effect, clinical data on the use of systemic ofloxacin are still insufficient.

Joint damage has been described in children treated with quinolones, but to date, no case of arthropathy secondary to exposure in utero has been reported.

As a result, use of this medicine should only be considered during pregnancy if necessary.

Breast-feeding

Administration of this medicine requires breastfeeding to be contraindicated, due to the passage of fluoroquinolones into breast milk and the risk of joint effects in the breastfed newborn.

As with any treatment that may cause blurred vision, drivers of vehicles and users of machinery should be warned of this potential risk.

The patient must wait until their vision returns to normal before driving a vehicle or using a machine.

Serious reactions after systemic use of ofloxacin are rare and most symptoms are reversible. As a small amount of ofloxacin is absorbed systemically after local administration, the adverse effects reported after systemic use may possibly occur.

The adverse effects reported after use of ofloxacin from clinical trial cases are classified by system organ class and listed below as: Very common (≥1/10); Common (≥1/100, <1/10); Uncommon (≥1/1 000, <1/100); Rare (≥1/10 000, <1/1 000); Very rare (<1/10 000) and frequency not known (cannot be estimated from the available data):

Immune system disorders

Frequency not known: hypersensitivity reactions including signs and symptoms of ocular allergy (such as ocular pruritus, eyelid pruritus), and anaphylactic reactions (such as angioedema, dyspnoea, anaphylactic shock, oropharyngeal oedema, facial oedema and tongue oedema).

Nervous system disorders

Frequency not known: dizziness.

Eye disorders

Common: eye irritation, eye discomfort.

Frequency not known: keratitis, conjunctivitis, blurred vision, photophobia, ocular oedema, foreign body sensation in the eyes, increased lacrimation, dry eye, ocular pain, ocular hyperaemia, periorbital oedema (including eyelid oedema).

Cardiac disorders

Frequency not known: ventricular arrhythmia and torsades de pointes (reported particularly in patients with known risk factors for QT interval prolongation), QT interval prolongation on ECG (see sections Warnings and precautions and Overdose).

Gastrointestinal disorders

Frequency not known: nausea.

Skin and subcutaneous tissue disorders

Frequency not known: Stevens-Johnson syndrome, toxic epidermal necrolysis.

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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: www.signalement-sante.gouv.fr.

In case of excessive local administration, wash abundantly with sterile physiological saline.

In case of overdose, symptomatic treatment must be instituted. ECG monitoring must be carried out because of possible QT interval prolongation.

Pharmacotherapeutic class: OPHTHALMOLOGICAL MEDICINES, ANTI-INFECTIVES, FLUOROQUINOLONES, ATC code: S01AE01.

Mechanism of action

Ofloxacin 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

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

S ≤ 1 mg/l and R > 4 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 France is known for a bacterial species, it is indicated in the table below:

 

 

 

Categories	Frequency of acquired resistance in France (> 10%) (extreme values)
SUSCEPTIBLE SPECIES
Gram-positive aerobes
Bacillus anthracis **
Staphylococcus methicillin-S
Gram-negative aerobes
Acinetobacter (mainly Acinetobacter baumannii)	50 - 75 %
Branhamella catarrhalis
Bordetella pertussis
Campylobacter
Citrobacter freundii	15 - 25 %
Enterobacter cloacae	15 - 25 %
Escherichia coli	0 - 10 %
Haemophilus influenzae
Klebsiella oxytoca	0 - 11 %
Klebsiella pneumoniae	0 - 25 %
Legionella
Morganella morganii
Neisseria
Pasteurella
Proteus mirabilis	0 - 10 %
Proteus vulgaris
Providencia	45 - 70 %
Pseudomonas aeruginosa	45 - 85 %
Salmonella
Serratia	40 - 45 %
Shigella
Vibrio
Yersinia
Anaerobes
Mobiluncus
Propionibacterium acnes
Other
Mycoplasma hominis
MODERATELY SUSCEPTIBLE SPECIES
(in vitro of intermediate susceptibility)
Gram-positive aerobes
Corynebacteria
Streptococcus
Streptococcus pneumoniae
Other
Chlamydiae
Mycoplasma pneumoniae
Ureaplasma urealyticum
RESISTANT SPECIES
Gram-positive aerobes
Enterococci
Listeria monocytogenes
Nocardia asteroides
Staphylococcus spp. meti-R *
Anaerobes
except for Mobiluncus and Propionibacterium acnes

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

** Bacillus anthracis : no animal study of experimental infection in anthrax disease has been performed.

Atypical mycobacteria : ofloxacin has in vitro moderate activity against certain mycobacteria species: Mycobacterium tuberculosis, Mycobacterium fortuitum, lesser on Mycobacterium kansasii and even less so on Mycobacterium avium.

Remark : this spectrum corresponds to that of the systemic forms of ofloxacin. With the 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.

Studies carried out in animals show that one hour after the instillation of one drop of this eye drops, the concentrations of the product are greater than the MICs of the main germs encountered in ocular infections, in tears, the cornea and in the aqueous humour.

Studies carried out in humans have confirmed the favourable kinetics of ofloxacin in the aqueous humour and in tears.

2 years.

After opening: to be used within 15 days.

This medicinal product must be stored protected from light.

For storage conditions of the medicine after first opening, see section Shelf life.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

List I

Marketing authorisation (AMM)

CIP 3400933170806 (Fl/5ml).

Price:

2,74 euros (Fl/5ml).

Social Security reimbursement at 65%.
Collection.