VISOF

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

Official recommendations regarding the appropriate use of antibacterials should be taken into account.

Data are insufficient to establish the efficacy and safety of use of ofloxacin 0.3% eye drops in the treatment of conjunctivitis in the newborn.

The eye drops must not be injected, nor swallowed.

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

After local administration, a small amount of ofloxacine may pass into the general circulation. Adverse effects reported after use of ofloxacine by general route, may possibly appear during ophthalmic administration.

Severe and sometimes fatal hypersensitivity reactions (anaphylactic shock), some occurring after administration of the first dose, have been observed in patients treated with quinolones administered by general route. 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.

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

The use of these eye drops must take into account a risk of rhinopharyngeal passage which may contribute to the emergence and spread of bacterial resistance. Like all pharmaceutical presentations of antibiotics, prolonged use may promote the emergence of resistant bacteria.

If an aggravation of the infection occurs or if no clinical improvement is observed within a reasonable timeframe, EXOCINE must be stopped and another treatment must be initiated.

Cardiac conditions

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

· congenital long QT syndrome,

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

· uncontrolled electrolyte imbalance (e.g.: hypokalemia, hypomagnesemia),

· a cardiac disease (e.g.: heart failure, myocardial infarction, bradycardia).

(See sections 4.5, 4.8 and 4.9).

Elderly patients and women may be more sensitive to medicines prolonging the QT interval. As a result, the use of fluoroquinolones including EXOCINE must be done with caution in these populations.

Ocular conditions

Non-clinical and clinical publications have reported the occurrence of corneal perforation in patients with corneal epithelium disorders or corneal ulcers, after local antibiotic treatment based on fluoroquinolone. However, significant confounding factors have been highlighted in most of these cases, such as advanced age, the presence of multiple ulcers, associated ocular conditions (e.g. dry eye syndrome), systemic inflammatory diseases (e.g. rheumatoid arthritis), and the concomitant use of ophthalmic steroids or non-steroidal anti-inflammatory drugs. Consequently, it is necessary to recommend caution regarding the risk of corneal perforation during fluoroquinolone treatment of patients with corneal ulcer or abscess.

Corneal deposits have been reported during ophthalmic treatment based on ofloxacine. However, a causal relationship has not been established.

Sun or UV exposure must be avoided during treatment with ofloxacine due to a potential risk of photosensitivity.

EXOCINE contains a preservative, benzalkonium chloride, which can cause eye irritation, symptoms of dry eye and can damage the tear film and corneal surface. EXOCINE must be used with caution in patients with dry eye and in patients whose corneal condition may be damaged. Patients must 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 discolor soft contact lenses.

The patient should be advised to wash 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 subjects

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

Pediatric population

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

The data are insufficient to establish the efficacy and safety of use of this ofloxacine 0,3% eye drop in the treatment of conjunctivitis in the newborn.

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

No specific drug interaction studies have been conducted with ofloxacin for ophthalmic use.

The efficacy of an eye drop may be disturbed by the simultaneous instillation of another eye drop. In case of concomitant treatment with a second eye drop, it is advisable to wait 15 minutes before its instillation.

EXOCINE, like other medicines in the quinolone family, must be used with caution in patients receiving medicines known to prolong the QT interval (such as class IA and III antiarrhythmics, tricyclic antidepressants, macrolides and antipsychotics) (see section 4.4).

Pregnancy

Although studies conducted on animals have not shown any 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 in utero exposure has been reported.

Consequently, the use of this medicine should only be considered during pregnancy if necessary.

Breastfeeding

Administration of this medicine is contraindicated during breastfeeding, due to the passage of fluoroquinolones into breast milk and the risk of joint damage for the breastfed newborn.

As with any treatment that may cause blurred vision, drivers of vehicles and users of machines 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 potentially occur.

Adverse effects reported after use of ofloxacin from clinical trial cases are classified by system organ classes 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 eye pruritus, eyelid pruritus), and anaphylactic reactions (such as angioedema, dyspnoea, anaphylactic shock, oropharyngeal oedema, face oedema and tongue oedema).

Nervous system disorders

Frequency not known: dizziness.

Eye disorders

Common: eye irritation, ocular discomfort.

Frequency not known: keratitis, conjunctivitis, vision blurred, photophobia, eye oedema, foreign body sensation in eyes, increased lacrimation, dry eye, eye 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 prolongation), QT prolongation on ECG (see sections 4.4 and 4.9).

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