EXOCIN^® 3 mg/ml Eye Drops, Solution.

One millilitre contains 3 mg ofloxacin.

For a full list of excipients, see section 6.1.

Eye drops, solution.

Clear, pale to light yellow-green solution, practically free from visible particles.

EXOCIN^® is indicated for the topical treatment of external ocular infections (such as conjunctivitis and keratoconjunctivitis) in adults and children caused by ofloxacin - sensitive organisms. Safety and efficacy in the treatment of ophthalmia neonatorum has not been established.

Topical ocular instillation.

For all ages: one to two drops in the affected eye(s) every two to four hours for the first two days and then four times daily. The length of treatment should not exceed ten days.

EXOCIN^® is contra-indicated in individuals who have shown hypersensitivity to ofloxacin or any of its excipients.

EXOCIN^® is not for injection.

Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.

If an allergic reaction to EXOCIN^® occurs, discontinue the drug. Use EXOCIN^® with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents.

When using EXOCIN^® the risk of rhinopharyngeal passage which can contribute to the occurrence and the diffusion of bacterial resistance should be considered. As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms.

If worsening infection occurs, or if clinical improvement is not noted within a reasonable period, discontinue use and institute alternative therapy.

Stevens-Johnson syndrome has been reported in patients receiving topical ophthalmic ofloxacin, however, a causal relationship has not been established.

Cardiac disorders

Caution should be taken when using fluoroquinolones, including EXOCIN^® in patients with known risk factors for prolongation of the QT interval such as, for example:

- congenital long QT syndrome

- concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)

- uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)

- elderly

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

(See section 4.2 Elderly, section 4.5, section 4.8, section 4.9).

Use EXOCIN^® with caution in patients who have exhibited sensitivities to other quinolone antibacterial agents.

Data are very limited to establish efficacy and safety of EXOCIN^® eye drops 0.3% in the treatment of conjunctivitis in neonates.

The use of EXOCIN^® in neonates with ophthalmia neonatorum caused by Neisseria gonorrhoeae or Chlamydia trachomatis is not recommended as it has not been evaluated in such patients. Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition, e.g. systemic treatment in cases caused by Chlamydia trachomatis or Neisseria gonorrhoeae.

Use in elderly: No comparative data are available with topical dosing in elderly versus other age groups.

Clinical and non-clinical publications have reported the occurrence of corneal perforation in patients with pre-existing corneal epithelial defect or corneal ulcer, when treated with topical fluoroquinolone antibiotics. However, significant confounding factors were involved in many of these reports, including advanced age, presence of large ulcers, concomitant ocular conditions (e.g. severe dry eye), systemic inflammatory diseases (e.g. rheumatoid arthritis), and concomitant use of ocular steroids or non-steroidal anti-inflammatory drugs. Nevertheless, it is necessary to advise caution regarding the risk of corneal perforation when using product to treat patients with corneal epithelial defects or corneal ulcers.

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

Long-term, high-dose use of other fluoroquinolones in experimental animals has caused lenticular opacities. However, this effect has not been reported in human patients, nor has it been noted following topical ophthalmic treatment with ofloxacin for up to six months in animal studies including studies in monkeys.

EXOCIN^® contains the preservative benzalkonium chloride which may cause ocular irritation and discolour soft contact lenses.

Use of contact lenses is not recommended in patients receiving treatment for an eye infection.

No interaction studies have been performed.

It has been shown that the systemic administration of some quinolones inhibits the metabolic clearance of caffeine and theophylline. Drug interaction studies conducted with systemic ofloxacin have demonstrated that metabolic clearance of caffeine and theophylline are not significantly affected by ofloxacin.

Although there have been reports of an increased prevalence of CNS toxicity with systemic dosing of fluoroquinolones when used concomitantly with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), this has not been reported with the concomitant systemic use of NSAIDs and ofloxacin.

EXOCIN^®, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4).

Use in pregnancy: There have been no adequate and well-controlled studies performed in pregnant women. Since systemic quinolones have been shown to cause arthropathy in immature animals, it is recommended that EXOCIN^® not be used in pregnant women.

Use during lactation: Because ofloxacin and other quinolones taken systemically are excreted in breast milk, and there is potential for harm to nursing infants, a decision should be made whether to temporarily discontinue nursing or not to administer the drug, taking into account the importance of the drug to the mother.

No studies on the effects on the ability to drive and use machines have been performed.

Transient blurring of vision may occur on instillation of eye drops. Do not drive or operate hazardous machinery unless vision is clear.

General

Serious reactions after use of systemic ofloxacin are rare and most symptoms are reversible. Since a small amount of ofloxacin is systemically absorbed after topical administration, side-effects reported with systemic use could possibly occur.

Frequency categories: 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) and not known (cannot be estimated from the available data):

Immune System Disorders:

Not known: Hypersensitivity (including Eye allergy)

Nervous System Disorders

Not known: Dizziness

Eye Disorders

Common: Eye irritation; Ocular discomfort

Not known: Keratitis; Conjunctivitis; Vision blurred; Photophobia; Eye oedema; Foreign body sensation in eyes; Lacrimation increased; Dry eye; Eye pain; Eye pruritus; Eyelids pruritus; Ocular hyperaemia

Cardiac disorders

Not known : ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9).

Gastrointestinal Disorders

Not known: Nausea

Skin and Subcutaneous Tissue Disorders

Not Known: Periorbital oedema

General Disorders and Administration Site Conditions

Not known: Facial oedema

In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.

Pharmacotherapeutic group: Ophthalmologicals, anti-infectives, quinolones

ATC code: S 01 AX 11.

ofloxacin is a synthetic fluorinated 4-quinolone antibacterial agent with activity against a broad spectrum of Gram negative and to a lesser degree Gram positive organisms.

ofloxacin has been shown to be active against most strains of the following organisms both in vitro and clinically in ophthalmic infections. Clinical trial evidence of the efficacy of EXOCIN^® against S. pneumoniae was based on a limited number of isolates.

Gram-negative bacteria: Acinetobacter calcoaceticus var. anitratum, and A. calcoaceticus var. iwoffi; Enterobacter Sp. including E. cloacae; Haemophilis Sp, including H. influenza and H. aegyptius; Klebsiella Sp., including K. Pneumoniae; Moraxella Sp., Morganella morganii; Proteus Sp., including P. Mirabilis; Pseudomonas Sp.; including P. Aeruginosa, P. cepacia, and P. fluoroscens; and Serratia Sp., including S. marcescens.

Gram-positive bacteria: Bacillus Sp.; Corynebacterium Sp.; Micrococcus Sp.; Staphylococcus Sp., including S. aureus and S. epidermidis; Streptococcus Sp., including S. Pneumoniae (see above), S. viridans and Beta-haemolytic.

The primary mechanisms of action is through inhibition of bacterial DNA gyrase, the enzyme responsible for maintaining the structure of DNA.

ofloxacin is not subject to degradation by beta-lactamase enzymes nor is it modified by enzymes such as aminoglycoside adenylases or phosphorylases, or chloramphenicol acetyltransferase.

After ophthalmic instillation, ofloxacin is well maintained in the tear-film.

In a healthy volunteer study, mean tear film concentrations of ofloxacin measured four hours after topical dosing (9.2 µg/g) were higher than the 2µg/ml minimum concentration of ofloxacin necessary to inhibit 90% of most ocular bacterial strains (MIC90) in-vitro.

Maximum serum ofloxacin concentrations after ten days of topical dosing were about 1000 times lower than those reported after standard oral doses of ofloxacin, and no systemic side-effects attributable to topical ofloxacin were observed.

There are no toxicological safety issues with this product in man as the level of systemic absorption from topical ocular administration of ofloxacin is minimal.

Animal studies in the dog have found cases of arthropathy in weight bearing joints of juvenile animals after high oral doses of certain quinolones. However, these findings have not been seen in clinical studies and their relevance to man is unknown.

Benzalkonium chloride (EP) 0.005% w/v

Sodium chloride (EP) 0.9% w/v

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

Purified water (EP)

None known.

2 years unopened.

Discard 28 days after first opening.

Do not store above 25°C.

A bottle and an applicator tip of low density polyethylene (LDPE) and medium or high impact polystyrene cap.

The bottle contains 5 ml or 10 ml of suspension.

Not all pack sizes may be marketed.

There is no special requirement for disposal.

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

Allergan Ltd

Marlow International

The Parkway

Marlow

Bucks SL7 1YL

United Kingdom

PL 00426/0070

Date of first authorisation: 26^th October 1992

Date of last renewal: 8^th November 2004

17^th May 2011