Alcon Laboratories (U.K) Limited

MOXIVIG 0.5%w/v eye drops, solution

1 ml of solution contains 5.45 mg moxifloxacin hydrochloride equivalent to 5 mg moxifloxacin base.

Each eye drop contains 190 micrograms of moxifloxacin.

For a full list of excipients, see section 6.1.

Eye drops (solution)

Clear, greenish-yellow solution.

Topical treatment of purulent bacterial conjunctivitis, caused by moxifloxacin susceptible strains (see sections 4.4 and 5.1). Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Ocular use

Use in adults including the elderly

The dose is one drop in the affected eye(s) 3 times a day.

The infection normally improves within 5 days and treatment should then be continued for a further 2-3 days. If no improvement is observed within 5 days of initiating therapy, the diagnosis and/or treatment should be reconsidered. The duration of treatment depends on the severity of the disorder and on the clinical and bacteriological course of infection.

Paediatric patients

No dosage adjustment is necessary.

Use in hepatic and renal impairment

No dosage adjustment is necessary.

To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle.

In order to prevent the drops from being absorbed via the nasal mucosa, particularly in new-born infants or children, the nasolacrimal ducts should be held closed for 2 to 3 minutes with the fingers after administering the drops.

If more than one topical ophthalmic medicinal product is being used, the medicinal products must be administered at least 5 minutes apart.

Hypersensitivity to the active substance, to any of the excipients, or to other quinolones

In patients receiving systemically administered quinolones, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial oedema), airway obstruction, dyspnoea, urticaria, and itching.

If an allergic reaction to MOXIVIG occurs, discontinue use of the medicinal product. Serious acute hypersensitivity reactions to moxifloxacin or any other product ingredient may require immediate emergency treatment. Oxygen and airway management should be administered where clinically indicated.

As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy.

Data are very limited to establish efficacy and safety of MOXIVIG in the treatment of conjunctivitis in neonates. Therefore use of this medicinal product to treat conjunctivitis in neonates is not recommended.

MOXIVIG should not be used for the prophylaxis or empiric treatment of gonococcal conjunctivitis, including gonococcal ophthalmia neonatorum, because of the prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae. Patients with eye infections caused by Neisseria gonorrhoeae should receive appropriate systemic treatment.

The medicinal product is not recommended for the treatment of Chlamydia trachomatis in patients less than 2 years of age as it has not been evaluated in such patients. Patients older than 2 years of age with eye infections caused by Chlamydia trachomitis should receive appropriate systemic treatment.

Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition, e.g. systemic treatment in cases caused by Chlamydia trachomitis or Neisseria gonorrhoeae.

Patients should be advised not to wear contact lenses if they have signs and symptoms of a bacterial ocular infection.

No specific interaction studies have been performed with MOXIVIG 0.5%w/v Eye Drops, Solution. Given the low systemic concentration of moxifloxacin following topical ocular administration of the medicinal product (see Section 5.2), drug interactions are unlikely to occur.

Pregnancy

There are no adequate data from the use of MOXIVIG in pregnant women. However, no effects on pregnancy are anticipated since the systemic exposure to moxifloxacin is negligible. The medicinal product can be used during pregnancy.

Lactation

It is unknown whether moxifloxacin is excreted in human breast milk. Animal studies have shown excretion of low levels in breast milk after oral administration of moxifloxacin. However, at therapeutic doses of MOXIVIG no effects on the suckling child are anticipated. The medicinal product can be used during breast-feeding.

As with any eye drops, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient should wait until their vision clears before driving or using machinery.

In clinical studies involving 1,740 patients, MOXIVIG was administered up to 8 times a day, with 1,452 of these patients receiving treatment 3 times daily. The overall safety population that received the medicinal product consisted of 877 patients from the United States and Canada, 586 patients from Japan and 277 patients from India. No serious ophthalmic or systemic undesirable effects related to the medicinal product were reported in any of the clinical studies. The most frequently reported treatment-related undesirable effects with the medicinal product were eye irritation and eye pain, occurring at an overall incidence of 1 to 2%. These reactions were mild in 97% of those patients who experienced them, with only 1 patient discontinuing therapy as a result.

The following undesirable effects were assessed to be treatment-related 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 <1/1000), or very rare (<1/10,000) or not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in decreasing order of seriousness.

Blood and lymphatic system disorders

Uncommon: haemoglobin decreased

Nervous system disorders

Common: dysgeusia

Uncommon: headache, paraesthesia

Eye disorders

Common: eye pain, eye irritation, dry eye, eye pruritus, conjunctival hyperaemia, ocular hyperaemia

Uncommon: corneal epithelium defect, punctate keratitis, corneal staining, conjunctival haemorrhage, conjunctivitis, eye swelling, ocular discomfort, vision blurred, visual acuity reduced, eyelid disorder, erythaema of eyelid, abnormal sensation in eye

Respiratory, thoracic, and mediastinal disorders

Uncommon: nasal discomfort, pharyngolaryngeal pain, sensation of foreign body (throat)

Gastrointestinal disorders

Uncommon: vomiting

Hepatobiliary disorders

Uncommon: alanine aminotransferase increased, gamma-glutamyltransferase increased

Adverse reactions identified from post-marketing experience that have not been reported previously in clinical trials with the medicinal product include the following. The frequency category in which these adverse reactions occur is not known and cannot be estimated from the available data.

Cardiac disorders:

Not known: palpitations

Nervous system disorders:

Not known: dizziness

Eye disorders:

Not known: endophthalmitis, ulcerative keratitis, corneal erosion, corneal abrasion, intraocular pressure increased, corneal opacity, corneal infiltrates, corneal deposits, eye allergy, keratitis, corneal oedema, photophobia, corneal disorder, blepharitis, eyelid oedema, lacrimation increased, eye discharge, foreign body sensation in eyes

Respiratory, thoracic, and mediastinal disorders:

Not known: dyspneoa

Gastrointestinal disorders:

Not known: nausea

Skin and subcutaneous tissue disorders:

Not known: erythema, rash, pruritus

Immune system disorders:

Not known: hypersensitivity

Paediatric population

Based on data from clinical trials involving paediatric patients, including neonates (see section 5.1), the type and severity of adverse reactions in the paediatric population are similar to those in adults

No case of overdose with MOXIVIG has been reported. The limited holding capacity of the conjunctival sac for ophthalmic products practically precludes any overdosing of the medicinal product.

The total amount of moxifloxacin in a single container is too small to induce adverse effects after accidental ingestion.

Pharmacotherapeutic group: Ophthalmologicals; anti-infectives, other anti-infectives, ATC code: S01A X22

Mode of Action:

Moxifloxacin, a fourth-generation fluoroquinolone, inhibits the DNA gyrase and topoisomerase IV required for bacterial DNA replication, repair, and recombination.

Mechanisms of Resistance:

Resistance to fluoroquinolones, including moxifloxacin, occurs generally by chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, moxifloxacin resistance can be due to mutations in mar (multiple antibiotic resistance) and the qnr (quinolone resistance) gene systems. Cross-resistance with beta-lactams, macrolides and aminoglycosides is not expected due to differences in mode of action.

Breakpoints

The minimal inhibitory concentration (MIC) breakpoints (mg/l) established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:

The in vitro breakpoints have been useful in predicting clinical efficacy of moxifloxacin when administered systemically. These breakpoints might not be applicable on topical ocular use of the medicinal product as higher concentrations are obtained in the eye and the local physical/chemical circumstances can influence the activity of the product on the site of administration.

Susceptibility:

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of moxifloxacin in at least some types of infections is questionable.

Following topical ocular administration of MOXIVIG, moxifloxacin was absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were measured in 21 male and female subjects who received bilateral topical ocular doses of the medicinal product 3 times a day for 4 days. The mean steady-state C_max and AUC were 2.7 ng/ml and 41.9 ng·hr/ml, respectively. These exposure values are approximately 1,600 and 1,200 times lower than the mean C_max and AUC reported after therapeutic 400 mg oral doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours.

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure following administration to the eye indicating little relevance to clinical use.

As with other quinolones, moxifloxacin was also genotoxic in vitro in bacteria and mammalian cells. As these effects can be traced to the interaction with bacterial gyrase and in considerably higher concentrations to the interaction with topoisomerase II in mammalian cells, a threshold level for genotoxicity can be assumed. In in vivo tests, no evidence of genotoxicity was found, despite high doses of moxifloxacin. The therapeutic doses for human use therefore provide adequate safety margin. No indication of a carcinogenic effect was observed in an initiation promotion model in rats.

Unlike other quinolones, moxifloxacin showed no phototoxic or photogenotoxic properties in extensive in vitro and in vivo studies.

Sodium chloride

Boric acid

Hydrochloric acid and/or sodium hydroxide (to adjust pH)

Purified water

Not applicable

3 years

Discard 4 weeks after first opening.

This medicinal product does not require any special storage conditions.

5 ml bottle with DROP-TAINER dispensing system consisting of a transparent low density polyethylene bottle and dispensing plug and white polypropylene closure. Tamper evidence is provided by a security seal around the closure of the bottle.

Pack size: box containing 1 bottle

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

Alcon Laboratories (UK) Ltd

Pentagon Park

Boundary Way

Hemel Hempstead

Herts

HP2 7UD

United Kingdom

PA 290/79/1

Date of first authorisation: 31^st July 2009

31/03/2010