Informations for option: Maxitrol Eye Drops, show other option

Select option:

1. Maxitrol Eye Drops
2. Maxitrol Eye Drops

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

MAXITROL EYE DROPS

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml suspension contains 1 mg dexamethasone, 6000 IU polymyxin B sulphate, 3500 IU neomycin sulphate (as base)

Excipients: 1 ml suspension contains 0.04 mg benzalkonium chloride

For a full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Eye drops, suspension

White sterile suspension for topical ocular administration.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

MAXITROL eye drops, suspension is indicated for the short-term treatment of steroid responsive conditions of the eye when prophylactic antibiotic treatment is also required, after excluding the presence of fungal and viral disease.

4.2. Posology and Method of Administration

Children and Adults (including the Elderly)

Apply one or two drops to each affected eye up to six times daily or, more frequently if required.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients.

•    Herpes simplex keratitis.

•    Vaccinia, varicella, and other viral infection of cornea or conjunctiva

•    Fungal diseases of ocular structures.

•    Mycobacterial ocular infections.

4.4 Special warnings and precautions for use

For ocular use only. Not for injection or ingestion.

After cap is removed, if tamper evident snap collar is loose, remove before using product.

As with all antibacterial preparation prolonged use may lead to overgrowth of non-susceptible bacterial strains or fungi. If superinfection occurs, appropriate therapy should be initiated.

Sensitivity to topically applied aminoglycosides may occur in some patients. Cross-sensitivity to other aminoglycosides may also occur. If signs of serious reactions or hypersensitivity occur, discontinue the use of this product.

Patients using ophthalmic preparations containing neomycin sulphate should be advised to consult a physician if ocular pain, redness, swelling, or irritation worsens or persists.

Serious adverse reactions including neurotoxicity, ototoxicity and nephrotoxicity have occurred in patients receiving systemic neomycin or when applied topically to open wounds or damaged skin. Nephrotoxic and neurotoxic reactions have also occurred with systemic polymyxin B. Although these effects have not been reported following topical ocular use of this product, caution is advised when used concomitantly with systemic aminoglycoside or polymyxin B therapy.

Prolonged use of ophthalmic corticosteroids may result in ocular hypertension and/or glaucoma, with damage to the optic nerve, reduced visual acuity and visual field defects, and posterior subcapsular cataract formation. In patients receiving prolonged ophthalmic corticosteroid therapy, intraocular pressure should be checked routinely and frequently. This is especially important in paediatric patients, as the risk of corticosteroid-induced ocular hypertension may be greater in children and may occur earlier than in adults.

The risk of corticosteroid-induced raised intraocular pressure and/or cataract formation is increased in predisposed patients (e.g. diabetes).

In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical corticosteroids.

Corticosteroids may reduce resistance to and aid in the establishment of nonsusceptible bacterial, viral, or fungal infections and mask the clinical signs of infection or may suppress hypersensitivity reactions to MAXITROL eye drops, suspension. Fungal infection should be suspected in patients with persistent corneal ulceration who have been or are receiving these drugs; corticosteroid therapy should be discontinued if fungal infection occurs.

To avoid the risk of enhancement of herpetic corneal disease, frequent slit lamp examination is essential.

Topical ophthalmic corticosteroids may slow corneal wound healing. Topical NSAIDs are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. (See section 4.5).

Contact lens wear is discouraged during treatment of an ocular infection. Therefore patients should be advised not to wear contact lenses during treatment with MAXITROL eye drops, suspension.

MAXITROL eye drops, suspension contains benzalkonium chloride which may cause eye irritation and is known to discolour soft contact lenses. In case patients are allowed to wear contact lenses, they must be instructed to remove contact lenses prior to application of MAXITROL eye drops, suspension and wait 15 minutes after instillation of the dose before reinsertion.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Concomitant use of topical steroids and topical NSAIDs may increase the potential for corneal healing problems.

Concomitant and/or sequential use of an aminoglycoside (neomycin) and other systemic, oral, or topical drugs that have neurotoxic, ototoxic, or nephrotoxic effects may result in additive toxicity and should be avoided, whenever possible.

If more than one ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.

4.6 Fertility, pregnancy and lactation

Fertility

There are no available data on the use of this medicine affecting male or female fertility.

Pregnancy

There are no or limited amount of data from the use of MAXITROL eye drops, suspension in pregnant women. Studies in animals with some active components of MAXITROL eye drops, suspension have shown reproductive toxicity (see section 5.3).

MAXITROL eye drops, suspension is not recommended during pregnancy.

Lactation

It is unknown whether topical ophthalmic dexamethasone, neomycin or polymyxin B are excreted in human milk. Because systemic corticosteroids and aminoglycosides may be distributed into milk, a risk to the suckling child cannot be excluded.

A decision must be made whether to discontinue/abstain from breast-feeding or to discontinue therapy with MAXITROL eye drops, suspension taking into account the benefit of breast-feeding for the child and the benefit of the product to the woman.

4.7 Effects on Ability to Drive and Use Machines

MAXITROL eye drops, suspension has no or negligible influence on the ability to drive and use machines. As with any other eye drop, temporarily blurred vision or other visual disturbances may affect the ability to drive or use machines. If transient blurred vision occurs upon instillation, the patient must wait until the vision clears before driving or using machinery.

4.8 Undesirable effects

Summary of the safety profile

In clinical trials with MAXITROL eye drops and MAXITROL eye ointment the most common adverse reactions were ocular discomfort, keratitis, and eye irritation, occurring in 0.7% to 0.9% of patients.

Tabulated summary of adverse reactions

The following adverse reactions 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), very rare (<1/10,000) or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in decreasing order of seriousness. The adverse reactions were obtained from clinical trials and post-marketing experience for MAXITROL eye drops and MAXITROL eye ointment

System Organ Classification	MedDRA Preferred Term (v.13.1)
Immune system disorders	Uncommon: hypersensitivity (systemic or ocular)
Nervous system disorders	Not known: headache
Eye disorders	Uncommon: keratitis, intraocular pressure increased, vision-blurred, photophobia, mydriasis, eyelid ptosis, eye pain, eye swelling, eye pruritus, ocular discomfort, foreign body sensation in eyes, eye irritation, ocular hyperaemia, increased lacrimation
	Not known: corneal thinning

Description of selected adverse event

Due to the steroid component, in diseases causing thinning of the cornea or sclera there is a higher risk for perforation especially after long treatments (See Section Special warnings and precautions for use).

Topical ophthalmic steroid use may result in increased intraocular pressure with damage to the optic nerve, reduced visual acuity and visual field defects. Also it may lead to posterior subcapsular cataract formation (See Section Special warnings and precautions for use).

Sensitivity to topically administered aminoglycosides may occur in some patients (See Section Special warnings and precautions for use). Systemic side effects may occur with extensive use.

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:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

4.9 Overdose

No case of overdose has been reported.

Signs and symptoms of an overdosage of MAXITROL eye drops, suspension may be similar to adverse reaction effects seen in some patients (punctuate keratitis, erythema, increased lacrimation, oedema and lid itching).

Due to the characteristics of this preparation, intended for topical use, no toxic effects are expected when administered to the eye neither at the recommended dose nor in the event of accidental ingestion of the contents of a bottle.

A topical ophthalmic overdose of MAXITROL eye drops, suspension may be flushed from the eye(s) with lukewarm water.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: ophthalmologicals; anti-infectives ATC code: S01CA01

Mechanism of Action

MAXITROL eye drops, suspension has a dual effect: suppression of inflammation symptoms by the corticosteroidal component dexamethasone, and an anti-infective effect due to the presence of two antibiotics, polymyxin B and neomycin.

Dexamethasone is a synthetic glucorticoid with potent anti-inflammatory activity. Polymyxin B is a cyclic lipopeptide that penetrates the cell wall of gram-negative bacilli to destabilize the cytoplasmic membrane. It is generally less active against gram-positive bacteria. Neomycin is an aminoglycoside antibiotic that primarily exerts its effect on bacterial cells by inhibiting polypeptide assembly and synthesis on the ribosome.

Mechanism of Resistance

Resistance of bacteria to polymyxin B is of chromosomal origin and is uncommon. A modification of the phospholipids of the cytoplasmic membrane appears to play a role.

Resistance to neomycin occurs by several different mechanisms including (1) alterations of the ribosomal subunit within the bacterial cell; (2) interference with the transport of neomycin into the cell, and (3) inactivation by an array of adenylating, phosphorylating, and acetylating enzymes. Genetic information for production of inactivating enzymes may be carried on the bacterial chromosome or on plasmids.

Breakpoints

Each gram of MAXITROL eye drops, suspension contains 6000 IU polymyxin B sulphate and 3500 IU neomycin sulphate. The breakpoints and the in vitro spectrum as mentioned below are based on the dual activity of either polymyxin B or neomycin. The breakpoints listed here are based upon acquired resistance for specific species found in ocular infections and the ratio in International Units of polymyxin B to neomycin in MAXITROL eye drops, suspension:

Resistance breakpoints: >5:2.5 to >40:20 depending upon the bacterial species Susceptibility

The information listed below provides guidance on the approximate probabilities on the susceptibility of microorganisms to polymyxin B or neomycin in MAXITROL eye drops, suspension. The presentation below lists bacterial species recovered from external ocular infections of the eye.

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 the combination of polymyxin B or neomycin as in MAXITROL eye drops, suspension in at least some types of infections is questionable.

following topical instillation, subconjunctival injection, or corneal bath. No significant polymyxin B penetration into the vitreous is demonstrable after parenteral or local administration of the drug.

Neomycin is poorly absorbed from the gastrointestinal tract and after topical administration an insufficient amount is absorbed to produce systemic effects. Absorption has been reported to occur from wounds and inflamed skin. After absorption neomycin is rapidly excreted by the kidneys in active form.

5.3 Preclinical safety data

Mutagenicity and Carcinogenicity

Genotoxicity studies performed with neomycin and polymyxin B, with and without metabolic activation, were negative in bacterial (Ames test) or mammalian cells (chromosomal aberration assay in CHO cells). Dexamethasone was clastogenic in vivo in the mouse micronucleus assay at doses in excess of those obtained following topical application. Conventional long term carcinogenicity studies with MAXITROL or its active constituents have not been performed.

Teratogenicity

Pregnant rats treated daily with high doses of neomycin produced offspring that exhibited significant ototoxicity. The teratogenic dose is far greater (> 10,000-fold) than the clinical daily exposure from MAXITROL. Dexamethasone has been found to be teratogenic in animal models. Dexamethasone induced abnormalities of foetal development including cleft palate, intra-uterine growth retardation and affects on brain growth and development.

Local Tolerance and Systemic Effects

Systemic exposure to dexamethasone is associated with its pharmacological effects as a potent glucocorticoid. Prolonged exposure to the steroid can result in glucocorticoid imbalance. Topical ocular safety studies with dexamethasone in rabbits have shown systemic effects after 1 month of treatment. In rabbits, MAXITROL was shown to have minimal irritation potential after administration to either control or irritated eyes.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sodium chloride

Polysorbate 20 Benzalkonium chloride Hydroxypropyl methylcellulose Hydrochloric acid/sodium hydroxide

6.2. Incompatibilities

None known.

6.3 Shelf Life

Unopened 24 months.

Discard 28 days after first opening

6.4. Special Precautions for Storage

Do not store above 25°C. Keep away from direct sunlight. Do not refrigerate. Keep the container tightly closed.

6.5    Nature and Contents of Container

5 ml & 10 ml DROP-TANIER, natural LDPE bottles and plugs with polystyrene or polypropylene caps.

6.6    Special precautions for disposal and other handling

Do not touch the tip of the bottle to any surface as this may contaminate the contents.

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

7    MARKETING AUTHORISATION HOLDER

Alcon Laboratories (UK) Ltd Frimley Business Park,

Frimley, Camberley,

Surrey, GU16 7SR,

United Kingdom 8. MARKETING AUTHORISATION NUMBER

PL 0649/5915R

9. DATE OF FIRST AUTHORISATION / RENEWAL OF AUTHORISATION

24 January 1991

10 DATE OF REVISION OF THE TEXT

09/09/2014