MAXITROL ointment

1 gram ointment contains 1 mg dexamethasone, 6000 IU polymyxin B sulphate, and 3500 IU neomycin sulphate (as base).

For a full list of excipients, see section 6.1.

Eye ointment

White to very pale yellow homogeneous translucent ointment

MAXITROL eye ointment 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.

Children and Adults (including the Elderly)

Apply a small amount into the conjunctival sac(s) up to three to four times daily or, may be used adjunctively with drops at bedtime.

• Hypersensitivity to the active substances or to any component of the preparation.

• Epithelial herpes simplex keratitis.

• Vaccinia, varicella, or other viral infection of cornea and conjunctiva (except herpes zoster keratitis).

• Fungal diseases of ocular structures.

• Mycobacterial ocular infections.

• For topical ophthalmic use only. Not for injection or ingestion.

• 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 use of MAXITROL eye ointment.

• 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 use 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.

• 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 bacterial, viral, or fungal infections and mask the clinical signs of infection, preventing recognition of ineffectiveness of the antibiotic, or may suppress hypersensitivity reactions to substances in the product. Fungal infection should be suspected in patients with persistent corneal ulceration who have been or are receiving these drugs and corticosteroid therapy should be discontinued if fungal infection occurs.

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

• Contact lens wear is not recommended during treatment of an ocular infection. Therefore patients should be advised not to wear contact lenses during treatment with MAXITROL eye ointment.

No interaction studies have been performed.

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.

Pregnancy

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

MAXITROL eye ointment 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 on whether to discontinue breast-feeding or to discontinue therapy with MAXITROL eye ointment taking into account the benefit of breast-feeding for the child and the benefit of the product to the woman.

MAXITROL eye ointment 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.

Tabulated summary of adverse reactions

The following adverse effects 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, undesirable effects are presented in decreasing order of seriousness. The adverse reactions were obtained from clinical trials and postmarketing spontaneous reports.

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.

No case of overdose has been reported.

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

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

Pharmacotherapeutic group: ophthalmologicals; anti-infectives

ATC code: S01CA01

Mechanism of Action

MAXITROL eye ointment 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 ointment 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 ointment:

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 ointment. 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 ointment in at least some types of infections is questionable.

Dexamethasone is a moderately powerful corticosteroid having good penetration in ocular tissue. Cortico-steroids have an anti-inflammatory as well as a vasoconstrictive effect. They suppress the inflammatory response and symptoms in various disorders without basically curing these disorders.

Dexamethasone, like other corticosteroids, is absorbed rapidly after oral administration and has a biological half-life of about 190 minutes. Sufficient absorption may occur after topical application to the skin and eye to produce systemic effects. Intraocular penetration of dexamethasone occurs in significant amounts and contributes to the effectiveness of dexamethasone in anterior segment inflammatory disease.

Polymyxin B sulphate is not absorbed from the gastrointestinal tract or through intact skin, although the intact corneal epithelium prevents penetration into the corneal stroma, therapeutic concentrations do enter the stroma after epithelial damage. Good stromal penetration occurs after epithelial abrasion 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.

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.

Methylparaben

Propylparaben

Liquid lanolin

Petrolatum

None known.

30 months

Discard 28 days after first opening.

Do not store above 25°C.

Keep away from direct sunlight.

Do not refrigerate.

Keep the container tightly closed.

3.5 g metal tube with nozzle and screw cap.

Do not touch the top of the tube to any surface as this may contaminate the contents.

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

HP2 7UD

UK

0649/5916R

18 January 1991 / April 2001

10/03/2011