4.1. Therapeutic indications

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.

4.2. Posology and method of administration

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.

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

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

Hepatic and renal impairment

Maxitrol Eye Ointment has not been studied in these subject populations. However, due to low systemic absorption of the active substances after topical administration of this product, dose adjustment is not necessary.

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 or untreated parasitic eye infections.

• Mycobacterial ocular infections.

4.4. Special warnings and precautions for use

• 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. Severity of hypersensitivity reactions may vary from local effects to generalized reactions such as erythema, itching, urticarial, skin rash, anaphylaxis, anaphylactoid reactions, or bullous reactions. 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 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).

• Cushing's syndrome and/or adrenal suppression associated with systemic absorption of ocular dexamethasone may occur after intensive or long-term continuous therapy in predisposed patients, including children and patients treated with CYP3A4 inhibitors (including ritonavir and cobicistat). In these cases, treatment should be progressively discontinued.

• 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 non-susceptible bacterial, fungal, parasitic or viral infections and mask the clinical signs of infection, 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.

• 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).

• Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

• 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 ointment.

• This product contains methylparahydroxybenzoate and propylparahydroxybenzoate which may cause allergic reactions (possibly delayed).

• This product also contains lanolin which may cause local skin reactions (e.g. contact dermatitis).

• In patients receiving systemic corticosteroids, new-onset or exacerbation of pre-existing diabetes mellitus may occur. Because of the possibility of reduced glucose tolerance/diabetes mellitus with topical ophthalmic corticosteroids, caution is recommended when administering MAXITROL eye ointment to patients with a personal or family history of diabetes.

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.

CYP3A4 inhibitors (including ritonavir and cobicistat): may decrease dexamethasone clearance resulting in increased effects and adrenal suppression/Cushing's syndrome. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid effects.

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.

The possibility of a higher need for hypoglycaemic medicinal products must be taken into consideration when administering MAXITROL eye ointment to diabetic patients because the hypoglycaemic effect of these medicinal products may be reduced (see section 4.4).

4.6. Fertility, pregnancy and lactation

Fertility

There are no data available on the use of this medicine affecting male or female fertility. There is limited clinical data to evaluate the effect of dexamethasone on male or female fertility. Dexamethasone was free of adverse effects on fertility in a chorionic gonadotropin primed rat model.

Pregnancy

There are no or limited amount of data from the use of MAXITROL eye ointment in pregnant women. Aminoglycoside antibiotics, such as neomycin, do cross the placenta after intravenous dosing in pregnant women. Non-clinical and clinical systemic exposure to aminoglycosides has been shown to induce ototoxicity and nephrotoxicity. At the low dose administered via this topical product, neomycin is not expected to cause ototoxicity or nephrotoxicity from in utero exposure. Prolonged or repeated corticoid use during pregnancy has been associated with an increased risk of intra-uterine growth retardation. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism (See Section 4.4).

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/abstain from 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.

4.7. Effects on ability to drive and use machines

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.

4.8. Undesirable effects

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.

System Organ Classification

MedDRA Preferred Term (v.18.0)

Immune system disorders

Not Known: hypersensitivity (systemic or ocular)

Endocrine disorders

Not known: Cushing's syndrome, adrenal suppression (see section 4.4)

Nervous system disorders

Not known: headache

Eye disorders

Uncommon: keratitis, intraocular pressure increased, eye pruritus, ocular discomfort, eye irritation,

Not known: ulcerative keratitis, corneal thinning, vision, blurred (see also section 4.4), photophobia, mydriasis, eyelid ptosis, eye pain, eye swelling, foreign body sensation in eyes, ocular hyperaemia, increased lacrimation

Skin and subcutaneous tissue disorders

Not known: Stevens-Johnson syndrome

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.

Corticosteroids may impair glucose tolerance, which can lead to new-onset or exacerbation of diabetes mellitus (see section 4.4).

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 ointment 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 ointment may be flushed from the eye(s) with lukewarm water.