TOBRADEX Eye drops, suspension Ref.[4793] Active ingredients: Dexamethasone Tobramycin

TOBRADEX is for topical use only and not for injection or oral use.

Prolonged use of topical ophthalmic corticosteroids (i.e., longer than the maximum duration used in clinical trials [24 days]) may result in ocular hypertension/glaucoma with resultant damage to the optic nerve and reduced visual acuity and visual fields defects and may also result in posterior subcapsular cataract formation.

It is advisable that the intraocular pressure be checked frequently. This is especially important in paediatric patients receiving dexamethasone-containing products, as the risk of steroid-induced ocular hypertension may be greater in children below 6 years of age and may occur earlier than a steroid response in adults. The frequency and duration of treatment should be carefully considered, and the intraocular pressure should be monitored from the outset of treatment, recognizing the risk for earlier and greater steroid-induced intraocular pressure increases in the paediatric patients.

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

Prolonged use may also result in secondary ocular infections due to suppression of host response. Corticosteroids may reduce resistance to and aid in the establishment of bacterial, viral or fungal infections and mask the clinical signs of infection.

Sensitivity to topically administered aminoglycosides may occur in some patients. If hypersensitivity develops during use of this medicine, treatment should be discontinued.

Cross-hypersensitivity to other aminoglycosides can occur, and the possibility that patients who become sensitized to topical tobramycin may also be sensitive to other topical and/or systemic aminoglycosides should be considered.

Serious adverse reactions including neurotoxicity, ototoxicity and nephrotoxicity have occurred in patients receiving systemic aminoglycoside therapy. Caution is advised when used concomitantly.

Fungal infection should be suspected in patients with persistent corneal ulceration. If fungal infection occurs, corticosteroids therapy should be discontinued.

Prolonged use of antibiotics such as tobramycin may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated.

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).

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

Benzalkonium chloride, used as a preservative in this product, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Benzalkonium chloride may cause eye irritation and discolour soft contact lenses.

Avoid contact with soft contact lenses. Contact lens wear is not recommended during treatment of an ocular infection or inflammation. If patients are allowed to wear contact lenses, they must be instructed to remove lenses prior to application of TOBRADEX and wait at least 15 minutes before reinsertion.

No clinically relevant interactions have been described with topical ocular dosing.

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

Pregnancy

There are no adequate data from the use of TOBRADEX in pregnant women. Animal studies with subcutaneous administration of tobramycin have not revealed any teratogenic effects. High systemic doses of aminoglycoside antibiotics have been associated with ototoxicity. However, after ocular, topical administration, systemic levels are expected to be very low and tobramycin is not expected to cause direct or indirect harmful effects on reproduction. Topical administration of corticosteroids to pregnant animals can cause abnormalities in foetal development, including cleft palate. The clinical relevance is not known. Further, animal and clinical data indicate that administration of pharmacological doses of glucocorticoids during pregnancy may increase the risk for intrauterine growth retardation, adult cardiovascular and/or metabolic disease and/or impaired neurobehavioral development. Treatment during pregnancy, and especially during the first three months, should only take place after a careful benefit-risk assessment. Therefore, women should inform their physician if pregnancy occurs. So far, use in humans has not generated any suspicion of embryotoxic effects. However, during long-term treatment growth disorders in the unborn child cannot be ruled out. Treatment towards the end of pregnancy may inhibit the body’s own production of glucocorticoids necessitating treatment after birth. Therefore, during pregnancy, TOBRADEX should only be used when the potential benefit justifies the potential risks.

Breast-feeding

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to product detectable quantities in human milk. TOBRADEX should not be used during breast-feeding unless the potential benefit outweighs the potential risk.

Fertility

Studies have not been performed to evaluate the effect of topical ocular administration of TOBRADEX on human fertility.

TOBRADEX has no or negligible influence on the ability to drive and use machines.

No studies on the effects on the ability to drive and use machines have been performed. As with any eye drop, temporarily blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs, the patient must wait until the vision is clear before driving or using machines.

Summary of the safety profile

In clinical studies involving over 1600 patients, TOBRADEX was administered up to six times daily. No serious ophthalmic or systemic adverse reactions related to TOBRADEX or components of the combination were reported in clinical studies. The most frequently reported adverse reactions with TOBRADEX were eye pain, intraocular pressure increased, eye irritation (burning upon instillation) and eye pruritus occurring in less than 1% of patients.

Tabulated list of adverse reactions

The following adverse reactions have been reported with TOBRADEX during clinical trials or during post marketing experience and are classified according to the subsequent convention: 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) and very rare (<1/10,000), and not known (cannot be estimated from the available data). Within each frequency-grouping, adverse reactions are presented in order of decreasing seriousness.

Immune system disorders

Not known: hypersensitivity

Nervous system disorders

Uncommon: headache

Not known: dizziness

Eye disorders

Uncommon: eye pain, eye pruritus, ocular discomfort, ocular hypertension, conjunctival oedema, increased intraocular pressure, eye irritation

Rare: keratitis, eye allergy, blurred vision, dry eye, ocular hyperaemia

Not known: eyelid oedema, erythema of the eyelid, mydriasis, lacrimation increased

Respiratory, thoracic, and mediastinal disorders

Uncommon: Rhinorrhoea, laryngospasm

Gastrointestinal disorders

Rare: dysgeusia

Not known: nausea, abdominal discomfort

Skin and subcutaneous tissue disorders

Not known: rash, swelling face, pruritus

Description of selected adverse reactions

The following adverse reactions have been observed following use with Dexamethasone ophthalmic suspension:

Nervous system disorders

Common: headache

Eye disorders

Common: eye irritation,* ocular hyperaemia,* erythema of eyelid, abnormal sensation in eye*

Respiratory, thoracic, and mediastinal disorders

Common: Post nasal drip

The following adverse reactions have been observed following use with Tobramycin ophthalmic solution:

Eye disorders

Common: ocular hyperaemia,* eye pain*

Uncommon: eye pruritus,* ocular discomfort,* eye allergy, eyelid oedema,* conjunctivitis,* glare, increased lacrimation,* keratitis*

* These adverse reactions were also observed with TOBRADEX during post marketing.

Prolonged use of topical ophthalmic corticosteroids may result in increased intraocular pressure with damage to the optic nerve, reduced visual acuity and visual field defects, posterior subcapsular cataract formation and delayed wound healing.

Due to the corticosteroid component, in diseases causing thinning of the cornea or sclera there is a higher risk for perforation especially after long treatments (See Section 4.4).

The development of secondary infection has occurred after the use of combinations containing corticosteroids and antimicrobials. Fungal infections of the cornea are particularly prone to develop coincidentally with long term applications of steroids.

Serious adverse reactions including neurotoxicity, ototoxicity and nephrotoxicity have occurred in patients receiving systemic tobramycin therapy (See Section 4.4).

Sensitivity to topically administered aminoglycosides may occur in some patients (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 benefit/risk balance of the medicinal product. Health care professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Not applicable.