Tobroft 1 mg, 3 mg Eye drops

TOBROFT is indicated for the reduction of ocular inflammation and prophylaxis of infection due to susceptible organisms, following intraocular surgery.

Posology
Instil one drop into the operative eye every four hours whilst awake for three days prior to surgery and one drop immediately upon conclusion of surgery. Beginning at the first dressing change one day following surgery, instil two drops every two hours whilst awake for two days. From post-operative day three, instil one drop into the eye four times a day for one week. Thereafter, instil one drop per day for ten days as maintenance therapy. Not more than 20 mL should be prescribed initially and the prescription should not be repeated without further evaluation as outlined under section 4.4. SHAKE WELL BEFORE USE. STORE UPRIGHT. When removing the cap for the first time, remove and discard the tamper evident ring to prevent the ring from falling into the patientu2019s eye.

Method of administration
TOBROFT is for ocular use only. If more than one topical ophthalmic medicine is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.

• Hypersensitivity to tobramycin and/or dexamethasone or to any of the excipients listed in section 6.1.
• Epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella and many other viral diseases of the cornea and conjunctiva.
• Mycobacterial infection of the eye.
• Fungal diseases of ocular structures, or untreated parasitic eye infections.
• Untreated purulent infection of the eye.
• The use of TOBROFT is always contra-indicated after uncomplicated removal of a corneal foreign body.
• TOBROFT should not be used in the treatment of mechanical lacerations and abrasions of the eye. TOBROFT will delay healing and promote the development and spread of infection.

TOBROFT is for topical use only and not for injection or oral use. Prolonged use of TOBROFT 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. Family or personal history of glaucoma has a higher risk of corticosteroid induced rise in intraocular pressure. 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. 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 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). 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. Corticosteroids such as TOBROFT may cause progression of the dendritic keratitis (herpes simplex infection), resulting in irreversible clouding of the cornea. 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, fungal or parasitic infections and mask the clinical signs of infection. Sensitivity to topically administered aminoglycosides may occur in some patients. 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 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 TOBROFT eye drops are used concomitantly with systemic aminoglycosides. Caution should be exercised when prescribing TOBROFT eye drops to patients with known or suspected neuromuscular disorders such as myasthenia gravis or Parkinson's disease. Aminoglycosides may aggravate muscle weakness because of their potential effect on neuromuscular function. Fungal infection should be suspected in patients with persistent corneal ulceration. If fungal infection occurs, corticosteroids therapy as in TOBROFT 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. Excipients: benzalkonium chloride TOBROFT contains benzalkonium chloride that 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 TOBROFT and wait at least 15 minutes before reinsertion. As the possibility of adverse effects on the corneal permeability, and the danger of disruption of the corneal epithelium with prolonged or repeated usage of benzalkonium chloride preserved ophthalmological preparations such as TOBROFT cannot be excluded, regular ophthalmological examination is required. Caution should be exercised in the use of benzalkonium chloride preserved topical medication such as TOBROFT over an extended period in patients with extensive ocular surface disease.

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. Dexamethasone is metabolized via cytochrome P450 3A4 (CYP3A4). 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.

Pregnancy
The safety of TOBROFT during pregnancy has not yet been established.
Breastfeeding
It is not known whether TOBROFT is excreted in human milk; therefore, caution should be observed when it is administered to mothers breastfeeding their infants.
Fertility
Studies have not been performed to evaluate the effect of tobramycin on human or animal fertility. There is limited clinical data to evaluate the effect of dexamethasone on male or female fertility.

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 reported clinical studies involving over 1 600 patients, ophthalmic dexamethasone and tobramycin as in TOBROFT was administered up to six times daily. No serious ophthalmic or systemic adverse reactions related to TOBROFT or components of the combination were reported in clinical studies. The most frequently reported adverse reactions with TOBROFT 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 table below shows all adverse drug reactions (ADRs) observed during reported clinical trials and postmarket spontaneous reports with TOBROFT.
System Organ Class Frequency Less Frequent Not known Immune system disorders anaphylactic reaction, hypersensitivity. Endocrine disorders Cushing's syndrome, adrenal suppression (see section 4.4). Nervous system disorders Headache. Dizziness. Eye disorders eye pain, eye pruritus, ocular discomfort, ocular hypertension, conjunctival oedema, increased intraocular pressure, eye irritation. keratitis, eye allergy, vision blurred (see also section 4.4), dry eye, ocular hyperaemia. eyelid oedema, erythema of the eyelid, mydriasis, lacrimation increased. Respiratory, thoracic and mediastinal disorders rhinorrhoea, laryngospasm Gastrointestinal disorders dysgeusia nausea, abdominal discomfort. Skin and subcutaneous tissue disorders erythema multiforme, rash, swelling face, pruritus.

See section 4.8 above. Discontinue use immediately. Treatment is symptomatic and supportive. A topical overdose of TOBROFT may be flushed from the eye(s) with lukewarm tap water.