TOBRADEX Eye drops

Posology

1-2 drops instilled into the conjunctival sac(s) every 4-6 hours.

During the initial 24-48 hours, the dosage may be increased to 1-2 drops every 2 hours. Frequency should be decreased gradually as warranted by improvement in clinical signs. Care should be taken not to discontinue therapy prematurely.

Use in children

The safety and efficacy of TOBRDEX ophthalmic suspension in children have not been established.

Use in patients with hepatic or renal impairment

The safety and efficacy of TOBRADEX ophthalmic suspension in patients with hepatic or renal impairment have not been established. However, due to low systemic absorption of tobramycin and dexamethasone after topical administration of this product, dose adjustment is not necessary.

Method of administration

For ocular use.

Shake well before use.

- 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.

- The use of TOBRADEX is always contraindicated after uncomplicated removal of a foreign body.

TOBRADEX-Eyeointment-Eyedrops-Sideeffects

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

- In patients treated with ritonavir, plasma concentrations of dexamethasone may be increased.

Pregnancy

TOBRADEX is not recommended during pregnancy. (See the package insert about details.)

Breast-feeding

Tobramycin is excreted in human milk after systemic administration. No data is available on the passage of dexamethasone into human breast milk. It is unknown whether tobramycin or dexamethasone are excreted in human milk following topical ocular administration. It is not likely that the amount of tobramycin and dexamethasone would be detectable in human milk or be capable of producing clinical effects in the infant following topical use of the product. A risk to the suckling child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue or abstain from therapy with TOBRADEX taking into account the benefit of breast-feeding for the child and the benefit of therapy for the women.

- Not for injection into the eye.

- 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, urticaria, 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 used concomitantly and care should be taken to monitor the total serum concentration.

- Prolonged use of topical 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. TOBRADEX is not approved for use in 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 ophthalmic dexamethasone may occur after intensive or long-term continuous therapy in predisposed patients, including children and patients treated with ritonavir. In these cases, treatment should not be discontinued abruptly, but progressively tapered.

- Corticosteroids may reduce resistance to and aid in the establishment of corneal ulceration. If fungi infection occurs, corticosteroids therapy should be discontinued.

- 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.

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

- Contact lens wear is not recommended during treatment of an ocular inflammation or infection. TOBRADEX ophthalmic suspension contains benzalkonium chloride which may cause eye irritation and is known to discolor soft contact lenses. Avoid contact with soft contact lenses. In case patients are allowed to wear contact lenses, they must be instructed to remove contact lenses prior to application of TOBRADEX ophthalmic suspension and wait at least 15 minutes before reinsertion.

- When multiple prescriptions are required, or whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.

TOBRADEX contains tobramycin, an antibiotic, and dexamethasone, a corticosteroid.

TOBRADEX is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists.

Ocular steroids are indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain a diminution in oedema and inflammation. They are also indicated in chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns or penetration of foreign bodies.

The use of a combination drug with an anti-infective component is indicated where the risk or superficial ocular infection is high or where there is an expectation that potentially dangerous numbers of bacteria will be present in the eye.

The particular anti-infective drug in this product is active against the common bacterial eye pathogens.

Pharmacodynamic properties

Pharmacotherapeutic group: anti-inflammatory agents and anti-infectives in combination- corticosteroids and anti-infectives in combination.

Mode of Action

Dexamethasone

Topical corticosteroid exert an anti-inflammatory action and have been used for the treatment of anterior inflammation. Aspects of the inflammatory process such as oedema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, deposition of collagen, scar formation and fibroblastic proliferation are suppressed. Topical corticosteroids are effective in acute inflammatory conditions of the conjunctiva, sclera, cornea, lids, iris and anterior segment of the globe as well as in ocular allergic conditions.

The exact mechanism of anti-inflammatory action of dexamethasone is unknown. It inhibits multiple inflammatory cytokines and produces multiple glucocorticoid and mineralocorticoid effects.

Dexamethasone is a potent corticoid. Corticoids suppress the inflammatory response to a variety of agents and they can delay or slow healing. Since corticoids may inhibit the body’s defense mechanism against infection, a concomitant antimicrobial drug may be used when this inhibition is considered clinically significant. Tobramycin is an antibacterial drug. It inhibits the growth of bacteria by inhibiting protein synthesis.

Tobramycin

The preparation contains tobramycin, a rapidly bactericidal aminoglycoside antibiotic. It exerts its primary effect on bacterial cells by inhibiting polypeptide assembly and synthesis on the ribosome.

Mechanism of resistance

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