TobraDex tobramycin and dexamethasone 3 mg/g; 1 mg/g Ointment, 3.5 g — NDC 0078-0876-01 (Billing 00078-0876-01)

WARNINGS: FOR TOPICAL OPHTHALMIC USE. NOT FOR INJECTION INTO THE EYE. Sensitivity to topically applied aminoglycosides may occur in some patients.

Severity of hypersensitivity reactions may vary from local effects to generalized reactions such erythema, itching, urticaria, skin rash, anaphylaxis, anaphylactoid reactions, or bullous reactions. If a sensitivity reaction does occur, discontinue use. Prolonged use of steroids may result in glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and posterior subcapsular cataract formation.

Intraocular pressure (IOP) should be routinely monitored even though it may be difficult in pediatric patients and uncooperative patients. Prolonged use may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions and parasitic infections of the eye, steroids may mask infection or enhance existing infection.

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

ADVERSE REACTIONS: Adverse reactions have occurred with steroid/anti-infective combination drugs which can be attributed to the steroid component, the anti-infective component, or the combination. Exact incidence figures are not available. The most frequent adverse reactions to topical ocular tobramycin [TOBREX ® (tobramycin ophthalmic ointment) 0.3%] are hypersensitivity and localized ocular toxicity, including lid itching and swelling, and conjunctival erythema.

These reactions occur in less than 4% of patients. The reactions due to the steroid component are: elevation of intraocular pressure with possible development of glaucoma, and infrequent optic nerve damage; posterior subcapsular cataract formation; and delayed wound healing. Secondary Infection .

The development of secondary infection has occurred after use of combinations containing steroids and antimicrobials. Fungal infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion must be considered in any persistent corneal ulceration where steroid treatment has been used.

Secondary bacterial ocular infection following suppression of host responses also occurs. Postmarketing Experience: Additional adverse reactions identified from postmarketing use include, anaphylactic reaction, erythema multiforme. The following additional adverse reactions have been reported with the individual components listed below: Dexamethasone : Cushing’s syndrome and adrenal suppression may occur after use of dexamethasone in excess of the listed dosing instructions in predisposed patients, including children and patients treated with CYP3A4 inhibitors.

Aminoglycosides : Neurotoxicity, ototoxicity, and nephrotoxicity have occurred in patients receiving systemic aminoglycoside therapy. Aminoglycosides may aggravate muscle weakness in patients with known or suspected neuromuscular disorders, such as myasthenia gravis or Parkinson’s disease, because of their potential effect on neuromuscular function.

PRECAUTIONS: General: The possibility of fungal infections of the cornea should be considered after long-term steroid dosing. As with other antibiotic preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated.

When multiple prescriptions are required, or whenever clinical judgement dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. Cross-sensitivity to other aminoglycoside antibiotics may occur; if hypersensitivity develops with this product, discontinue use and institute appropriate therapy. Ophthalmic ointment may retard corneal wound healing.

Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial ocular infection. Information for Patients: Do not touch tube tip to any surface, as this may contaminate the contents. Contact lenses should not be worn during the use of this product.

Do not use the product if the imprinted carton seals have been damaged, or removed. Carcinogenesis, Mutagenesis, Impairment of Fertility: No studies have been conducted to evaluate the carcinogenic or mutagenic potential. No impairment of fertility was noted in studies of subcutaneous tobramycin in rats at doses of 50 and 100 mg/kg/day.

Pregnancy: Corticosteroids have been found to be teratogenic in animal studies. Ocular administration of 0.1% dexamethasone resulted in 15.6% and 32.3% incidence of fetal anomalies in two groups of pregnant rabbits. Fetal growth retardation and increased mortality rates have been observed in rats with chronic dexamethasone therapy.

Reproduction studies have been performed in rats and rabbits with tobramycin at doses up to 100 mg/kg/day parenterally and have revealed no evidence of impaired fertility or harm to the fetus. There are no adequate and well-controlled studies in pregnant women. However, prolonged or repeated corticoid use during pregnancy has been associated with an increased risk of intra-uterine growth retardation.

TOBRADEX ® (tobramycin and dexamethasone ophthalmic ointment) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism. Nursing Mothers: 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 produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when TOBRADEX ® (tobramycin and dexamethasone ophthalmic ointment) is administered to a nursing woman.