Tobradex ST

Dosage Forms And Strengths

TOBRADEX ST (tobramycin / dexamethasone ophthalmic suspension 0.3%/0.05%) ophthalmic suspension contains 3 mg/mL tobramycin and 0.5 mg/mL dexamethasone.

Storage And Handling

TOBRADEX® ST (tobramycin / dexamethasone ophthalmic suspension 0.3%/0.05%) is supplied as a 2.5 mL, 5 mL, or 10 mL suspension in a 4 mL, 8 mL or 10 mL natural polyethylene DROP-TAINER® bottle with a natural polyethylene dispenser tip and a pink polypropylene overcap. Tamper evidence is provided with a shrink band around the closure and neck area of the bottle.

NDC 0065-0652-25: 2.5 mL
NDC 0065-0652-05: 5 mL
NDC 0065-0652-10: 10 mL

Storage

Store at 2 to 25°C (36 to 77°F). Protect from light.

Alcon Laboratories, Inc., Fort Worth, Texas 76134 USA. Revised: February 2009

Mechanism of Action

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 to be clinically significant.

Tobramycin is an antibacterial drug. It inhibits the growth of bacteria by inhibiting protein synthesis. Tobramycin is included in this combination product to provide action against susceptible bacteria.

Pharmacokinetics

In a multi-center, double-masked, parallel-group, randomized, single-dose pharmacokinetic study in male and female cataract surgery patients, mean dexamethasone concentrations following administration of TOBRADEX ST (tobramycin / dexamethasone ophthalmic suspension 0.3%/0.05%) were similar to dexamethasone concentrations following administration of TOBRADEX (tobramycin /dexamethasone ophthalmic suspension) 0.3%/0.1%. Aqueous humor concentrations reached a mean peak of 33.7 ng/mL 2 hours following single-dose administration of TOBRADEX ST (tobramycin / dexamethasone ophthalmic suspension 0.3%/0.05%) .

No data are available on the extent of systemic absorption of dexamethasone or tobramycin from TOBRADEX ST (tobramycin / dexamethasone ophthalmic suspension 0.3%/0.05%) ophthalmic suspension. Following multiple-dose (QID for 2 days) bilateral ocular administration of TOBRADEX (Tobramycin 0.3%/Dexamethasone 0.1% ophthalmic suspension) in healthy male and female volunteers, peak plasma concentrations of dexamethasone were less than 1 ng/mL and occurred within 2 hours post-dose across all subjects.

Microbiology

The antibiotic component (tobramycin) in the combination is included to provide action against susceptible bacteria. In vitro studies have demonstrated that tobramycin is active against susceptible isolates of the following bacteria: Staphylococcus aureus (includes penicillin-resistant isolates), Staphylococcus epidermidis (includes penicillin-resistant isolates), Streptococci, including some Group A other beta-hemolytic species, some nonhemolytic species, and some Streptococcus pneumoniae. Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Haemophilus influenzae, Haemophilus aegypticus, Klebsiella pneumoniae, Moraxella lacunata, Morganella morganii, Neisseria perflava, Neisseria sicca, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa.

In vitro bacterial studies demonstrate that in some cases bacteria resistant to gentamicin are susceptible to tobramycin.

In the U.S.

• Tobradex
• Tobradex ST

In Canada

• Tobradex Ointment
• Tobradex Suspension

Available Dosage Forms:

• Ointment
• Suspension

Therapeutic Class: Aminoglycoside/Corticosteroid Combination

Pharmacologic Class: Adrenal Glucocorticoid

Chemical Class: Aminoglycoside

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of ophthalmic tobramycin and dexamethasone in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of ophthalmic tobramycin and dexamethasone in the elderly with use in other age groups.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Artemether
• Ataluren
• Desmopressin
• Praziquantel
• Rilpivirine
• Rotavirus Vaccine, Live

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Alcuronium
• Aldesleukin
• Amtolmetin Guacil
• Atracurium
• Bemiparin
• Boceprevir
• Bosutinib
• Bromfenac
• Bufexamac
• Bupropion
• Celecoxib
• Ceritinib
• Cholera Vaccine, Live
• Choline Salicylate
• Cidofovir
• Cisatracurium
• Clarithromycin
• Clonixin
• Cobicistat
• Colistimethate Sodium
• Conivaptan
• Daclatasvir
• Darunavir
• Dasatinib
• Decamethonium
• Desogestrel
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Dienogest
• Diflunisal
• Dipyrone
• Doxacurium
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Drospirenone
• Droxicam
• Efavirenz
• Elvitegravir
• Enzalutamide
• Estradiol
• Ethacrynic Acid
• Ethinyl Estradiol
• Ethynodiol
• Etodolac
• Etofenamate
• Etonogestrel
• Etoricoxib
• Etravirine
• Fazadinium
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Fosamprenavir
• Foscarnet
• Furosemide
• Gallamine
• Gestodene
• Hexafluorenium
• Ibuprofen
• Idelalisib
• Indomethacin
• Ixabepilone
• Ketoprofen
• Ketorolac
• Lapatinib
• Levonorgestrel
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Lysine
• Mannitol
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Mestranol
• Metocurine
• Mivacurium
• Morniflumate
• Nabumetone
• Nadroparin
• Naproxen
• Nepafenac
• Nevirapine
• Nifedipine
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nimodipine
• Norethindrone
• Norgestimate
• Norgestrel
• Olaparib
• Oxaprozin
• Oxyphenbutazone
• Pancuronium
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Pipecuronium
• Piperaquine
• Piroxicam
• Pixantrone
• Pranoprofen
• Proglumetacin
• Propyphenazone
• Proquazone
• Rapacuronium
• Ritonavir
• Rocuronium
• Rofecoxib
• Romidepsin
• Salicylic Acid
• Salsalate
• Saquinavir
• Sodium Salicylate
• Succinylcholine
• Sulindac
• Sunitinib
• Tacrolimus
• Telaprevir
• Tenoxicam
• Thalidomide
• Tiaprofenic Acid
• Ticagrelor
• Tolfenamic Acid
• Tolmetin
• Tubocurarine
• Ulipristal
• Valdecoxib
• Vancomycin
• Vecuronium
• Vincristine Sulfate Liposome
• Vortioxetine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alcuronium
• Aminoglutethimide
• Aprepitant
• Aspirin
• Atracurium
• Caspofungin
• Cisplatin
• Cyclosporine
• Fluindione
• Fosaprepitant
• Fosphenytoin
• Gallamine
• Hexafluorenium
• Licorice
• Metocurine
• Netupitant
• Ospemifene
• Pancuronium
• Phenobarbital
• Phenytoin
• Rifampin
• Rifapentine
• Saiboku-To
• Vecuronium
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Glaucoma—The dexamethasone in the eyedrops may cause glaucoma or make it worse if the eyedrops are used for a long time

• Herpes infection of the eye or
• Any other eye infection, including bacterial and fungal—The dexamethasone in the eyedrops may make existing infections worse or cause new infections

This section provides information on the proper use of a number of products that contain tobramycin and dexamethasone. It may not be specific to Tobradex ST. Please read with care.

For patients using the ophthalmic suspension (eye drops) form of this medicine:

• Always shake the container very well just before applying the eye drops.
• To use:
  • First, wash your hands. Tilt the head back and, pressing your finger gently on the skin just beneath the lower eyelid, pull the lower eyelid away from the eye to make a space. Drop the medicine into this space. Let go of the eyelid and gently close the eyes. Do not blink. Keep the eyes closed and apply pressure to the inner corner of the eye with your finger for 1 or 2 minutes to allow the medicine to be absorbed by the eye.
  • If you think you did not get the drop of medicine into your eye properly, use another drop.
  • To keep the medicine as germ-free as possible, do not touch the applicator tip to any surface (including the eye). Always keep the container tightly closed.

For patients using the ophthalmic ointment form of this medicine:

• To use:
  • First, wash your hands. Tilt the head back and, pressing your finger gently on the skin just beneath the lower eyelid, pull the lower eyelid away from the eye to make a space. Squeeze a thin strip of ointment into this space. A 1/2-inch strip of ointment is usually enough. Let go of the eyelid and gently close the eyes. Keep the eyes closed for 1 or 2 minutes to allow the medicine to come into contact with the irritation.
  • To keep the medicine as germ-free as possible, do not touch the applicator tip to any surface (including the eye). After using the eye ointment, wipe the tip of the ointment tube with a clean tissue. Do not wash the tip with water. Always keep the tube tightly closed.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For ophthalmic ointment dosage form:
  • For eye disorders:
    • Adults—Use about a 1/2-inch strip of ointment in the eye up to three or four times a day.
    • Children—Use and dose must be determined by your doctor.
• For ophthalmic suspension (eye drops) dosage form:
  • For eye disorders:
    • Adults—Use 1 or 2 drops in the eye every four to six hours. Your doctor may have you use the drops more frequently during the first day or two and will probably have you space the doses farther apart as the eye gets better.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Itching and swelling of eyelid
• redness of eye

• Delayed wound healing
• eye pain
• gradual blurring or loss of vision

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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®) are hypersensitivity and localized ocular toxicity, including eye pain, eyelids pruritus, eyelid edema, and conjunctival hyperemia. These reactions occur in less than 4% of patients. Similar reactions may occur with the topical use of other aminoglycoside antibiotics.

The reactions due to the steroid component are: increased intraocular pressure (IOP) with possible development of glaucoma, and infrequent optic nerve disorder; subcapsular cataract; and impaired 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.

Non-ocular adverse events occurring at an incidence of 0.5% to 1% included headache and increased blood pressure.

Pregnancy

Pregnanacy Category C. Corticosteroids have been shown 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 (equivalent to human doses of 16 and 32 mg/kg/day, respectively) and have revealed no evidence of impaired fertility or harm to the fetus. There are no adequate and well controlled studies in pregnant women. TOBRADEX® ST ophthalmic suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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® ST is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Storage and Handling

Patients should be instructed to store the bottle upright and away from light. Shake well before using.

Avoid Contamination

Patients should be instructed not to touch dropper tip to any surface, as this may contaminate the contents.

Contact Lens Wear

Contact lenses should not be worn during the use of this product.

Alcon Laboratories, Inc.

Fort Worth, Texas 76134 USA

Printed in USA

U.S. Patent No. 7,795,316

©2008, 2011 Alcon, Inc.

9006383-0111

Applies to dexamethasone / tobramycin ophthalmic: ophthalmic ointment, ophthalmic suspension

Hypersensitivity

Frequency not reported: Hypersensitivity[Ref]

Ocular

Uncommon (0.1% to 1%): Eye pain, eye pruritus, ocular discomfort, ocular hypertension, conjunctival edema, increased intraocular pressure, eye irritation
Rare (less than 0.1%): Keratitis, eye allergy, blurred vision, dry eye, ocular hyperemia
Frequency not reported: Eyelid edema, erythema of the eyelid, mydriasis, increased lacrimation

Dexamethasone:
-Common (1% to 10%): Ocular hyperemia, erythema of eyelid, abnormal sensation in eye, eye pain
-Uncommon (0.1% to 1%): Eye pruritus, ocular discomfort, eye allergy, eyelid edema, conjunctivitis, glare, increased lacrimation, keratitis
-Frequency not reported: Optic nerve damage, posterior subcapsular cataract formation, fungal infections of the cornea, bacterial ocular infection

Tobramycin:
-Common (1% to 10%):
-Frequency not reported: Conjunctival erythema, ocular toxicity[Ref]

Other

Frequency not reported: Swelling face[Ref]

Dermatologic

Frequency not reported: Rash, pruritus[Ref]

General

The most commonly reported side effects were eye irritation, ocular hyperemia, erythema of eyelid, abnormal sensation in eye, ocular hyperemia, and eye pain.[Ref]

Gastrointestinal

Rare (less than 0.1%): Dysgeusia
Frequency not reported: Nausea, abdominal discomfort[Ref]

Immunologic

Dexamethasone:
-Frequency not reported: Delayed wound healing[Ref]

Nervous system

Uncommon (0.1% to 1%): Headache
Frequency not reported: Dizziness[Ref]

Respiratory

Uncommon (0.1% to 1%): Rhinorrhea, laryngospasm[Ref]

Some side effects of Tobradex ST may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.