Prevention and treatment of inflammation and prevention of infection associated with
cataract surgery in adults and children aged 2 years and older.

Adults:
One drop instilled into the conjunctival sac(s) every 4 to 6 hours while the patient is awake.
During the initial 24 to 48 hours, the dosage may be increased to one drop every two hours
while the patient is awake. Dosing should continue for 14 days not to exceed a maximum of
24 days. Frequency should be decreased gradually as warranted by improvement in clinical
signs. Care should be taken not to discontinue therapy prematurely.
Use in the Elderly:
Clinical studies have indicated dosage modifications are not required for use in the elderly.

Paediatric population:
Optidex-T Ophthalmic Suspension may be used in children 2 years of age and older at the
same dose as in adults. Currently available data is described in section 5.1.
The safety and efficacy in children younger than 2 years of age have not been established,
and no data is available.
Shake the bottle well before use. To prevent contamination of the dropper tip and
suspension, care should be taken not to touch the eyelids, surrounding areas, or other
surfaces with the dropper tip of the bottle. Keep the bottle tightly closed when not in use.
In case of concomitant therapy with other topical ophthalmic medicinal products, an interval
of 10 minutes should be allowed between successive applications.

Epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella and other viral disease of the cornea and conjunctiva. Mycobacterial infections of the eye caused by, but not limited to, acid-fast bacilli such as Mycobacterium tuberculosis, Mycobacterium leprae, or Mycobacterium avium. Fungal diseases of ocular structures. Untreated purulent infection of the eye. Hypersensitivity to tobramycin or dexamethasone or to any of the excipients.

Optidex-T Ophthalmic Suspension is for topical use only and not for injection or oral use.
Prolonged use (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 defects
in visual acuity and visual fields. Prolonged use of steroids may also result in posterior
subcapsular cataract formation. Prolonged use may also result in secondary ocular infections
due to suppression of host response. Acute purulent infections of the eye may be masked or
exacerbated by the presence of corticosteroids . In those diseases causing thinning of the
cornea or sclera, perforation has been known to occur with topical steroids. 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.
Sensitivity to topically applied aminoglycosides may occur in some patients. If sensitivity
does occur, discontinue use.
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. Contact lenses should be removed before
instillation and not reinserted for at least 15 minutes.

No specific interactions studies were performed with Optidex-T Ophthalmic Suspension.

Pregnancy:
There are no adequate data from the use of Optidex-T Ophthalmic Suspension 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, Optidex-T Ophthalmic Suspension
should only be used when the potential benefit justifies the potential risks.

Lactation:
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. Optidex-T Ophthalmic
Suspension should not be used during breast-feeding unless the potential benefit outweighs
the potential risk.

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.

In clinical studies involving over 600 patients, Optidex-T Ophthalmic Suspension was
administered up to six times daily. No serious ophthalmic or systemic adverse reactions
related to Optidex-T Ophthalmic Suspension or components of the combination were
reported in clinical studies. The most frequently reported treatment-related undesirable
effect with Optidex-T Ophthalmic Suspension was eye irritation (burning upon instillation)
(0.8%).
The following adverse reactions have been reported with Optidex-T Ophthalmic Suspension
or one of its components either during clinical trials or during postmarketing experience:
Common: >1/100 to < 1/10; Uncommon: > 1/1000 to ≤ 1/100.
Nervous system disorders:
Optidex-T Ophthalmic Suspension:
Uncommon: headache.*
Dexamethasone ophthalmic suspension:
Common: headache.*

Eye disorders:
Optidex-T Ophthalmic Suspension :
Uncommon: ocular irritation,* eye pain,* eye pruritus,* ocular hyperaemia,* ocular
discomfort,* ocular hypertension,* eye allergy, keratitis,* foreign body sensation in eyes,
conjunctival oedema, blurred vision,* dry eye.
Tobramycin ophthalmic solution:
Common: ocular hyperaemia,* eye pain.*
Uncommon: eye pruritus,* ocular discomfort,* eye allergy, eyelid oedema,* conjunctivitis,*
glare, increased lacrimation,* keratitis.*
Dexamethasone ophthalmic suspension:
Common: eye irritation,* ocular hyperaemia,* erythema of eyelid, abnormal sensation in
eye.*
Respiratory, thoracic, and mediastinal disorders:
Optidex-T Ophthalmic Suspension:
Uncommon: rhinorrhoea,* laryngospasm .
Dexamethasone ophthalmic suspension:
Common: postnasal drip.
Investigations:
Optidex-T Ophthalmic Suspension:
Uncommon: increased intraocular pressure.*
* These adverse reactions were also observed with Optidex-T Ophthalmic Suspension
during postmarketing.
A review of all spontaneous postmarketing adverse events since the launch of Optidex-T Ophthalmic Suspension has indicated no change in the safety profile based upon the
evaluation of all ocular, systemic and pharmacological class effects.

A topical overdose of Optidex-T Ophthalmic Suspension may be flushed from the eye(s)
with lukewarm tap water.

Pharmacotherapeutic group: Anti-inflammatory agents and anti-infectives in combination,
corticosteroids and anti-infectives in combination
ATC code: S01C A01
Dexamethasone:
The efficacy of corticosteroids for the treatment of inflammatory conditions of the eye is
well established. Corticosteroids achieve their anti-inflammatory effects through suppression
of vascular endothelial cell adhesion molecules, cyclooxygenase I or II, and cytokine
expression. This action culminates in a reduced expression of pro-inflammatory mediators
and the suppression of adhesion of circulating leukocytes to the vascular endothelium,
thereby preventing their migration into inflamed ocular tissue. Dexamethasone has marked
anti-inflammatory activity with reduced mineralocorticoid activity compared with some
other steroids, and is one of the most potent anti-inflammatory agents.
Tobramycin:
Tobramycin is a potent, broad-spectrum, rapidly bactericidal aminoglycoside antibiotic. It
exerts its primary effect on bacterial cells by inhibiting polypeptide assembly and synthesis
on the ribosome. Tobramycin in this combination provides antibacterial protection against
susceptible bacteria.
The following MIC breakpoints, separating susceptible from intermediate susceptible
organisms, and intermediate susceptible from resistant organisms, are suggested: S ( < 4
μg/ml, R ( > 8 μg/ml). The prevalence of resistance may vary geographically and with time
for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local
prevalence of resistance is such that the utility of the agent in at least some types of
infections is questionable. The following information gives only an approximate guidance
on probabilities whether bacteria will be susceptible to tobramycin in Optidex-T Ophthalmic
Suspension.
The breakpoint definitions classifying isolates as susceptible or resistant are useful in
predicting clinical efficacy of antibiotics that are administered systemically. However, when
the antibiotic is administered in very high concentrations topically directly on the site of
infection, these breakpoint definitions may not be applicable. Most isolates that would be
classified as resistant by systemic breakpoints are indeed successfully treated topically.
In vitro studies have shown tobramycin to be active against most strains of common ocular
pathogens and common skin flora bacteria as listed in the Table below:

Categories Frequency of Acquired Resistance in Europe SENSITIVE SPECIES Aerobic Gram-Positive Microorganisms Corynebacterium species 0-3% Staphylococcus aureus Methicillin -S a 0-3% Staphylococcus epidermidis Methicillin -S a 0-28% Other Coagulase-negative Staphylococci 0-40% Aerobic Gram-Negative Microorganisms Acinetobacter species 0% Citrobacter species Escherichia coli 0% Enterobacter species 0% Haemophilus influenzae 0% Klebsiella species 0 %

Moraxella species 0% Proteus species 0% Pseudomonas aeruginosa 0% MODERATELY SUSCEPTIBLE SPECIES (in vitro, intermediate susceptibility) Aerobic Gram-Negative Microorganisms Serratia marcescens INHERENTLY RESISTANT SPECIES Aerobic Gram-Positive Microorganisms Enterococcus species Staphylococcus aureus Methicillin –R a 50 – 70% Staphylococcus epidermidis Methicillin –R a 30 – 40% Streptococcus pneumoniae Streptococcus species Aerobic Gram-negative microorganisms Burkholderia cepacia Stenotrophomonas maltophilia Anaerobic microorganisms Strict anaerobic bacteria Others Chlamydia species Mycoplasma species Rickettsia species

a Methicillin-susceptible (S), Methicillin-resistant (R). The beta-lactam (i.e., methicillin;
penicillin) resistance phenotype is unrelated to the aminoglycoside resistance phenotype and
both are unrelated to the virulence phenotypes. Some methicillin-resistant (R) S. aureus
strains (MRSA) are susceptible to tobramycin (MIC: S <4); conversely some strains of
methicillin–susceptible (S) S. aureus (MSSA) are resistant to tobramycin (MIC: S >8).
The frequency of methicillin resistance (R) may be up to 50 % of all staphylococci in some
European countries.
Paediatric Population
The safety and efficacy of Optidex-T Ophthalmic Suspension in children have been
established by broad clinical experience, but only limited data are available. In a clinical
study of Optidex-T Ophthalmic Suspension suspension for the treatment of bacterial
conjunctivitis, 29 paediatric patients, ranging in age from 1 to 17 years, were treated with 1
or 2 drops of Optidex-T Ophthalmic Suspension every 4 or 6 hours for 5 or 7 days. In this
study, differences in the safety profile between adult and paediatric patients were not
observed.
Other information
Cross-resistance between aminoglycosides (e.g., gentamicin and tobramycin) is due to the
specificity of the enzyme modifications, Adenyltransferase (ANT) and Acetyltransferase
(ACC). However, cross-resistance varies between the aminoglycoside antibiotics due to the
differing specificity of the various modifying enzymes. The most common mechanism of
acquired resistance to aminoglycosides is antibiotic inactivation by plasmid and transposonencoded
modifying enzymes.

Tobramycin:
Animal studies have shown that tobramycin is absorbed into the cornea following ocular
administration. Following systemic administration to patients with normal renal function, a
plasma half-life of approximately 2 hours has been observed. Tobramycin is eliminated
almost exclusively by glomerular filtration with little if any biotransformation. Plasma
concentrations of tobramycin following the 2-day topical ocular regimen of Optidex-T
Ophthalmic Suspension were below the limit of quantification in most subjects or low
(≤0.25 microgram/ml).

Dexamethasone:
Following ocular administration, dexamethasone is absorbed into the eye with maximum
concentrations in the cornea and aqueous humour attained within 1-2 hours. The plasma
half-life of dexamethasone is approximately 3 hours. Dexamethasone is eliminated
extensively as metabolites. Systemic exposure to dexamethasone is low following topical
ocular administration of Optidex-T Ophthalmic Suspension. Peak dexamethasone plasma
levels after the last topical dose ranged from 220 to 888pg/ml (mean 555 ± 217pg/ml) after
administration of one drop of Optidex-T Ophthalmic Suspension to each eye four times per
day for two consecutive days.

The systemic toxicity profile of the individual actives is well established. Preclinical effects
of tobramycin and dexamethasone were observed only at exposures considered sufficiently
in excess of the maximum human exposure indicating little relevance to human use.

Disodium edetate
Hydroxypropyl methylcellulose
Benzalkonium chloride
Water for injection
Sodium chloride
Sodium sulphate anhydrous
Sulphuric acid 5N sol. or Sodium hydroxide 1N
Tyloxapol

Not applicable

2 years unopened. Discard after 30 days of opening.

Do not store above 30°C.

Primary:
Immediate Container: LDPE (Low-Density Polyethylene) Bottle 24-25 mm dia;
white (around 1% TiO2), round shape with rounded shoulder;
indented ring for tamper evident cap locking mechanism.
Cap: HDPE (High-Density Polyethylene) White (around 1% TiO2),
round shape with locking ring.
Nozzle: LDPE (Low-Density Polyethylene) Nozzle White
Secondary:
Outer carton: Grammage: Not Less Than 260 g/m2 Dimensions: 30 mm x
29 mm x 73 mm, Colored printed carton, text and colour
similar to approved artwork.
Label: 20 x 73mm, Colored printed self-adhesive labels with rounded
corners.
Insert/Leaflet: 50-60 g/m2 paper, both size printed.

No special requirements .
Any unused product or waste material should be disposed of in accordance with local
requirements.