MYLAN-LATANOPROST/TIMOLOL

1 Dosing Considerations • The use of MYLAN-LATANOPROST/TIMOLOL may be considered in patients who require both timolol and latanoprost. It has not been fully investigated whether patients who are adequately controlled with timolol twice daily plus latanoprost once daily will be effectively controlled with MYLAN-LATANOPROST/TIMOLOL once daily.

The IOP lowering effect of MYLAN-LATANOPROST/TIMOLOL once daily may be less than that seen with the concomitant administration of timolol twice daily and latanoprost once daily based on the results from a short term clinical trial.

For details of information obtained from the clinical trial, please refer to the 14 CLINICAL TRIALS section. MYLAN-LATANOPROST/TIMOLOL (latanoprost and timolol) Page 5 of 36 • MYLAN-LATANOPROST/TIMOLOL contains benzalkonium chloride which may be absorbed by contact lenses.

4 Drug-Drug Interactions) Therefore, contact lenses should be removed before installation of the eye drops and may be reinserted after 15 minutes. 2 Recommended Dose and Dosage Adjustment The recommended adult (including the elderly) dosage of MYLAN-LATANOPROST/TIMOLOL is one drop in the affected eye(s) once daily.

3 Pediatrics). 4 Administration When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity. 5 Missed Dose If one dose is missed, treatment should continue with the next dose as normal.

2 Clinical Trial Adverse Reactions). 2 Clinical Trial Adverse Reactions). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Combination therapy of latanoprost and timolol maleate was generally well tolerated.

No adverse events specific to the combination therapy of latanoprost and timolol maleate have been observed in clinical studies. The adverse events have been limited to those that were reported previously with latanoprost and/or timolol maleate.

Combination therapy of latanoprost and timolol maleate was evaluated for safety in 394 patients with open-angle glaucoma or ocular hypertension in three long-term studies. Two percent (2%) of patients discontinued therapy with combination therapy of latanoprost and timolol maleate due to adverse events.

Adverse events occurring at a frequency of ≥ 1% in three randomized, double blind comparative trials (004, 005 and 053) are presented in Tables 2 and 3. Table 2. 3) MYLAN-LATANOPROST/TIMOLOL (latanoprost and timolol) Page 13 of 36 * Despite a low frequency of reports, some AEs are included in the listing due to the implication of a potentially sight-threatening condition.

** A patient is counted only once per preferred term † Studies 004 and 005 included a 6 month and 053 a 12 month double-blinded period ‡ Includes darkening, lengthening and growing of eye lashes Table 3. 0) * A patient is counted only once per preferred term.

AEs that occurred in <1 % of the patients but were very similar to an event that did occur in ≥ 1% of the patients (such as “hypertension” and “hypertension aggravated”) are listed. Also, groups of mutually related AEs, where each AE may be reported in < 1%, but together they sum up to ≥ 1% (such as “diabetes mellitus aggravated” and “hyperglycaemia” together with “glucosuria”) are summarised.

General There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of ocular epithelial surface (see PATIENT MEDICATION INFORMATION).

There is no or limited experience with latanoprost in inflammatory, neovascular, chronic angle closure or congenital glaucoma, open angle glaucoma in pseudophakic patients and pigmentary glaucoma. 4 Drug-Drug Interactions). The effect on intraocular pressure or the known effects of systemic beta-adrenergic blocking agents may be exaggerated when MYLAN-LATANOPROST/TIMOLOL is given to patients already receiving an oral beta-blocking agent.

The use of two local beta- Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Ophthalmic Solution / fixed combination of latanoprost 50 mcg / mL and timolol 5 mg / mL as timolol maleate Benzalkonium chloride, disodium hydrogen phosphate anhydrous, hydrochloric acid, sodium chloride, sodium dihydrogen phosphate monohydrate, sodium hydroxide and water for injection MYLAN-LATANOPROST/TIMOLOL (latanoprost and timolol) Page 7 of 36 adrenergic blocking agents is not recommended.

There have been reports of paradoxical elevations in IOP following the concomitant ophthalmic administration of two prostaglandin analogs. Therefore, the use of two or more prostaglandins, prostaglandin analogs, or prostaglandin derivatives is not recommended.

Systemic Effects:

Like other topically applied ophthalmic agents, is absorbed systemically. Due to the beta-adrenergic component timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur including aggravation of Prinzmetal’s angina, aggravation of peripheral and central circulatory disorders, bradycardia, and hypotension.

Latanoprost and timolol maleate is contraindicated in patients with: • reactive airway disease including bronchial asthma, a history of bronchial asthma, or severe chronic obstructive pulmonary disease. • sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker, overt cardiac failure, or cardiogenic shock.

• known hypersensitivity to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.