Latanoprostside effects

The following adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the label: Iris pigmentation changes Eyelid skin darkening Eyelash changes (increased length, thickness, pigmentation, and number of lashes) Intraocular inflammation (iritis/uveitis) Macular edema, including cystoid macular edema Most common adverse reactions (5-15%) from clinical trials are blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, and punctate keratitis. To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 609-250-7990 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Latanoprost ophthalmic solution was studied in three multicenter, randomized, controlled clinical trials. Patients received 50 mcg/mL latanoprost ophthalmic solution once daily or 5 mg/mL active-comparator (timolol) twice daily. The patient population studied had a mean age of 65±10 years. Seven percent of patients withdrew before the 6-month endpoint.

Table 1: Ocular Adverse Reactions and Ocular Signs/Symptoms Reported by 5-15% of Patients Receiving Latanoprost Symptom/Finding Adverse Reactions (incidence (%)) Latanoprost (n=460) Timolol (n=369) Foreign body sensation 13 8 Punctate keratitis 10 9 Stinging 9 12 Conjunctival hyperemia 8 3 Blurred vision 8 8 Itching 8 8 Burning 7 8 Increased pigmentation of the Iris 7 0 Less than 1% of the patients treated with latanoprost ophthalmic solution required discontinuation of therapy because of intolerance to conjunctival hyperemia.

Table 2: Adverse Reactions That Were Reported in 1-5% of Patients Receiving Latanoprost Adverse Reactions (incidence (%)) Latanoprost (n=460) Timolol (n=369) Ocular Events/Signs and Symptoms Excessive tearing 4 6 Eyelid discomfort/pain 4 2 Dry eye 3 3 Eye pain 3 3 Eyelid margin crusting 3 3 Erythema of the eyelid 3 2 Photophobia 2 1 Eyelid edema 1 3 Blepharitis 1 3 Systemic Events Upper respiratory tract infection/nasopharyngitis/influenza 3 3 Myalgia/arthralgia/back pain 1 0.5 Rash/allergic skin reaction 1 0.3

6.2 Postmarketing

Experience The following reactions have been identified during postmarketing use of latanoprost ophthalmic solution in clinical practice. Because they are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to latanoprost, or a combination of these factors, include: Nervous System Disorders: Dizziness; headache; toxic epidermal necrolysis Eye Disorders: Eyelash and vellus hair changes of the eyelid (increased length, thickness, pigmentation, and number of eyelashes); keratitis; corneal edema and erosions; intraocular inflammation (iritis/uveitis); macular edema, including cystoid macular edema; trichiasis; periorbital and lid changes resulting in deepening of the eyelid sulcus; iris cyst; eyelid skin darkening; localized skin reaction on the eyelids; conjunctivitis; pseudopemphigoid of the ocular conjunctiva. Respiratory, Thoracic and Mediastinal Disorders: Asthma and exacerbation of asthma; dyspnea Gastrointestinal Disorders: Nausea; vomiting Skin and Subcutaneous Tissue Disorders: Pruritis Infections and Infestations: Herpes keratitis Cardiac Disorders: Angina; palpitations; angina unstable General Disorders and Administration Site Conditions: Chest pain