Brimonidineside effects

The following serious adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Potential for Severe Respiratory or Cardiac Reactions Cardiac Failure Potentiation of Vascular Insufficiency Increased Reactivity to Allergens Potentiation of Muscle Weakness Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus Masking of Thyrotoxicosis Ocular Hypersensitivity Contamination of Topical Ophthalmic Products after Use Impairment of Beta-adrenergically Mediated Reflexes During Surgery Most common adverse reactions occurring in approximately 5% to 15% of patients included allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging. To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 866-770-7144 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, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution In clinical trials of 12 months duration with brimonidine tartrate/timolol maleate ophthalmic solution, the most frequent reactions associated with its use occurring in approximately 5% to 15% of the patients included: allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging. The following adverse reactions were reported in 1% to 5% of patients: asthenia, blepharitis, corneal erosion, depression, epiphora, eye discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, eyelid pruritus, foreign body sensation, headache, hypertension, oral dryness, somnolence, superficial punctate keratitis, and visual disturbance. Other adverse reactions that have been reported with the individual components are listed below. Brimonidine Tartrate (0.1% - 0.2%) Abnormal taste, allergic reaction, blepharoconjunctivitis, blurred vision, bronchitis, cataract, conjunctival blanching, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, dyspepsia, dyspnea, fatigue, flu syndrome, follicular conjunctivitis, gastrointestinal disorder, hypercholesterolemia, hypotension, infection (primarily colds and respiratory infections), hordeolum, insomnia, keratitis, lid crusting, lid disorder, muscular pain, nasal dryness, ocular allergic reaction, pharyngitis, photophobia, rash, rhinitis, sinus infection, sinusitis, superficial punctate keratopathy, tearing, upper respiratory symptoms, visual field defect, vitreous detachment, vitreous disorder, vitreous floaters, and worsened visual acuity. Timolol (Ocular Administration) Body as a whole: chest pain Cardiovascular: Arrhythmia, bradycardia, cardiac arrest, cardiac failure, cerebral ischemia, cerebral vascular accident, claudication, cold hands and feet, edema, heart block, palpitation, pulmonary edema, Raynaud’s phenomenon, syncope, and worsening of angina pectoris Digestive: anorexia, diarrhea, nausea Immunologic: Systemic lupus erythematosus Nervous System/Psychiatric: Increase in signs and symptoms of myasthenia gravis, insomnia, nightmares, paresthesia, behavioral changes and psychic disturbances including confusion, hallucinations, anxiety, disorientation, nervousness, and memory loss Skin: Alopecia, psoriasiform rash or exacerbation of psoriasis Hypersensitivity: Signs and symptoms of systemic allergic reactions, including anaphylaxis, angioedema, urticaria, and generalized and localized rash Respiratory: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), dyspnea, nasal congestion, respiratory failure, upper respiratory infections Endocrine: Masked symptoms of hypoglycemia in diabetes patients Special Senses: diplopia, choroidal detachment following filtration surgery, cystoid macular edema, decreased corneal sensitivity, pseudopemphigoid, ptosis, refractive changes, tinnitus Urogenital: Decreased libido, impotence, Peyronie’s disease, retroperitoneal fibrosis

6.2 Postmarketing

Experience The following reactions have been identified during postapproval use of brimonidine tartrate ophthalmic solutions, timolol ophthalmic solutions, or both in combination, in clinical practice. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Bradycardia, eyelid erythema extending to the cheek or forehead, hypersensitivity, iritis, keratoconjunctivitis sicca, miosis, nausea, skin reactions (including erythema, rash, and vasodilation), syncope, and tachycardia. Apnea, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine tartrate ophthalmic solutions. Oral Timolol/Oral Beta-blockers The following additional adverse reactions have been reported in clinical experience with ORAL timolol maleate or other ORAL beta-blocking agents and may be considered potential effects of ophthalmic timolol maleate: Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress Body as a whole: Decreased exercise tolerance, extremity pain, weight loss Cardiovascular: Vasodilatation, worsening of arterial insufficiency Digestive: Gastrointestinal pain, hepatomegaly, ischemic colitis, mesenteric arterial thrombosis, vomiting Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura Endocrine: Hyperglycemia, hypoglycemia;

Skin: Increased pigmentation, pruritus, skin irritation, sweating Musculoskeletal: Arthralgia Nervous System/Psychiatric: An acute reversible syndrome characterized by disorientation for time and place, decreased performance on neuropsychometrics, diminished concentration, emotional lability, local weakness, reversible mental depression progressing to catatonia, slightly clouded sensorium, vertigo Respiratory: Bronchial obstruction, rales Urogenital: Urination difficulties.