Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
In clinical studies involving 2732 patients treated with brinzolamide as monotherapy or adjunctive therapy to timolol maleate 5 mg/ml, the most frequently reported treatment-related adverse reactions were: dysgeusia (6.0%) (bitter or unusual taste, see description below) and temporary blurred vision (5.4%) upon instillation, lasting from a few seconds to a few minutes (see also section 4.7).
Tabulated summary of adverse reactions
The following adverse reactions have been reported with brinzolamide 10mg/ml eye drops, suspension and are classified according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions were obtained from clinical trials and post-marketing spontaneous reports.


System Organ Classification                                   MedDRA Preferred Term (v.15.1) 
Infections and infestations             Uncommon: nasopharyngitis, pharyngitis, sinusitis Not Known: rhinitis

Blood and lymphatic system disorders    Uncommon: red blood cell count decreased, blood chloride increased 
Immune system disorders                 Not Known: hypersensitivity

Metabolism and nutrition disorders      Not known: decreased appetite 
Psychiatric disorders                   Uncommon: apathy, depression, depressed mood, libido decreased, nightmare, nervousness
Rare: insomnia

Nervous system disorders                Uncommon: motor dysfunction, amnesia, dizziness, paraesthesia, headache
Rare: memory impairment, somnolence
Not Known: tremor, hypoaesthesia, ageusia

Eye disorders                           Common: blurred vision, eye irritation, eye pain, foreign body sensation in eyes, ocular hyperaemia
Uncommon: corneal erosion, keratitis, punctate keratitis, keratopathy, deposit eye, corneal staining, corneal epithelium defect, corneal epithelium disorder, blepharitis, eye pruritus, conjunctivitis, eye swelling, meibomianitis, glare, photophobiadry eye, allergic conjunctivitis,
pterygium, scleral pigmentation, asthenopia, ocular discomfort, abnormal sensation in eye, keratoconjunctivitis sicca, subconjunctival cyst,
conjunctival hyperaemia, eyelids pruritus, eye discharge, eyelid margin crusting, lacrimation increased
Rare: corneal oedema, diplopia, visual acuity reduced, photopsia,
hypoaesthesia eye, periorbital oedema, intraocular pressure increased, optic nerve cup/disc ratio increased


Not Known: corneal disorder, visual disturbance, eye allergy, madarosis, eyelid disorder, erythema of eyelid

Ear and labyrinth disorders             Rare: tinnitus
Not Known: vertigo

Cardiac disorders                       Uncommon: cardio-respiratory distress, bradycardia, palpitations Rare: angina pectoris, heart rate irregular
Not Known: arrhythmia, tachycardia, hypertension, blood pressure increased, blood pressure decreased, heart rate increased

Respiratory, thoracic and mediastinal   Uncommon: dyspnoea, epistaxis, oropharyngeal pain, pharyngolaryngeal disorders                               pain, throat irritation, upper airway cough syndrome, rhinorrhoea, sneezing
Rare: bronchial hyperreactivity, upper respiratory tract congestion, sinus congestion, nasal congestion, cough, nasal dryness
Not Known: asthma

Gastrointestinal disorders              Common: dysgeusia
Uncommon: oesophagitis, diarrhoea, nausea, vomiting, dyspepsia, upper abdominal pain, abdominal discomfort, stomach discomfort, flatulence, frequent bowel movements, gastrointestinal disorder, hypoaesthesia oral, paraesthesia oral, dry mouth

Hepato-biliary disorders                Not Known: liver function test abnormal Skin and subcutaneous tissue disorders        Uncommon: rash, rash maculo-papular, skin tightness Rare: urticaria, alopecia, pruritus generalised
Not Known: Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis
(TEN) (see section 4.4), dermatitis, erythema

Musculoskeletal and connective tissue         Uncommon: back pain, muscle spasms, myalgia disorders
Not Known: arthralgia, pain in extremity

Renal and urinary disorders                   Uncommon: renal pain
Not Known: pollakiuria

Reproductive system and breast disorders      Uncommon: erectile dysfunction 
General disorders and administration site     Uncommon: pain, chest discomfort, fatigue, feeling abnormal conditions
Rare: chest pain, feeling jittery, asthenia, irritability
Not Known: peripheral oedema, malaise

Injury, poisoning and procedural              Uncommon: foreign body in eye complications

Description of selected adverse events
Dysgeusia (bitter or unusual taste in the mouth following instillation) was the most frequently reported systemic adverse reaction associated with the use of brinzolamide during clinical studies. It is likely caused by passage of the eye drops in the nasopharynx via the nasolacrimal canal. Nasolacrimal occlusion or gently closing the eyelid after instillation may help reduce the incidence of this effect (see also section 4.2).
brinzolamide is a sulphonamide inhibitor of carbonic anhydrase with systemic absorption. Gastrointestinal, nervous system, haematological, renal and metabolic effects are generally associated with systemic carbonic anhydrase inhibitors. The same type of adverse reactions that are attributable to oral carbonic anhydrase inhibitors may occur with topical administration.
No unexpected adverse reactions have been observed with brinzolamide when used as adjunctive therapy to travoprost.
The adverse reactions seen with the adjunctive therapy have been observed with each active substance alone.
Paediatric population
In small short-term clinical trials, approximately 12.5% of paediatric patients were observed to experience adverse reactions, the majority of which were local, non-serious ocular reactions such as conjunctival hyperaemia, eye irritation, eye discharge, and lacrimation increased (see also section 5.1).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form http://sideeffects.health.gov.il