Adverse reactions : תופעות לוואי

4.8      Undesirable effects

Summary of the safety profile
In clinical studies involving 2732 patients treated with Azopt 1% 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 disorders         Uncommon: dyspnoea, epistaxis, oropharyngeal pain, pharyngolaryngeal 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 disorders      Uncommon: back pain, muscle spasms, myalgia 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 conditions Uncommon: pain, chest discomfort, fatigue, feeling abnormal
Rare: chest pain, feeling jittery, asthenia, irritability
Not Known: peripheral oedema, malaise
Injury, poisoning and procedural complications         Uncommon: foreign body in eye 

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 Azopt 1% 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).

Azopt 1% 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 Azopt 1% 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 authorisation 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 https://sideeffects.health.gov.il