Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
In clinical trials involving SIMBRINZA dosed twice daily the most common adverse reactions were ocular hyperaemia and ocular allergic type reactions occurring in approximately 6-7% of patients, and dysgeusia (bitter or unusual taste in the mouth following instillation) occurring in approximately 3% of patients.


Tabulated summary of adverse reactions
The following adverse reactions have been reported during clinical studies with SIMBRINZA twice-daily dosing and during clinical studies and post-marketing surveillance with the individual components brinzolamide and brimonidine. They are classified according to the subsequent convention: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), 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.

System Organ             Adverse reactions
Classification

Infections and           Uncommon: nasopharyngitis2, pharyngitis2, sinusitis2 infestations
Not known: rhinitis2

Blood and lymphatic      Uncommon: red blood cells decreased2, blood chloride system disorders         increased2

Immune system            Uncommon: hypersensitivity3 disorders

Psychiatric disorders    Uncommon: apathy2, depression2,3, depressed mood2, insomnia1, libido decreased2, nightmares2, nervousness2

Nervous system           Common: somnolence1, dizziness3, dysgeusia1 disorders
Uncommon: headache1, motor dysfunction2, amnesia2,
memory impairment2, paraesthesia2

Very rare: syncope3

Not known: tremor2, hypoaesthesia2, ageusia2
Eye disorders            Common: eye allergy1, keratitis1, eye pain1, ocular discomfort1, blurred vision1, abnormal vision3, ocular hyperaemia1, conjunctival blanching3

Uncommon: corneal erosion1, corneal oedema2,
blepharitis1, corneal deposits (keratic precipitates)1,
conjunctival disorder (papillae)1, photophobia1, photopsia2, eye swelling2, eyelid oedema1, conjunctival oedema1, dry eye1, eye discharge1, visual acuity reduced2, lacrimation increased1, pterygium2, erythema of eyelid1,
meibomianitis2, diplopia2, glare2, hypoaesthesia eye2,
scleral pigmentation2, subconjunctival cyst2,abnormal sensation in eye1, asthenopia1

Very rare: uveitis3, miosis3

System Organ              Adverse reactions
Classification
Not known: visual disturbances2, madarosis2

Ear and labyrinth         Uncommon: vertigo1, tinnitus2 disorders

Cardiac disorders         Uncommon: cardio-respiratory distress2, angina pectoris2, arrhythmia3, palpitations2,3, heart rate irregular2,
bradycardia2,3, tachycardia3

Vascular disorders        Uncommon: hypotension1

Very rare: hypertension3
Respiratory, thoracic     Uncommon: dyspnoea2, bronchial hyperactivity2, and mediastinal           pharyngolaryngeal pain2, dry throat1, cough2, epistaxis2, disorders                 upper respiratory tract congestion2, nasal congestion1, rhinorrhoea2, throat irritation2, nasal dryness1, postnasal drip1, sneezing2

Not known: asthma2

Gastrointestinal          Common: dry mouth1 disorders
Uncommon: dyspepsia1, oesophagitis2, abdominal discomfort1, diarrhoea2, vomiting2, nausea2, frequent bowel movements2, flatulence2, hypoaesthesia oral2,
paraesthesia oral1
Hepatobiliary disorders   Not known: liver function test abnormal2 
Skin and subcutaneous     Uncommon: dermatitis contact1, urticaria2, rash2, rash tissue disorders          maculopapular2, pruritus generalised2, alopecia2, skin tightness2

Not known: Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) (see section 4.4), face oedema3, dermatitis2,3, erythema2,3

Musculoskeletal and       Uncommon: back pain2, muscle spasms2, myalgia2 connective tissue disorders                 Not known: arthralgia2, pain in extremity2 
Renal and urinary         Uncommon: renal pain2 disorders
Not known: pollakiuria2

Reproductive system       Uncommon: erectile dysfunction2 and breast disorders

System Organ            Adverse reactions
Classification

General disorders and   Uncommon: pain2, chest discomfort2, feeling abnormal2, administration site     feeling jittery2, irritability2, medication residue1 conditions
Not known: chest pain2, peripheral oedema2,3
1 adverse reaction observed with SIMBRINZA
2 additional adverse reaction observed with brinzolamide monotherapy 3 additional adverse reaction observed with brimonidine monotherapy 
Description of selected adverse reactions

Dysgeusia was the most common systemic adverse reaction associated with the use of SIMBRINZA (3.4%). It is likely to be caused by passage of the eye drops in the nasopharynx via the nasolacrimal canal and is mainly attributable to the brinzolamide component of SIMBRINZA. Nasolacrimal occlusion or gently closing the eyelid after instillation may help reduce the occurrence of this effect (see section 4.2).

SIMBRINZA contains brinzolamide, which 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 attributable to oral carbonic anhydrase inhibitors may occur with topical administration.

Adverse reactions commonly associated with the brimonidine component of SIMBRINZA include the development of ocular allergic type reactions, fatigue and/or drowsiness, and dry mouth. The use of brimonidine has been associated with minimal decreases in blood pressure. Some patients who dosed with SIMBRINZA experienced decreases in blood pressure similar to those observed with the use of brimonidine as monotherapy.

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