Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
AZOPT is a sulphonamide inhibitor of carbonic anhydrase and, although administered topically, is absorbed systemically. The same types of adverse reactions that are attributable to sulphonamides may occur with topical administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.
Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. Use with caution in patients with risk of renal impairment because the possible risk of metabolic acidosis (see section 4.2).
Brinzolamide has not been studied in pre-term infants (less than 36 weeks gestational age) or those less than 1 week of age. Patients with significant renal tubular immaturity or abnormalities should only receive brinzolamide after careful consideration of the risk benefit balance because of the possible risk of metabolic acidosis.
Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination. AZOPT is absorbed systemically and therefore this may occur with topical administration.
There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and AZOPT. The concomitant administration of AZOPT and oral carbonic anhydrase inhibitors has not been studied and is not recommended (see also section 4.5).
AZOPT was primarily evaluated in concomitant administration with timolol during adjunctive glaucoma therapy. Additionally the IOP-reducing effect of AZOPT as adjunctive therapy to the prostaglandin analogue travoprost has been studied. No long term data are available on the use of AZOPT as adjunctive therapy to travoprost(see also section 5.1).
There is limited experience with AZOPT in the treatment of patients with pseudoexfoliative glaucoma or pigmentary glaucoma. Caution should be used in treating these patients and close monitoring of intraocular pressure (IOP) is recommended. AZOPT has not been studied in patients with narrow-angle glaucoma and its use is not recommended in these patients.
The possible role of brinzolamide on corneal endothelial function has not been investigated in patients with compromised corneas (particularly in patients with low endothelial cell count). Specifically, patients wearing contact lenses have not been studied and careful monitoring of these patients when using brinzolamide is recommended, since carbonic anhydrase inhibitors may affect corneal hydration and wearing contact lenses might increase the risk for the cornea. Careful monitoring of patients with compromised corneas such as patients with diabetes mellitus or corneal dystrophies is recommended.
Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since AZOPT contains benzalkonium chloride, close monitoring is required with frequent or prolonged use in dry eye patients, or in conditions where the cornea is compromised.
AZOPT has not been studied in patients wearing contact lenses. AZOPT contains benzalkonium chloride which may cause eye irritation and is known to discolour soft contact lenses. Contact with soft contact lenses is to be avoided. Patients must be instructed to remove contact lenses prior to the application of AZOPT and wait at least 15 minutes after instillation of the dose before reinsertion.
Potential rebound effects following cessation of treatment with AZOPT have not been studied; the IOP-lowering effect is expected to last for 5-7 days.
The safety and efficacy of AZOPT in infants, children and adolescents aged 0 to 17 years have not been established and its use is not recommended in infants, children or adolescents.
Specific interaction studies with other medicinal products have not been performed with AZOPT.
In clinical studies, AZOPT was used concomitantly with prostaglandin analogues and timolol ophthalmic preparations without evidence of adverse interactions. Association between AZOPT and miotics or adrenergic agonists has not been evaluated during adjunctive glaucoma therapy.
AZOPT is a carbonic anhydrase inhibitor and, although administered topically, is absorbed systemically. Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. The potential for interactions must be considered in patients receiving AZOPT.
The cytochrome P-450 isozymes responsible for metabolism of brinzolamide include CYP3A4 (main), CYP2A6, CYP2C8 and CYP2C9. It is expected that inhibitors of CYP3A4 such as ketoconazole, itraconazole, clotrimazole, ritonavir and troleandomycin will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly. However, accumulation of brinzolamide is unlikely as renal elimination is the major route. Brinzolamide is not an inhibitor of cytochrome P-450 isozymes.
There are no or limited amount of data from the use of ophthalmic brinzolamide in pregnant women. Studies in animals have shown reproductive toxicity following systemic administration (see also section 5.3).
AZOPT is not recommended during pregnancy and in women of childbearing potential not using contraception.
It is unknown whether brinzolamide/metabolites are excreted in human milk following topical ocular administration. Animal studies have shown the excretion of minimal levels of brinzolamide in breast milk following oral administration.
A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from AZOPT therapy taking in to account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Animal studies with brinzolamide demonstrated no effect on fertility. Studies have not been performed to evaluate the effect of topical ocular administration of brinzolamide on human fertility.
AZOPT has a minor influence on the ability to drive and use machines.
Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines (see also section 4.8). If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.
Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination (see also section 4.4 and section 4.8).
In clinical studies involving 2732 patients treated with AZOPT 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).
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-respiratorv 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: 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 |
Dysgeusia (bitter or unusual taste in the mouth following instillation) was the most frequently reported systemic adverse reaction associated with the use of AZOPT 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 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 when used as adjunctive therapy to travoprost. The adverse reactions seen with the adjunctive therapy have been observed with each active substance alone.
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 suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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