Simbrinza

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 

SIMBRINZA 10 mg/mL + 2 mg/mL eye drops, suspension 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

1 mL of suspension contains 10 mg of brinzolamide and 2 mg of brimonidine tartrate equivalent to 

1.3 mg of brimonidine. 

 

Excipient with known effect 

 

Each mL of suspension contains 0.03 mg of benzalkonium chloride. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Eye drops, suspension (eye drops). 

 

White-to-off-white uniform suspension, pH 6.5 (approximately). 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Decrease of elevated intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular 

hypertension for whom monotherapy provides insufficient IOP reduction(see section 5.1). 

 

4.2 Posology and method of administration 

 

Posology 

 

Use in adults, including the elderly 

The recommended dose is one drop of SIMBRINZA in the affected eye(s) two times daily. 

 

Missed dose 

If a dose is missed, treatment should be continued with the next dose as planned. 

 

Hepatic and/or renal impairment 

SIMBRINZA has not been studied in patients with hepatic impairment and caution is therefore 

recommended in this population (see section 4.4). 

 

SIMBRINZA has not been studied in patients with severe renal impairment (CrCl <30 mL/min) or in 

patients with hyperchloraemic acidosis. Since the brinzolamide component of SIMBRINZA and its 

metabolite are excreted predominantly by the kidney, SIMBRINZA is contraindicated in such patients 

(see section 4.3). 

 

Paediatric population 

The safety and efficacy of SIMBRINZA in children and adolescents aged 2 to 17 years have not been 

established. No data are available. 

 

SIMBRINZA is contraindicated in neonates and infants aged less than 2 years in the decrease of 

elevated intraocular pressure (IOP) with open-angle glaucoma or ocular hypertension for whom 

monotherapy provides insufficient IOP reduction because of safety concerns (see section 4.3). 



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Method of administration 

 

For ocular use. 

 

Patients should be instructed to shake the bottle well before use. 

 

When nasolacrimal occlusion is used and the eyelids are closed for 2 minutes, systemic absorption is 

reduced. This may result in a decrease in systemic side effects and an increase in local activity (see 

section 4.4). 

 

To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, 

surrounding areas or other surfaces with the dropper tip of the bottle. Patients should be instructed to 

keep the bottle tightly closed when not in use. 

 

SIMBRINZA may be used concomitantly with other topical ophthalmic medicinal products to lower 

intraocular pressure. If more than one topical ophthalmic medicinal product is being used, the 

medicinal products must be administered at least 5 minutes apart. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1. 

Hypersensitivity to sulphonamides (see section 4.4). 

Patients receiving monoamine oxidase (MAO) inhibitor therapy (see section 4.5). 

Patients on antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and 

mianserin) (see section 4.5). 

Patients with severe renal impairment (see section 4.4). 

Patients with hyperchloraemic acidosis. 

Neonates and infants under the age of 2 years (see section 4.4). 

 

4.4 Special warnings and precautions for use 

 

The medicinal product should not be injected. Patients should be instructed not to swallow 

SIMBRINZA. 

 

Ocular effects 

 

SIMBRINZA has not been studied in patients with narrow-angle glaucoma and its use is not 

recommended in these patients. 

 

The possible effect 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 (for further 

instructions on wearing contact lenses, see below under “Benzalkonium chloride”). Careful 

monitoring of patients with compromised corneas, such as patients with diabetes mellitus or corneal 

dystrophies, is recommended. 

 

Brimonidine tartrate may cause ocular allergic reactions. If allergic reactions are observed, treatment 

should be discontinued. Delayed ocular hypersensitivity reactions have been reported with 

brimonidine tartrate, with some reported to be associated with an increase in IOP. 

 

The potential effects following cessation of treatment with SIMBRINZA have not been studied. While 

the duration of IOP-lowering effect for SIMBRINZA has not been studied, the IOP-lowering effect of 

brinzolamide is expected to last for 5-7 days. The IOP-lowering effect of brimonidine may be longer. 

 



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Systemic effects 

 

SIMBRINZA contains brinzolamide, 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, the use of this medicinal product should be discontinued. 

 

Cardiac disorders 

 

Following administration of SIMBRINZA, small decreases in blood pressure were observed in some 

patients. Caution is advised when using medicinal products such as antihypertensives and/or cardiac 

glycosides concomitantly with SIMBRINZA or in patients with severe or unstable and uncontrolled 

cardiovascular disease (see section 4.5). 

 

SIMBRINZA should be used with caution in patients with depression, cerebral or coronary 

insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangiitis obliterans. 

 

Acid/base disturbances 

 

Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. SIMBRINZA 

contains brinzolamide, an inhibitor of carbonic anhydrase, and although administered topically, is 

absorbed systemically. The same types of adverse reactions that are attributable to oral carbonic 

inhibitors (i.e. acid-base disturbances) may occur with topical administration (see section 4.5). 

 

SIMBRINZA should be used with caution in patients with risk of renal impairment because of the 

possible risk of metabolic acidosis. SIMBRINZA is contraindicated in patients with severe renal 

impairment (see section 4.3). 

 

Hepatic impairment 

 

SIMBRINZA has not been studied in patients with hepatic impairment; caution should be used in 

treating such patients (see section 4.2). 

 

Mental alertness 

 

Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness 

and/or physical coordination in elderly patients. SIMBRINZA is absorbed systemically and this may 

therefore occur with topical administration (see section 4.7). 

 

Paediatric population 

 

The safety and efficacy of SIMBRINZA in children and adolescents aged 2 to 17 years have not been 

established. Symptoms of brimonidine overdose (including loss of consciousness, hypotension, 

hypotonia, bradycardia, hypothermia, cyanosis and apnoea) have been reported in neonates and infants 

receiving brimonidine eye drops as part of medical treatment of congenital glaucoma. SIMBRINZA is 

therefore contraindicated in children below 2 years of age (see section 4.3). 

 

Treatment of children 2 years and above (especially those in the 2-7 age range and/or weighing 

<20 kg) is not recommended because of the potential for central nervous system-related side effects 

(see section 4.9). 

 

Benzalkonium chloride 

 

SIMBRINZA contains benzalkonium chloride which may cause eye irritation and is known to 

discolour soft contact lenses. Contact with soft contact lenses should be avoided. Patients must be 

instructed to remove contact lens prior to application of SIMBRINZA and wait at least 15 minutes 

before reinsertion. 



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Benzalkonium chloride has been reported to cause eye irritation and symptoms of dry eyes and may 

affect the tear film and corneal surface. It should be used with caution in dry eye patients and in 

patients whose cornea may be compromised. Patients should be monitored in case of prolonged use. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

No specific drug interaction studies have been performed with SIMBRINZA. 

 

SIMBRINZA is contraindicated in patients receiving monoamine oxidase inhibitors and in patients on 

antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin), 

(see section 4.3). Tricyclic antidepressants may blunt the ocular hypotensive response of 

SIMBRINZA. 

 

Caution is advised due to the possibility of an additive or potentiating effect with CNS depressants 

(e.g. alcohol, barbiturates, opiates, sedatives or anaesthetics). 

 

No data on the level of circulating catecholamines after SIMBRINZA administration are available. 

However, caution is advised in patients taking medicinal products which can affect the metabolism 

and uptake of circulating amines (e.g. chlorpromazine, methylphenidate, reserpine, serotonin-

norepinephrine reuptake inhibitors). 

 

Alpha adrenergic agonists (e.g. brimonidine tartrate), as a class, may reduce pulse and blood pressure. 

Following administration of SIMBRINZA, small decreases in blood pressure were observed in some 

patients. Caution is advised when using medicinal products such as antihypertensives and/or cardiac 

glycosides concomitantly with SIMBRINZA. 

 

Caution is advised when initiating (or changing the dose of) concomitant systemic medicinal products 

(irrespective of pharmaceutical form) which may interact with α-adrenergic agonists or interfere with 

their activity, i.e. agonists or antagonists of the adrenergic receptor (e.g. isoprenaline, prazosin). 

 

Brinzolamide 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 SIMBRINZA. 

 

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 topical brinzolamide. The 

concomitant administration of SIMBRINZA and oral carbonic anhydrase inhibitors is not 

recommended. 

 

The cytochrome P-450 isozymes responsible for metabolism of brinzolamide include CYP3A4 (main), 

CYP2A6, CYP2B6, 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. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

There are no or limited amount of data from the use of SIMBRINZA in pregnant women. 

Brinzolamide was not teratogenic in rats and rabbits, following systemic administration (oral gavage). 

Animal studies with oral brimonidine do not indicate direct harmful effects with respect to 

reproductive toxicity. In animal studies, brimonidine crossed the placenta and entered into the foetal 

circulation to a limited extent (see section 5.3). SIMBRINZA is not recommended during pregnancy 

and in women of childbearing potential not using contraception. 



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Breast-feeding 

 

It is unknown whether topical SIMBRINZA is excreted in human milk. Available 

pharmacodynamic/toxicological data in animals have shown that following oral administration, 

minimal levels of brinzolamide are excreted in breast milk. Brimonidine administered orally is 

excreted in breast milk. SIMBRINZA should not be used by women who are breast-feeding. 

 

Fertility 

 

Non-clinical data do not show any effects of brinzolamide or brimonidine on fertility. There are no 

data on the effect of topical ocular administration of SIMBRINZA on human fertility. 

 

4.7 Effects on ability to drive and use machines 
 

SIMBRINZA has a moderate influence on the ability to drive and use machines. 

 

SIMBRINZA may cause dizziness, fatigue and/or drowsiness, which may impair the ability to drive or 

use machines. 

 

Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. 

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 of elderly patients to perform tasks requiring 

mental alertness and/or physical coordination (see section 4.4). 

 

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 

Classification 

Adverse reactions 

Infections and 

infestations 

Uncommon: nasopharyngitis2, pharyngitis2, sinusitis2 

Not known: rhinitis2 

Blood and lymphatic 

system disorders 

Uncommon: red blood cells decreased2, blood chloride increased2 

Immune system disorders Uncommon: hypersensitivity3 

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

decreased2, nightmares2, nervousness2 



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System Organ 

Classification 

Adverse reactions 

Nervous system disorders Common: somnolence1, dizziness3, dysgeusia1 

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 

Not known: visual disturbances2, madarosis2 

Ear and labyrinth 

disorders 

Uncommon: vertigo1, tinnitus2 

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 and 

mediastinal disorders 

Uncommon: dyspnoea2, bronchial hyperactivity2, pharyngolaryngeal 

pain2, dry throat1, cough2, epistaxis2, upper respiratory tract congestion2, 

nasal congestion1, rhinorrhoea2, throat irritation2, nasal dryness1, 

postnasal drip1, sneezing2 

Not known: asthma2 

Gastrointestinal disorders Common: dry mouth1 

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 

tissue disorders 

Uncommon: dermatitis contact1, urticaria2, rash2, rash maculopapular2, 

pruritus generalised2, alopecia2, skin tightness2 

Not known: face oedema3, dermatitis2,3, erythema2,3 

Musculoskeletal and 

connective tissue 

disorders 

Uncommon: back pain2, muscle spasms2, myalgia2 

Not known: arthralgia2, pain in extremity2 

Renal and urinary 

disorders 

Uncommon: renal pain2 

Not known: pollakiuria2 

Reproductive system and 

breast disorders 

Uncommon: erectile dysfunction2 

General disorders and 

administration site 

conditions 

Uncommon: pain2, chest discomfort2, feeling abnormal2, feeling jittery2, 

irritability2, medication residue1 

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 

 



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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. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

If overdose with SIMBRINZA occurs treatment should be symptomatic and supportive. The patient’s 

airway should be maintained. 

 

Due to the brinzolamide component of SIMBRINZA, electrolyte imbalance, development of an 

acidotic state, and possible nervous system effects may occur. Serum electrolyte levels (particularly 

potassium) and blood pH levels must be monitored. 

 

There is very limited information regarding accidental ingestion with the brimonidine component of 

SIMBRINZA in adults. The only adverse reaction reported to date was hypotension. It was reported 

that the hypotensive episode was followed by rebound hypertension. 

 

Oral overdoses of other alpha-2-agonists have been reported to cause symptoms such as hypotension, 

asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnoea, hypotonia, 

hypothermia, respiratory depression and seizure. 

 

Paediatric population 

 

Serious adverse reactions following inadvertent ingestion with the brimonidine component of 

SIMBRINZA by paediatric subjects have been reported. The subjects experienced symptoms of CNS 

depression, typically temporary coma or low level of consciousness, lethargy, somnolence, hypotonia, 

bradycardia, hypothermia, pallor, respiratory depression and apnoea, and required admission to 

intensive care with intubation if indicated. All subjects were reported to have made a full recovery, 

usually within 6-24 hours. 

 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Ophthalmologicals, Antiglaucoma preparations and miotics, ATC 

code: S01EC54 

 

Mechanism of action 

 

SIMBRINZA contains two active substances: brinzolamide and brimonidine tartrate. These two 

components lower intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular 

hypertension (OHT) by suppressing the formation of aqueous humour from the ciliary process in the 

eye. Although both brinzolamide and brimonidine lower IOP by suppressing aqueous humour 

formation, their mechanisms of action are different. 

 

Brinzolamide acts by inhibiting the enzyme carbonic anhydrase (CA-II) in the ciliary epithelium that 

reduces the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport 

across the ciliary epithelium, resulting in decreased aqueous humour formation. Brimonidine, an 

alpha-2 adrenergic agonist, inhibits the enzyme adenylate cyclase and suppresses the cAMP-dependent 

formation of aqueous humour. Additionally, administration of brimonidine results in an increase in 

uveoscleral outflow. 

 

Pharmacodynamic effects 

 

Clinical efficacy and safety 

 

Monotherapy 

In a 6-month, controlled, contribution of elements clinical study enrolling 560 patients with open-

angle glaucoma (including pseudoexfoliation or pigment dispersion component) and/or ocular 

hypertension who, in the investigator’s opinion, were insufficiently controlled on monotherapy or 

already on multiple IOP-lowering medicinal products, and who had mean baseline diurnal IOP of 

26 mmHg, the mean diurnal IOP-lowering effect of SIMBRINZA dosed twice daily was 

approximately 8 mmHg. Statistically superior reductions in the mean diurnal IOP were observed with 

SIMBRINZA compared to brinzolamide 10 mg/ml or brimonidine 2 mg/ml dosed twice daily at all 

visits throughout the study (Figure 1). 

 



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Figure 1 Meana diurnal (9 AM, +2 hrs, +7 hrs) IOP change from baseline (mmHg) — 

Contribution of elements study 

 

 
aLeast squares means derived from a statistical model that accounts for study site, 9 AM baseline IOP stratum, 

and correlated IOP measurements within patient. 

All treatment differences (SIMBRINZA versus individual components) were statistically significant with 

p=0.0001 or less. 

 

Mean IOP reductions from baseline at each time point at each visit were greater with SIMBRINZA (6 

to 9 mmHg) than monotherapy with either brinzolamide (5 to 7 mmHg) or brimonidine (4 to 

7 mmHg). Mean percent IOP reductions from baseline with SIMBRINZA ranged from 23 to 34%. The 

percentages of patients with an IOP measurement less than 18 mmHg were greater in the 

SIMBRINZA group than in the Brinzolamide group at 9 of 12 assessments through Month 6 and were 

greater in the SIMBRINZA group than in the Brimonidine group at all 12 assessments through 

Month 6. At the +2 h time point (the time corresponding to the morning efficacy peak) for the primary 

efficacy visit at Month 3, the percentage of patients with an IOP less than 18 mmHg was 61.7% in the 

SIMBRINZA group, 40.1% in the Brinzolamide group, and 40.0% in the Brimonidine group. 

 

In a 6-month, controlled, non-inferiority clinical study enrolling 890 patients with open-angle 

glaucoma (including pseudoexfoliation or pigment dispersion component) and/or ocular hypertension 

who, in the investigator’s opinion, were insufficiently controlled on monotherapy or already on 

multiple IOP-lowering medicinal products, and who had mean baseline diurnal IOP of 26 to 

27 mmHg, non-inferiority of SIMBRINZA compared to brinzolamide 10 mg/mL + brimonidine 

2 mg/mL dosed concomitantly was demonstrated at all visits throughout the study with respect to 

mean diurnal IOP reduction from baseline (Table 1). 

 

Table 1 Comparison of mean diurnal IOP (mmHg) change from baseline – Non-inferiority 

study 

 

Visit SIMBRINZA 

Meana 

Brinzolamide + Brimonidine 

Meana 

Difference 

Meana (95% CI) 

Week 2 -8.4 (n=394) -8.4 (n=384) -0.0 (-0.4, 0.3) 

Week 6 -8.5 (n=384) -8.4 (n=377) -0.1 (-0.4, 0.2) 

Month 3 -8.5 (n=384) -8.3 (n=373) -0.1 (-0.5, 0.2) 

Month 6 -8.1 (n=346) -8.2 (n=330) 0.1 (-0.3, 0.4) 
a Least squares means derived from a statistical model that accounts for study site, 9 AM 

baseline IOP stratum, and correlated IOP measurements within patient 



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Mean IOP reductions from baseline at each time point at each visit with SIMBRINZA or the 

individual components administered concomitantly were similar (7 to 10 mmHg). Mean percent IOP 

reductions from baseline with SIMBRINZA ranged from 25 to 37%.The percentages of patients with 

an IOP measurement less than 18 mmHg were similar across study visits for the same time point 

through Month 6 in the SIMBRINZA and Brinzolamide + Brimonidine groups. At the +2 h time point 

(the time corresponding to the morning efficacy peak) for the primary efficacy visit at Month 3, the 

percentage of patients with an IOP less than 18 mmHg was 65.6% in the SIMBRINZA group and 

63.7% in the Brinzolamide + Brimonidine groups. 

 

Adjunct therapy 

 

Clinical data on the use of SIMBRINZA adjunctive to prostaglandin analogues (PGA) also showed 

superior IOP-lowering efficacy of SIMBRINZA + PGA compared with the PGA alone. In study 

CQVJ499A2401, SIMBRINZA + PGA (i.e. travoprost, latanoprost, or bimatoprost) demonstrated 

superior IOP-lowering efficacy from baseline compared to Vehicle + PGA after 6 weeks of treatment, 

with between-treatment difference in model-adjusted mean change from baseline in diurnal IOP 

of -3.44 mmHg (95% CI, -4.2, -2.7; p-value <0.001). 

 

Clinical data on the use of SIMBRINZA adjunctive to travoprost-timolol maleate fixed dose 

combination eye drops, solution also showed superior IOP-lowering efficacy of SIMBRINZA + 

travoprost-timolol maleate eye drops compared with the travoprost-timolol maleate alone. In study 

CQVJ499A2402, SIMBRINZA + travoprost-timolol maleate eye drops demonstrated superior IOP-

lowering efficacy from baseline compared to Vehicle + travoprost-timolol maleate eye drops after 

6 weeks of treatment, with between-treatment difference in model-adjusted mean change from 

baseline in diurnal IOP of -2.15 mmHg (95% CI, -2.8, -1.5; p-value <0.001). 

 

The safety profile of SIMBRINZA in adjunct therapy was similar to that observed with SIMBRINZA 

monotherapy. 

 

There are no efficacy and safety data for adjunct therapy beyond 6 weeks. 

 

Paediatric population 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

SIMBRINZA in all subsets of the paediatric population in the treatment of glaucoma and ocular 

hypertension (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Brinzolamide is absorbed through the cornea following topical ocular administration. The substance is 

also absorbed into the systemic circulation, where it binds strongly to carbonic anhydrase in red blood 

cells (RBCs). Plasma concentrations are very low. Whole blood elimination half-life is prolonged 

(>100 days) in humans due to RBC carbonic anhydrase binding. 

 

Brimonidine is rapidly absorbed into the eye following topical administration. In rabbits, maximum 

ocular concentrations were achieved in less than one hour in most cases. Maximum human plasma 

concentrations are <1 ng/mL and achieved within <1 hour. Plasma levels decline with a half-life of 

approximately 2-3 hours. No accumulation occurs during chronic administration. 

 

In a topical ocular clinical study comparing the systemic pharmacokinetics of SIMBRINZA 

administered two or three times daily to brinzolamide and brimonidine administered individually using 

the same two posologies, the steady-state whole blood brinzolamide and N-desethylbrinzolamide 

pharmacokinetics were similar between the combination product and brinzolamide administered alone. 

Likewise, the steady-state plasma pharmacokinetics of brimonidine from the combination were similar 



12 

to those observed for brimonidine administered alone, with the exception of the twice daily 

SIMBRINZA treatment group, for which the mean AUC0-12 hours was about 25% lower than that for 

brimonidine alone administered twice daily. 

 

Distribution 

 

Studies in rabbits showed that maximum brinzolamide ocular concentrations following topical 

administration are in the anterior tissues such as cornea, conjunctiva, aqueous humour and iris-ciliary 

body. Retention in ocular tissues is prolonged due to binding to carbonic anhydrase. Brinzolamide is 

moderately (about 60%) bound to human plasma proteins. 

 

Brimonidine exhibits affinity for pigmented ocular tissues, particularly iris-ciliary body, due to its 

known melanin binding properties. However, clinical and non-clinical safety data show it to be well-

tolerated and safe during chronic administration. 

 

Biotransformation 

 

Brinzolamide is metabolised by hepatic cytochrome P450 isozymes, specifically CYP3A4, CYP2A6, 

CYP2B6, CYP2C8 and CYP2C9. The primary metabolite is N-desethylbrinzolamide, followed by the 

N-desmethoxypropyl and O-desmethyl metabolites, as well as an N-propionic acid analogue formed 

by oxidation of the N-propyl side chain of O-desmethyl brinzolamide. Brinzolamide and N-

desethylbrinzolamide do not inhibit cytochrome P450 isozymes at concentrations at least 100-fold 

above maximum systemic levels. 

 

Brimonidine is extensively metabolised by hepatic aldehyde oxidase, with formation of 2-

oxobrimonidine, 3-oxobrimonidine and 2,3-dioxobrimonidine being the major metabolites. Oxidative 

cleavage of the imidazoline ring to 5-bromo-6-guanidinoquinoxaline is also observed. 

 

Elimination 

 

Brinzolamide is primarily eliminated in urine unchanged. In humans, urinary brinzolamide and N-

desethylbrinzolamide accounted for about 60 and 6% of the dose, respectively. Data in rats showed 

some biliary excretion (about 30%), primarily as metabolites. 

 

Brimonidine is primarily eliminated in the urine as metabolites. In rats and monkeys, urinary 

metabolites accounted for 60 to 75% of oral or intravenous doses. 

 

Linearity/non-linearity 

 

Brinzolamide pharmacokinetics are inherently non-linear due to saturable binding to carbonic 

anhydrase in whole blood and various tissues. Steady-state exposure does not increase in a dose-

proportional manner. 

 

In contrast, brimonidine exhibits linear pharmacokinetics over the clinically therapeutic dose range. 

 

Pharmacokinetic/pharmacodynamic relationship(s) 

 

SIMBRINZA is intended for local action within the eye. Assessment of human ocular exposure at 

efficacious doses is not feasible. The pharmacokinetic/pharmacodynamic relationship in humans for 

IOP-lowering has not been established. 

 

  



13 

Other special populations 

 

Studies to determine the effects of age, race, and renal or hepatic impairment have not been conducted 

with SIMBRINZA. A study of brinzolamide in Japanese versus non-Japanese subjects showed similar 

systemic pharmacokinetics between the two groups. In a study of brinzolamide in subjects with renal 

impairment, a 1.6- to 2.8-fold increase in the systemic exposure to brinzolamide and 

N-desethylbrinzolamide between normal and moderately renally-impaired subjects was demonstrated. 

This increase in steady-state RBC concentrations of substance-related material did not inhibit RBC 

carbonic anhydrase activity to levels that are associated with systemic side effects. However, the 

combination product is not recommended for patients with severe renal impairment (creatinine 

clearance <30 mL/minute). 

 

The Cmax, AUC and elimination half-life of brimonidine are similar in elderly (>65 years of age) 

subjects compared to young adults. The effects of renal and hepatic impairment on the systemic 

pharmacokinetics of brimonidine have not been evaluated. Given the low systemic exposure to 

brimonidine following topical ocular administration, it is expected that changes in plasma exposure 

would not be clinically relevant. 

 

Paediatric population 

 

The systemic pharmacokinetics of brinzolamide and brimonidine, alone or in combination, in 

paediatric patients have not been studied. 

 

5.3 Preclinical safety data 
 

Brinzolamide 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. 

 

Effects in non-clinical reproduction and development toxicity studies were observed only at exposures 

considered sufficiently in excess of the maximum human exposure indicating little relevance to 

clinical use. In rabbits oral, maternally toxic doses of brinzolamide of up to 6 mg/kg/day (261 times 

the recommended daily clinical dose of 23 µg/kg/day) revealed no effect on foetal development. In 

rats doses of 18 mg/kg/day (783 times the recommended daily clinical dose), but not 6 mg/kg/day, 

resulted in slightly reduced ossification of skull and sternebrae of foetuses. These findings were 

associated with metabolic acidosis with decreased body weight gain in dams and decreased foetal 

weights. Dose related decreases in foetal weights were observed in pups of dams given 2 to 

18 mg/kg/day. During lactation, the no adverse effect level in the offspring was 5 mg/kg/day. 

 

Brimonidine 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 

and development. 

 

 



14 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Benzalkonium chloride 

Propylene glycol 

Carbomer 974P 

Boric acid 

Mannitol 

Sodium chloride 

Tyloxapol 

Hydrochloric acid and/or sodium hydroxide (to adjust pH) 

Purified water 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

2 years. 

 

4 weeks after first opening. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 

 

8 mL round, opaque, low density polyethylene (LDPE) bottles with a LDPE dropper tip and white 

polypropylene screw cap (Drop-Tainer) containing 5 mL suspension. 

 

Carton containing 1 or 3 bottles. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

No special requirements for disposal. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/933/001-002 

 

 



15 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 18 July 2014 

Date of last renewal: 20 February 2019 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

 

  

http://www.ema.europa.eu/


16 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



17 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Alcon-Couvreur N.V. 

Rijksweg 14 

BE-2870 Puurs 

Belgium 

 

or 

 

Alcon Cusí, S.A. 

Camil Fabra 58 

08320 El Masnou 

Barcelona 

Spain 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are 

set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 

Directive 2001/83/EC and any subsequent updates published on the European medicines web-

portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

  



18 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



20 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 5 ml BOTTLE 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

SIMBRINZA 10 mg/ml + 2 mg/ml eye drops, suspension 

brinzolamide/brimonidine tartrate 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 ml of suspension contains 10 mg brinzolamide and 2 mg brimonidine tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

Benzalkonium chloride, propylene glycol, carbomer 974P, boric acid, mannitol, sodium chloride, 

tyloxapol, hydrochloric acid and/or sodium hydroxide (to adjust pH) and purified water. See leaflet for 

further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Eye drops, suspension 

 

1 x 5 ml 

3 x 5 ml 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Shake well before use. 

Read the package leaflet before use. 

Ocular use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 



21 

8. EXPIRY DATE 

 

EXP 

Discard 4 weeks after first opening. 

Opened: 

Opened (1): 

Opened (2): 

Opened (3): 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/933/001 1 x 5 ml 

EU/1/14/933/002 3 x 5 ml 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

simbrinza 

 

 

17. UNIQUE IDENTIFIER-2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 



22 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



23 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

SIMBRINZA 10 mg/ml + 2 mg/ml eye drops 

brinzolamide/brimonidine tartrate 

 

Ocular use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 ml 

 

 

6. OTHER 

 

 

  



24 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



25 

Package leaflet: Information for the user 

 

SIMBRINZA 10 mg/ml + 2 mg/ml eye drops, suspension 

brinzolamide/brimonidine tartrate 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, optometrist (optician) or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, optometrist (optician) or pharmacist. This 
includes any possible side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 
 

1. What SIMBRINZA is and what it is used for 

2. What you need to know before you use SIMBRINZA 

3. How to use SIMBRINZA 

4. Possible side effects 

5. How to store SIMBRINZA 

6. Contents of the pack and other information 

 

 

1. What SIMBRINZA is and what it is used for 

 

SIMBRINZA contains two active substances, brinzolamide and brimonidine tartrate. Brinzolamide 

belongs to a group of medicines called carbonic anhydrase inhibitors and brimonidine tartrate belongs 

to a group of medicines called alpha-2 adrenergic receptor agonists. Both substances work together to 

reduce pressure within the eye. 

 

SIMBRINZA is used to lower pressure in the eyes in adult patients (aged 18 years and over) who have 

eye conditions known as glaucoma or ocular hypertension and whose high pressure in the eyes cannot 

be controlled effectively by one medicine alone. 

 

 

2. What you need to know before you use SIMBRINZA 

 

Do not use SIMBRINZA 

- if you are allergic to brinzolamide or brimonidine tartrate or any of the other ingredients of this 

medicine (listed in section 6) 

- if you are allergic to sulphonamides (examples include medicines used to treat diabetes and 

infections and also diuretics (water tablets)) 

- if you are taking a monoamine oxidase (MAO) inhibitors (examples include medicines to treat 

depression or Parkinson’s disease) or certain antidepressants. You must inform your doctor if 

you are taking any antidepressant medicines 

- if you have severe kidney problems 

- if you have too much acidity in your blood (a condition called hyperchloraemic acidosis) 

- in babies and infants aged less than 2 years. 

 

  



26 

Warnings and precautions 

Talk to your doctor, optometrist (optician) or pharmacist before using SIMBRINZA if you have now 

or have had in the past: 

- liver problems 

- a type of high pressure in the eyes called narrow-angle glaucoma 

- dry eyes or cornea problems 

- coronary heart disease (symptoms can include chest pain or tightness, breathlessness or 

choking), heart failure, high or low blood pressure 

- depression 

- disturbed or poor blood circulation (such as Raynaud’s disease, Raynaud’s syndrome or cerebral 

insufficiency). 

 

If you wear soft contact lenses, do not use the drops with your lenses in. See section “Wearing contact 

lenses - SIMBRINZA contains benzalkonium chloride” below). 

 

Children and adolescents 

SIMBRINZA is not intended for use by children and adolescents aged below 18 years because it has 

not been studied in this age group. It is particularly important that the medicine is not used in children 

under the age of 2 years (see section ‘Do not use SIMBRINZA’ above) because it is unlikely to be 

safe. 

 

Other medicines and SIMBRINZA 

Tell your doctor, optometrist (optician) or pharmacist if you are using, have recently used, or might 

use any other medicines. 

 

SIMBRINZA can affect or be affected by other medicines you are using, including other eye drops for 

the treatment of glaucoma. 

 

Tell your doctor if you are taking or intend to take any of the following medicines: 

- medicines to lower blood pressure 
- heart medicines including digoxin (used to treat heart conditions) 
- other medicines for glaucoma that also treat altitude sickness known as acetazolamide, 

methazolamide and dorzolamide 

- medicines that can affect the metabolism, such as chlorpromazine, methylphenidate and 
reserpine 

- antiviral, antiretroviral (used to treat Human Immunodeficiency Virus (HIV)) or antibiotic 
medicines 

- antiyeast or antifungal medicines 
- monoamine oxidase (MAO) inhibitors, or antidepressants including amitriptyline, nortriptyline, 

clomipramine, mianserin, venlafaxine and duloxetine 

- anaesthetics 
- sedatives, opiates, or barbiturates 
 

You should also tell your doctor if the dose of any of your current medicines is changed. 

 

SIMBRINZA with alcohol 

If you regularly consume alcohol, ask your doctor, optometrist (optician) or pharmacist for advice 

before taking this medicine. SIMBRINZA can be affected by alcohol. 

 

Pregnancy and breast-feeding 

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor, 

optometrist (optician) or pharmacist for advice before taking this medicine. Women who may become 

pregnant are advised to use effective contraception during SIMBRINZA treatment. The use of 

SIMBRINZA is not recommended during pregnancy. Do not use SIMBRINZA unless clearly 

indicated by your doctor. 

 



27 

If you are breast-feeding, SIMBRINZA may pass into your milk. The use of SIMBRINZA is not 

recommended during breast-feeding. 

 

Driving and using machines 

You may find that your vision is blurred or abnormal for a time just after using SIMBRINZA. 

SIMBRINZA may also cause dizziness, drowsiness or tiredness in some patients. 

 

Do not drive or use machines until the symptoms are cleared. 

 

Wearing contact lenses - SIMBRINZA contains benzalkonium chloride 

 

This medicine contains 0.15 mg benzalkonium chloride in each 5 ml, which is equivalent to 

0.03 mg/ml. 

 

Benzalkonium chloride may be absorbed by soft contact lenses and may change the colour of the 

contact lenses. You should remove contact lenses before using this medicine and put them back 

15 minutes afterwards. Benzalkonium chloride may also cause eye irritation, especially if you have 

dry eyes or a disorder of the cornea (the clear layer at the front of the eye). If you feel abnormal eye 

sensation, stinging or pain in the eye after using this medicine, talk to your doctor. 

 

 

3. How to use SIMBRINZA 

 

Always use this medicine exactly as your doctor, optometrist (optician) or pharmacist has told you. 

Check with your doctor, optometrist (optician) or pharmacist if you are not sure. 

 

Only use SIMBRINZA for your eyes. Do not swallow or inject. 

 

The recommended dose is one drop in the affected eye or eyes two times a day. Use at the same time 

each day. 

 

How to use 

 

Wash your hands before you start. 

 

  
1 2 

 

Shake well before use. 

Twist off the bottle cap. After the cap is removed, if the tamper evident snap collar is loose, remove it 

before using the medicine. 

Do not touch the dropper with your fingers when opening or closing the bottle. It could infect the 

drops. 

Hold the bottle, pointing down, between your thumb and fingers. 

Tilt your head back. 

Pull down your lower eyelid with a clean finger, until there is a ‘pocket’ between the eyelid and your 

eye. The drop will go in here (picture 1). 

Bring the bottle tip close to the eye. Do this in front of a mirror if it helps. 

Do not touch your eye or eyelid, surrounding areas or other surfaces with the dropper. It could infect 

the drops. 

Gently press on the base of the bottle to release one drop of SIMBRINZA. 

Do not squeeze the bottle: it is designed so that a gentle press on the bottom is all that it needs 

(picture 2). 



28 

 

To reduce the amount of medicine that could come into the rest of the body after application of the eye 

drop, close your eye and apply gentle pressure to the corner of the eye next to the nose with a finger 

for at least 2 minutes. 

 

If you use drops in both eyes, repeat the steps for your other eye. It is not necessary to close and 

shake the bottle before you apply the drop in your other eye. Close the bottle cap firmly immediately 

after use. 

 

If you are using other eye drops as well as SIMBRINZA, wait at least five minutes between using 

SIMBRINZA and the other drops. 

 

If a drop misses your eye, try again. 

 

If you use more SIMBRINZA than you should 

Rinse your eye with warm water. Do not put in any more drops until it is time for your next regular 

dose. 

 

Adults who accidentally swallowed medicines containing brimonidine experienced a decreased heart 

rate, decreased blood pressure which may be followed by increased blood pressure, heart failure, 

difficulty breathing and effects in the nervous system. Should this happen, contact your doctor 

immediately. 

 

Serious side effects have been reported in children who accidently swallowed medicines containing 

brimonidine. Signs included sleepiness, floppiness, low body temperature, paleness and breathing 

difficulties. Should this happen, contact your doctor immediately. 

 

If SIMBRINZA has been accidentally swallowed then you should contact your doctor immediately. 

 

If you forget to use SIMBRINZA 

Continue with the next dose as planned. Do not use a double dose to make up for a forgotten dose. Do 

not use more than one drop in the affected eye(s) two times a day. 

 

If you stop using SIMBRINZA 

Do not stop using SIMBRINZA without first speaking to your doctor. If you stop using SIMBRINZA 

the pressure in your eye will not be controlled, which could lead to loss of sight. 

 

If you have any further questions on the use of this medicine, ask your doctor, optometrist (optician) or 

pharmacist. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

If you experience any of the following side effects, please stop using this medicine and seek immediate 

medical attention as these could be signs of a reaction to the medicine. The frequency of an allergic 

reaction to the medicine is not known (frequency cannot be estimated from the available data). 

 Severe skin reactions, including rash or redness or itching on your body or eyes 

 Trouble breathing 

 Chest pain, irregular heart beat 
 

Contact your doctor immediately if you develop extreme tiredness or dizziness. 

 

The following side effects have been observed with SIMBRINZA and other medicines containing 

brinzolamide or brimonidine alone. 

 



29 

Common side effects (may affect up to 1 in 10 people) 

 Effects in the eye: allergic conjunctivitis (eye allergy), eye surface inflammation, eye pain, eye 
discomfort, blurred or abnormal vision, eye redness 

 General side effects: drowsiness, dizziness, bad taste in mouth, dry mouth 
 

Uncommon side effects (may affect up to 1 in 100 people) 

 Effects in the eye: eye surface damage with loss of cells, inflammation of the eyelid, deposits on 
the eye surface, sensitivity to light, swelling of the eye (affecting the cornea or eyelid), dry eye, 

eye discharge, watery eye, eyelid redness, abnormal or decreased sensation in eye, tired eye, 

reduced vision, double vision, product particles in eyes. 

 General side effects: decreased blood pressure, chest pain, irregular heartbeat, slow or fast heart 
rate, palpitations, difficulty sleeping (insomnia), nightmares, depression, generalised weakness, 

headache, dizziness, nervousness, irritability, general feeling of being unwell, memory loss, 

shortness of breath, asthma, nose bleeds, cold symptoms, dry nose or throat, sore throat, throat 

irritation, cough, runny nose, stuffy nose, sneezing, sinus infection, chest congestion, ringing in 

ear, indigestion, intestinal gas or stomach ache, nausea, diarrhoea, vomiting, abnormal sensation 

in mouth, increased allergic symptoms on skin, rash, abnormal skin sensation, hair loss, 

generalised itching, increased blood chlorine levels, or decreased red blood cell count as seen in 

a blood test, pain, back pain, muscle pain or spasm, kidney pain such as lower back pain, 

decreased libido, male sexual difficulty. 

 

Very rare (may affect up to 1 in 10,000 people) 

 Effects in the eye: decreased pupil size 

 General side effects: fainting, increased blood pressure 
 

Not known (frequency cannot be estimated from the available data) 

 Effects in the eye: decreased growth of eyelashes 

 General side effects: tremor, decreased sensation, loss of taste, abnormal liver function values as 
seen in a blood test, swelling of the face, joint pain, frequent urination, chest pain, swelling of 

the extremities. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor, optometrist (optician) or pharmacist. This includes any 

possible side effects not listed in this leaflet. You can also report side effects directly via the national 

reporting system listed in Appendix V. By reporting side effects you can help provide more 

information on the safety of this medicine. 

 

 

5. How to store SIMBRINZA 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the bottle and the carton after “EXP”. 

The expiry date refers to the last day of that month. 

 

This medicine does not require any special storage conditions. 

 

Throw away the bottle 4 weeks after first opening to prevent infections and use a new bottle. Write 

down the date of opening on the carton in the space provided. 

 

Do not throw away any medicines via wastewater or household waste. Ask your optometrist (optician) 

or pharmacist how to throw away medicines you no longer use. These measures will help protect the 

environment. 

 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


30 

6. Contents of the pack and other information 

 

What SIMBRINZA contains 

- The active substances are brinzolamide and brimonidine tartrate. One ml of suspension contains 
10 mg of brinzolamide and 2 mg of brimonidine tartrate equivalent to 1.3 mg brimonidine. 

- The other ingredients are benzalkonium chloride (see section 2 “Wearing contact lenses - 
SIMBRINZA contains benzalkonium chloride”), propylene glycol, carbomer 974P, boric acid, 

mannitol, sodium chloride, tyloxapol, hydrochloric acid and/or sodium hydroxide and purified 

water. 

 

Tiny amounts of hydrochloric acid and/or sodium hydroxide are added to keep acidity levels (pH 

levels) normal. 

 

What SIMBRINZA looks like and contents of the pack 

SIMBRINZA eye drops, suspension, is a liquid (white-to-off-white suspension) supplied in a pack 

containing one or three 5 ml plastic bottles with screw cap. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Alcon-Couvreur N.V. 

Rijksweg 14 

B-2870 Puurs 

Belgium 

 

Manufacturer 

Alcon Cusí, S.A. 

Camil Fabra 58 

08320 El Masnou 

Spain 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA „Novartis Baltics“ Lietuvos filialas 

Tel: +370 5 269 16 50 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

 



31 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: + 421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

Latvija 

SIA “Novartis Baltics” 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. 

 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET