Composition
>1 ml of the drug contains: active ingredients: brimonidine tartrate-2 mg, brinzolamide-10 mg; excipients: carbomer 974 P, sodium chloride, mannitol, propylene glycol, tyloxapol, boric acid, benzalkonium chloride, sodium hydroxide and / or hydrochloric acid, purified water
Pharmacological action
Pharmacotherapy group: Anti-glaucoma drugs and myotics. Carbonic anhydrase inhibitors. Brinzolamide in combination with other drugs.
ATX code: S01EC 54
Pharmacological properties
Pharmacodynamics
Mechanism of action
Simbrinza® contains two active ingredients: brinzolamide and brimonidine tartrate. These two components reduce intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and intraocular hypertension (IOH) by suppressing the formation of aqueous humor in the ciliary body. Although both brinzolamide and brimonidine reduce IOP by suppressing the formation of watery moisture, their mechanisms of action are different.
Brinzolamide acts by inhibiting the enzyme carbonic anhydrase type 2 (KA-II) in the ciliary epithelium, which reduces the formation of bicarbonate ions, followed by a decrease in the passage of sodium and liquid through the ciliary epithelium, which leads to a decrease in the formation of watery moisture. Brimonidine, an alpha-2-adrenergic receptor agonist, inhibits the enzyme adenylate cyclase and inhibits CAMP-dependent formation of aqueous humor. In addition, the use of brimonidine leads to an increase in uveoscleral outflow.
Pharmacokinetics
Absorption rate
After topical application, brinzolamide is absorbed through the cornea. The substance also enters the systemic circulation, where it binds strongly to carbonic anhydrase in red blood cells. Brinzolamide plasma concentrations are very low. The blood half-life in humans is long (>100 days), due to binding to red blood cell carbonic anhydrase. Brimonidine is rapidly absorbed into the eye tissue after topical application. In studies on rabbits, the maximum concentration in eye tissues in most cases was reached in less than an hour. The maximum concentrations in human blood plasma are <1 ng / ml and are reached within The plasma elimination half-life is about 2-3 hours. With constant use, accumulation is not observed.
A clinical study examined the pharmacokinetics of Simbrinza® when administered topically 2 and 3 times a day in comparison with monotherapy with brinzolamide and brimonidine, used in the same dosage regimens.
The pharmacokinetics of brinzolamide and N-desethylbrinzolamide in whole blood at steady-state concentrations were similar when combined with Simbrinza and brinzolamide monotherapy. Similarly, the pharmacokinetics of brimonidine at steady state in plasma when using a fixed combination were similar to those observed with individual use of brimonidine, with the exception of the Simbrinza® twice-daily group, in which the average AUC0-12 hours was approximately 25% less than with monotherapy with brimonidine twice-daily.
Distribution
In studies on rabbits, the maximum concentrations of brinzolamide in eye tissues after topical application are achieved in the anterior segment of the eye: in the cornea, conjunctiva, watery moisture, iris and ciliary body. The long-term presence in the eye tissues is due to the binding of the drug to carbonic anhydrase. Brinzolamide is moderately bound (about 60%) to human plasma proteins.
Brimonidine shows an affinity for pigmented tissues of the eye, in particular, the iris and ciliary body, which is due to the known ability of the molecule to bind to melanin. However, clinical and preclinical safety data indicate that the drug is well tolerated and safe when used continuously.
Metabolism
Brinzolamide is metabolized by cytochrome P 450 isoenzymes in the liver, in particular, CYP3A4, CYP2A6, CYP2B6, CYP2C8 and CYP2C9. The main metabolite is N-Deethylbrinzolamide, followed by N-desmethoxypropyl and O-desmethyl metabolites, as well as an analog of N-propionic acid formed by oxidation of the Npropyl side chain of O-desmethylbrinzolamide. Brinzolamide and Ndesethylbrinzolamide do not inhibit cytochrome P 450 isoenzymes at concentrations at least 100 times higher than the maximum systemic concentrations.
Brimonidine is extensively metabolized by hepatic aldehyde oxidase to form 2-oxobrimonidine,3-oxobrimonidine, and 2,3-dioxobrimonidine, which are the main metabolites. Oxidative cleavage of the imidazoline ring to 5-bromo-6-guanidinoquinoxaline is also observed.
Deduction
Brinzolamide is mainly excreted unchanged in the urine. In humans,60% of brinzolamide and 6% of N-desethylbrinzolamide from the administered dose are determined in the urine. In rats, the drug was also shown to be excreted in bile (about 30% of the administered dose) mainly in the form of metabolites.
Brimonidine is mainly excreted in the urine as metabolites. In preclinical experiments in vivo, urinary metabolites accounted for 60% to 75% of the administered dose of the drug, both by oral and intravenous routes.
Linearity / non-linearity
The pharmacokinetics of brinzolamide are inherently non-linear due to saturable binding to carbonic anhydrase in whole blood and various tissues.
Exposure at steady state does not increase in proportion to the dose. In contrast, brimonidine exhibits linear pharmacokinetics over the clinical therapeutic dose range.
Relationship between pharmacokinetics and Pharmacodynamics
The drug Simbrinza is intended for local action inside the eye tissues. Evaluation of human intraocular exposure to effective doses is not possible.
The effect of pharmacokinetics and Pharmacodynamics of the drug in humans on IOP reduction has not been established.
Other special patient populations
No studies have been conducted to determine the effect of age, race, or impaired renal or hepatic function when using Simbrinza®.
A study of the use of brinzolamide in Japanese compared with patients of other nationalities showed similar systemic pharmacokinetics in both groups.
A study of brinzolamide in patients with impaired renal function showed that the systemic exposure of brinzolamide and N-desethylbrinzolamide in patients with moderate renal impairment is 1.6-2.8 times higher than that in patients with normal renal function. This increase in steady-state concentrations of the drug and its metabolites did not cause inhibition of erythrocyte carbonic anhydrase to levels associated with systemic side effects. However, the use of the combined drug is contraindicated in patients with severe renal impairment (creatinine clearance Cmax, AUC, and half-life of brimonidine are similar in elderly patients (>65 years) and younger adult patients. The effect of impaired renal and hepatic function on the systemic pharmacokinetics of brimonidine has not been evaluated. Given the low systemic exposure of brimonidine after topical ophthalmic use, it is assumed that changes in plasma exposure will not be clinically significant.
Children
The systemic pharmacokinetics of brinzolamide and brimonidine, alone or in combination, in paediatric patients have not been studied.
Indications
Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ophthalmic hypertension in whom monotherapy does not provide sufficient IOP reduction
Use during pregnancy and lactation
Pregnancy
Data on the use of Simbrinza® in pregnant women are not available or limited. Brinzolamide did not have a teratogenic effect in rats and rabbits after systemic use.
In studies of oral use of brinzolamide in animals, no direct negative effect on reproductive function was found. In animal studies, brimonidine passed through the placenta and in limited quantities entered the bloodstream of the embryo. It is not recommended to use Simbrinza® during pregnancy and in women of reproductive age who do not use reliable contraceptive measures.
Breast-feeding
It has not been established whether Simbrinza® is excreted in breast milk in women. Available pharmacodynamic / toxicological data from animal studies have shown that minimal amounts of brinzolamide are released into breast milk after oral use. Brimonidine is excreted in breast milk after oral use.
Simbrinza should not be used during breast-feeding.
Fertility
Preclinical data showed no effect of brinzolamide or brimonidine on fertility.
There are no data on the effect of Simbrinza® on fertility with topical ophthalmic use in humans.
Contraindications
Hypersensitivity to active or auxiliary substances, or to sulfonamides:
– During therapy with monoamine oxidase (MAO)inhibitors;- When using antidepressants that affect noradrenergic transmission (for example, tricyclic antidepressants and mianserin);- Severe renal impairment; – Hyperchloremic acidosis;- Newborns and children under 2 years of age;
With caution:
– A history of angle-closure glaucoma;- Liver function disorders;- Corneal disorders;- Severe, unstable and / or uncontrolled cardiovascular diseases;- Depression;- Cerebral or coronary insufficiency, Raynaud’s syndrome, orthostatic hypotension or obliterating thrombangiitis;- Pregnancy and breast-feeding period (seesection “Use during pregnancy and lactation”); – Children aged 2 to 18 years due to insufficient data on efficacy and safety;- When used concomitantly with substances that depress the central nervous system;- When used in combination with drugs that may affect the metabolism and uptake of circulating amines;- When combined with antihypertensive agents and(or) cardiac glycosides;- With simultaneous treatment (or dose adjustment) with systemic drugs (regardless of the dosage form) that may interact with alpha-adrenergic agonists or interfere with the manifestation of their activity;- Wearing contact lenses; – Patients at risk of impaired renal function.
Side effects
In clinical trials using Simbrinza ® 2 times a day, the most common adverse reactions were eye hyperemia and allergic reactions from the eyes, occurring in approximately 6-7% of patients, and dysgeusia (bitter or unusual taste in the mouth after instillation), observed in approximately 3% of patients. The safety profile of Simbrinza® was similar to that of its individual components (brinzolamide 10 mg / ml and brimonidine 2 mg / ml).
The following adverse reactions were reported during clinical trials with Simbrinza ® 2 times a day, as well as during clinical trials and post-marketing surveillance with the use of individual components, brinzolamide and brimonidine.
Adverse reactions are classified according to the following classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare(≥1/10000, <1/1000), very rare ( Within each group, the frequency of occurrence of undesirable reactions is presented in descending order of their severity.
Infectious and parasitic diseases: infrequently-nasopharyngitis 2, pharyngitis 2, sinusitis 2; frequency unknown-rhinitis 2.
Disorders of the blood and lymphatic system: infrequently-a decrease in the number of red blood cells 2, an increased level of chlorides 2.
Immune system disorders: infrequently – hypersensitivity reactions 3.
Mental disorders: infrequently-apathy 2, depression 2.3, depressed mood 2, insomnia 1, decreased libido 2, nightmares 2, nervousness 2.
Nervous system disorders: often-drowsiness 1, dizziness 3, dysgeusia 1; Infrequently-headache 1, motor dysfunction 2, amnesia 2, memory impairment 2, paresthesia 2; very rarely-syncope 3; frequency unknown-tremor 2, hypesthesia 2, ageusia 2.
Visual disorders: often-allergic reaction from the eyes 1, keratitis 1, eye pain 1, eye discomfort 1, blurred vision 1, visual impairment 3, eye hyperemia 1, conjunctival pallor 3; infrequently – corneal erosion 1, corneal edema 2, blepharitis 1, corneal deposits (precipitates)1, violations of the conjunctiva (papillae)1, photophobia 1, photopsia 2,2 eye swelling, swelling of the century,1,1 swelling of the conjunctiva, dry eyes 1, discharge from the eyes 1, decreased visual acuity 2, silenceisgolden 1,2 pterygium, erythema century 1, meibomian 2,2 diplopia, eye pain at bright light 2, hypesthesia of the eye 2, the pigmentation of the sclera 2,2 subconjunctival cyst, discomfort in the eyes 1, asthenopia 1; very rarely – uveitis 3, cramps 3; frequency unknown – blurred vision 2, maduras 2.
Hearing disorders and labyrinth disorders: infrequently-dizziness 1, tinnitus 2.
Cardiac disorders:infrequently-cardiorespiratory distress 2, angina 2, arrhythmia 3, palpitation sensation 2.3, irregular heart rate 2, bradycardia 2.3, tachycardia 3.
Vascular disorders: infrequently-a decrease in blood pressure 1; very rarely-an increase in blood pressure 3.
Violations of the respiratory system, chest and mediastinum: infrequently – shortness of breath 2, bronchial hyperreactivity 2, pharyngeal-laryngeal pain 2, dry throat 1,2, cough, epistaxis,2, congestion of the upper respiratory tract 2, nasal congestion,1,2 runny nose, irritation of the pharynx 2, dryness in the nasal cavity 1, postnatally syndrome 1, sneezing 2;frequency unknown – asthma 2.
Gastrointestinal disorders: often-dry mouth 1; infrequently-dyspepsia 1, esophagitis 2, abdominal discomfort 1, diarrhea 2, vomiting 2, nausea 2, frequent bowel movements 2, flatulence 2, oral hypesthesia 2, oral paresthesia. 1
Disorders of the liver and biliary tract: frequency unknown-deviation of liver function indicators from the norm 2.
Skin and subcutaneous tissue disorders: infrequently-contact dermatitis 1, urticaria 2, rash 2, maculopapular rash 2, generalized pruritus 2, alopecia 2, skin compaction 2; frequency unknown-facial edema 3, dermatitis 2.3, erythema 2.3.
Musculoskeletal and connective tissue disorders: infrequently-back pain 2, muscle spasms 2, myalgia 2; frequency unknown-arthralgia 2, limb pain 2.
Renal and urinary tract disorders: infrequently-kidney pain 2
Genital and breast disorders: infrequently-erectile dysfunction 2;
General disorders and disorders at the injection site: infrequently-pain 2, chest discomfort 2, deterioration of well-being 2, anxiety 2, irritability 2, drug residues 1; frequency unknown-chest pain 2, peripheral edema 2.3.
Note
1 Adverse reactions observed with the use of Simbrinza®.2 additional adverse reactions observed with brinzolamide monotherapy. 3 additional adverse reactions observed with brimonidine monotherapy.
Description of individual adverse reactions
Dysgeusia was the most common systemic adverse reaction associated with the use of Simbrinza® (3.4%). This is probably due to eye drops entering the nasopharynx through the nasolacrimal canal and is mainly due to the presence of brinzolamide in the composition of Simbrinza®. Occlusion of the nasolacrimal canal or slight closing of the eyelids after instillation may reduce the frequency of this effect (see the section “Dosage and use”).
Simbrinza ® contains brinzolamide, a sulfonamide carbonic anhydrase inhibitor that penetrates the systemic circulation. Effects from the gastrointestinal tract, nervous system, blood system, kidneys and metabolism are mainly associated with the systemic action of carbonic anhydrase inhibitors. Topical use of carbonic anhydrase inhibitors may result in the same adverse reactions as oral use.
Adverse reactions associated with the content of brimonidine in the composition of Simbrinza® include the development of allergic reactions from the eyes, increased fatigue and / or drowsiness, as well as dry mouth. The use of brimonidine is associated with a minimal reduction in blood pressure. Some patients who received Simbrinza® experienced a decrease in blood pressure similar to that observed with brimonidine alone.
Interaction
Special studies of drug interactions with Simbrinza® have not been conducted. Simbrinza® is contraindicated in patients receiving monoamine oxidase inhibitors and antidepressants that affect noradrenergic transmission (for example, tricyclic antidepressants and mianserin) (see section “Contraindications”). Tricyclic antidepressants may impair the ability of Simbrinza to reduce IOP.
Caution is recommended when used concomitantly with substances that depress the central nervous system (alcohol, barbiturates, opiates, sedatives or anaesthetics) due to the possibility of developing an additive or potentiating effect.
There are no data on the concentration of circulating catecholamines after the use of Simbrinza®. However, caution is recommended when treating patients receiving drugs that may affect the metabolism and uptake of circulating amines (for example, chlorpromazine, methylphenidate, reserpine, serotonin-norepinephrine reuptake inhibitors). Drugs of the alpha-adrenergic agonist class (for example, brimonidine tartrate) they can reduce your heart rate and lower your blood pressure. Following use of Simbrinza, some patients experienced a slight decrease in blood pressure. Caution is recommended when Simbrinza is co-administered with antihypertensive medications and / or cardiac glycosides.
Caution is recommended when starting concomitant treatment (or changing the dose) with drugs with systemic action (regardless of the drug form), which may interact with alpha-adrenergic agonists or interfere with their activity, i. e. agonists or antagonists of adrenergic receptors (for example, isoprenaline, prazosin).
Brinzolamide is a carbonic anhydrase inhibitor that, despite being applied topically, penetrates the systemic circulation. Acid-base balance disorders have been reported with oral carbonic anhydrase inhibitors. Possible interactions should be considered in patients receiving Simbrinza. The known systemic effects of carbonic anhydrase inhibitors are likely to increase in patients receiving the oral carbonic anhydrase inhibitor ibrinzolamide for topical use. Concomitant use of Simbrinza and oral carbonic anhydrase inhibitors is not recommended.
Cytochrome P-450 isoenzymes responsible for brinzolamide metabolism include CYP3A4 (main), CYP2A6, CYP2B6, CYP2C8, and CYP2C9. CYP3A4 inhibitors such as ketoconazole, itraconazole, clotrimazole, ritonavir, and troleandomycin are expected to inhibit the metabolism of brinzolamide involving CYP3A4. Caution is recommended when concomitantly using CYP3A4 inhibitors. However, the accumulation of brinzolamide is unlikely, since the main route of elimination is through cells. Brinzolamide is not an inhibitor of cytochrome P-450 isoenzymes.
How to take, course of use and dosage
The drug is intended for topical use.
In adults, the drug is used 1 drop of Simbrinza® in the conjunctival sac 2 times a day.
Shake the bottle well before use.
After applying the drug, to reduce the risk of developing systemic adverse reactions, it is recommended to close the eyelids and lightly press your finger on the area of projection of the lacrimal sacs at the inner corner of the eye for 2 minutes after instillation of the drug – this reduces the systemic absorption of the drug and increases the local effect. (see the section “Special Instructions”).
Do not touch the tip of the pipette bottle to the eyelids and other surfaces to avoid contamination of the solution. Close the bottle tightly after use. Simbrinza® can be used simultaneously with other topical ophthalmic medications to reduce intraocular pressure. If more than one topical ophthalmic drug is used, a minimum interval of 5 minutes should be observed between the use of the drugs.
If a dose is missed, treatment should be continued with the next dose according to the schedule. The dose should not exceed 1 drop in the affected eye(s) 2 times a day.
Special patient groups
Elderly patients (over 65 years of age)
No dose adjustment is required in patients over 65 years of age.
Use in patients with impaired liver and/or kidney function
The use of Simbrinza® in patients with impaired liver function has not been studied, so it is recommended to use the drug with caution in such patients(see the section “With caution”).
The use of Simbrinza has not been studied in patients with severe renal impairment (creatinine clearance).
Since brinzolamide in Simbrinza® and its metabolites are mainly excreted from the body by the kidneys, Simbrinza® is contraindicated in such patients (see the section “Contraindications”).
Children
The safety and efficacy of Simbrinza® in children and adolescents from 2 to 18 years of age have not been studied, so the use of the drug in this category of patients is not recommended (see the section “Contraindications “). Simbrinza® is contraindicated in newborns and children under 2 years of age for safety reasons (see section “Contraindications”).
Overdose
In case of overdose of Simbrinza®, symptomatic and supportive therapy should be performed. It is necessary to monitor the patient’s airway patency.
Due to the presence of brinzolamide in the composition of Simbrinza®, electrolyte imbalance, acidosis, and nervous system disorders may occur.
It is necessary to monitor the content of electrolytes in the blood serum (in particular, potassium) and blood pH.
Very limited information is available regarding the accidental ingestion of brimonidine as part of Simbrinza® in adult patients. To date, the only reported adverse event is a decrease in blood pressure. Hypotension episodes were reported to be accompanied by a rebound increase in blood pressure.
Overdose with other oral alpha-2 agonists has been reported to cause symptoms such as low blood pressure, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnea, hypotension, hypothermia, respiratory depression, and convulsions.
Children
Serious adverse events have been reported in children following accidental ingestion of brimonidine in Simbrinza. Patients experienced symptoms of CNS depression: temporary comatose or reduced level of consciousness, lethargy, drowsiness, hypotension, bradycardia, hypothermia, pallor, respiratory depression and apnea, which required hospitalization in the intensive care unit and intubation as indicated. All phenomena were reported to be reversible within 6-24 hours
Description
Homogeneous suspension of white or almost white color.
Special instructions
The drug should not be administered by injection. Patients should be instructed not to take Simbrinza orally.
Influence on the organ of vision
The use of Simbrinza® has not been studied in patients with angle-closure glaucoma and its use in such patients is not recommended. The possible effect of brinzolamide on corneal endothelial function in patients with corneal disorders has not been studied (especially in patients with a small number of endothelial cells). Also, the use of the drug in patients who wear contact lenses has not been studied, and therefore careful monitoring of such patients is recommended when using brinzolamide, since carbonic anhydrase inhibitors can affect corneal hydration, and wearing contact lenses can increase the risk of corneal damage. Careful monitoring of patients with corneal disorders, including those with diabetes mellitus or corneal dystrophy, is recommended. Simbrinza® can be used when wearing contact lenses under close supervision (see the section “Benzalkonium chloride” below).
Brimonidine tartrate may cause allergic reactions from the eyes. If allergic reactions occur, treatment with the drug should be discontinued. There are reports of delayed hypersensitivity reactions from the eye with the use of brimonidine tartrate, in some cases occurring with an increase in IOP.
Potential effects after discontinuation of treatment with Simbrinza® have not been studied, in particular, the duration of the drug’s effect on IOP levels has not been evaluated. After stopping the use of brinzolamide, the effect on reducing IOP is expected to persist for 5-7 days. The decrease in IOP with brimonidine may last longer.
System effects
Simbrinza ® contains brinzolamide, a sulfonamide carbonic anhydrase inhibitor that, despite topical application, penetrates the systemic circulation. Topical use of sulfonamides may cause the same adverse reactions as systemic use. If there are signs of a serious hypersensitivity reaction, the drug should be discontinued immediately.
Cardiac disorders
Following use of Simbrinza, some patients experienced a slight decrease in blood pressure. Caution is recommended when concomitantly using antihypertensive drugs and / or cardiac glycosides, as well as in patients with severe or unstable and uncontrolled cardiovascular diseases (see the section “Interaction with other drugs”).
Simbrinza should be used with caution in patients with depression, cerebrovascular insufficiency or coronary insufficiency, Raynaud’s syndrome, orthostatic hypotension or obliterating thrombangiitis.
Acid-base balance disorders
Acid-base balance disorders have been reported with oral carbonic anhydrase inhibitors. Simbrinza ® contains brinzolamide, a carbonic anhydrase inhibitor that, despite topical application, penetrates the systemic circulation. When Simbrinza® is applied topically, the same adverse reactions may occur as when using oral carbonic anhydrase inhibitors (i. e., acid-base balance disorders) (see the section “Interaction with other drugs”).
The drug should be used with caution in patients at risk of impaired renal function due to the possible risk of developing metabolic acidosis. Simbrinza®is contraindicated in patients with severe renal impairment (see section “Contraindications”).
Impaired liver function
The use of Simbrinza® has not been studied in patients with impaired liver function; caution should be exercised when treating such patients (see section “Dosage and use”).
Ability to concentrate your attention
Oral carbonic anhydrase inhibitors may impair the ability to perform tasks that require concentration and/or physical coordination in elderly patients. The drug Simbrinza® penetrates the systemic circulation, so these phenomena can be observed with topical application of the drug (see the section “Effects on the ability to drive vehicles, mechanisms”).
Benzalkonium chloride
Simbrinza ® contains benzalkonium chloride, which can irritate the eyes and change the color of soft contact lenses. Avoid contact with soft contact lenses. Patients should be instructed to remove their contact lenses before instilling Simbrinza and wait at least 15 minutes before reinserting them.
Benzalkonium chloride has been reported to cause pinpoint keratopathy and / or toxic ulcerative keratopathy. With frequent or prolonged use, careful monitoring is required.
Use in children
The safety and efficacy of Simbrinza in children and adolescents aged 2 to 18 years have not been established.In cases where brimonidine eye drops are used as part of the treatment of congenital glaucoma in newborns and infants, symptoms of brimonidine overdose (such as loss of consciousness, decreased blood pressure, hypotension, bradycardia, hypothermia, cyanosis, and apnea) have been reported. Therefore, Simbrinza® is contraindicated in children under 2 years of age (see section “Contraindications”).
Treatment of children aged 2 years and older (especially those aged 2-7 years and / or weighing less than 20 kg) is not recommended due to possible side effects from the central nervous system (see the section “Overdose”).
Influence on the ability to drive vehicles and mechanisms
Simbrinza® has a moderate effect on the ability to drive vehicles and work with mechanisms.
Simbrinza® may cause dizziness, fatigue and / or drowsiness, which may have a negative effect on the ability to drive vehicles or work with mechanisms.
Temporary blurred vision or other visual disturbances may occur, which may affect the ability to drive vehicles or work with mechanisms.
Form of production
Eye drops. 5 ml each in a low-density polyethylene dropper bottle with a “Droptainer TM” dosing tip made of low-density polyethylene and a polypropylene lid. 1 or 3 vials together with the instructions for medical use in a cardboard pack. It is allowed to apply the control of the first opening on a cardboard pack.
Storage conditions
At a temperature not exceeding 30°C in the original packaging (bottle in a pack). Keep out of reach of children.
Shelf
life is 2 years. Do not use after the expiration date indicated on the package. Use within 28 days after opening the bottle.
Active ingredient
Brimonidine, Brinzolamide
Conditions of release from pharmacies
By prescription
Dosage form
eye drops
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