Instructions for Simbrinza eye drops dropper bottle 5 ml
Composition
active substances: 1 ml of suspension contains brinzolamide 10 mg and brimonidine tartrate 2 mg;
excipients: benzalkonium chloride, propylene glycol, carbomer 974P, boric acid, mannitol (E 421), sodium chloride, tyloxapol, hydrochloric acid and/or sodium hydroxide (for pH adjustment), purified water.
Dosage form
Eye drops.
Main physicochemical properties: homogeneous suspension of white or almost white color, pH 6.5 (approximately).
Pharmacotherapeutic group
Drugs used in ophthalmology. Antiglaucoma drugs and miotics. Carbonic anhydrase inhibitors. ATX code S01E C54.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Simbrinza® contains two active ingredients: brinzolamide and brimonidine tartrate. These two ingredients reduce intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and elevated intraocular pressure (IOP) by inhibiting the production of aqueous humor, although their mechanisms of action are different.
Brinzolamide acts by inhibiting the enzyme carbonic anhydrase (CA-II) in the ciliary body of the eye, reducing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport across the ciliary body, which leads to a decrease in the production of intraocular fluid. Brimonidine, an alpha-2-adrenergic agonist, inhibits the formation of adenylate cyclase and the production of intraocular fluid, which is caused by cAMP. In addition, the use of brimonidine leads to an improvement in the uveoscleral outflow of intraocular fluid.
Pharmacodynamic action
Clinical efficacy and safety
The mean daily IOP reduction with Simbrinza® twice daily was 8 mmHg in a 6-month, controlled, component-distribution mechanism clinical study in 560 patients with open-angle glaucoma (including pseudoexfoliative or pigment dispersion syndrome) and/or ocular hypertension who were inadequately controlled on monotherapy or multiple IOP-lowering medicinal products by the investigator and who had a mean daily baseline IOP of 26 mmHg. All patients had statistically significantly greater mean daily IOP reduction with Simbrinza® compared to brinzolamide 10 mg/ml or brimonidine 2 mg/ml twice daily at follow-up visits throughout the study.
The mean IOP reductions from baseline at each follow-up visit in patients receiving Simbrinza® were greater (6-9 mmHg) than those receiving brinzolamide (5-7 mmHg) or brimonidine (4-7 mmHg) monotherapy. The mean percentage IOP reductions after Simbrinza® ranged from 23-34%. The percentage of patients with IOP <18 mmHg was greater in the Simbrinza® group than in the brinzolamide group at follow-up visits 9 to 12 over the 6-month period and greater than in the brimonidine group at all 12 follow-up visits over the 6-month period. At month 3 of the study, the percentage of patients with 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 at the +2 hour time point (time corresponding to the morning peak of efficacy) at the primary efficacy assessment.
In a controlled 6-month clinical efficacy study involving 890 patients with open-angle glaucoma (including pseudoexfoliative or pigment dispersion syndrome) and/or ocular hypertension, in whom, in the opinion of the investigator, IOP was inadequately controlled with monotherapy or with multiple IOP-lowering medicinal products and who had a mean daily baseline IOP of 26-27 mmHg at all follow-up visits during the study, Simbrinza® was shown to be comparable in efficacy to brinzolamide 10 mg/ml + brimonidine 2 mg/ml co-administered (Table 1).
Table 1
Comparison of change in mean daily IOP (mmHg) with baseline values – Corresponding efficacy study
| Follow-up visit | Simbrinza®, mean valuea | Brinzolamide + brimonidine, average valuea | Difference, average valuea (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) |
At each follow-up visit, patients treated with Simbrinza® or its individual components had similar mean IOP reductions from baseline (7-10 mmHg). Mean IOP reductions with Simbrinza® ranged from 25% to 37%. Throughout the study, the percentage of patients with IOP <18 mmHg was similar in the Simbrinza® group and in the brimonidine and brinzolamide groups at the same time points during the 6-month study. At month 3, the percentage of patients with IOP <18 mmHg was similar. Hg was 65.6% in the Simbrinza® group and 63.7% in the brinzolamide + brimonidine groups at time point +2 hours (time corresponding to the peak of morning efficacy) in the primary efficacy test.
Use in children
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).
Pharmacokinetics
Absorption
After topical ocular administration, brinzolamide is absorbed through the cornea. It is also absorbed into the systemic circulation, where it binds strongly to carbonic anhydrase in erythrocytes. The concentration of this component in plasma is very low. The half-life in humans is longer (more than 100 days) due to binding to carbonic anhydrase in erythrocytes.
Brimonidine is rapidly absorbed into the eye after topical application. In rabbits, peak ocular concentrations were achieved in most cases less than 1 hour after application. Peak plasma concentrations in humans are < 1 ng/mL and are achieved within < 1 hour. Plasma levels decline over a half-life of approximately 2-3 hours. No accumulation occurs with prolonged use.
In a clinical study of topical ocular administration comparing the systemic pharmacokinetics of Simbrinza® administered twice or three times daily to brinzolamide or brimonidine administered alone, at the same dosing regimen, steady-state whole blood concentrations of brinzolamide and the pharmacokinetics of N-desethylbrinzolamide were similar when the combination was administered as well as when brinzolamide was administered alone. Similarly, the steady-state plasma pharmacokinetics of brimonidine with the combination were similar to those observed with brimonidine alone, except in the Simbrinza® twice daily group, where AUC0-12 hours was approximately 25% lower than with brimonidine administered alone twice daily.
Distribution
Results of studies in rabbits showed that the maximum concentration of brinzolamide in the eye after topical administration is observed in the tissues of the anterior segment of the eye, such as the cornea, conjunctiva, intraocular fluid, iris and ciliary body. Retention of the substance in the tissues of the eye is prolonged due to binding to carbonic anhydrase. Brinzolamide binds moderately to human plasma proteins (approximately 60%).
Brimonidine exhibits affinity for pigmented structures of the eye, particularly the iris and ciliary body, due to its known melanin binding properties. However, clinical and preclinical safety data have demonstrated that brimonidine is well tolerated and safe for long-term use.
Biotransformation
Brinzolamide is metabolized in the liver by cytochrome P450 isoenzymes, including CYP3A4, CYP2A6, CYP2B6, CYP2C8, and CYP2C9. The primary metabolite is N-desethylbrinzolamide, with subsequent metabolites being N-desmethoxypropyl and O-desmethyl, as well as an N-propionic acid analogue formed by oxidation of the N-propyl side chain of O-desmethylbrinzolamide. Brinzolamide and N-desethylbrinzolamide do not inhibit cytochrome P450 isoenzymes at concentrations 100 times higher than the maximum systemic exposure.
Brimonidine is extensively metabolized by aldehyde oxidase to form 2-oxobrimonidine, 3-oxobrimonidine, and 2,3-dioxobrimonidine (major metabolites). Oxidative cleavage of the imidazole ring to 5-bromo-6-guanidino-quinoxaline is also observed.
Breeding
Brinzolamide is excreted primarily in the urine as unchanged drug. In humans, the urinary excretion of brinzolamide and N-desethylbrinzolamide is 60% and 6% of the dose, respectively. Studies in rats also show that a small amount (approximately 30%) is excreted in the bile, primarily as metabolites.
Brimonidine is excreted primarily in the urine as metabolites. In rats and monkeys, the proportion of metabolites excreted in the urine is 60-75% of the oral or intravenous dose.
Linearity/nonlinearity
Pharmacokinetic/pharmacodynamic relationship
Simbrinza® is intended for topical ocular use. It is not possible to assess the effects on the human eye at effective doses. The pharmacokinetic/pharmacodynamic relationship in humans for IOP lowering has not been established.
Application to specific patient groups
Studies to determine the effect of Simbrinza® on age, race, and renal or hepatic impairment have not been conducted. The results of a study of brinzolamide in Japanese subjects compared to non-Japanese subjects demonstrated similar pharmacokinetic properties in both patient groups. Studies of brinzolamide in patients with renal impairment demonstrated a 1.6- to 2.8-fold increase in systemic exposure to brinzolamide and N-desethylbrinzolamide in patients with normal and moderate renal impairment. This increase in steady-state erythrocyte concentrations of the substance-bound material did not suppress erythrocyte carbonic anhydrase activity to levels associated with systemic adverse effects. However, the combination product is not recommended for use in patients with severe renal impairment (creatinine clearance < 30 mL/min).
The Cmax, AUC, and half-life of brimonidine are similar in elderly (> 65 years) and young subjects. The effect of renal or hepatic impairment on the systemic pharmacokinetics of brimonidine has not been evaluated. Given the low systemic exposure of brimonidine following topical ocular administration, changes in plasma concentrations are not expected to be clinically significant.
Use in children
The systemic pharmacokinetic properties of brinzolamide and brimonidine have not been studied in children when administered alone or in combination.
Indication
Reduction of elevated intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension in whom monotherapy has not resulted in sufficient reduction of intraocular pressure.
Contraindication
Hypersensitivity to the active substances or to any of the components of the drug.
Use of monoamine oxidase inhibitors (MAOIs) (see section "Interaction with other medicinal products and other types of interactions").
Use of antidepressants that affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin) (see section "Interaction with other medicinal products and other types of interactions").
Severe renal impairment (see section "Special warnings and precautions for use").
Hyperchloremic acidosis.
Newborns and infants under 2 years of age (see section "Special instructions").
Interaction with other medicinal products and other types of interactions
Specific drug interaction studies of Simbrinza® with other drugs have not been conducted.
Simbrinza® is contraindicated in patients receiving monoamine oxidase inhibitors and antidepressants that affect noradrenergic transmission (e.g., tricyclic antidepressants and mianserin) (see Contraindications). Tricyclic antidepressants may inhibit the intraocular pressure-lowering effects of Simbrinza®.
Caution should be exercised when used concomitantly with substances that depress the central nervous system (such as alcohol, barbiturates, opiates, sedatives, anesthetics) due to possible additive or potentiating effects.
There are no data on circulating catecholamine levels following administration of Simbrinza®. However, Simbrinza® should be used with caution in patients receiving medications that may affect the metabolism and accumulation of amines in the vascular system (e.g., chlorpromazine, methylphenidate, reserpine, serotonin-norepinephrine reuptake inhibitors).
Alpha-adrenergic agonists (e.g. brimonidine tartrate) may decrease heart rate and blood pressure as a class-specific effect. Some patients have experienced a small decrease in blood pressure after administration of Simbrinza®. Caution should be exercised when Simbrinza® is co-administered with antihypertensive drugs and/or cardiac glycosides.
Caution should be exercised when prescribing or adjusting the dose of other systemic medicinal products (regardless of dosage form) that may interact with alpha-adrenergic agonists or affect their function, i.e. adrenergic receptor agonists or antagonists (e.g. isoprenaline, prazosin) when used concomitantly with Simbrinza®.
Brinzolamide is a carbonic anhydrase inhibitor and despite topical administration is absorbed into the systemic circulation. Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. The possibility of drug interactions should be considered when prescribing Simbrinza® to patients.
The cytochrome P450 isoenzymes responsible for the metabolism of brinzolamide include CYP3A4 (major), CYP2A6, CYP2B6, CYP2C8 and CYP2C9. CYP3A4 inhibitors, such as ketoconazole, itraconazole, clotrimazole, ritonavir and troleandomycin, are expected to inhibit the metabolism of brinzolamide through their effects on CYP3A4. Caution should be exercised when concomitantly administering CYP3A4 inhibitors. However, accumulation of brinzolamide is unlikely as it is primarily excreted by the kidneys. Brinzolamide is not an inhibitor of cytochrome P450 isoenzymes.
Application features
This medicinal product is not intended for parenteral administration. Patients should be advised that Simbrinza® should not be administered orally.
Ophthalmological effects
Simbrinza® has not been studied in patients with angle-closure glaucoma, therefore its use in this patient population is not recommended.
The potential effects of brinzolamide on endothelial function in patients with corneal damage (particularly in patients with low endothelial cell counts) have not been studied. No direct studies have been conducted in patients wearing contact lenses, and close monitoring is recommended in such patients, as carbonic anhydrase inhibitors may affect corneal hydration and contact lens wear during treatment may increase the risk of corneal damage. Close monitoring is recommended in patients with impaired corneal function, such as diabetes mellitus or corneal dystrophy. Patients wearing contact lenses should only use Simbrinza® under medical supervision (see below, Benzalkonium chloride).
Brimonidine tartrate may cause allergic ocular reactions. If such reactions occur, treatment with the drug should be discontinued. Delayed-type ocular hypersensitivity reactions, some of which were accompanied by increased IOP, have been reported with the use of brimonidine tartrate.
Studies on the possible adverse reactions upon discontinuation of Simbrinza® have not been conducted. Although the duration of IOP reduction following Simbrinza® administration 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 last longer.
Systemic effect
Simbrinza® contains brinzolamide, a sulfonamide-type carbonic anhydrase inhibitor. Although the drug is administered topically, it is absorbed into the systemic circulation. The same types of adverse reactions as those seen with sulfonamides may occur with topical administration. The drug should be discontinued if signs of serious adverse reactions or hypersensitivity occur.
Cardiac disorders
Some patients have experienced a slight decrease in blood pressure after taking Simbrinza®. Particular caution should be exercised when Simbrinza® is used concomitantly with medicinal products such as antihypertensives and/or cardiac glycosides, and in patients with severe or unstable and uncontrolled cardiovascular disease (see section 4.5).
Simbrinza® should be administered with caution to patients suffering from depression, as well as to patients with cerebral or heart failure, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans.
Acid-base imbalance
Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. Simbrinza® contains brinzolamide, a carbonic anhydrase inhibitor, which, despite topical administration, is absorbed into the systemic circulation. Adverse reactions typical of oral carbonic anhydrase inhibitors may occur with topical administration (see section 4.5).
Due to the risk of metabolic acidosis, the drug should be used with caution in patients at risk of renal impairment. The drug is contraindicated for use in patients with severe renal impairment (see section "Contraindications").
Liver dysfunction
Simbrinza® has not been studied in patients with hepatic impairment, therefore caution should be exercised when using the drug in this category of patients (see section “Method of administration and dosage”).
Concentration and attention
Oral administration of carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination in elderly patients. Since the components of Simbrinza® are absorbed into the systemic circulation, such reactions are also possible with topical administration of the drug (see section "Ability to influence the speed of reactions when driving vehicles or using other mechanisms").
Simbrinza® eye drops contain benzalkonium chloride, which may cause eye irritation and is known to discolor soft contact lenses. Contact with soft contact lenses should be avoided. Therefore, patients should be advised to remove contact lenses before using Simbrinza® and to wait 15 minutes after instillation before reinserting contact lenses.
Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Patients should be closely monitored with frequent or prolonged use of the drops.
Use in children
The safety and efficacy of Simbrinza® in children aged 2 to 18 years have not been established. Cases of brimonidine overdose (including loss of consciousness, hypotension, hypotonia, bradycardia, hypothermia, cyanosis, and apnea) have been reported in neonates and young children receiving brimonidine eye drops for the treatment of congenital glaucoma. Therefore, Simbrinza® is contraindicated for use in children under 2 years of age (see Contraindications).
The use of the drug for the treatment of children aged 2 years and older (especially those aged 2-7 years and/or whose body weight is < 20 kg) is not recommended due to the possibility of adverse reactions from the central nervous system (see section "Overdose").
Ability to influence reaction speed when driving vehicles or other mechanisms
Simbrinza® may affect the ability to drive and use machines.
Simbrinza® may cause dizziness, fatigue and/or drowsiness, which may affect the ability to drive and use machines.
Temporary blurred vision or other visual disturbances may adversely affect the ability to drive or operate machinery. If blurred vision occurs during instillation, the patient should wait until vision clears before driving or operating machinery.
Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination in the elderly (see section "Special warnings and precautions for use").
Use during pregnancy or breastfeeding
Pregnancy
There are no or limited data on the use of Simbrinza® in pregnant women. When administered systemically, brinzolamide was not teratogenic in rats and rabbits. The results of studies of oral administration of brimonidine in animals did not indicate direct harmful effects on reproductive function. Animal studies have shown that brimonidine crosses the placenta and enters the fetal circulation in limited amounts. Therefore, the drug is not recommended for use during pregnancy and in women of childbearing potential not using contraceptives.
Breast-feeding
It is not known whether Simbrinza® is excreted in human milk following topical administration. Available pharmacodynamic and toxicological data in animals indicate that minimal amounts of brinzolamide are excreted in human milk following oral administration. Brimonidine is excreted in human milk following oral administration. Simbrinza® is not recommended for use in breast-feeding women.
Reproductive function
No effects of brinzolamide or brimonidine on reproductive function were observed in nonclinical studies. There are no data on the effects of Simbrinza® on human reproductive function when used topically.
Method of administration and doses
Doses
Use in adults, including elderly patients
The recommended dose is one drop of Simbrinza® in the affected eye(s) twice daily.
Use in patients with impaired liver and/or kidney function
The use of Simbrinza® in patients with impaired liver function has not been studied, therefore it is recommended to use this drug with caution in the treatment of this category of patients (see section "Special instructions for use").
Simbrinza® has not been studied in patients with severe renal impairment (creatinine clearance < 30 mL/min) or in patients with hyperchloremic acidosis. Since brinzolamide, the active substance, and its metabolites, are primarily excreted by the kidneys, Simbrinza® is contraindicated in these patients (see section 4.3).
Use in children
The safety and efficacy of the drug in children aged 2 to 18 years have not been established. There are no data on the use of the drug in children. Simbrinza® is not recommended for use in children (see section "Special instructions").
For safety reasons, Simbrinza® is contraindicated for the treatment of neonates and infants under 2 years of age (see section “Contraindications”).
Method of application
For ophthalmic use.
Systemic absorption is reduced by applying pressure to the nasolacrimal orifice or closing the eyelids for 2 minutes. This reduces systemic side effects and increases local activity (see section "Special instructions").
To prevent contamination of the dropper tip and contents of the bottle, care should be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip.
Patients should be advised to close the bottle tightly after using the drops.
Simbrinza® can be used concomitantly with other topical ophthalmic medicinal products to reduce intraocular pressure. If more than one topical ophthalmic medicinal product is used, the interval between their applications should be at least 5 minutes.
If a dose is missed, treatment should be continued with the next dose as per the treatment schedule. The dose should not exceed one drop in the affected eye(s) twice daily.
Children
The safety and efficacy of the drug in children aged 2 to 18 years have not been established. There are no data on the use of the drug in children. Simbrinza® is not recommended for use in children (see section "Special instructions").
Overdose
In the event of an overdose with Simbrinza®, treatment should be symptomatic and supportive. The patient's airway should be maintained.
Due to the presence of brinzolamide in Simbrinza®, electrolyte imbalance, acidosis and nervous system disorders may occur. In such cases, it is necessary to monitor serum electrolyte levels (especially potassium) and blood pH.
There is very limited data on the effects of accidental ingestion of the brimonidine component of Simbrinza® in adults. To date, the only adverse reaction reported has been a decrease in blood pressure. Rebound hypertension has also been reported following an episode of hypotension.
Oral overdose with other alpha-2-agonists has been reported to cause symptoms such as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmia, miosis, apnea, hypotension, hypothermia, respiratory failure, and convulsions.
Use in children
Serious adverse reactions have been reported in children following accidental ingestion of brimonidine, a component of Simbrinza®. Patients have experienced symptoms of CNS depression, reversible coma or depression of consciousness, lethargy, somnolence, hypotension, bradycardia, hypothermia, pallor, respiratory failure, and apnea, requiring intensive care with intubation if necessary. It has been reported that all patients generally recover fully within 6 to 24 hours.
Adverse reactions
In clinical studies with Simbrinza® administered twice daily, the most common adverse reactions were ocular hyperemia and allergic-type ocular reactions, occurring in approximately 6-7% of patients, and dysgeusia (bitter or unusual taste in the mouth after instillation) occurring in 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 have been reported in clinical studies with Simbrinza® administered twice daily, as well as in clinical studies and post-marketing experience with the individual components of the drug, brinzolamide and brimonidine. They are classified according to their frequency: 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) and rare (<1/10,000) or not known. Within each grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2
| Organ system classes | Adverse reactions |
| Infections and infestations | Uncommon: nasopharyngitis2, pharyngitis2, sinusitis2 Frequency unknown: rhinitis2 |
| Blood and lymphatic system disorders | Uncommon: decreased red blood cell count2, increased blood chloride2 |
| On the part of the immune system | Uncommon: hypersensitivity3 |
| From the psyche | Uncommon: apathy2, depression2,3, depressed mood2, insomnia1, decreased libido2, nightmares2, nervousness2 |
| From the nervous system | Common: somnolence1, dizziness3, dysgeusia1 Uncommon: headache1, coordination abnormal2, amnesia2, memory impairment2, paraesthesia2 Very rare: loss of consciousness3 Frequency not known: tremor2, hypoesthesia2, ageusia2 |
| From the organs of vision | Uncommon: corneal erosion1, corneal oedema2, blepharitis1, corneal precipitate1, conjunctival disorder1 (papillary), photophobia1, photopsia2, eye oedema2, eyelid oedema1, conjunctival oedema1, dry eye1, eye discharge1, visual acuity reduced2, lacrimation increased1, pterygium2, eyelid redness1, meibomianitis2, diplopia2, hypersensitivity to bright light2, hypoaesthesia2, scleral pigmentation2, subconjunctival cyst2, abnormal ocular sensitivity1, asthenopia1 Very rare: uveitis3, miosis3 Frequency unknown: visual impairment2, madarosis2 |
| Hearing and balance disorders | Uncommon: vertigo1, tinnitus2 |
From the side of the cardiovascular system | Uncommon: cardiorespiratory distress2, angina2, arrhythmia3, palpitations2,3, cardiac arrhythmia2, bradycardia2,3, tachycardia3, hypotension1 |
From the vascular system | Uncommon: hypotension1 Very rare: hypertension3 |
| Respiratory, thoracic and mediastinal disorders | Uncommon: dyspnoea2, bronchial hyperactivity2, throat and larynx pain2, dry throat1, cough2, epistaxis2, upper respiratory tract congestion2, nasal congestion1, rhinorrhea2, throat irritation2, nasal dryness1, nasopharyngeal mucus hypersecretion1, sneezing2 Frequency not known: asthma2 |
| From the digestive system | Common: dry mouth1 Uncommon: dyspepsia1, oesophagitis2, gastric discomfort1, diarrhoea, vomiting2, nausea2, increased intestinal peristalsis2, flatulence2, decreased sensitivity of the oral mucosa2, paraesthesia of the oral mucosa1 |
| Liver and biliary tract | Frequency not known: liver function tests abnormal2 |
| Skin and subcutaneous tissue disorders | Uncommon: contact dermatitis1, urticaria2, rash2, maculopapular rash2, pruritus generalised2, alopecia2, skin induration2 Frequency not known: facial edema3, dermatitis2,3, erythema2,3 |
| Musculoskeletal and connective tissue disorders | Uncommon: back pain2, muscle spasms2, myalgia2 Frequency not known: arthralgia2, pain in extremity2 |
| Renal and urinary disorders | Uncommon: kidney pain2 Frequency not known: pollakiuria2 |
| Reproductive and breast function disorders | Uncommon: erectile dysfunction2 |
| General disorders and administration site conditions | Uncommon: pain2, chest discomfort2, discomfort2, anxiety2, irritability2, drug residue1 Frequency not known: chest pain2, peripheral oedema2,3 |
1 Adverse reactions observed after use of Simbrinza®.
2 Additional adverse reactions observed with brinzolamide monotherapy.
3 Additional adverse reactions observed with brimonidine monotherapy.
Description of some adverse reactions
The most common systemic adverse reaction following the use of Simbrinza® was dysgeusia (3.4%). It was probably caused by the eye drops entering the nasopharynx via the nasolacrimal duct. This adverse reaction is typical mainly for brinzolamide, which is a component of Simbrinza®. Gently closing the eyelids or applying pressure to the nasolacrimal orifice helps to reduce the incidence of this adverse reaction (see section “Method of administration and dosage”).
Simbrinza® contains brinzolamide, a sulfonamide carbonic anhydrase inhibitor that is absorbed into the systemic circulation. Adverse reactions from the digestive and nervous systems, as well as hematological, renal and metabolic disorders, usually occur with systemic use of carbonic anhydrase inhibitors. The same types of adverse reactions that are characteristic of carbonic anhydrase inhibitors when administered orally can also occur with their topical use.
