Brinzopt, eye drops 10 mg/ml 5 ml

Increased intraocular pressure, Glaucoma

Brinzopt is used as monotherapy in adult patients who do not respond to beta-adrenoblockers or in adult patients for whom beta-adrenoblockers are contraindicated, or as adjunctive therapy to beta-adrenoblockers or prostaglandin analogues to reduce increased intraocular pressure in
– intraocular hypertension;
– open-angle glaucoma.

Active ingredient

Composition

1 ml brinzolamide 10 mg

Supplementary substances:

tiloxapol, carbomer 974P,

mannitol,

Sodium chloride,

dinatrium edetate dihydrate,

benzalkonium chloride,

1M hydrochloric acid solution or 1M sodium hydroxide solution,

purified water.

How to take, the dosage

For local ophthalmic use.

When used as monotherapy or in combination therapy, 1 drop of the drug is put into the conjunctival sac of the affected eye (eye) 2 times/day. If necessary, 1 drop 3 times daily is prescribed to improve the patient’s response.
After the injection it is recommended to press the inner corner of the eye slightly to close the nasolacrimal duct or slightly cover the eyelids. This may reduce systemic absorption of topical medications, resulting in fewer systemic side effects.

The bottle should be shaken well before use. To prevent contamination of the drug, the tip of the dropper should not touch any surface (eyelids, eye area, eyelashes, etc.). After application the bottle should be closed tightly.

When replacing any other anti-glaucoma drug for local use, you should stop its use and start therapy with brinzolamide from the next day. When using more than one ophthalmic drug for topical use they should be used separately, with an interval between the doses of at least 5 minutes.

If a dose is missed the therapy should be continued with the next dose in accordance with the schedule. The dosage should not exceed 1 drop in the affected eye(s) 3 times/day.

In elderly patients there is no need to adjust the dose.

The efficacy and safety of brinzolamide in children and adolescents under the age of 18 years has not been established, so it is not recommended to use the drug in this group of patients. However, there is limited experience with brinzolamide in children. Safety and efficacy of brinzolamide has been studied in a small number of patients under the age of 6 years.

Studies of the effects of brinzolamide in patients with hepatic impairment have not been conducted, so Brinzopt is not recommended for use in this group of patients.

There have been no studies of the effect of brinzolamide in patients with severe renal insufficiency (CK <30 ml/min) or in patients with hyperchloremic acidosis. Since brinzolamide and its main metabolite are excreted mainly by the kidneys, the drug is contraindicated in these patients.

Interaction

Special studies on the interaction of brinzolamide with other drugs have not been conducted.

In clinical studies, brinzolamide has been used in combination with prostaglandin analogues and timolol-based ophthalmic drugs; no undesirable interactions have been observed. No interactions between brinzolamide and myotics or adrenergic receptor agonists in combination therapy for glaucoma have been analyzed.

Brinzolamide is a carboanhydrase inhibitor and is absorbed systemically despite topical use. There have been reported cases of acid-base imbalance when using oral carboanhydrase inhibitors. The possibility of such interaction in patients receiving brinzolamide should be considered.

The cytochrome P450 isoenzymes that are responsible for the metabolism of brinzolamide include CYP3A4 (major), CYP2A6, CYP2C8 and CYP2C9. CYP3A4 inhibitors such as ketoconazole, itraconazole, clotrimazole, ritonavir and troleandomycin can be expected to inhibit the CYP3A4 isoenzyme-related metabolism of brinzolamide.

Caution should be exercised when using CYP3A4 inhibitors concomitantly. However, accumulation of brinzolamide is unlikely because it is excreted mainly with the kidneys. Brinzolamide is not an inhibitor of cytochrome P450 isoenzymes.

Special Instructions

Systemic effects

Brinzolamide is a sulfonamide carboenhydrase inhibitor and is absorbed systemically despite topical use. Undesirable adverse reactions typical of sulfonamides may occur when used topically. In case of serious adverse reactions or in case of signs of hypersensitivity the drug should be discontinued.

In cases of acid-base imbalance have been reported with oral use of carboanhydrase inhibitors. Studies of the effect of brinzolamide in premature infants (with a term of less than 36 weeks) or in children less than 1 week old have not been conducted. In patients with significant underdevelopment or impaired renal tubular function, brinzolamide should be used only after careful assessment of the risk/benefit ratio, since there is a risk of metabolic acidosis.

Orally administered carboanhydrase inhibitors may impair the ability of elderly patients to perform activities requiring attention and/or physical coordination. Brinzolamide is absorbed systemically, so this effect may also appear when used topically.

Combination therapy

When used in patients receiving oral carboanhydrase inhibitor therapy and brinzolamide, there is a risk of additive effect of carboanhydrase inhibition. Studies of concomitant use of oral brinzolamide and carboanhydrase inhibitors have not been conducted, and such use of these drugs is not recommended.

The effects of brinzolamide have mainly been analyzed when concomitantly used with timolol as adjunctive therapy in the treatment of glaucoma. The effect of brinzolamide on reducing intraocular pressure (IOP) was also investigated when brinzolamide was used as adjunctive therapy to the prostaglandin analogue travoprost. There are no data on long-term use of brinzolamide as concomitant therapy to travoprost.

There are limited data on the use of brinzolamide in the treatment of patients with pseudoexfoliative glaucoma or pigmentary glaucoma. Caution should be exercised when treating such patients and IOP levels should be monitored at all times. Studies of the effect of brinzolamide in patients with closed-angle glaucoma have not been conducted, so its use in these patients is not recommended.

Studies of possible effects of brinzolamide on corneal endothelial function in patients with corneal dysfunction (in particular, in patients with low endothelial cell count) have not been conducted.

No studies have been conducted on the use of the drug in patients who use contact lenses, so close monitoring of such patients is recommended when using brinzolamide because carboangidase inhibitors may affect corneal hydration and contact lens use may increase the risk of corneal exposure. Close monitoring is also recommended in other similar cases involving corneal dysfunction, such as patients with diabetes.

There are reports that benzalkonium chloride, which is commonly used in ophthalmic preparations as a preservative, may cause the development of pitting keratopathy and/or toxic ulcerative keratopathy. Because the drug contains benzalkonium chloride, close monitoring is required during frequent or prolonged treatment with the drug in patients with dry eyes or corneal damage.

The effect of brinzolamide on patients who use contact lenses has not been studied. The drug contains benzalkonium chloride, which may irritate the mucous membrane of the eye and which has been reported to discolor soft contact lenses. Contact of the drug with soft contact lenses should be avoided. Patients should be warned that contact lenses should be removed before using the drug and inserted no sooner than 15 min after injection.

Possible reverse effects after discontinuation of treatment with brinzolamide have not been studied; the estimated period of effect of reducing intraocular pressure is 5-7 days.

Contraindications

– severe renal insufficiency;
– hyperchloremic acidosis;
– hypersensitivity to the active substance or to any of the excipients;
– hypersensitivity to sulfonamides.

Side effects

In clinical studies involving over 1800 patients treated with brinzolamide as monotherapy or in combination with 5 mg/mL timolol maleate, the most common treatment-related adverse reactions were dysgeusia (5.8%) (bitter or unusual taste in the mouth after dosing) and temporary blurred vision (5.8%) lasting from a few seconds to several minutes.

The frequency of adverse reactions was defined as follows: very common (≥1/10), common (≥1/100 and <1/10), infrequent (≥1/1000 and <1/100), rare (≥1/10 000 and <1/1000), very rare (<1/10 000), frequency unknown (could not be determined based on available data). Adverse reactions in each group are presented by frequency and in descending order of severity/danger.

Infectious and parasitic diseases: infrequent – nasopharyngitis, pharyngitis, sinusitis; frequency unknown – rhinitis.

Hematopoietic system: infrequent – anemia.

The immune system: frequency unknown – hypersensitivity reactions.

Mental disorders: infrequent – apathy, depression, depressed mood, decreased libido, nightmares, insomnia, nervousness.

Nervous system disorders: frequent – dysgeusia, headache; infrequent – somnolence, motor dysfunction, amnesia, memory disturbances, dizziness, paresthesia; frequency unknown – tremor, hypoesthesia, aguesia.

Visual organs: common – blepharitis, blurred vision, eye irritation, eye pain, dry eyes, ocular discharge, itchy eyes, sensation of foreign body in eyes, hyperemia; infrequent – corneal erosions, keratitis, pitting keratitis, keratopathy, corneal deposits, corneal staining, corneal epithelium defects, increased intraocular pressure, increased cup/disc ratio at optic nerve level, corneal edema, conjunctivitis, eye edema, meibomian gland inflammation, diplopia, glare, photophobia, photopsia, decreased visual acuity, allergic conjunctivitis, pterygium, sclera pigmentation, asthenopia, eye discomfort, unusual sensations in the eye, dry keratoconjunctivitis, hypoesthesia of the eye, subconjunctival cysts, conjunctival hyperemia, itching of the eyelids, crusts at the edges of the eyelids, eyelid edema, increased tear production; frequency unknown – visual disturbances, ocular inflammation, allergic manifestations, madarosis, erythema of the eyelids.

Hearing and vestibular system disorders: infrequent – tinnitus; frequency unknown – dizziness.

Cardiovascular system: infrequent – cardiorespiratory distress syndrome, angina pectoris, bradycardia, palpitations, heart rhythm disorders; frequency unknown – arrhythmia, tachycardia, hypertension, increased BP, increased heart rate.

Respiratory system disorders: infrequent – shortness of breath, bronchial hyperresponsiveness, cough, nasal bleeding, pharyngeal throat pain, throat irritation, nasal congestion, congestion of upper airways, postnasal congestion, runny nose, sneezing, dry nose; frequency unknown – bronchial asthma.

Digestive system disorders: frequent – xerostomia; infrequent – esophagitis, diarrhea, nausea, dyspepsia, upper abdominal pain, abdominal discomfort, stomach discomfort, flatulence, frequent bowel emptying, gastrointestinal disorders, oral hypoesthesia, oral paresthesia.

Skin and subcutaneous tissue disorders: infrequent – urticaria, rash, maculopapular skin rash, generalized itching, hair loss, feeling of tightness of the skin; frequency unknown – dermatitis, erythema.

Muscular system disorders: infrequent – back pain, muscle cramps, myalgia; frequency unknown – arthralgia, pain in the extremities.

Urinary system: infrequent – renal colic; frequency unknown – pollakiuria.

Reproductive system disorders: infrequent – erectile dysfunction.

Laboratory data: infrequent hyperchloremia; frequency unknown – abnormal results of liver function tests.

General and local reactions: infrequent – pain, chest discomfort, asthenia, fatigue, feeling malaise, feeling anxious, irritability; frequency unknown – chest pain, peripheral edema, malaise, feeling of a foreign body in the eye.

In short-term clinical trials, adverse effects were observed in about 12.5% of pediatric patients; most were local and were non-serious ocular reactions such as conjunctival hyperemia, mucosal irritation, ocular discharge, and increased lacrimation.

Dysgeusia (bitter or unusual taste in the mouth after injection) is the most common systemic side effect associated with brinzolamide use noted in clinical trials. It is most likely due to the eye drops entering the nasopharynx through the nasolacrimal duct. Pressing the inner corner of the eye with a finger after injection to close the nasolacrimal duct or gently covering the eyelids may help to reduce the incidence of this effect.

Brinzolamide is a sulfonamide carboanhydrase inhibitor and is absorbed systemically. The use of systemic carboanhydrase inhibitors is usually associated with adverse effects on the gastrointestinal tract, nervous system, hematopoiesis, renal system and metabolic phenomena. Adverse events of the same type as those associated with oral use of carboangiidrase inhibitors may occur with topical administration.

No unexpected adverse events have been reported when using brinzolamide in combination therapy with travoprost. The adverse events reported in combination therapy are also observed when using each drug in monotherapy.

Overdose

No cases of overdose have been reported.

Symptoms: electrolyte imbalance, acidosis and adverse effects on the nervous system may develop.

Treatment: conducting symptomatic and supportive therapy. It is recommended to monitor the electrolyte level in plasma (especially potassium) and blood pH.

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