Bromfenac-SZ (Drops) Instructions for Use

Marketing Authorization Holder

Severnaya Zvezda NAO (Russia)

Contact Information

SEVERNAYA ZVEZDA NAO (Russia)

ATC Code

S01BC11 (Bromfenac)

Dosage Form

Bromfenac-SZ

Eye drops 0.09%: 5 ml dropper bottle

Dosage Form, Packaging, and Composition

Eye drops as a clear yellow solution.

Excipients: boric acid, disodium tetraborate decahydrate, sodium sulfite, disodium edetate dihydrate, povidone K30 (medium molecular weight polyvinylpyrrolidone), polysorbate 80, benzalkonium chloride, 1M sodium hydroxide solution, purified water.

5 ml – polyethylene dropper bottles (1) with dropper caps – cardboard packs.

Clinical-Pharmacological Group

NSAIDs for topical use in ophthalmology

Pharmacotherapeutic Group

NSAID

Pharmacological Action

Bromfenac is an NSAID, whose anti-inflammatory effect is realized by blocking the synthesis of prostaglandins through the inhibition of COX 1 and 2.

In in vitro studies, Bromfenac inhibited prostaglandin synthesis in the rabbit ciliary body. The half-maximal inhibitory concentration (IC50) for bromfenac (1.1 µmol) was lower than for indomethacin (4.2 µmol) and pranoprofen (11.9 µmol). In an experimental model of uveitis in rabbits, Bromfenac at concentrations of 0.02%, 0.05%, 0.1% and 0.2% inhibited almost all symptoms of ocular inflammation.

Pharmacokinetics

Absorption

Bromfenac effectively penetrates the cornea of patients with cataract: after a single instillation, the mean C_max in the aqueous humor is 79±68 ng/ml 150-180 minutes after application. This concentration persists for 12 hours in the aqueous humor with measurable concentrations maintained in key eye tissues, including the retina, for up to 24 hours. When bromfenac eye drops were applied twice daily, plasma concentrations were not quantifiable.

Distribution

Bromfenac is highly bound to plasma proteins. According to in vitro studies, binding to proteins in human plasma was 99.8%.

In vitro studies did not reveal biologically significant binding to melanin.

According to a study in rabbits using radiolabeled bromfenac, C_max after topical application is observed in the cornea, followed by the conjunctiva and aqueous humor of the eye. Bromfenac is detected in low concentrations in the lens and vitreous body.

Metabolism

According to the results of in vitro studies, the primary metabolism of bromfenac is carried out by the CYP2C9 enzyme, which is absent in the iridociliary zone, retina, and choroid. The activity of this enzyme in the cornea is less than 1% compared to the corresponding activity in the liver.

After oral administration in humans, the unchanged parent substance is mainly detected in plasma. Several conjugated and unconjugated metabolites have been isolated, the main one being a cyclic amide, which is excreted in the urine.

Elimination

When instilled into the eyes, the T_1/2 of bromfenac from the aqueous humor of the eye is about 1.4 hours, indicating rapid elimination.

After oral administration of ¹⁴C-bromfenac to healthy volunteers, it was found that Bromfenac is predominantly excreted by the kidneys (about 82% of the administered dose), while about 13% of the administered dose is excreted through the intestines.

Indications

• Symptomatic treatment of non-infectious inflammatory diseases of the anterior segment of the eye, including inflammation after ophthalmic surgery in patients over 18 years of age.

ICD codes

Dosage Regimen

Treatment of non-infectious inflammatory diseases of the anterior segment of the eye

1-2 drops into the conjunctival sac 2 times/day. The course of treatment is determined by the attending physician depending on the severity of the disease.

Treatment of postoperative inflammation

1 drop once daily. Treatment should be started 1 day before surgery and continued for the first 14 days of the postoperative period (including the day of surgery).

Missed dose

If a dose of the drug is missed, the drug should be applied as soon as possible at the dosage indicated in the instructions for use. If the missed dose is about 24 hours, the drug should be applied at the next scheduled time, without doubling the dose to compensate for the missed one.

Special patient groups

No dose adjustment is required when treating elderly patients.

Children

The drug Bromfenac-SZ is contraindicated in children under 18 years of age (see section “Contraindications”).

Method of administration

It is used topically as instillations into the conjunctival cavity.

Do not touch the tip of the dropper bottle to the eyes or any other surface to avoid contamination of the dropper tip and the contents of the bottle.

After use, it is recommended to close the bottle tightly with the cap.

Adverse Reactions

Summary of the safety profile

Adverse reactions (ARs) to this drug were noted in 72 cases out of 3843 patients (1.87%), data for which were obtained from clinical studies or post-registration use.

The main ARs included corneal erosion in 16 cases (0.42%), conjunctivitis (including conjunctival injection and conjunctival follicles) in 11 cases (0.29%), blepharitis in 9 cases (0.23%), irritation in 8 cases (0.21%), eye pain (transient) in 8 cases (0.21%), superficial punctate keratitis in 6 cases (0.16%), itching in 6 cases (0.16%), corneal epithelial detachment in 1 case (0.03%) and burning sensation in the eyelid area in 1 case (0.03%) (upon completion of the review).

Tabulated summary of adverse reactions

ARs are classified according to the following frequency gradation: very common (>1/10), common (from >1/100 to <1/10), uncommon (from >1/1000 to <1/100), rare (from >1/10000 to <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available data).

Within each group, ARs are presented in order of decreasing seriousness and are grouped by frequency and system-organ class.

Tabulated summary of adverse reactions

* If an AR occurs, treatment with the drug should be discontinued.

** If clinically significant ARs occur, such as the development of corneal epithelial diseases, etc., it is necessary to discontinue treatment with this drug and take appropriate measures.

*** Serious AR, isolated reports from post-registration surveillance experience.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after registration of a medicinal product in order to ensure continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are recommended to report any suspected adverse drug reactions through the national adverse reaction reporting system of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to bromfenac or to any of the excipients included in the drug;
• Patients in whom attacks of bronchial asthma, urticaria and symptoms of acute rhinitis are aggravated by taking acetylsalicylic acid and other NSAIDs;
• Childhood and adolescence under 18 years of age (efficacy and safety in patients of this age group have not been established).

Use in Pregnancy and Lactation

Pregnancy

Sufficient data on the use of bromfenac in pregnant women are not available. Data on reproductive toxicity have been obtained in animal studies. The potential risk to humans is unknown. Since systemic exposure after treatment with bromfenac in non-pregnant women is negligible, the risk during pregnancy can be considered low. However, due to the known effects of drugs that inhibit prostaglandin biosynthesis on the fetal cardiovascular system (ductus closure), the use of bromfenac in the third trimester of pregnancy should be avoided. In general, the use of bromfenac during pregnancy is not recommended, except in cases where the benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding

Bromfenac can be used during breastfeeding only if the expected benefit of treatment for the mother outweighs the potential risk to the child associated with treatment, since data on the excretion of bromfenac or its metabolites into breast milk are insufficient.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

No dose adjustment is required when treating elderly patients.

Special Precautions

The drug Bromfenac-SZ should be used as part of symptomatic treatment, and not for the purpose of etiotropic therapy.

The medicinal product Bromfenac-SZ should be used only as instillations into the conjunctival cavity.

This drug should be instilled carefully, making sure that the tip of the bottle does not touch the surface of the eye.

All topical NSAIDs may slow down or delay healing, similar to topical corticosteroids. The concomitant use of NSAIDs and topical steroids may increase the likelihood of healing problems.

Cross-sensitivity

There is a possibility of cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives and other NSAIDs. Therefore, caution should be exercised when treating individuals who have previously shown sensitivity to these drugs, and the potential risks and benefits should be carefully assessed.

Special patient groups

In susceptible patients, prolonged use of topical NSAIDs, including Bromfenac, may lead to epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration, or corneal perforation. These events may threaten vision loss. Patients with signs of corneal epithelial breakdown should immediately discontinue the use of topical NSAIDs and corneal health must be closely monitored. Consequently, in patients at risk, the concomitant use of ophthalmic corticosteroids with NSAIDs may lead to an increased risk of corneal adverse events.

Post-registration experience

Post-registration experience with topical NSAIDs indicates that patients with complications after ophthalmic surgery, with corneal denervation, corneal epithelial defects, diabetes mellitus and superficial eye diseases, rheumatoid arthritis or repeated ophthalmic surgeries performed within a short period of time may have an increased risk of corneal adverse events, which may become vision-threatening. Topical NSAIDs should be used with caution in such patients.

Ophthalmic NSAIDs have been reported to cause increased bleeding in eye tissues (including hyphema) in conjunction with ophthalmic surgery. Topical NSAIDs should be used with caution in patients with a history of bleeding tendency, or if patients are taking other medications that may increase clotting time.

Eye infections

The use of the drug should be carefully monitored and it should be prescribed with caution to patients with inflammation caused by infections, as the drug may mask the symptoms of infectious eye diseases.

Use of contact lenses

In general, wearing contact lenses during treatment with the drug is not recommended. In this regard, patients are not recommended to wear contact lenses unless clear instructions from the attending physician are received.

Excipients

Since the drug contains benzalkonium chloride, careful monitoring of patients is necessary in case of frequent or prolonged use of the drug.

Benzalkonium chloride may cause eye irritation, punctate keratopathy and/or toxic ulcerative keratopathy.

Benzalkonium chloride is known to discolor soft contact lenses. Contact with soft contact lenses should be avoided.

Bromfenac-SZ also contains sodium sulfite, which may cause allergic-type reactions, including anaphylaxis symptoms and life-threatening or less severe asthmatic episodes in susceptible patients.

Effect on ability to drive vehicles and machinery

Patients who experience transient blurred vision after instillation should refrain from driving vehicles and operating machinery until visual clarity is restored.

Overdose

With topical use

Currently, there is no information on overdose with topical use in humans.

Accidental administration of more than 1 drop of bromfenac solution should not lead to increased local exposure, since the excess volume is washed out of the eye due to the limited capacity of the conjunctival sac.

In case of accidental ingestion (adult patients)

According to foreign reports, in patients who took the drug Bromfenac orally in a total dose exceeding 1500 mg over a long period of time of more than 1 month, serious liver dysfunction (including fatal cases) was observed. In this regard, if abnormalities are detected that are presumably associated with early symptoms of liver failure, it is necessary to stop use and take appropriate measures.

Drug Interactions

No drug interaction studies have been conducted.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Shelf life after opening the dropper bottle – 28 days.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.