Broxinac^® (Drops) Instructions for Use

Marketing Authorization Holder

Sentiss Pharma, Pvt. Ltd. (India)

Contact Information

SENTISS RUS LLC (Russia)

ATC Code

S01BC11 (Bromfenac)

Active Substance

Bromfenac (Rec.INN registered by WHO)

Dosage Form

Broxinac®

Eye drops 0.09%: 1.7 ml or 2.5 ml bottle

Dosage Form, Packaging, and Composition

Eye drops in the form of a clear greenish-yellow solution.

Excipients : benzalkonium chloride – 0.05 mg, boric acid – 11 mg, disodium edetate dihydrate – 0.2 mg, polysorbate 80 – 1.5 mg, povidone K-30 – 20 mg, sodium borate decahydrate – 11 mg, sodium sulfite anhydrous – 2 mg, sodium hydroxide – to adjust pH to 8.3, purified water – up to 1 ml.

1.7 ml – plastic bottles (1) – cardboard boxes.
2.5 ml – plastic bottles (1) – cardboard boxes.

Clinical-Pharmacological Group

NSAIDs for topical use in ophthalmology

Pharmacotherapeutic Group

NSAID

Pharmacological Action

Bromfenac is a non-steroidal anti-inflammatory drug (NSAID), whose anti-inflammatory effect is realized by blocking the synthesis of prostaglandins through the inhibition of COX-1 and COX-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 suffering from cataracts: 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 concentration levels maintained in the major ocular 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 was observed in the aqueous humor and most ocular tissues 2 hours after instillation. The highest concentrations were in the cornea, conjunctiva, and sclera. Similar amounts were found in the aqueous humor, iridociliary zone, choroid, and, to a somewhat lesser extent, in the retina. Significant penetration and measurable amounts of bromfenac were found in all samples after 24 hours, including the retina.

Metabolism

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

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.

Excretion

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 the drug is predominantly excreted in the urine (about 82% of the administered dose), while approximately 13% of the administered dose is excreted in the feces.

Indications

For adult patients over 18 years of age

• Symptomatic treatment of non-infectious inflammatory diseases of the anterior segment of the eye; inflammation after ophthalmic surgeries.

ICD codes

Dosage Regimen

Topically, as instillations into the conjunctival sac.

Treatment of postoperative inflammation 1 drop once daily. Treatment is started 1 day before surgery and continued for the first 14 days of the postoperative period (including the day of surgery). Depending on the severity of the condition, the doctor may determine a longer course of treatment.

Treatment of non-infectious inflammatory diseases of the anterior segment of the eye 1 drop twice daily. The course of treatment is determined by the doctor depending on the severity of the condition.

Special patient groups

Patients with impaired liver and/or kidney function

The efficacy and safety of bromfenac in patients with renal and hepatic insufficiency have not been studied.

Children

The efficacy and safety of bromfenac in children under 18 years of age have not been established.

Elderly patients

The dosage regimen for patients over 65 years of age does not differ from that for younger patients.

Instructions in case of missing one or more doses of the drug

If a dose is missed, the medicine should be applied as soon as possible at the dosage provided for in the instructions. If the missed application is close to 24 hours, the drug should be applied at the next scheduled time, without doubling the dose to compensate for the missed one.

Adverse Reactions

WHO classification of frequency of side effects: 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 (from <1/10000, including isolated reports).

When using the drug once daily, the following undesirable phenomena were observed

From the organ of vision: common (observed in 2-7% of patients) – discomfort and unusual sensations in the eyes, eye irritation, pain, itching and burning in the eyes, eye redness, conjunctival hyperemia, inflammation of the iris; very rarely – there are isolated post-marketing reports of corneal erosion, corneal perforation, corneal thinning, epithelial breakdown.

From the nervous system headache.

When using the drug twice daily, the following undesirable phenomena may occur

From the organ of vision: uncommon – decreased visual acuity, retinal hemorrhage, corneal edema, photophobia, eyelid vessel bleeding, exudates in the fundus, corneal erosion, conjunctivitis, blepharitis, irritation, transient eye pain, superficial punctate keratitis, itching; rare – corneal ulcer, corneal epithelial detachment, burning sensation in the eyelid area.

From the respiratory system, thoracic and mediastinal organs nosebleed, cough, nasal discharge, asthma.

General disorders and administration site conditions: isolated cases – facial edema, contact dermatitis.

If serious adverse reactions occur, treatment with the drug should be discontinued.

Contraindications

• Hypersensitivity to the components of the drug, as well as to other NSAIDs;
• Use of the drug is contraindicated in patients in whom attacks of bronchial asthma, urticaria and symptoms of acute rhinitis are exacerbated by taking acetylsalicylic acid and other NSAIDs;
• Age under 18 years (safety and efficacy of the drug in children have not been studied).

With caution

The sodium sulfite contained in the drug can cause an allergic reaction, including anaphylactic shock, asthma attacks in susceptible individuals. Sensitivity to sulfites is increased in persons with bronchial asthma and a history of allergic reactions.

When using the drug Broxinac^®, there is a possibility of developing cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, as well as other NSAIDs. Caution should be exercised when treating individuals who have previously shown sensitivity to these drugs.

NSAIDs may increase bleeding time as a result of impaired platelet aggregation. The use of topical NSAIDs in combination with ophthalmic surgery may increase bleeding of the eye tissues (including in the anterior chamber of the eye). Broxinac^® 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.

Experience with topical NSAIDs shows that patients with complications after ophthalmic surgical interventions, corneal denervation, corneal epithelial defects, diabetes mellitus, superficial eye diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeated surgical interventions performed within a short period of time may have an increased risk of developing corneal adverse reactions.

Use in Pregnancy and Lactation

Pregnancy

The safety of using bromfenac 0.09% eye drops during pregnancy has not been studied. However, data from some animal embryotoxicity studies indicate the possibility of reduced embryo viability. Use of the drug is possible if the expected benefit to the mother outweighs the potential risk to the fetus. Prescribing the drug in late pregnancy should be avoided.

Breastfeeding period

Caution should be exercised when using in women during breastfeeding.

Sufficient data on the use of bromfenac in pregnant women are not available. Animal studies have demonstrated reproductive toxicity. The potential risk to humans is unknown. Since systemic exposure after treatment with the drug 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 this drug in the third trimester of pregnancy should be avoided. In general, the use of this drug during pregnancy is not recommended, except in cases where the benefit outweighs the potential risk.

Pediatric Use

The use of the drug is contraindicated in children and adolescents under 18 years of age.

Geriatric Use

The dosage regimen for patients over 65 years of age does not differ from that for younger patients.

Special Precautions

The drug Broxinac^® should be used as part of symptomatic treatment, and not for the purpose of etiotropic therapy.

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

This drug contains sodium sulfite, which can cause allergic-type reactions, including anaphylaxis symptoms and life-threatening or less severe asthmatic episodes in susceptible patients.

All topical NSAIDs may slow or delay healing similar to topical corticosteroids. Concomitant use of NSAIDs and topical corticosteroids 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 rupture, 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 should 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 surgical interventions, with corneal denervation, corneal epithelial defects, diabetes mellitus and superficial eye diseases, rheumatoid arthritis, or repeated ophthalmic surgical interventions 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.

It has been reported that ophthalmic NSAIDs may cause increased bleeding in the 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 this drug is not recommended.

Excipients

The drug contains the preservative benzalkonium chloride, which with prolonged use can cause punctate or ulcerative toxic keratopathy when used by patients with concomitant corneal diseases or dry eye syndrome. Monitoring of the corneal condition of such patients during treatment with the drug is required.

Since the drug contains benzalkonium chloride, careful monitoring of patients is necessary in case of frequent or prolonged use of the drug. Benzalkonium chloride is known to discolor soft contact lenses. Contact with soft contact lenses should be avoided.

Effect on ability to drive vehicles and machinery

The drug has a minor effect on the ability to drive vehicles and operate machinery. Short-term blurred vision may occur after administration of the drug, so it is recommended to wait until vision is completely restored before driving vehicles and operating machinery.

Overdose

Treatment in case of accidental ingestion of the drug, it is necessary to immediately drink a large amount of fluid to reduce the concentration of the drug in the stomach.

Drug Interactions

The drug can be used simultaneously with other ophthalmic drugs: alpha-adrenergic agonists, beta-blockers, carbonic anhydrase inhibitors, mydriatics. In this case, the drugs should be applied with an interval of at least 5 minutes.

Storage Conditions

The drug should be stored out of the reach of children at a temperature from 15°C (59°F) to 25°C (77°F).

Shelf Life

Shelf life – 2 years. Do not use after the expiration date printed on the packaging.

Shelf life after opening the bottle – 30 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.