Ivinak^®-SOLOpharm (Drops) Instructions for Use

Marketing Authorization Holder

Grotex, LLC (Russia)

ATC Code

S01BC11 (Bromfenac)

Active Substance

Bromfenac (Rec.INN registered by WHO)

Dosage Form

Ivinak®-SOLOpharm

Eye drops 0.09%: dropper bottle 2.5 ml or 5 ml 1 pc.

Dosage Form, Packaging, and Composition

Eye drops as a clear greenish-yellow solution.

Excipients : benzalkonium chloride – 0.01 mg, hydroxypropylbetadex – 20 mg, boric acid – 12.5 mg, sodium tetraborate decahydrate – 12.5 mg, polysorbate 80 – 1.5 mg, disodium edetate dihydrate – 0.2 mg, 10M sodium hydroxide solution or 1M hydrochloric acid solution – to pH 8.3, water for injections – up to 1 ml.

2.5 ml – dropper bottles made of high-pressure polyethylene^× (1) – cardboard packs.
5 ml – dropper bottles made of high-pressure polyethylene^× (1) – cardboard packs.

^× with or without a restraining device.

Clinical-Pharmacological Group

NSAIDs for topical use in ophthalmology

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID. The anti-inflammatory effect of bromfenac is realized by blocking the synthesis of prostaglandins through inhibition of COX 1 and 2.

In in vitro studies, Bromfenac inhibited prostaglandin synthesis in the rabbit ciliary body. The 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

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 after 150-180 minutes of application. This concentration is maintained 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 was applied as eye drops twice daily, plasma concentrations were not quantifiable.

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

According to a study in rabbits using radiolabeled bromfenac, C_max after topical application is observed in the cornea, high levels are found in the conjunctiva and aqueous humor, and low levels are found in the lens and vitreous body.

According to in vitro study results, the primary metabolism of bromfenac is carried out by the enzyme CYP2C9, 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.

When taken orally 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.

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 active substance is predominantly excreted in the urine (about 82% of the administered dose), and about 13% is excreted in the feces.

Indications

Treatment of non-infectious inflammatory diseases of the anterior segment of the eye and postoperative inflammation.

ICD codes

Dosage Regimen

Instill one to two drops into the conjunctival sac of the affected eye(s).

Apply the drops twice daily, approximately every 12 hours.

Begin treatment one day prior to cataract surgery.

Continue treatment on the day of surgery and for the first 14 days of the postoperative period.

The total duration of treatment for postoperative inflammation should not exceed 15 days.

For the treatment of other non-infectious inflammatory conditions, use for the shortest effective period as determined by a physician.

Do not use the product while wearing contact lenses.

Remove contact lenses prior to application and wait at least 15 minutes before reinserting them.

The preservative benzalkonium chloride may be absorbed by soft contact lenses.

To prevent contamination of the dropper tip and solution, avoid contact with the eyelids, surrounding areas, or any other surface.

Keep the bottle tightly closed when not in use.

Discard the container 4 weeks after first opening, even if solution remains.

Do not use the solution if it changes color or becomes cloudy.

Adverse Reactions

Ophthalmic disorders 0.42% – conjunctivitis (including conjunctival injection and conjunctival follicles), 0.29% – blepharitis, 0.23% – irritation, 0.21% – transient eye pain, 0.16% – superficial punctate keratitis, 0.16% – itching, 0.03% – corneal epithelial detachment; and 0.03% – burning sensation (eyelids).

Allergic reactions frequency unknown – contact dermatitis.

Contraindications

Patients in whom symptoms of bronchial asthma, urticaria, and acute rhinitis are exacerbated by taking acetylsalicylic acid and other NSAIDs; children and adolescents under 18 years of age; hypersensitivity to bromfenac.

Use in Pregnancy and Lactation

Use during pregnancy is not recommended unless the benefit outweighs the potential risk.

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 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 synthesis on the fetal cardiovascular system (ductus closure), use of this drug in the third trimester of pregnancy should be avoided.

Pediatric Use

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

Special Precautions

Bromfenac should be used only as part of symptomatic treatment and not for the purpose of etiotropic therapy.

All topical NSAIDs may slow down or delay healing, similar to topical corticosteroids.

Concomitant use of topical NSAIDs and corticosteroids may slow the healing process.

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

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 the health of the cornea 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-marketing experience with topical NSAIDs suggests that patients with complications after ophthalmic surgical procedures, with corneal denervation, corneal epithelial defects, diabetes mellitus and superficial eye diseases, rheumatoid arthritis, or repeated ophthalmic surgical procedures performed within a short period of time may have an increased risk of corneal adverse events that may become vision-threatening. Topical NSAIDs should be used with caution in such patients.

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

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

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

Effect on ability to drive vehicles and operate machinery

Transient blurred vision may occur after instillation. If blurred vision develops after instillation, it is necessary to refrain from driving a car or operating machinery until clear vision is restored.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.