Nevanac, eye drops 0.1% 5 ml

Nepafenac is a precursor of the active form of non-steroidal anti-inflammatory drugs with analgesic and anti-inflammatory effects, it penetrates the cornea of the eye where it is converted by hydrolases into amphenac, the active form. Amphenac inhibits the action of cyclooxygenase (prostaglandin-N synthase), an enzyme necessary for the production of prostaglandins.

When used topically, nepafenac reduces ocular swelling and pain, and has no significant effect on intraocular pressure.

Pharmacokinetics

Absorption

Nevanac is rapidly absorbed through the cornea. Three daily injections of Nevanac in both eyes revealed low measurable plasma concentrations of nepafenac and amphenac after 2 and 3 h, respectively. The Cmax of nepafenac in plasma after topical application was 0.310±0.104 ng/mL; the Cmax of amphenac was 0.422±0.121 ng/mL.

The average Cmax of nepafenac in aqueous humor is observed after 1 hour.

Distribution

Amphenac has a high affinity for serum albumin. In vitro binding to rat albumin, human albumin and human serum was 98.4%, 95.4% and 99.1%, respectively.

Rat studies have shown that radioactively labeled substances bound to the active ingredient are widely distributed in the body after single and multiple oral doses of 14C-nepafenac.

Metabolism

Nepafenac undergoes rapid hydrolysis to amphenac under the action of intraocular hydrolases when administered topically.

The further metabolism of amphenac proceeds by hydroxylation of the aromatic ring, which leads to the formation of conjugates with glucuronic acid. Radiochromatographic analysis performed before and after hydrolysis with P-glucuronidase showed that all metabolites were in the form of conjugates with glucuronic acid, except for amphenac. Amphenac was the major metabolite in plasma, accounting for about 13% of the total radioactivity detected in plasma. The second most common plasma metabolite was 5-hydroxynepafenac with 9% of total radioactivity at Cmax.

Excretion

Nepafenac is excreted primarily by the kidneys (about 85% of the radioactive label with oral administration of 14C-nepafenac is found in the urine, about 6% in the feces), but urinary concentrations of nepafenac and amphenac are not quantifiable.

Indications

Cataract

Prevention and treatment:

• Postoperative pain.
• Inflammatory phenomena in cataract surgery.

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Active ingredient

Nepafenac

Composition

Ocular drops 0.1% in the form of light yellow to light orange suspension.

1 ml – nepafenac 1 mg

Supplementary substances:

benzalkonium chloride (as 50% solution) 0.05 mg,

carbomer 974P 5.0 mg,

tiloxapol 0.1 mg,

dinatrium edetate 0.1 mg,

mannitol 24.0 mg,

sodium chloride 4.0 mg,

sodium hydroxide and/or hydrochloric acid to adjust the pH,

purified water to 1 ml.

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How to take, the dosage

Topically. Shake the bottle before use.

1 drop into the conjunctival sac of the eye (eye) 3 times a day.

The treatment is started 1 day before surgical intervention to remove cataracts and is continued during the first 2 weeks of postoperative period (including the day of surgery). An additional drop of the drug must be put in 30-120 min before the operation.

Interaction

In in-vitro studies, neither; nepafenac nor amphenac inhibit the metabolic activity of human cytochrome P450 (CYP1A2 isoenzyme, 2C9, 2C19, 2D6, 2E1 and WA4) at concentrations up to 300 ng/ml. Consequently, when concomitant use with other drugs, interaction with the involvement of cytochrome P450 isoenzymes is unlikely. Interactions mediated by binding to plasma proteins are also unlikely.

There are no data on concomitant use of Nevanac and prostaglandin analogues. Given their mechanisms of action, concomitant use is not recommended.

If necessary, it can be used in combination with other ophthalmic drugs for topical use. In this case, the interval between their application should be at least 5 minutes.

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Special Instructions

Patients should avoid sun exposure when using Nevanac.

The drug contains the preservative benzalkonium chloride, which may cause eye irritation and discoloration of soft contact lenses. In addition, the use of contact lenses is not recommended during the postoperative period after cataract surgery. Contact lens use is not recommended during treatment with Nevanac.

Experience with topical NSAIDs suggests that patients with complications from ophthalmic surgery, corneal denervation, corneal epithelial defects, diabetes mellitus, superficial eye disease (such as dry eye syndrome), rheumatoid arthritis or repeated surgery performed within a short period of time may have an increased risk of corneal adverse reactions, which may pose a risk of vision loss. Topical NSAIDs should be used with caution when treating these patients. Prolonged use may increase the risk and severity of corneal adverse reactions.

The use of the drug, as well as other topical NSAIDs, may cause keratitis. Prolonged use may increase the risk or severity of corneal adverse reactions.

The use of the drug in conjunction with eye surgery can cause intense bleeding in the eye (including hyphema).

Nevanac should be prescribed with caution in patients with a history of bleeding tendency or when patients are receiving other medications that increase blood clotting time.

The drug contains benzalkonium chloride, which can cause eye irritation and discoloration in soft contact lenses, so they are not used. Also, contact lens use is prohibited during the recovery period after cataract surgery.

Do not touch any surface with the dropper bottle to avoid contaminating the bottle and infecting the contents. The bottle should be closed tightly after each use.

Cross-sensitivity

When using Nepafenac it is possible to develop cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives and other NSAIDs.

Impact on driving and operating machinery

After using Nevanac a temporary decrease in visual acuity and visual acuity may occur, so driving or engaging in activities that require adequate reaction and increased attention is prohibited until visual function is fully restored.

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Contraindications

• Individual hypersensitivity to the components of the drug, as well as to other non-steroidal anti-inflammatory drugs.
• Caused by taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs:
  • Bronchial asthma.
  • Hives.
  • Acute rhinitis.
• Age under 18 years of age (safety and efficacy of the drug in children has not been studied).

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Side effects

• Point keratitis, pain or itching in the eye, blurred vision, dry conjunctiva, crusting around the eyelid margin, iritis, keratitis, chorioidal effusion, corneal deposits, eye discharge, eye irritation, photophobia.
• Allergic conjunctivitis, eye discomfort, lacrimation, conjunctival hyperemia.
• Headaches, dyspepsia, dry mouth, sinusitis, skin distensibility (dermatochalasis), hypersensitivity.
• Eraven keratitis, corneal epithelial abnormalities, corneal damage, inflammatory anterior chamber infiltrates, delayed corneal healing, corneal scarring, decreased visual acuity, corneal opacity.

. If there are signs of corneal damage, the drug shall be immediately discontinued and the cornea shall be thoroughly examined, because it is known from the experience of using nonsteroidal anti-inflammatory drugs that patients with complications after ophthalmic surgical interventions, as well as with defects of the corneal epithelium Corneal denervation, diabetes mellitus, superficial eye conditions (e.g., dry eye syndrome), and rheumatoid arthritis or repeat surgeries have a high risk for corneal side effects that can lead to loss of visual function.

Overdose

There are no data on overdose of the drug.

In case of contact with the eyes with an excessive amount of the drug, it is recommended to rinse the eyes with warm water.

Pregnancy use

The use during pregnancy and lactation is not recommended. If it is necessary to prescribe during lactation, it is recommended to stop breastfeeding for the period of treatment.

Tests on animals have shown reproductive toxicity. In a study of the effects of nepafenac on reproductive organs of rats, administration of toxic doses of >10 mg/kg resulted in dystocia, increased number of spontaneous abortions in the post-implantation stage, decreased body weight and embryo growth, and decreased embryo survival. In pregnant rabbits, administration of low-toxic doses of 30 mg/kg resulted in increased malformations of the offspring.

Preventive use in children

Contraindicated in children under 18 years of age.