NEPAVON OD | Nepafenac Ophthalmic Suspension 0.3% x/v

DOSAGE AND ADMINISTRATION

Posology

The recommended dose is One drop of Nepafenac should be applied to the affected eye three-times-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period or As directed by the physician.

Method of administration: For ocular use only.

CONTRAINDICATIONS

Nepafenac is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formula or to other NSAID.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

• Increased Bleeding Time with some nonsteroid anti-inflammatory drugs including Nepafenac, there exists the potential for increased bleeding time due to interfere with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery. It is recommended that Nepafenac ophthalmic suspension be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.
• Delayed Healing Topical nonsteroid anti-inflammatory drugs (NSAIDs) including Nepafenac, may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may  increase the potential for healing problems.
• Corneal Effects Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDS may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs including Nepafenac and should be closely monitored for corneal health. Postmarketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eyes syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Postmarketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk and severity of corneal adverse events.
• Contact Lens Wear Nepafenac should not be administered while using contact lenses

DRUG INTERACTIONS

In vitro studies have demonstrated a very low potential for interaction with other medicinal products and protein binding interactions. Prostaglandin analogues. There are very limited data on the concomitant use of prostaglandin analogues and Nepafenac. Considering their mechanism of action, the concomitant use of these medicinal products is not recommended. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. Concomitant use of Nepafenac with medications that prolong bleeding time may increase the risk of haemorrhage.

USE IN SPECIAL POPULATION

Pregnancy

Teratogenic Effects.

Pregnancy Category C:

Reproduction studies performed with nepafenac in rabbits and rats at oral doses up to 10 mg/kg/day have revealed no evidence of teratogenicity due to nepafenac, despite the induction of maternal toxicity. At this dose, the animal plasma exposure to nepafenac and amfenac was approximately 260 and 2400 times human plasma exposure at the recommended human topical ophthalmic dose for rats and 80 and 680 times human plasma exposure for rabbits, respectively. In rats, maternally toxic doses ≥10 mg/kg were associated with dystocia, increased post implantation loss, reduced fetal weights and growth, and reduced fetal survival. Nepafenac has been shown to cross the placental barrier in rats. There are  no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Nepafenac should be used during pregnancy only if the potential benefits justifies the potential risk of the fetus. Non-teratogenic Effects. Because of the known effects of prostaglandins biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of nepafenac during late pregnancy should be avoided.

Nursing Mothers

Nepafenac is excreted in milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nepafenac ophthalmic suspension is administered to a nursing women.

Pediatric Use

The safety and effectiveness of Nepafenac in pediatric patients below the age of 10 years have not been established.

Geriatric Use

No overall differences in safety and effectiveness have been observed between elderly and younger patients.

EFFECT ON ABILITY TO DRIVE AND USE MACHINES

Nepafenac has no or negligible influence on the ability to drive and use machines. Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.

UNDESIRABLE EFFECTS

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.

• Ocular Adverse Reactions The most frequently reported ocular adverse reactions following cataract surgery were capsular opacity, decreased visual acuity, foreign body sensation, increased intraocular pressure, and sticky sensation. These reactions occurred in approximately 5 to 10% of patients. Other ocular adverse reactions occurring at an incidence of approximately 1 to 5% included conjunctival edema, corneal edema, dry eye, lid margin crusting, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, photophobia, tearing and vitreous detachment. Some of these reactions may be the consequence of the cataract surgical procedure.
• Non-Ocular Adverse Reactions Non-Ocular adverse reactions reported at an incidence of 1 to 4% included headache, hypertension, nausea/vomiting, and sinusitis.

OVERDOSE

No toxic effects are likely to occur in case of overdose with ocular use, nor in the event of accidental oral ingestion.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

After topical ocular dosing, nepafenac penetrates the cornea and is converted by ocular tissue hydrolases to amfenac, a nonsteroidal anti-inflammatory drug. Amfenac is thought to inhibit the action of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production.

Pharmacokinetic properties

Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours postdose, respectively, following bilateral topical ocular three-times-daily dosing of nepafenac ophthalmic suspension, 0.1%. The mean steady-state Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration. Nepafenac at concentrations up to 300 ng/ml did not inhibit the in vitro metabolism of 6 specific marker substrates of cytochrome P450 (CYP) isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). Therefore, drug-drug interactions involving CYP mediated metabolism of concomitantly administered drugs are unlikely. Drug-drug interactions mediated by protein binding are also unlikely.

INCOMPATIBILITIES

Not known.

STORAGE

Store below 25°C. Protect from light & moisture. Do not freeze.

Store medicine out of reach of children.

Use the solution within one month after opening the container.

NOT FOR INJECTION

FOR TOPICAL OPHTHALMIC USE ONLY

PRESENTATION:

NEPAVON-OD Eye Drops is available in a 3ml pack.