Nepafenac

Nepafenac is a Cyclooxygenase-1 and 2 (COX-1 and 2) inhibitor / non-steroidal anti-inflammatory drugs (NSAIDs) belonging to Analgesic / anti-inflammatory.

Nepafenac is an ophthalmic NSAID used for the symptomatic treatment of pain and inflammation associated with cataract surgery.

Nepafenac rapidly crosses the cornea. Nepafenac (prodrug) is deaminated to amfenac (active compound) has a high affinity toward serum albumin proteins. In vitro, the percentage bound to human albumin and human serum was 95.4% and 99.1% respectively. Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation.

Urinary excretion was found to be the major route of radioactivity elimination, accounting for approximately 85% of the dose, while fecal excretion represented approximately 6% of the dose. Nepafenac (prodrug) and amfenac (active compound) were not quantifiable in the urine.

Nepafenac shows common side effects like headache, runny nose, pain or pressure in the face, nausea, vomiting, dry, itchy, or sticky eyes.

Nepafenac is available in the form of Ophthalmic suspension.

Nepafenac is available in India, US, UK, Canada, Australia, China, Italy, Japan, France, Malaysia, Spain, and Russia.

Nepafenac is an Analgesic / anti-inflammatory belonging to the class Cyclooxygenase-1 and2 (COX-1 and 2) inhibitor / non-steroidal anti-inflammatory drug (NSAIDs).

Nepafenac is a prodrug. After penetrating the cornea, nepafenac undergoes rapid bioactivation to amfenac, which is a potent NSAID that uniformly inhibits the COX1 and COX2 activity.

The onset and duration of action of Nepafenac is not clinically established.

Nepafenac is available in the form of Ophthalmic suspension.

Nepafenac Ophthalmic suspension is usually instilled in eyes three times a day.

Nepafenac is an ophthalmic anti-inflammatory medicine. It is used to treat symptoms such as eye swelling, redness, pain, etc. that occur after cataract surgery (a procedure in which the natural lens of the eye is removed due to clouding and replaced with an artificial lens).

Nepafenac is a Cyclooxygenase-2 (COX-2) inhibitor belonging to non-steroidal anti-inflammatory drugs (NSAIDs).

Nepafenac is an NSAID and analgesic prodrug that penetrates the cornea after topical ocular administration. It is converted by ocular tissue hydrolases to amfenac, the active form that inhibits prostaglandin synthesis by reducing the activity of the enzyme, cyclooxygenase, resulting in decreased formation of prostaglandin precursors.

Nepafenac is approved for use in the following clinical indications

• Nepafenac ophthalmic suspension is indicated for the treatment of pain and inflammation associated with cataract surgery.

• Ocular pain and inflammation associated with cataract surgery: Ophthalmic:

Adult Dose and Children ≥10 years and Adolescents:

0.1% suspension: Instill 1 drop into affected eye(s) 3 times daily, beginning 1 day prior to surgery, the day of surgery, and through the first 2 weeks of the postoperative period.

0.3% suspension: Instill 1 drop into affected eye(s) once daily, beginning 1 day prior to surgery, the day of surgery, and through the first 2 weeks of the postoperative period. Instill 1 additional drop 30 to 120 minutes prior to surgery.

Nepafenac is available in various strengths as 0.1%; 0.3%.

Nepafenac is available in the form of Ophthalmic suspension.

Nepafenac is contraindicated in patients with

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

• Increased Bleeding Time

With some nonsteroidal anti-inflammatory drugs including Nepafenac, there exists the potential for increased bleeding time due to interference 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 nonsteroidal 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 eye 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.

• Aspirin/NSAID sensitivity

Use with caution in patients with previous sensitivity to acetylsalicylic acid and phenylacetic acid derivatives, including patients who experience bronchospasm, asthma, rhinitis, or urticaria following NSAID or aspirin.

• Keratitis

May cause keratitis; continued use in a patient with keratitis may cause severe corneal adverse reactions, potentially resulting in loss of vision. Immediately discontinue use in patients with evidence of corneal epithelial damage.

• Diabetes

Use with caution in patients with diabetes mellitus; may be at risk of corneal adverse events, potentially resulting in loss of vision.

• Ocular disease

Use with caution in patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, ocular surface disease, or repeat ocular surgeries (within a short timeframe); may be at risk of corneal adverse events, potentially resulting in loss of vision.

• Rheumatoid arthritis

Use with caution in patients with rheumatoid arthritis; may be at risk of corneal adverse events, potentially resulting in loss of vision.

• Surgery patients

May slow/delay healing or prolong bleeding time following surgery. Increased intraocular bleeding (including hyphema) has been reported. To minimize the risk of infection following surgery of both eyes, two separate bottles of eye drops (one for each eye) should be used; instruct patients not to use the same bottle for both eyes.

Nepafenac is excreted in the 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 woman.

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 benefit justifies the potential risk to the fetus.

Common

Hypertension, Foreign body sensation of eye, headache, Nausea vomiting, Decreased visual acuity, increased intraocular pressure, sticky sensation of eye, conjunctival edema, corneal edema, crusting of eyelid, eye discomfort, eye pain, eye pruritus, lacrimation, ocular hyperemia, photophobia, vitreous detachment, xerophthalmia, Sinusitis.

Anticoagulants

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic) may enhance the anticoagulant effect of Anticoagulants.

Corticosteroids (Ophthalmic)

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic) may enhance the adverse/toxic effect of Corticosteroids (Ophthalmic). Healing of ophthalmic tissue during concomitant administration of ophthalmic products may be delayed.

Prostaglandins (Ophthalmic)

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic) may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents (Ophthalmic) may enhance the therapeutic effect of Prostaglandins (Ophthalmic).

The common side effects of Nepafenac include the following

• Common side effects

Headache, runny nose, pain or pressure in the face, nausea, vomiting, dry, itchy, or sticky eyes.

• Rare side effects

Red or bloody eyes, eye pain, feeling that something is in the eye, sensitivity to light, blurred or decreased vision, seeing specks or spots, teary eyes, eye discharge or crusting.

• Pregnancy

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 benefit justifies the potential risk to the fetus.

• Nursing Mothers

Nepafenac is excreted in the 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 woman.

• Pediatric Use

The safety and effectiveness of Nepafenac in pediatric patients under 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.

• Pharmacodynamic

Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in most subjects 2- and 3-hours post dose, respectively, following bilateral topical ocular TID 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.

• Pharmacokinetics

Absorption

Nepafenac rapidly crosses the cornea.

Distribution

Nepafenac (prodrug) is deaminated to amfenac (active compound) has a high affinity toward serum albumin proteins. In vitro, the percentage bound to human albumin and human serum was 95.4% and 99.1% respectively.

Metabolism and Excretion

Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation.

Urinary excretion was found to be the major route of radioactivity elimination, accounting for approximately 85% of the dose, while fecal excretion represented approximately 6% of the dose. Nepafenac (prodrug) and amfenac (active compound) were not quantifiable in the urine.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021862s008lbl.pdf
• https://medlineplus.gov/druginfo/meds/a606007.html#:~:text=Nepafenac is in a class,that cause pain and swelling.
• https://www.uptodate.com/contents/nepafenac-drug-information?search=nepafenac&usage_type=panel&kp_tab=drug_general&source=panel_search_result&selectedTitle=1~2&display_rank=1
• https://reference.medscape.com/drug/nevanac-ilevro-nepafenac-ophthalmic-343662
• https://www.rxlist.com/nevanac-drug.html
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• https://www.drugs.com/dosage/nepafenac-ophthalmic.html