Nepafenac

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# Overview
Nepafenac is an antiinflammatory that is FDA approved for the treatment of pain and inflammation associated with cataract surgery.   Common adverse reactions include discharge from eye, disorder of lens capsule, foreign body sensation, raised intraocular pressure, reduced visual acuity.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Nepafenac ophthalmic suspension, 0.3% is indicated for the treatment of pain and inflammation associated with cataract surgery.
- One drop of ILEVRO- (nepafenac ophthalmic suspension), 0.3% should be applied to the affected eye one-time-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period. An additional drop should be administered 30 to 120 minutes prior to surgery.
- ILEVRO- (nepafenac ophthalmic suspension), 0.3% may be administered in conjunction with other topical ophthalmic medications such as beta-blockers, carbonic anhydrase inhibitors, alpha-agonists, cycloplegics, and mydriatics.
- If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Nepafenac in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Nepafenac in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Nepafenac in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Nepafenac in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Nepafenac in pediatric patients.

# Contraindications
- ILEVRO- (nepafenac ophthalmic suspension), 0.3% is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formula or to other NSAIDs.

# Warnings
- With some nonsteroidal anti-inflammatory drugs including ILEVRO- (nepafenac ophthalmic suspension), 0.3%, 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 hyphema) in conjunction with ocular surgery.
- It is recommended that ILEVRO- (nepafenac ophthalmic suspension), 0.3% be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.
- Topical nonsteroidal anti-inflammatory drugs (NSAIDs) including ILEVRO- (nepafenac ophthalmic suspension), 0.3%, 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.
- 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 ILEVRO- (nepafenac ophthalmic suspension), 0.3% 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.
- ILEVRO- (nepafenac ophthalmic suspension), 0.3% should not be administered while using contact lenses.

# Adverse Reactions

## Clinical Trials Experience
There is limited information regarding Nepafenac Clinical Trials Experience in the drug label.

## Postmarketing Experience
- 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.
- The following adverse reactions are discussed in greater detail in other sections of labeling.
- Increased Bleeding Time
- Delayed Healing
- Corneal Effects
- 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 reported at an incidence of 1 to 4% included headache, hypertension, nausea/vomiting, and sinusitis.

# Drug Interactions
There is limited information regarding Nepafenac Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 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 70 and 630 times human plasma exposure at the recommended human topical ophthalmic dose for rats and 20 and 180 times human plasma exposure for rabbits, respectively. In rats, maternally toxic doses  10 mg/kg were associated with dystocia, increased postimplantation 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, ILEVRO- (nepafenac ophthalmic suspension), 0.3% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Because of the known effects of prostaglandin biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ILEVRO- (nepafenac ophthalmic suspension), 0.3% during late pregnancy should be avoided.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Nepafenac in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Nepafenac during labor and delivery.

### 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 ILEVRO- (nepafenac ophthalmic suspension), 0.3% is administered to a nursing woman.

### Pediatric Use
The safety and effectiveness of ILEVRO- (nepafenac ophthalmic suspension), 0.3% in pediatric patients below the age of 10 years have not been established.

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

### Gender
There is no FDA guidance on the use of Nepafenac with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Nepafenac with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Nepafenac in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Nepafenac in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Nepafenac in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Nepafenac in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Oral
- Topical

### Monitoring
- Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs including ILEVRO- (nepafenac ophthalmic suspension), 0.3% and should be closely monitored for corneal health.

# IV Compatibility
There is limited information regarding IV Compatibility of Nepafenac in the drug label.

# Overdosage
There is limited information regarding Nepafenac overdosage.  If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

# Pharmacology

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

## Structure

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Nepafenac in the drug label.

## Pharmacokinetics
- Following bilateral topical ocular once-daily dosing of ILEVRO- (nepafenac ophthalmic suspension), 0.3%, the concentrations of nepafenac and amfenac peaked at a median time of 0.5 hour and 0.75 hour, respectively on both Day 1 and Day 4. The mean steady-state Cmax for nepafenac and for amfenac were 0.847  0.269 ng/mL and 1.13  0.491 ng/mL, respectively.
- Nepafenac at concentrations up to 3000 ng/mL and amfenac at concentrations up to 1000 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.

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Nepafenac in the drug label.

# Clinical Studies
- In two double masked, randomized clinical trials in which patients were dosed daily beginning one day prior to cataract surgery, continued on the day of surgery and for the first two weeks of the postoperative period, ILEVRO- (nepafenac ophthalmic suspension), 0.3% demonstrated superior clinical efficacy compared to its vehicle in treating postoperative pain and inflammation.
- Treatment effect over vehicle for resolution of ocular pain occurred as early as day 1 post-surgery. Treatment effect over vehicle for resolution of inflammation was significantly better than vehicle in both studies at day 7 and day 14 post-surgery.

# How Supplied
- LEVRO- (nepafenac ophthalmic suspension), 0.3% is supplied in a white, oval, low density polyethylene DROP-TAINER dispenser with a natural low density polyethylene dispensing plug and gray polypropylene cap presented in an overwrap. Tamper evidence is provided with a shrink band around the closure and neck area of the package.
- 1.7 mL in 4 mL bottle                NDC 0065-1750-07
- 3 mL in a 4 mL bottle                NDC 0065-1750-14

## Storage
- Storage: Store at 2 - 25 C (36 - 77 F).
- Protect from light.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Nepafenac in the drug label.

# Precautions with Alcohol
- Alcohol-Nepafenac interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- ILEVRO 

# Look-Alike Drug Names
There is limited information regarding Nepafenac Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price