Components:
Method of action:
Treatment option:
Medically reviewed by Kovalenko Svetlana Olegovna, PharmD. Last updated on 22.03.2022
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Nepafenac Alcon 3 mg/ml eye drops, suspension is indicated in adults for:
- Prevention and treatment of postoperative pain and inflammation associated with cataract surgery
- Reduction in the risk of postoperative macular oedema associated with cataract surgery in diabetic patients
Nepafenac Alcon (nepafenac ophthalmic suspension), 0.3% is indicated for the treatment of pain and inflammation associated with cataract surgery.
ILEVRO (nepafenac ophthalmic suspension), 0.3% is indicated for the treatment of pain and inflammation associated with cataract surgery.
Posology
Adults, including the elderly
For the prevention and treatment of pain and inflammation, the dose is 1 drop of Nepafenac Alcon in the conjunctival sac of the affected eye(s) once a day beginning 1 day prior to cataract surgery, continued on the day of surgery and for the first 2 weeks of the postoperative period. Treatment can be extended to the first 3 weeks of the postoperative period, as directed by the clinician. An additional drop should be administered 30 to 120 minutes prior to surgery.
In clinical trials, patients were treated for up to 21 days with Nepafenac Alcon 3 mg/ml eye drops, suspension.
For the reduction in the risk of postoperative macular oedema associated with cataract surgery in diabetic patients, the dose is 1 drop of Nepafenac Alcon in the conjunctival sac of the affected eye(s) once daily beginning 1 day prior to cataract surgery, continued on the day of surgery and up to 60 days of the postoperative period as directed by the clinician. An additional drop should be administered 30 to 120 minutes prior to surgery.
Once-daily dosing with Nepafenac Alcon 3 mg/ml eye drops, suspension provides the same total daily dose of nepafenac as three-times-daily dosing with Nepafenac Alcon 1 mg/ml eye drops, suspension.
Special populations
Patients with renal or hepatic impairment
Nepafenac Alcon has not been studied in patients with hepatic disease or renal impairment. Nepafenac is eliminated primarily through biotransformation and the systemic exposure is very low following topical ocular administration. No dose adjustment is warranted in these patients.
Paediatric population
The safety and efficacy of Nepafenac Alcon in children and adolescents have not been established.
No data are available. Its use is not recommended in these patients until further data become available.
Geriatric population
No overall differences in safety and effectiveness have been observed between elderly and younger patients.
Method of administration
For ocular use.
Patients should be instructed to shake the bottle well before use. After cap is removed, if a tamper evident snap collar is present and is loose, remove before using product.
If more than one topical ophthalmic medicinal product is being used, the medicinal products must be administered at least 5 minutes apart. Eye ointments should be administered last.
To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle. Patients should be instructed to keep the bottle tightly closed when not in use.
If a dose is missed, a single drop should be applied as soon as possible before reverting to regular routine. Do not use a double dose to make up for the 1 missed.
Recommended Dosing
One drop of Nepafenac Alcon (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.
Use With Other Topical Ophthalmic Medications
Nepafenac Alcon (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.
Recommended Dosing
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.
Use With Other Topical Ophthalmic Medications
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.
Hypersensitivity to other nonsteroidal anti-inflammatory drugs (NSAIDs).
Patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs.
Nepafenac Alcon (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.
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.
The medicinal product should not be injected. Patients should be instructed not to swallow Nepafenac Alcon.
Patients should be instructed to avoid sunlight during treatment with Nepafenac Alcon.
Ocular 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 Nepafenac Alcon and should be monitored closely for corneal health.
Topical NSAIDs 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. Therefore, it is recommended that caution should be exercised if Nepafenac Alcon is administered concomitantly with corticosteroids, particularly in patients at high risk for corneal adverse reactions described below.
Post-marketing 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 reactions which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Prolonged use of topical NSAIDs may increase patient risk for occurrence and severity of corneal adverse reactions.
There have been reports that ophthalmic NSAIDs may cause increased bleeding of ocular tissues (including hyphaemas) in conjunction with ocular surgery. Nepafenac Alcon should be used with caution in patients with known bleeding tendencies or who are receiving other medicinal products which may prolong bleeding time.
An acute ocular infection may be masked by the topical use of anti-inflammatory medicinal products. NSAIDs do not have any anti-microbial properties. In case of ocular infection, their use with anti-infectives should be undertaken with care.
Contact lenses
Contact lens wear is not recommended during the postoperative period following cataract surgery. Therefore, patients should be advised not to wear contact lenses unless clearly indicated by their doctor.
Benzalkonium chloride
Nepafenac Alcon contains benzalkonium chloride which may cause eye irritation and is known to discolour soft contact lenses. If contact lenses need to be used during treatment, patients should be advised to remove contact lenses prior to application and wait at least 15 minutes before reinsertion.
Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since Nepafenac Alcon contains benzalkonium chloride, close monitoring is required with frequent or prolonged use.
Cross-sensitivity
There is a potential for cross-sensitivity of nepafenac to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Increased Bleeding Time
With some nonsteroidal anti-inflammatory drugs including Nepafenac Alcon (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 Nepafenac Alcon (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.
Delayed Healing
Topical nonsteroidal anti-in_ammatory drugs (NSAIDs) including Nepafenac Alcon (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.
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 Alcon (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.
Contact Lens Wear
Nepafenac Alcon (nepafenac ophthalmic suspension), 0.3% should not be administered while using contact lenses.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Nepafenac has not been evaluated in long-term carcinogenicity studies. Increased chromosomal aberrations were observed in Chinese hamster ovary cells exposed in vitro to nepafenac suspension. Nepafenac was not mutagenic in the Ames assay or in the mouse lymphoma forward mutation assay. Oral doses up to 5,000 mg/kg did not result in an increase in the formation of micronucleated polychromatic erythrocytes in vivo in the mouse micronucleus assay in the bone marrow of mice.
Nepafenac did not impair fertility when administered orally to male and female rats at 3 mg/kg.
Use In Specific Populations
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 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, Nepafenac Alcon (nepafenac ophthalmic suspension), 0.3% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Non-teratogenic Effects
Because of the known effects of prostaglandin biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of Nepafenac Alcon (nepafenac ophthalmic suspension), 0.3% during late pregnancy should be avoided.
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 Alcon (nepafenac ophthalmic suspension), 0.3% is administered to a nursing woman.
Pediatric Use
The safety and effectiveness of Nepafenac Alcon (nepafenac ophthalmic suspension), 0.3% 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.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Increased Bleeding Time
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.
Delayed Healing
Topical nonsteroidal anti-in_ammatory 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.
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 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.
Contact Lens Wear
ILEVRO (nepafenac ophthalmic suspension), 0.3% should not be administered while using contact lenses.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Nepafenac has not been evaluated in long-term carcinogenicity studies. Increased chromosomal aberrations were observed in Chinese hamster ovary cells exposed in vitro to nepafenac suspension. Nepafenac was not mutagenic in the Ames assay or in the mouse lymphoma forward mutation assay. Oral doses up to 5,000 mg/kg did not result in an increase in the formation of micronucleated polychromatic erythrocytes in vivo in the mouse micronucleus assay in the bone marrow of mice.
Nepafenac did not impair fertility when administered orally to male and female rats at 3 mg/kg.
Use In Specific Populations
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 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.
Non-teratogenic Effects
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.
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.
Geriatric Use
No overall differences in safety and effectiveness have been observed between elderly and younger patients.
Nepafenac Alcon 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.
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.
Serious And Otherwise Important Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of labeling.
- Increased Bleeding Time (WARNINGS AND PRECAUTIONS)
- Delayed Healing (WARNINGS AND PRECAUTIONS)
- Corneal Effects (WARNINGS AND PRECAUTIONS)
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.
No information provided.
Pharmacotherapeutic group: Ophthalmologicals, anti-inflammatory agents, non-steroids, ATC code: S01BC10
Mechanism of action
Nepafenac is a non-steroidal anti-inflammatory and analgesic prodrug. After topical ocular dosing, nepafenac penetrates the cornea and is converted by ocular tissue hydrolases to amfenac, a nonsteroidal anti-inflammatory drug. Amfenac inhibits the action of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production.
Secondary pharmacology
In rabbits, nepafenac has been shown to inhibit blood-retinal-barrier breakdown, concomitant with suppression of PGE2 synthesis. Ex vivo, a single topical ocular dose of nepafenac was shown to inhibit prostaglandin synthesis in the iris/ciliary body (85%-95%) and the retina/choroid (55%) for up to 6 hours and 4 hours, respectively.
Pharmacodynamic effects
The majority of hydrolytic conversion is in the retina/choroid followed by the iris/ciliary body and cornea, consistent with the degree of vascularised tissue.
Results from clinical studies indicate that Nepafenac Alcon 3 mg/ml eye drops, suspension have no significant effect on intraocular pressure.
Clinical efficacy and safety
Prevention and treatment of postoperative pain and inflammation associated with cataract surgery.
The efficacy and safety of Nepafenac Alcon 3 mg/ml in the prevention and treatment of postoperative pain and inflammation associated with cataract surgery has been demonstrated in two masked, double blind, placebo-controlled clinical trials in a total of 1339 patients. In these studies in which patients were dosed daily beginning one day prior to cataract surgery, continued on the day of surgery and for the first 14 days of the postoperative period, Nepafenac Alcon 3 mg/ml eye drops, suspension demonstrated superior clinical efficacy compared to its vehicle in treating postoperative pain and inflammation.
Patients treated with Nepafenac Alcon were less likely to have ocular pain and measurable signs of inflammation (aqueous cells and flare) in the early postoperative period through to the end of treatment than those treated with its vehicle. In the two studies, Nepafenac Alcon cleared inflammation at day 14 post operation in 65% and 68% of patients compared to 25% and 35% of patients on vehicle. Pain free rates in the Nepafenac Alcon group were 89% and 91% compared to 40% and 50% of patients on vehicle.
Some patients received Nepafenac Alcon 3 mg/ml eye drops, suspension for up to 21 days post operation. However, efficacy beyond day 14 post operation was not measured.
In addition, in one of the two clinical trials, Nepafenac Alcon 3 mg/ml eye drops, suspension dosed once a day was non-inferior to Nepafenac Alcon 1 mg/ml eye drops, suspension dosed three times a day for the prevention and treatment of postoperative pain and inflammation following cataract surgery. Inflammation clearing and pain free rates were similar for both products at all postoperative evaluations.
Reduction in the risk of postoperative macular oedema associated with cataract surgery in diabetic patients:
Two studies in diabetic patients were conducted to assess the efficacy and safety of Nepafenac Alcon 3 mg/ml eye drops, suspension dosed once a day for the prevention of postoperative macular oedema associated with cataract surgery. In these studies, study medication was initiated the day prior to surgery, continued on the day of surgery and for up to 90 days of the postoperative period.
In both double-masked, randomised vehicle-controlled studies, conducted in diabetic retinopathy patients, a significantly greater percentage of patients in the vehicle group developed macular oedema (17.3% and 14.3%) compared to patients treated with Nepafenac Alcon 3 mg/ml (2.3% and 5.9%). The corresponding percentages in integrated analysis of the 2 studies were 15.9% in vehicle group and 4.1% in Nepafenac Alcon group, p<0.001). A significantly greater percentage of patients achieved improvement of 15 or more letters at Day 14 and maintained the improvement through Day 90 in Nepafenac Alcon 3 mg/ml group (61.7%) compared to vehicle group (43%) in one study; the percentage of subjects was similar in the 2 treatment groups for this endpoint in the second study (48.8% in Nepafenac Alcon group and 50.5% in vehicle group). In integrated analysis of the 2 studies, the percentage of subjects with 15 letter improvement at Day 14 and maintained to Day 90 was higher in Nepafenac Alcon 3 mg/ml group (55.4%) compared to vehicle group (46.7%, p=0.003).
Absorption
Following one drop of Nepafenac Alcon 3 mg/ml eye drops, suspension in both eyes once daily for four days, low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours post-dose, respectively. The mean steady-state plasma Cmax for nepafenac and for amfenac were 0.847 ± 0.269 ng/ml and 1.13 ± 0.491 ng/ml, respectively, following ocular administration.
Distribution
Amfenac has a high affinity toward serum albumin proteins. In vitro, the percent bound to rat albumin, human albumin and human serum was 98.4%, 95.4% and 99.1%, respectively.
Studies in rats have shown that radioactive labelled active substance-related materials distribute widely in the body following single and multiple oral doses of 14C-nepafenac.
Studies in rabbits demonstrated that the topically administered nepafenac is distributed locally from the front of the eye to the posterior segments of the eye (retina and choroid).
Biotransformation
Nepafenac undergoes relatively rapid bioactivation to amfenac via intraocular hydrolases. Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation.
Radiochromatographic analyses before and after β-glucuronidase hydrolysis indicated that all metabolites were in the form of glucuronide conjugates, with the exception of amfenac. Amfenac was the major metabolite in plasma, representing approximately 13% of total plasma radioactivity. The second most abundant plasma metabolite was identified as 5-hydroxy nepafenac, representing approximately 9% of total radioactivity at Cmax.
Interactions with other medicinal products: Neither nepafenac nor amfenac inhibit any of the major human cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4) metabolic activities in vitro at concentrations up to 3000 ng/ml. Therefore, interactions involving CYP-mediated metabolism of concomitantly administered medicinal products are unlikely. Interactions mediated by protein binding are also unlikely.
Elimination
After oral administration of 14C-nepafenac to healthy volunteers, urinary excretion was found to be the major route of radioactive excretions, accounting for approximately 85% while faecal excretion represented approximately 6% of the dose.
Following bilateral topical ocular once-daily dosing of Nepafenac Alcon (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.
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.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Nepafenac has not been evaluated in long-term carcinogenicity studies.
In reproduction studies performed with nepafenac in rats, maternally toxic doses > 10 mg/kg were associated with dystocia, increased postimplantation loss, reduced foetal weights and growth, and reduced foetal survival. In pregnant rabbits, a maternal dose of 30 mg/kg that produced slight toxicity in the mothers showed a statistically significant increase in the incidence of litter malformations.
Not applicable.
No special requirements for disposal.
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