ILEVRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ILEVRO (ILEVRO).
Nepafenac is a prodrug that is metabolized to amfenac, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) activity, reducing prostaglandin synthesis.
| Metabolism | Nepafenac is hydrolyzed to amfenac by ocular tissue hydrolases. Amfenac undergoes further metabolism via CYP450 enzymes, primarily CYP2C9. |
| Excretion | Nepafenac is extensively metabolized, and its active metabolite amfenac is primarily excreted renally (approximately 80% as metabolites, including amfenac glucuronide, and 20% as unchanged drug in urine). Biliary/fecal excretion accounts for less than 10%. |
| Half-life | Terminal elimination half-life of amfenac is approximately 0.7 hours in plasma, but due to prolonged residence in ocular tissues, the clinical effect lasts up to 24 hours with once-daily dosing. |
| Protein binding | Amfenac is approximately 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.16 L/kg, indicating distribution mainly in extracellular fluid. |
| Bioavailability | Ocular bioavailability is low due to limited systemic absorption; plasma concentrations are undetectable after topical administration in most patients. |
| Onset of Action | Onset of analgesic effect following ophthalmic administration occurs within 1 hour; anti-inflammatory effect begins within 2 hours. |
| Duration of Action | Duration of action is approximately 24 hours after a single ophthalmic dose, allowing once-daily dosing for inflammation and pain associated with cataract surgery. |
| Molecular Weight | 254.29 |
1 drop of the 0.3% ophthalmic solution administered to the affected eye(s) four times daily.
| Dosage form | SUSPENSION/DROPS |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No overall differences in safety or efficacy observed between elderly and younger patients; no specific dose adjustment recommended. |
| 1st trimester | Nepafenac ophthalmic suspension is not recommended during the first trimester due to potential NSAID-related risks, including oligohydramnios and premature ductus arteriosus closure; use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | May be used cautiously if benefit outweighs risk, but avoid chronic use; consider alternative therapies; monitor amniotic fluid if used for prolonged periods. |
| 3rd trimester | Avoid during third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios; contraindicated after 30 weeks gestation. |
Clinical note
Comprehensive clinical and safety monograph for ILEVRO (ILEVRO).
| Placental transfer | Unknown but expected to cross placenta due to low molecular weight; no specific human data; animal studies show placental transfer after oral administration. Topical ocular use results in negligible systemic levels. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Common Effects | Decreased vision Foreign body sensation in eyes Increased intraocular pressure Stickiness |
| Serious Effects |
Hypersensitivity to nepafenac or any component of the formulationPatients with history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsActive ocular infection (e.g., herpes simplex keratitis)Third trimester of pregnancy (after 30 weeks)
| Precautions | Increased bleeding time due to antiplatelet effect, Risk of corneal adverse events including keratitis and corneal perforation, Potential for cross-sensitivity to aspirin or other NSAIDs, May mask signs of infection, Use with caution in patients with prior ocular surgery or epithelial defects |
| Food/Dietary | No known food interactions. Avoid concurrent use with oral NSAIDs due to potential additive systemic effects, though no specific dietary restrictions are required. |
Loading safety data…
| Following topical ocular administration, systemic exposure is minimal (<10% of oral dose). Nepafenac is not expected to cause adverse effects in breastfed infants. Caution is advised with prolonged use. Use only if clearly needed. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Nepafenac is an NSAID; risk of premature closure of ductus arteriosus and oligohydramnios starting at 20 weeks gestation. Avoid in third trimester. No adequate studies in first trimester; animal studies show no teratogenicity at clinically relevant doses. |
| Fetal Monitoring | Monitor for signs of premature ductus arteriosus closure and oligohydramnios if used after 20 weeks; perform fetal echocardiography and amniotic fluid index assessments if exposure occurs. Also monitor maternal renal function. |
| Fertility Effects | NSAIDs may impair female fertility via inhibition of prostaglandin synthesis affecting ovulation and implantation; reversible upon discontinuation. No direct data for nepafenac, but class effect applies. |
| Clinical Pearls | ILEVRO (nepafenac ophthalmic suspension 0.3%) is a nonsteroidal anti-inflammatory drug (NSAID) prodrug used for pain and inflammation after cataract surgery. It is dosed one drop three times daily starting 1 day before surgery, continuing on the day of surgery, and for 2 weeks postoperatively. It has good intraocular penetration due to its prodrug formulation, which is converted by intraocular hydrolases to amfenac. Use with caution in patients with bleeding tendencies or those on anticoagulants; monitor for corneal adverse events like keratitis or corneal melt, especially in patients with ocular surface disease or multiple surgeries. May be used concomitantly with topical corticosteroids, but increase monitoring for intraocular pressure elevation. |
| Patient Advice | Shake the bottle well before each use to ensure the suspension is evenly mixed. · Wash hands before and after applying the eye drops to prevent contamination. · Tilt your head back, pull down the lower eyelid, and instill one drop into the affected eye; avoid touching the dropper tip to any surface. · Wait at least 5 minutes between applying ILEVRO and any other eye drops to allow proper absorption. · Use exactly as prescribed: one drop three times daily starting one day before surgery, on the day of surgery, and for two weeks after surgery. · Do not wear contact lenses during treatment unless directed by your doctor. · If you experience eye pain, vision changes, redness, or discharge, contact your healthcare provider immediately. · You may experience temporary blurred vision after instilling the drops; avoid driving or operating machinery until vision clears. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Do not stop using ILEVRO without consulting your doctor, even if symptoms improve. |