4.1. Therapeutic indications

NEVANAC 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 (see section 5.1)

4.2. Posology and method of administration

Posology

Adults, including the elderly

For the prevention and treatment of pain and inflammation, the dose is 1 drop of NEVANAC 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 NEVANAC 3 mg/ml eye drops, suspension (see section 5.1).

For the reduction in the risk of postoperative macular oedema associated with cataract surgery in diabetic patients, the dose is 1 drop of NEVANAC 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 NEVANAC 3 mg/ml eye drops, suspension provides the same total daily dose of nepafenac as three-times-daily dosing with NEVANAC 1 mg/ml eye drops, suspension.

Special populations

Patients with renal or hepatic impairment

NEVANAC 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 NEVANAC 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.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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.

4.4. Special warnings and precautions for use

The medicinal product should not be injected. Patients should be instructed not to swallow NEVANAC.

Patients should be instructed to avoid sunlight during treatment with NEVANAC.

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 (see section 4.8). These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of NEVANAC 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 NEVANAC 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. NEVANAC 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

NEVANAC 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 NEVANAC 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.

4.5. Interaction with other medicinal products and other forms of interaction

In vitro studies have demonstrated a very low potential for interaction with other medicinal products and protein binding interactions (see section 5.2).

Prostaglandin analogues

There are very limited data on the concomitant use of prostaglandin analogues and NEVANAC. 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 NEVANAC with medications that prolong bleeding time may increase the risk of haemorrhage (see section 4.4).

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

NEVANAC should not be used by women of child bearing potential not using contraception.

Pregnancy

There are no adequate data regarding the use of nepafenac in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Since the systemic exposure in non-pregnant women is negligible after treatment with NEVANAC, the risk during pregnancy could be considered low. Nevertheless, as inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonal/foetal development and/or parturition and/or postnatal development, NEVANAC is not recommended during pregnancy.

Breast-feeding

It is unknown whether nepafenac is excreted in human milk. Animal studies have shown excretion of nepafenac in the milk of rats. However, no effects on the suckling child are anticipated since the systemic exposure of the breast-feeding woman to nepafenac is negligible. NEVANAC can be used during breast-feeding.

Fertility

There are no data on the effect of NEVANAC on human fertility.

4.7. Effects on ability to drive and use machines

NEVANAC 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.

4.8. Undesirable effects

Summary of the safety profile

In clinical studies involving over 1 900 patients receiving NEVANAC 3 mg/ml eye drops, suspension, the most frequently reported adverse reactions were punctate keratitis, keratitis, foreign body sensation in eyes and eye pain which occurred in between 0.4% and 0.1% of patients.

Diabetic patients

In the two clinical studies involving 594 patients, diabetic patients were exposed to NEVANAC eye drops, suspension treatment for 90 days for the prevention of macular oedema post cataract surgery. The most frequently reported adverse reaction was punctate keratitis which occurred in 1% of patients, resulting in a frequency category of common. The other most frequently reported adverse reactions were keratitis and foreign body sensation in eyes which occurred in 0.5% and 0.3% of patients, respectively both adverse reactions with a frequency category of uncommon.

Tabulated list of adverse reactions

The following adverse reactions are classified according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions were obtained from clinical trials or post-marketing reports with NEVANAC 3 mg/ml eye drops, suspension and NEVANAC 1 mg/ml eye drops, suspension.

System organ classification

Adverse reactions

Immune system disorders

Rare: hypersensitivity

Nervous system disorders

Rare: dizziness, headache

Eye disorders

Uncommon: keratitis, punctate keratitis, corneal epithelium defect, foreign body sensation in eyes, eyelid margin crusting

Rare: iritis, choroidal effusion, corneal deposits, eye pain, ocular discomfort, dry eye, blepharitis, eye irritation, eye pruritus, eye discharge, allergic conjunctivitis, increased lacrimation, conjunctival hyperaemia

Not known: corneal perforation, impaired healing (cornea), corneal opacity, corneal scar, reduced visual acuity, eye swelling, ulcerative keratitis, corneal thinning, blurred vision

Vascular disorders

Not known: blood pressure increased

Gastrointestinal disorders

Rare: nausea

Not known: vomiting

Skin and subcutaneous tissue disorders

Rare: cutis laxa (dermatochalasis), allergic dermatitis

Description of selected adverse reactions

Patients with evidence of corneal epithelial breakdown including corneal perforation should immediately discontinue use of NEVANAC and should be monitored closely for corneal health (see section 4.4).

From post-marketing experience with NEVANAC 1 mg/ml eye drops, suspension, cases reporting corneal epithelium defect/disorder have been identified. Severity of these cases vary from non serious effects on the epithelial integrity of the corneal epithelium to more serious events where surgical interventions and/or medical therapy are required to regain clear vision.

Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (eg, 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.

Paediatric population

The safety and efficacy of NEVANAC in children and adolescents have not been established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

4.9. Overdose

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