Nepafenac

Registered South African indications:

• Pain and inflammation associated with cataract surgery
• Reduction in the risk of macular oedema associated with cataract surgery

Contraindications

South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of the excipients 
• Hypersensitivity to other non-steroidal anti-inflammatory drugs (NSAIDs) 
• Patients in whom attacks of asthma, urticaria or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs 
• Heart failure (1mg/ml) 
• History of gastrointestinal bleeding or perforation related to previous NSAIDs (1mg/ml)
• Active or history of recurrent ulcer, haemorrhage or perforations  (1mg/ml)
• Third trimester of pregnancy  (1mg/ml)

International manufacturer recommendations

• Hypersensitivity to the active ingredient or any of the excipients 
• Hypersensitivity to other non-steroidal anti-inflammatory drugs (NSAIDs) 
• Patients in whom attacks of asthma, urticaria or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs

Cautions 

South African manufacturer recommendations

• Pregnancy 
• Women of childbearing potential
• Breastfeeding (1mg/ml)
• Renal impairment 
• Hepatic impairment 
• Elderly (1mg/ml)
• Diabetes mellitus 
• Complicated ocular surgeries 
• Repeated ocular surgeries within a short period of time 
• Corneal denervation 
• Corneal epithelial defects 
• Ocular surface diseases (e.g. dry eye syndrome) 
• Rheumatoid arthritis  
• Frequent or prolonged use 
• Known bleeding tendencies 
• Acute ocular infection 
• Concomitant use of contact lenses
• Exposure to sunlight (3mg/ml)
• History of hypertension and/or heart failure (1mg/ml)
• Higher doses (1mg/ml)
• History of ulcers (1mg/ml)
• History of gastrointestinal disease (1mg/ml)
  - Ulcerative colitis
  - Crohn’s disease
  - Hiatus hernia
  - Gastro-oesophageal reflux disease
  - Angiodysplasia
• Risk for heart failure (1mg/ml)
• Coadministration with another NSAID
• Coadministration with selective serotonin reuptake inhibitors (SSRIs) (1mg/ml)
• Coadministration with anticoagulants (e.g. warfarin) (1mg/ml) 
• Coadministration with antiplatelet agents (1mg/ml) 
• May impair ability to drive and operate machinery 

International manufacturer recommendations

• Pregnancy 
• Women of childbearing potential
• Renal impairment 
• Hepatic impairment 
• Diabetes mellitus
• Complicated ocular surgeries 
• Repeated ocular surgeries within a short period of time 
• Corneal denervation 
• Corneal epithelial defects
• Ocular surface diseases (e.g. dry eye syndrome) 
• Rheumatoid arthritis  
• Frequent or prolonged use
• Known bleeding tendencies 
• Acute ocular infection 
• Concomitant use of contact lenses
• Exposure to sunlight
• May impair ability to drive and operate machinery 

Forms avail. in SA and covered in this monograph: opd

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Prevention and treatment of postoperative pain and inflammation associated with cataract surgery
1mg/ml

• Ophthalmic (opd): 1 drop into affected eye(s), 8hrly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), 8hrly; Treatment duration: 2 weeks OR extended to 3 weeks post-operatively, as directed by the clinician

3mg/ml

• Ophthalmic (opd): 1 drop into affected eye(s), dly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), dly; Treatment duration: 2 weeks OR extended to 3 weeks post-operatively, as directed by the clinician

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Use the lowest effective dose for the shortest possible duration of treatment

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Reduction in risk of postoperative macular oedema associated with cataract surgery
1mg/ml

• Ophthalmic (opd): 1 drop into affected eye(s), 8hrly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), 8hrly; Treatment duration: Up to 60 days post-operatively 

Reduction in risk of postoperative macular oedema associated with cataract surgery in diabetic patients
3mg/ml

• Ophthalmic (opd): 1 drop into affected eye(s), dly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), dly; Treatment duration: Up to 60 days post-operatively

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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 

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Patients should be instructed to shake the bottle well before use. After cap is removed, if tamper evident snap collar is loose, remove before using product 

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If more than one topical ophthalmic medicinal product is being used, the medicinal product must be administered at least 5 minutes apart. Eye ointments should be administered last 

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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 

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Nepafenac contains benzalkonium chloride which may cause irritation and is known to discolour soft contact lenses.Patients should be advised not to wear 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 

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International manufacturer recommendations

Prevention and treatment of postoperative pain and inflammation associated with cataract surgery
1mg/ml

• Ophthalmic (opd): 1 drop into affected eye(s), 8hrly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), 8hrly; Treatment duration: 2 weeks OR extended to 3 weeks post-operatively, as directed by the clinician

3mg/ml

• Ophthalmic (opd) 1 drop into affected eye(s), dly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), dly; Treatment duration: 2 weeks OR extended to 3 weeks post-operatively, as directed by the clinician

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For ocular use only

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Reduction in risk of postoperative macular oedema associated with cataract surgery in diabetic patients
1mg/ml

• Ophthalmic (opd): 1 drop into affected eye(s), 8hrly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), 8hrly; Treatment duration: Up to 60 days post-operatively

3mg/ml

• Ophthalmic (opd): 1 drop into affected eye(s), dly, one day prior to surgery; On day of surgery: 1 drop into affected eye(s), 30-120min prior surgery; Maintenance: 1 drop into affected eye(s), dly; Treatment duration: Up to 60 days post-operatively

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For ocular use only

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Once-daily dosing with 3mg/ml eye drops provides the same total daily dose of nepafenac as three-times-daily dosing with 1mg/ml eye drops

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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

---

Patients should be instructed to shake the bottle well before use. After cap is removed, if tamper evident snap collar is loose, remove before using product

---

If more than one topical ophthalmic medicinal product is being used, the medicinal product 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

---

Nepafenac contains benzalkonium chloride which may cause irritation and is known to discolour soft contact lenses. Patients should be advised not to wear contact lenses unless clearly indicated by their doctor. 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

Not established for use in children

Pregnancy

South African manufacturer recommendations

• Caution; not recommended
• Contraindicated in the third trimester (1mg/ml)
• There are no adequate data regarding the use of nepafenac in pregnant women 
• Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown 
• Since systemic exposure in non-pregnant women is negligible after treatment with nepafenac, the risk during pregnancy could be considered low. Nevertheless, as inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryo/foetal development and/or parturition and/or postnatal development, nepafenac is not recommended during pregnancy
• Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) during the third trimester of pregnancy, may result in premature closure of the foetal ductus arteriosus in utero and possibly in persistent pulmonary hypertension of the newborn. The onset of labour may be delayed and its duration increased
• Women of childbearing potential: no information available
• Should not be used by women of childbearing potential not using contraception

International manufacturer recommendations

• Caution; not recommended
• There are no adequate data regarding the use of nepafenac in pregnant women 
• Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown 
• Since the systemic exposure in non-pregnant women is negligible after treatment with nepafenac, the risk during pregnancy could be considered low.  Nevertheless, as inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryo/foetal development and/or parturition and/or postnatal development, nepafenac is not recommended during pregnancy
• Should not be used by women of childbearing potential not using contraception

Breastfeeding

South African manufacturer recommendations
1mg/ml 

• Caution; not recommended 
• It is unknown whether nepafenac is excreted in human milk
• Animal studies have shown excretion of nepafenac in the milk of lactating rats 
• Nepafenac should not be used in women breastfeeding their infants

3mg/ml 

• Compatible 
• 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 breastfeeding child are anticipated since the systemic exposure of the breastfeeding woman to nepafenac is negligible

International manufacturer recommendations

• Compatible 
• 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 breastfeeding child are anticipated since the systemic exposure of the breastfeeding woman to nepafenac is negligible

Fertility

• There are no data on the effect on human fertility

Renal Impairment

• Caution; no information available  
  Nepafenac has not been studied in patients with 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

Hepatic Impairment

• Caution; no information available 
  Nepafenac has not been studied in patients with hepatic disease. 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

Elderly

South African manufacturer recommendations
1mg/ml 

• Caution; no dose adjustment recommended 
  The risk of gastrointestinal bleeding or perforation is higher with increasing doses in the elderly

3mg/ml 

• No dose adjustment recommended  

International manufacturer recommendations

• No dose adjustment recommended 

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness 
• Headache 

Cardiovascular Disorders

• Increased blood pressure 
• Hypertension (3mg/ml) 

Gastrointestinal Disorders

• Nausea and vomiting 

Skin and Subcutaneous Tissue Disorders

• Cutis laxa (dermatochalasis)
• Allergic dermatitis

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity 

Sensory Disorders

• Keratitis 
  - Punctate keratitis 
  - Ulcerative keratitis 
• Corneal epithelium defects 
• Foreign body sensation in eyes 
• Eyelid margin crusting 
• Iritis 
• Choroidal effusion
• Corneal deposits 
• Eye pain 
• Ocular discomfort 
• Dry eye 
• Blepharitis 
• Eye irritation 
• Eye pruritus 
• Eye discharge 
• Allergic conjunctivitis 
• Increased lacrimation 
• Conjunctival hyperaemia 
• Corneal perforation 
• Impaired healing (cornea) 
• Corneal opacity 
• Corneal scar 
• Reduced visual acuity 
• Eye swelling 
• Corneal thinning 
• Blurred vision 

• Prostaglandin analogues 
• Corticosteroids
• Agents that prolong bleeding time 

None routine

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 non-steroidal anti-inflammatory drug. Amfenac inhibits the action of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production.

Eye drops (per ml) 1mg

• Nevanac (Novartis) originator

Eye drops (per ml) 3mg

• Ilevro (Novartis) originator