Nepafenac Ophthalmic Suspension 0.1%w/v Eye Drop (Each 15ml contains Nepafenac 0.1%w/v / Benzalkonium Chloride 0.0005w/v)

Indications

• Seborrhoeic dermatitis
• Dandruff
• Scalp psoriasis
• Bacterial infections affecting the scalp

Dosage

Children: For children, apply 3 times a week for 1 week, then apply twice weekly as needed. Refer to BNF for Children for further details.

Adults: Apply to the affected area as directed, typically 1-3 times weekly depending on the condition being treated. Refer to specific product guidelines for detailed dosing.

Mechanism of action

Benzalkonium chloride exerts its antimicrobial effect by disrupting the cell membrane of microorganisms, leading to leakage of cellular contents and ultimately cell death. This is facilitated by its cationic nature, which allows it to bind to negatively charged bacterial surfaces.

Pharmacodynamics

Benzalkonium chloride demonstrates rapid bactericidal activity, with effectiveness observed against gram-positive and gram-negative bacteria, fungi, and some viruses. Its antiseptic properties may be enhanced in the presence of moisture and are typically influenced by the concentration of the solution used.

Pharmacokinetics

Benzalkonium chloride is poorly absorbed through the skin. After topical application, it remains primarily at the site of application, where it exerts localized effects. Systemic absorption is minimal, and it is primarily eliminated through the skin and urine. However, specific pharmacokinetic data may vary based on formulation and application site.

Pregnancy

Benzalkonium chloride should be used with caution during pregnancy. Refer to specific guidelines or consult a healthcare professional.

Breast-feeding

Benzalkonium chloride should be used with caution while breastfeeding. Refer to specific guidelines or consult a healthcare professional.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Shampoo
• Soap or detergent
• Topical solution

Indications

• Postoperative pain and inflammation associated with cataract surgery
• Reduction in the risk of postoperative macular oedema in diabetic patients undergoing cataract surgery

Dosage

Children: Child 4–17 years: Apply 4 times a day, with treatment duration sometimes extending up to 4 weeks, depending on the clinical response.

Adults: Apply 4 times a day, with treatment duration sometimes extending up to 4 weeks, depending on the clinical response.

Mechanism of action

Nepafenac is a prodrug that is rapidly bioactivated to amfenac after penetrating the cornea. Amfenac inhibits both COX-1 and COX-2 enzymes, leading to a reduction in the synthesis of prostaglandins, which are mediators of inflammation and pain.

Pharmacodynamics

Following topical ocular administration, low but measurable plasma concentrations of nepafenac and amfenac are observed. The mean steady-state peak plasma concentrations (Cmax) for nepafenac and amfenac are approximately 0.310 ng/ml and 0.422 ng/ml, respectively, indicating effective local action with minimal systemic absorption.

Pharmacokinetics

Nepafenac is applied topically to the eye, where it is rapidly converted to its active form, amfenac. The pharmacokinetics involve minimal systemic absorption, allowing for targeted action at the site of inflammation with low plasma levels. The exact half-life and clearance rates are not well defined due to the localized use, but the rapid action suggests a quick onset of therapeutic effects.

Adverse effects

• Dry eye
• Eye discomfort
• Dizziness
• Headache
• Nausea
• Vision disorders
• Corneal deposits
• Allergic dermatitis
• Rash
• Taste altered
• Nasal complaints

Precautions

• Avoid sunlight exposure
• Discontinue if evidence of corneal epithelial breakdown or symptoms of infection occur

Pregnancy

Use in pregnancy should be assessed based on the benefit-risk balance, as safety data is limited.

Breast-feeding

Limited data available; caution is advised as it is not known if nepafenac is excreted in breast milk.

Storage

Store at room temperature, protect from light, and keep out of reach of children.

Formulations

• Nepafenac 3 mg/mL eye drops (Nevanac)

Indications

• Disinfection of surfaces
• Antiseptic for skin
• Preservative in pharmaceuticals
• Treatment of minor cuts and abrasions

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in pediatric populations.

Adults: Refer to the BNF for specific formulations and concentrations as doses may vary based on the application and preparation.

Mechanism of action

The bactericidal action of benzalkonium chloride is believed to result from the disruption of intermolecular interactions, which leads to the dissociation of cellular membrane lipid bilayers in bacteria. This disruption compromises cellular permeability, causing leakage of vital cellular contents. Moreover, the agent can deactivate important molecular complexes such as enzymes that regulate various respiratory and metabolic activities within the cells. Cationic surfactants like benzalkonium chloride can thus effectively disrupt critical intermolecular interactions and tertiary structures in biochemical systems, impairing bacterial function.

Pharmacodynamics

Benzalkonium chloride is classified as a biocidal agent with a relatively long duration of action. It exhibits a spectrum of activity against various microorganisms, including bacteria, certain viruses, fungi, and protozoa; however, it is ineffective against bacterial spores. The agent tends to demonstrate greater efficacy against gram-positive bacteria compared to gram-negative ones. The mode of action can be bacteriostatic (preventing growth) or bactericidal (killing bacteria), depending on its concentration. The activity of benzalkonium chloride is generally stable across different pH levels but is enhanced at elevated temperatures and with extended exposure.

Pharmacokinetics

The pharmacokinetic properties of benzalkonium chloride, including absorption, distribution, metabolism, and excretion, are not fully characterized. Its topical application limits systemic exposure, and it primarily exerts localized effects at the site of application. The duration of action and efficacy may be influenced by the formulation and concentration used.

Pregnancy

Benzalkonium chloride is generally considered safe for use during pregnancy when applied topically, but systemic absorption should be minimized. Always consult a healthcare provider for use during pregnancy.

Breast-feeding

Benzalkonium chloride is considered safe for topical application during breastfeeding, but care should be taken to avoid exposure to the infant. Consultation with a healthcare provider is recommended.

Storage

Store at room temperature, away from moisture and heat. Keep in a tightly closed container, protected from light.

Formulations

• Topical solution
• Disinfectant wipes
• Liquid antiseptics

Mechanism of action

Although not entirely elucidated, the bactericidal action of benzalkonium chloride is believed to be due to the disruption of intermolecular interactions. Such disruption can cause the dissociation of cellular membrane lipid bilayers of bacteria, resulting in compromised cellular permeability control and the leakage of important cellular contents. Additionally, other important molecular complexes like enzymes which control the maintenance of a great range of respiratory and metabolic cellular activities, are also susceptible to such deactivation. Consequently, a variety of critical intermolecular interactions and tertiary structures in very highly specific biochemical systems that allow bacterial agents to function normally can be readily disrupted or deactivated by cationic surfactants like benzalkonium chloride..

Pharmacodynamics

Benzalkonium chloride solutions are generally categorized as biocidal agents with relative long durations of action. Their spectrum of activity has been demonstrated against bacteria, to some viruses, fungi, and protozoa, although bacterial spores are treated as being resistant to the agent. Additionally, the agent generally shows more activity against gram-positive than gram-negative bacteria. Finally, solutions of benzalkonium chloride are bacteriostatic or bactericidal based on their concentration. Bacteriostatic agents act to prevent further growth of bacterial organisms that are present while bactericidal agents function to kill bacteria that are present. In general, the activity of the agent is not largely affected by pH, but such activity does increase substantially at higher temperatures and prolonged exposure times.

Mechanism of action

Nepafenac is a prodrug. After penetrating the cornea, nepafenac undergoes rapid bioactivation to amfenac, which is a potent NSAID that uniformly inhibits the COX1 and COX2 activity.

Pharmacodynamics

Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours postdose, respectively, following bilateral topical ocular TID dosing of nepafenac ophthalmic suspension, 0.1%. The mean steady-state Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration.