cenegermin

Action and Spectrum

Actions and spectrum: 

cenegermin is a medication that contains the active ingredient nerve growth factor (NGF). It is a recombinant form of human NGF and is used for ophthalmic purposes. 

The actions of cenegermin include promoting corneal nerve regeneration, improving corneal sensitivity, and maintaining the health of the cornea. It helps in the treatment of neurotrophic keratitis, a condition characterized by reduced corneal sensitivity and impaired healing of the cornea. 

The spectrum of cenegermin is specific to the treatment of neurotrophic keratitis, which is a rare eye condition caused by damage to the trigeminal nerve, leading to decreased corneal sensation and poor corneal healing. cenegermin is designed to address these specific problems and promote corneal healing in patients with this condition. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Foreign body sensation 

Ocular tearing and inflammation 

Corneal deposits 

Ocular hyperemia  

>10% 

Eye pain after installation (~16%) 

Black Box Warning

Black Box Warning: 

there were no black box warnings associated with cenegermin. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: cenegermin is contraindicated in individuals who have a known hypersensitivity or allergic reaction to cenegermin or any of its components. 

Caution: 

• Ocular Conditions: cenegermin is specifically indicated for the treatment of neurotrophic keratitis. Caution should be exercised when using cenegermin in patients with pre-existing ocular conditions, such as active corneal infections or inflammation. 
• Allergic Reactions: While uncommon, allergic reactions to cenegermin may occur. Patients should be monitored for signs of hypersensitivity, including rash, itching, swelling, or difficulty breathing. In case of an allergic reaction, the use of cenegermin should be discontinued, and appropriate medical treatment should be initiated. 
• Bacterial Keratitis: cenegermin should not be used in patients with active bacterial keratitis, as it is not effective against bacterial infections. Proper diagnosis and treatment of bacterial keratitis should be done before considering cenegermin therapy. 
• Contact Lens Use: cenegermin should not be used while wearing contact lenses. Patients using contact lenses should remove them before administering cenegermin and wait at least 15 minutes before reinserting the lenses.

Comorbidities: 

• Diabetes Mellitus: Diabetes can lead to nerve damage, including peripheral neuropathy, which can contribute to neurotrophic keratitis. 
• Herpes Simplex Virus (HSV) Infection: HSV infection can cause corneal damage and subsequent neurotrophic keratitis. 
• Ocular Surface Disorders: Conditions affecting the ocular surface, such as dry eye syndrome, Sjögren’s syndrome, or exposure keratitis, can predispose individuals to neurotrophic keratitis. 
• Trauma or Surgery: Corneal trauma, previous corneal surgeries, or other ocular procedures can result in corneal nerve damage and neurotrophic keratitis. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

• Neurotrophic Activity: cenegermin promotes the growth and survival of corneal nerves by binding to tropomyosin receptor kinase A (TrkA) receptors on corneal epithelial cells. This stimulates the proliferation and differentiation of corneal nerve fibers. 
• Corneal Epithelial Healing: By enhancing the innervation of the cornea, cenegermin facilitates the healing process of the corneal epithelium. It promotes the migration, adhesion, and proliferation of corneal epithelial cells, leading to the restoration of the damaged cornea. 
• Anti-inflammatory Effects: cenegermin exhibits anti-inflammatory properties by suppressing the release of pro-inflammatory cytokines and chemokines. This helps in reducing inflammation associated with neurotrophic keratitis. 

Pharmacodynamics: 

• Nerve Growth Factor (NGF) Receptor Activation: cenegermin binds to tropomyosin receptor kinase A (TrkA) receptors on corneal epithelial cells. This receptor activation triggers a cascade of intracellular signalling events, leading to the stimulation of nerve growth and survival pathways. 
• Corneal Nerve Regeneration: cenegermin promotes the regeneration of corneal nerves by inducing the outgrowth of nerve fibers. It enhances the proliferation and differentiation of corneal nerve cells, facilitating the regrowth of damaged or impaired nerves. 
• Corneal Epithelial Cell Proliferation: cenegermin stimulates the proliferation of corneal epithelial cells, which are responsible for the renewal and regeneration of the corneal surface. This effect helps in the healing of corneal epithelial defects and improves overall corneal health. 
• Neurite Outgrowth and Guidance: cenegermin provides guidance cues to growing nerve fibers, helping them navigate to their appropriate targets and establish functional connections within the cornea.

Pharmacokinetics: 

Absorption 

cenegermin is administered as eye drops directly onto the surface of the eye. It is designed to penetrate the cornea and provide neurotrophic support to the damaged cells. The absorption of cenegermin into the cornea is expected to occur locally at the site of application. 

Distribution 

Since cenegermin is administered topically to the eye, it is anticipated to have limited systemic distribution. It is expected to exert its therapeutic effect primarily within the cornea and nearby tissues. 

Metabolism 

The metabolism of cenegermin has not been extensively characterized. However, as a recombinant protein, it is likely to undergo metabolic processes like endogenous proteins. It may be subject to degradation by proteolytic enzymes in the eye or potentially in other tissues if it reaches the systemic circulation. 

Elimination and excretion 

The excretion pathway of cenegermin has not been well-documented. It is expected that any systemic absorption would be eliminated from the body through normal routes of protein clearance, such as renal excretion. 

Adminstartion

Administration: 

• Wash hands thoroughly with soap and water before handling the eye drops. 
• Tilt your head back and look up. 
• Gently pull lower eyelid to create a small pocket. 
• Hold the dropper close to your eye without touching it. 
• Squeeze the prescribed number of drops into the lower eyelid pocket. 
• Release the lower eyelid and close eye gently. Do not blink immediately after instilling the drops to allow them to spread evenly across the eye. 
• If instructed to use multiple eye drops, wait at least 5 minutes between each medication to prevent any interactions or dilution effects. 
• Wipe away any excess liquid around the eye with a clean tissue. 
• If you need to administer the drops to both eyes, repeat the process for the other eye. 
• Recap the eye drop bottle tightly. 
• Wash hands again to remove any residual medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: cenegermin 

Pronounced: (sen-uh-jer-min)  

Why do we use cenegermin? 

cenegermin, also known as recombinant human nerve growth factor (rhNGF), is primarily used for the treatment of neurotrophic keratitis, a rare eye condition characterized by impaired corneal sensitivity and damage to the cornea. 

• Neurotrophic Keratitis: cenegermin is indicated for the treatment of neurotrophic keratitis. It works by promoting the growth, survival, and differentiation of corneal cells, helping to heal the damaged cornea and restore its normal function. cenegermin can improve corneal sensitivity, reduce corneal damage, and enhance the healing process in patients with neurotrophic keratitis.