Cenegermin

Use of ophthalmic topical agents known to inhibit epithelial healing, including corticosteroids or eye drops containing preservatives such as benzalkonium chloride, polyquaternium-1, benzododecinium bromide, cetrimide and other quaternary ammonium derivatives, should be avoided during treatment of neurotrophic keratitis, as they could interfere with corneal healing.

An eye infection should be treated before use of cenegermin. Should an eye infection occur, cenegermin should be suspended until infection resolution.

Patients should be instructed to remove contact lenses before applying cenegermin and to wait 15 minutes after instillation of the dose before reinsertion, because the presence of a contact lens (either therapeutic or corrective) could theoretically limit the distribution of cenegermin onto the area of the corneal lesion.

Cenegermin may theoretically affect ocular cancer, as it is a growth factor. Cenegermin should be used with caution in patients with ocular cancer. It is recommended that these patients continue to be monitored for cancer progression during and after treatment with this medicinal product.

There are no data from the use of cenegermin in pregnant women. Animal studies with cenegermin do not indicate direct or indirect harmful effects with respect to reproductive toxicity when administered subcutaneously.

Systemic exposure to cenegermin is negligible or does not occur. As a precautionary measure, it is preferable to avoid the use of cenegermin during pregnancy.

It is not known whether cenegermin is excreted in human milk. A risk to the suckling child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from this therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on the effects of cenegermin on human fertility.

The treatment has minor influence on the ability to drive and use machines, as it may cause temporary blurred vision or other visual disturbances, which is expected to last a few minutes after instillation. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.

Summary of the safety profile

The most commonly reported adverse reactions in patients suffering from neurotrophic keratitis and treated with cenegermin during clinical studies include eye pain (11.1%), eye inflammation (8.3%), which may include anterior chamber inflammation and hyphaema; lacrimation increased (5.6%), with symptoms such as eye discharge; eyelid pain (5.6%) and foreign body sensation in the eye (5.6%).

Eye pain was the most frequently reported adverse reaction, followed by eye irritation and abnormal sensation in the eye, when considering the whole population treated with the medicinal product (i.e. population included in clinical trials also on indications other than neurotrophic keratitis).

List of adverse reactions

The following adverse reactions listed below were observed in clinical studies in patients suffering from neurotrophic keratitis, treated with cenegermin 20 μg/ml.

Adverse drug reactions are presented below according to MedDRA system organ classification (SOC and Preferred Term Level).

They are ranked according to system organ class and 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).

Infections and infestations

Uncommon: Corneal abscess

Nervous system disorders

Common: Headache

Eye disorders

Very common: Eye pain

Common: Eye inflammation, eyelid pain, foreign body sensation in the eye, lacrimation increased, blepharitis, conjunctival hyperaemia, photophobia, eye irritation

Uncommon: Corneal neovascularization