OXERVATE Eye drops, solution Ref.[7635] Active ingredients: Cenegermin

Risk of corneal melting or impending perforation

It is important that the risk of corneal melting or impending perforation, and the need to undergo emergency surgery or another procedure is assessed before starting therapy with OXERVATE as cenegermin should not be used in patients requiring immediate surgery.

Eye reactions

OXERVATE may cause mild to moderate eye discomfort, such as eye pain, to the patient. The patient should be advised to contact the doctor in case of concern or a more severe eye reaction.

Use of corticosteroids or eye drops containing preservatives

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 (see section 4.5).

Eye infections

An eye infection should be treated before use of OXERVATE. Should an eye infection occur, OXERVATE should be suspended until infection resolution (see section 4.2).

Ocular cancer

Cenegermin may theoretically affect ocular cancer, as it is a growth factor. OXERVATE 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.

Contact lenses

Patients should be instructed to remove contact lenses before applying OXERVATE 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.

Other topical ophthalmic products may be used during treatment with OXERVATE when used 15 minutes apart, with the exception of agents known to inhibit epithelial healing (e.g. corticosteroids or eye drops containing preservatives such as benzalkonium chloride, polyquaternium-1, benzododecinium bromide, cetrimide and other quaternary ammonium derivatives) (see sections 4.2 and 4.4). If eye ointment, gel or other viscous eye drops are used, OXERVATE should be administered first.

No interaction studies with other medicinal products have been performed.

As systemic absorption of cenegermin after use of the medicinal product is negligible or not detectable, no drug interactions are anticipated.

Pregnancy

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 (see section 5.3).

Systemic exposure to cenegermin is negligible or does not occur.

As a precautionary measure, it is preferable to avoid the use of OXERVATE during pregnancy.

Breastfeeding

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 OXERVATE 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).

Tabulated list of adverse reactions

The following adverse reactions listed below were observed in clinical studies in patients suffering from neurotrophic keratitis, treated with OXERVATE 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).

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 listed in Appendix V.

Not applicable.