FILSUVEZ Gel Ref.[50097] Active ingredients: Betulin

Hypersensitivity

Hypersensitivity has occurred in patients treated with Filsuvez (see section 4.8). If signs and symptoms of local or systemic hypersensitivity occur, Filsuvez should be discontinued immediately and appropriate therapy should be initiated.

Wound infection

The gel is sterile. However, wound infection is an important and serious complication that can occur during wound healing. In the case of infection, it is recommended to interrupt treatment. Additional standard treatment may be required (see section 4.5). Treatment may be re-initiated once the infection has resolved.

Squamous cell carcinoma and other skin malignancies

Patients with dystrophic EB (DEB) and junctional EB (JEB) may be at increased risk of development of squamous cell carcinoma. While there has been no increased risk of skin malignancies associated with Filsuvez to date, a theoretical increased risk of skin malignancies associated with use of Filsuvez cannot be ruled out. In the case of diagnosis of squamous cell carcinoma or other skin malignancies, treatment to the affected area should be discontinued.

Use in dominant dystrophic EB (DDEB) and junctional EB (JEB)

The quantity of clinical data from use of Filsuvez in patients with DDEB and JEB is limited (see section 5.1). The patient’s condition should be regularly evaluated to assess the benefit of continued treatment.

Birch pollen allergy

Filsuvez is safe to use for people who are allergic to birch pollen, as these allergens are not present in this medicinal product.

Accidental eye exposure

In the case of exposure to eyes product should be removed by eye irrigation.

No interaction studies have been performed. Since the systemic exposure of the main component betulin following cutaneous application is negligible no interaction with systemic treatments is expected. Interactions with topical products have not been investigated in clinical trials. Other topical products should not be concomitantly used together with Filsuvez but rather sequentially or alternatively depending on the clinical need.

Pregnancy

There are no data from the use of Filsuvez in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). No effects during pregnancy are anticipated, since systemic exposure to Filsuvez is negligible. Filsuvez can be used during pregnancy.

Breast-feeding

It is unknown whether birch bark extract/metabolites are excreted in human milk. No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breastfeeding woman to Filsuvez is negligible. Filsuvez can be used during breast-feeding, unless the chest area is subject to treatment.

Fertility

No adverse effects on fertility were observed in male and female rats administered birch bark extract. No effects on human fertility are anticipated, since the systemic exposure is negligible.

Filsuvez has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequently observed adverse reactions were wound complication (in 11.6% of EB patients and 2.9% of patients with other partial thickness wounds (PTW)), application site reaction (in 5.8% of EB patients), wound infections (in 4.0% of EB patients), pruritus (in 3.1% of EB patients and 1.3% of patients with other PTW), pain of skin (in 2.5% of patients with other PTW) and hypersensitivity reactions (in 1.3% of EB patients). There were no clinically relevant differences in the reactions reported in EB patients compared to patients with other PTW.

Tabulated list of adverse reactions

In the following table, adverse reactions are listed by MedDRA system organ class and preferred term. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The frequency of adverse reactions is defined as follows: 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), not known (cannot be estimated from the available data).

Table 1 lists all adverse reactions reported across clinical studies.

Table 1. Adverse reactions:

^* see Description of selected adverse reactions
^a adverse reactions observed in studies of patients with grade 2a burn wounds or split-thickness skin grafts

Description of selected adverse reactions

Hypersensitivity

Common cases of hypersensitivity-like reactions have been observed during clinical trials in EB patients. These reactions include rash, urticaria and eczema which were mild in 1.3% of patients and severe in 0.4% of patients. For specific recommendations, see section 4.4.

Application site reactions

Mild or moderate application site reactions are common and include application site pain and application site pruritis.

Wound complication

In studies with EB patients, wound complication comprised different kinds of local complications such as increase in wound size, wound re-opening and wound pain.

In studies in patients with burn wounds or split-thickness skin grafts, wound complications comprised different kinds of local complications such as post-procedural complications, wound necrosis, wound secretion, impaired healing, or inflammation of wound.

Paediatric population

70% (n=156) of patients randomised in the pivotal study (see section 5.1) were under the age of 18 with a median age of 12 years. 8% (n=17) of patients were below 4 years of age and 2 patients were under 1 year of age. The adverse reactions observed in the overall population were similar to those observed in the paediatric population.

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.