Ameluz · 4.4 Special warnings and precautions for use · 1

HOS-155189 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile In clinical trials with Ameluz, local skin reactions at the application site were observed in most of the subjects treated for actinic keratosis and basal cell carcinoma. This is to be expected as the therapeutic principle of photodynamic therapy is based on phototoxic effects of protoporphyrin IX which is synthesized from the active ingredient 5-aminolaevulinic acid. The most common signs and symptoms are application site irritation, erythema, pain, and oedema. The intensity of these effects is dependent on the type of illumination used for photodynamic therapy. The increased effects correlate with the higher clearance rate of red-light narrow spectrum lamps (see section 5.1). In rare cases, adverse reactions, e.g. pain, required interruption or discontinuation of the illumination. The study of Ameluz using natural and artificial daylight showed similar types of side effects. However, intensity of some adverse reactions, particularly pain, was lower when Ameluz was used in combination with daylight PDT. Most adverse reactions occur during illumination or shortly afterwards. The symptoms are usually of mild or moderate intensity (investigator’s assessment on a 4-point scale), and last for 1 to 4 days in most cases; in some cases, however, they may persist for 1 to 2 weeks or even longer. Tabulated list of adverse reactions The incidence of adverse reactions in 624 subjects exposed to photodynamic therapy with Ameluz in pivotal clinical trials is listed below. All these adverse reactions were non serious. The table additionally includes serious adverse reactions reported post-marketing. Frequencies are defined as 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), and not known (frequency cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table 1: Summary of related adverse drug reactions (ADRs) reported in patients treated with photodynamic therapy with 5-aminolaevulinic acid System organ class Frequency Adverse reaction At application site: Pustules Infections and infestations Uncommon Not at application site: Rash pustular Psychiatric disorders Uncommon Nervousness Common He

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HOS-155185 · has-contraindication-information · PDF-Seite 4

• Hypersensitivity to the active substance, to porphyrins, to soya or peanuts, or to any of the excipients listed in section 6.1. • Porphyria. • Known photodermatoses of varying pathology and frequency, e.g. metabolic disorders such as aminoaciduria, idiopathic or immunological disorders such as polymorphic light reaction, genetic disorders such as xeroderma pigmentosum, and diseases precipitated or aggravated by exposure to sun light such as lupus erythematosus or pemphigus erythematosus. 4

HOS-155184 · has-indication-information · PDF-Seite 2

Treatment of actinic keratosis of mild to moderate severity (Olsen grade 1 to 2; see section 5.1) and of field cancerization in adults. Treatment of superficial and/or nodular basal cell carcinoma unsuitable for surgical treatment due to possible treatment-related morbidity and/or poor cosmetic outcome in adults.

HOS-155187 · has-interaction-information · PDF-Seite 5

Ameluz does not significantly increase the natural plasma levels of 5-aminolaevulinic acid or protoporphyrin IX following topical application (see section 5.2). No interaction studies have been performed.

HOS-155188 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of 5-aminolaevulinic acid in pregnant women. Animal studies do not indicate direct or indirect harmful 5 effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Ameluz during pregnancy. Breast-feeding It is unknown whether 5-aminolaevulinic acid/metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued for 12 hours after treatment with Ameluz. Fertility There are no data available on the effect of 5-aminolaevulinic acid on fertility.

HOS-155186 · has-warning-information · PDF-Seite 5

Risk of Transient Global Amnesia (TGA) Photodynamic therapy (PDT) may be a precipitating factor for transient global amnesia in very rare instances. Although the exact mechanism is not known, stress and pain associated with PDT may increase the risk to develop transient amnesia. If amnesia is observed, the PDT must be discontinued immediately (see section 4.8). Use of immunosupressants As inflammatory response is important for the effect of PDT, the trials investigating the efficacy and safety of Ameluz excluded patients who were undergoing treatment with immunosuppression therapy. No experience exists for the use of Ameluz in patients taking immunosuppressants. Therefore, the use of immunosuppressants during treatment with Ameluz is not recommended. Ameluz should not be used on bleeding lesions Any bleeding must be stopped before application of the gel. No experience exists for the use of Ameluz in patients with inherited or acquired coagulation defects. Special care should be taken to avoid bleeding during lesion preparation in such patients (see section 4.2). Risk of mucous membrane and eye irritation Ameluz can cause mucous membrane or eye irritation. The excipient sodium benzoate may be mildly irritant to the skin, eyes, and mucous membranes. Special care should be taken to avoid applying Ameluz into eyes or to mucous membranes. In case of accidental contact, the site must be rinsed with water. Ameluz should not be used on skin areas affected by other diseases or tattoos. The success and assessment of treatment may be impaired if the treated area is affected by the presence of skin diseases (e.g. skin inflammation, located infection, psoriasis, eczema, and malignant skin cancers other than indicated) as well as tattoos. No experience exists with these situations. Intensive lesion preparation might lead to increased pain Some intensive lesion preparation protocols (e.g. chemical peel followed by ablative laser) might increase the frequency and intensity of pain sensation during PDT. This was noticed in the scope of artificial daylight PDT but should also be considered for red-light PDT and natural daylight PDT. Ameluz transiently increases phototoxicity Any UV-therapy should be discontinued before treatment. As a general precaution, sun exposure on the treated lesion sites and surrounding skin should be avoided for approximately 48 hours following treatment. Concomitant use of medicinal products with known phototoxic or photoallergic potential su

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