Package Insert: Information for the User

Ameluz 78mg/g gel

5‑aminolevulinic acid

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor.
• This medication has been prescribed only for you, and you should not give it to others, even if they have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this package insert. See section4.

1.What Ameluz is and for what it is used

2.What you need to know before starting to use Ameluz

3.How to use Ameluz

4.Possible adverse effects

1. Storage of Ameluz

6. Contents of the container and additional information

Ameluz contains the active ingredient 5‑aminolevulinic acid. It is used for thetreatment:

• of slightly palpable or moderately thick actinic keratosis or of entire fields affected by actinic keratosis in adults. Actinic keratosis is caused by a series of changes in the outer layer of the skin that can lead to skin cancer.
• of superficial and/or nodular basal cell carcinoma that is not susceptible to surgical treatment due to possible morbidity related to the treatment and/or a poor aesthetic outcome in adults. Basal cell carcinoma is a type of skin cancer that can cause the appearance of reddish, flaking plaques or one or several small, easily bleeding bumps that do not heal.

After application, the active ingredient of Ameluz becomes a photosensitizing substance that accumulates in the affected cells. Illumination with suitable light produces reactive oxygen molecules that attack the target cells. This treatment is called photodynamic therapy (PDT).

No use Ameluz

• if you areallergicto

• el ácido 5‑aminolevulínico o a cualquiera de los demás componentes de este medicamento (incluidos en la sección 6)
• sustancias fotoactivas denominadas porfirinas
• la soja o los cacahuetes

• si tiene una alteración de la formación de los pigmentos rojos de la sangre llamadaporfiria
• si padeceotherskin conditions,caused, or worsened,by exposure to light

Advertencias y precauciones

Consult your doctor before starting to use Ameluz.

• In rare cases, photodynamic therapy may increase the risk of developing

temporary memory loss.

• Ameluz is not recommended for use if you are using immunosuppressants.
• Do not apply Ameluz:
• • in bleeding lesions.
  • in the eyes or mucous membranes.
  • in areas of skin affected by other diseases or with tattoos, as this may hinder the success and evaluation of treatment.

• Intensive preparation of lesions (e.g., chemical exfoliation followed by laser ablation) may increase pain during photodynamic therapy.

• Discontinue any UV therapy before treatment.
• Avoid exposure to sunlight of treated lesions and surrounding skin for up to 48hours

after treatment.

Children and adolescents

Actinic keratosis and basal cell carcinoma do not affect children and adolescents, except in extremely rare cases.

Use of Ameluz with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Inform your doctor if you are using medications that increase allergic reactions or other adverse reactions after exposure to light, such as

• St. John's Wort or its preparations: medications for depression treatment

• griseofulvin: medication for fungal infections treatment
• diureticswith active ingredients whose names almost always end in «tiazida» or «tizida» (or «tiacida», «ticida»), such as hydrochlorothiazide
• certain medicationsfor diabetes treatment, such as glibenclamide or glimepiride
• medications for mental disorders,nausea or vomitingwith active ingredients whose names almost always end in «azina» (or «acina»), such as phenothiazine
• medications for bacterial infectionswith active ingredients whose names start with «sulfa» or end in «oxacina» or «ciclina», such as tetracycline

Pregnancy and lactation

Ameluz is not recommended during pregnancy, as there is insufficient information.

Lactation should be interrupted for 12hours after Ameluz application.

Driving and operating machinery

Ameluz has no or insignificant influence on the ability to drive and operate machinery.

Ameluz contains

• 2.4 mg of sodium benzoate (E211) per gram of gel. Sodium benzoate may cause local irritation.
• soybean phosphatidylcholine:if you are allergic to peanuts or soy, do not use this medication.

Ameluz is only applied to the skin. The treatment consists of the application of Ameluz and exposure to light. A single treatment session can be administered to treat single or multiple lesions, or entire treatment fields. The light source for the treatment of lesions or fields of actinic keratosis can be daylight (natural or artificial) or a special red light lamp. Your doctor will decide which therapeutic option to use, depending on your lesions.

The light source for photodynamic therapy must always be a red light lamp in the treatment of actinic keratosis in the body regions of the trunk, neck, and limbs and basal cell carcinoma.

Treatment of actinic keratosis and basal cell carcinoma lesions or fields with a red light lamp

The use of Ameluz with a red light lamp requires specific equipment and knowledge of photodynamic therapy. Therefore, this treatment is performed in the doctor's office.

Preparation of the lesions

The area of application is cleaned with a cotton swab soaked in alcohol to degrease the skin. The scales and crusts are carefully removed and the surface of all lesions is gently scraped. Bleeding of the lesions should be avoided.

Application of the gel

Ameluz is applied forming a film of approximately 1 mm in thickness that covers all lesions or fields and approximately 5 mm of the surrounding area, with the fingertips protected with a glove or a spatula.

A minimum distance of 1 cm should be maintained from the eyes and mucous membranes. In case of accidental contact, wash with water.

Allow the gel to dry for about 10 minutes before placing an opaque dressing over the treated area. Remove the dressing after 3 hours. Wash to remove any remaining gel.

Exposure to a red light lamp

After cleaning the remaining gel, the entire treated area is exposed to a red light source. The efficacy and adverse effects, such as temporary pain, depend on the light source used.

Both patients and healthcare professionals should follow the safety instructions that accompany the lamp used during treatment. Appropriate protective eyewear should be used during illumination. No protection is necessary for untreated healthy skin.

Treatment of actinic keratosis and basal cell carcinoma lesions and fields of the face and scalp with natural daylight

Considerations before treatment

Use only daylight treatment if the weather is suitable for pleasant outdoor stay for 2 hours (with temperatures > 10°C). If it is raining or likely to rain, do not use daylight treatment.

Preparation of the lesions

Apply a sunscreen to the exposed skin 15 minutes before the lesion treatment. Use only sunscreens with chemical filters and a sun protection factor of 30 or higher. Do not use sunscreens with physical filters such as titanium dioxide or zinc oxide, as these inhibit light absorption and may affect treatment efficacy.
Then, clean the area of application with a cotton swab soaked in alcohol to degrease the skin. Carefully remove scales and crusts and gently scrape the surface of all lesions. Be careful not to cause bleeding.

Application of the gel

Apply a thin layer of Ameluz over the lesions or entire fields and approximately 5 mm of the surrounding area with the fingertips protected with a glove or a spatula.

Avoid direct contact with the eyes and mucous membranes, maintaining a distance of at least 1 cm. In case of contact, wash the affected area with water.

No dressing is necessary. Do not clean the gel during the entire daylight treatment session.

Exposure to natural daylight for the treatment of actinic keratosis

If the conditions are suitable (see previous Considerations before treatment), you should go outside 30 minutes after applying the gel and stay in full daylight for 2 consecutive hours. It is acceptable to protect yourself in the shade if it is hot. If the time is interrupted outside, you should compensate by increasing the illumination time. Remove any remaining gel after 2 hours of exposure to light.

Treatment of actinic keratosis lesions and fields of the face and scalp with artificial daylight

The use of Ameluz with an artificial daylight lamp requires specific equipment and knowledge of photodynamic therapy. Therefore, this treatment is performed in the doctor's office.

Preparation of the lesions

The area of application is cleaned with a cotton swab soaked in alcohol to degrease the skin. The scales and crusts are carefully removed and the surface of all lesions is gently scraped. Bleeding of the lesions should be avoided.

Application of the gel

A thin layer of Ameluz is applied that covers all lesions or fields and approximately 5 mm of the surrounding area with the fingertips protected with a glove or a spatula.

A minimum distance of 1 cm should be maintained from the eyes and mucous membranes. In case of accidental contact, wash with water.

Incubation and illumination with an artificial daylight lamp

After application, the total treatment time (including incubation and illumination) should be 2 hours and not exceed 2.5 hours. However, illumination should start between 0.5 and 1 hour after gel application.No occlusive dressing is necessary during incubation; it can be used optionally, but it should be removed at the latest before illumination.Both patients and healthcare professionals should follow the safety instructions that accompany the light source used during treatment.No protection is necessary for untreated healthy skin. After exposure to light, the remaining gel is removed.

Number of treatments

• Actinic keratosis lesions and fields are treated with a single session.
• Basal cell carcinoma is treated with two sessions, with a one-week interval between sessions.

The treated lesions are evaluated 3 months after treatment. Your doctor will determine how each skin lesion has responded, and it may be necessary to repeat the treatment at that time.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them. Approximately 9 out of 10 patients experience side effects at the application site, indicating that the affected cells are responding to treatment.

Generally, side effects are of mild or moderate intensity, and appear habitually during exposure to light or up to 4 days after. However, in some cases, they may persist for 1 to 2 weeks or even longer. In rare cases, due to adverse reactions, such as pain, it may be necessary to interrupt or suspend lighting. After longer periods of time, treatment with Ameluz often results in continuous improvement of skin quality-related parameters.

The side effects listed below have been reported with the use of Ameluz with a red light lamp. The Ameluz study with natural or artificial daylight showed similar types of side effects, although, especially for pain, of lower intensity. Some reactions at the application site have been observed before using the light.

Very common: may affect more than 1 in 10 people

• reactions at the application site

- redness of the skin

- pain (including burning sensation)

- irritation

- itching

- inflammation of tissues caused by excess fluid

- crusts

- skin peeling

- hardening

- abnormal sensations, such as prickling, tingling, or numbness

Common: may affect up to 1 in 10 people

• reactions at the application site

- vesicles

- secretion

- abrasion

- other reaction

- discomfort

- increased sensitivity to pain

- bleeding

- heat

• headache

Rare: may affect up to 1 in 100 people

• reactions at the application site

- change in color

- pustules

- ulcer

- swelling

- inflammation

- eczema with pustules

- allergic reaction1

• blister
• dry skin
• inflammation of the eyelids caused by excess fluid, blurred vision, visual impairment
• unpleasant and abnormal tactile sensation
• chills
• sensation of heat, fever, hot flashes
• temporary loss of memory1
• pain
• nervousness
• suppuration of the wound
• fatigue
• eruption, red or purple spots on the body
• ulcer
• swelling
• tightening of the skin

1Post-marketing period data

Reporting of adverse reactions

If you experience any adverse reactions, consult your doctor, even if they do not appear in this prospectus.You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of sight and out of reach of children.

Do not use this medication after the expiration date that appears on the packaging after «CAD». The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C and 8 °C).

Keep the tube perfectly closed after the first opening.Dispose of opened tubes4 months afteropening.

Medicines should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

Composition of Ameluz

• The active ingredient is 5-aminolevulinic acid.

Each gram of Ameluz contains 78 mg of 5-aminolevulinic acid (as hydrochloride).

• The other components are:

sodium dihydrogen phosphate dihydrate, isopropyl alcohol, polysorbate 80, purified water, sodium benzoate (E211), sodium dihydrogen phosphate dihydrate, soy phosphatidylcholine, medium-chain triglycerides, xanthan gum. See section 2.

Appearance of the product and contents of the container

Ameluz is a white or yellowish gel.

Each box contains an aluminum tube with 2 g of gel closed with a polyethylene screw cap.

Marketing Authorization Holder

Biofrontera Bioscience GmbH

Hemmelrather Weg 201

51377 Leverkusen, Germany

Tel.: +49 214 87632 66, Fax: +49 214 87632 90

Email:[email protected]

Responsible for manufacturing

Biofrontera Pharma GmbH

Hemmelrather Weg 201

51377 Leverkusen, Germany

Tel.: +49 214 87632 66, Fax: +49 214 87632 90

Email:[email protected]

For more information about this medication, please contact the local representative of the marketing authorization holder:

Belgium/Belgique/Belgien Czech Republic

Biofrontera Pharma GmbH Biofrontera Pharma GmbH

Germany / Allemagne / Deutschland Czech Republic

Tel/Tel: +49 214 87632 66 Tel: +49 214 87632 66

[email protected][email protected]

Denmark

Biofrontera Pharma GmbH Galenica AB

???????? Sweden

Te?.: +49 214 87632 66 Tlf:+46 40 32 10 95

[email protected][email protected]

Germany Estonia

Biofrontera Pharma GmbH Biofrontera Pharma GmbH

Tel: +49 214 87632 66 Tel: +49 214 87632 66

[email protected][email protected]

Greece Croatia

Biofrontera Pharma GmbH Biofrontera Pharma GmbH

Germany Nemacka

Τel: +49 214 87632 66 Tel: +49 214 87632 66

[email protected][email protected]

Spain Ireland

Biofrontera Pharma GmbH sucursal en España Biofrontera Pharma GmbH

Tel: 900 974943 Germany

[email protected]Tel: +49 214 87632 66

[email protected]

France Iceland

Biofrontera Pharma GmbH Galenica AB

Germany Sweden

Tél: 0800 904642 Sími:+46 40 32 10 95

[email protected][email protected]

ItalyGreece

Biofrontera Pharma GmbH Biofrontera Pharma GmbH

Germany Germany

Tel: +49 214 87632 66 Τel: +49 214 87632 66

[email protected][email protected][email protected]

Luxembourg/Luxemburg Hungary

Biofrontera Pharma GmbH Biofrontera Pharma GmbH

Germany / Deutschland Németország

Tél/Tel:+49 214 87632 66 Tel.: +49 214 87632 66

[email protected][email protected]

Malta Norway

Biofrontera Pharma GmbH Galenica AB

Germany Sweden

Tel: +49 214 87632 66 Tlf:+46 40 32 10 95

[email protected][email protected]

Netherlands Austria

Biofrontera Pharma GmbH Pelpharma Handels GmbH

Germany Tel: +43 2273 70 080

Tel: +49 214 87632 66 [email protected]

[email protected]

Poland Romania

medac GmbH Sp. z o.o. Biofrontera Pharma GmbH

Branch in Poland Germany

Tel.: +48 (0)22 430 00 30 Tel: +49 214 87632 66

[email protected][email protected]

Portugal Slovenia

Biofrontera Pharma GmbH Biofrontera Pharma GmbH

Germany Németország

Tel: +49 214 87632 66 Tel: +49 214 87632 66

[email protected][email protected]

Slovak Republic Finland

Biofrontera Pharma GmbH Galenica AB

Germany Sweden

Tel: +49 214 87632 66 Puh/Tel:+46 40 32 10 95

[email protected][email protected]

Sweden United Kingdom (Northern Ireland)

Galenica AB Biofrontera Pharma GmbH

Tfn:+46 40 32 10 95 Germany

[email protected]Tel: +49 214 87632 66

[email protected]

Last review date of this leaflet: 07/2024

For more detailed information about this medication, please visit the website of the European Medicines Agencyhttp://www.ema.europa.eu.