ACTIKERALL 5 mg/g + 100 mg/g CUTANEOUS SOLUTION

2. What you need to know before you start using Actikerall

Do not use Actikerall

• if you are allergic to fluorouracil, salicylic acid, or any of the other ingredients of this medicine (listed in section 6).
• during breast-feeding.
• during pregnancy or if you think you may be pregnant.
• if you have kidney problems.
• if it can come into contact with the eyes, the inside of the mouth or nose, or the genitals (mucous membranes).

Certain medicines may increase the side effects of Actikerall or cause other side effects. See the section "Other medicines and Actikerall" below.

Warnings and precautions

Talk to your doctor or pharmacist before you start using Actikerall

• if you know you have no activity of the enzyme dihydropyrimidine dehydrogenase (DPD) (complete DPD deficiency). It is important that you do not apply more Actikerall than indicated in section 3 of this leaflet.

• if your ability to notice physical contact, pain, or temperature is reduced (e.g., if you have diabetes). In this case, the lesions to be treated should be strictly controlled by your doctor.

• Actikerall should not be used on bleeding lesions.

• The treated area should be protected from direct sunlight as much as possible during the use of Actikerall, and the patient should not use sunlamps or tanning beds.

• There is no experience with Actikerall in the treatment of skin cancers such as basal cell carcinoma and Bowen's disease, so they should not be treated with the medicine.

• When treating an area with actinic keratosis that is also affected by another skin disease, it should be taken into account that the treatment outcome may vary.

• Currently, there is no data on the treatment of Actikerall in other body areas different from the face, forehead, and bald scalp.

• There is no experience with Actikerall in repeated treatment cycles in patients with actinic keratosis or in retreatment in case of recurrence of a lesion.

Children and adolescents

Actikerall should not be used in children or adolescents under 18 years of age. Actinic keratosis usually does not occur in children.

Other medicines and Actikerall

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. If you take several medicines at the same time, the effect of each of them may be increased or decreased.

In particular, tell your doctorif you are taking one of the following medicines:

• medicines used to treat viruses, such as chickenpox or herpes (brivudine, sorivudine, or similar medicines). Do not use Actikerall if you are taking or have taken one of these medicines in the last 4 weeks, as they may increase side effects.
• medicines for the treatment of epilepsy (phenytoin). The use of Actikerall may lead to high levels of phenytoin in the blood.
• medicines for the treatment of cancer and autoimmune diseases (methotrexate). This medicine may interact with Actikerall, causing side effects.
• medicines for the treatment of diabetes (sulfonylureas). This medicine may interact with Actikerall, causing side effects.

Pregnancy, breast-feeding, and fertility

You should not use Actikerall during breast-feeding, during pregnancy, or if you think you may be pregnant.

Driving and using machines

No special precautions are needed.

Actikerall contains dimethyl sulfoxide and ethanol.

Dimethyl sulfoxide may irritate the skin.

This medicine contains 160 mg of alcohol (ethanol) per gram. It may cause a burning sensation on damaged skin.

3. How to use Actikerall

Follow exactly the administration instructions of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

Posology

It is recommended to apply Actikerall once a dayunless your doctor has told you otherwise.

If you have actinic keratosis on a thin skin area, for example, around the eyes and on the temple, your doctor may tell you to apply Actikerall less frequently. If severe side effects occur, reduce the application frequency to three times a week until they improve. It may also be necessary for your doctor to control your treatment more frequently.

Method of administration

For application on the skin (cutaneous use).

• Remove the white film from the skin of the previous day's application by simply peeling it off (unless it is the first time you apply this medicine). Warm water facilitates the removal of the film.
• To open the bottle, press the cap down and turn it.
• Remove excess solution from the brush by sliding it along the neck of the bottle.
• Apply the solution once a day to the actinic keratosis and a small area of healthy skin around the affected area. The border of healthy skin should not be more than 0.5 cm wide.
• Multiple actinic keratosis lesions can be treated at the same time (up to 10 lesions), although application of the product to large areas of skin should be avoided. The total skin area treated simultaneously with Actikerall should not exceed 25 cm2 (5 cm x 5 cm).
• Let the solution dry and form a film.
• Do not cover with a dressing.
• Close the bottle tightly to prevent the product from drying out. If Actikerall dries out, do not use the product anymore. Do not use Actikerall if you notice the formation of crystals.
• Do not apply to skin with hair, as it may cause hair to clump in the affected area. If applied to areas with hair, consider shaving or other suitable methods of hair removal before application.

Other instructions

Direct contact of Actikerall with the eyes, the inside of the mouth or nose, or the genitals (mucous membranes) should be avoided.

Actikerall solution may permanently stain clothing, fabrics, or acrylics (e.g., acrylic bathtubs), so contact with these materials should be avoided.

Warning: flammable product. Keep away from fire and do not use near flames, lit cigarettes, or some appliances (e.g., hair dryers).

Consult your doctor regularly during treatment.

Duration of treatment

Actikerall is applied once a day to the actinic keratosis lesions until they disappear completely or for a maximum of 12 weeks. Improvement of actinic keratosis will start to be seen from the fourth week of starting treatment and will be gradually observed over a period of up to twelve weeks. Elimination of actinic keratosis may continue for a period of up to 8 weeks after the end of treatment. Treatment should be continued even if no effect is seen after the first 4 weeks.

If you think the effect of Actikerall is too strong or too weak, talk to your doctor or pharmacist.

If you use more Actikerall than you should

If you apply Actikerall more than once a day, it is more likely that skin reactions will occur and that they will be more severe. In this case, contact your doctor.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to use Actikerall

Do not apply a double dose to make up for forgotten doses. Continue your treatment as your doctor has told you or as described in this leaflet.

If you stop using Actikerall

Contact your doctor if you want to stop treatment.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Actikerall can cause side effects, although not everybody gets them.

Most patients treated with Actikerall experience mild to moderate irritation and inflammation in the application area. If these reactions worsen, contact your doctor.

As this medicine has a very strong skin-softening effect, white discoloration and skin peeling may occur.

The salicylic acid in Actikerall may cause mild irritation, such as skin inflammation (dermatitis) and contact allergic reactions in patients with sensitive skin or in people allergic to salicylic acid. Symptoms of contact allergic reactions may include itching, redness, and small blisters, even outside the application area.

Side effects may occur with the following frequencies:

Very common, may affect more than 1 in 10 people

• reactions at the application site

• redness of the skin (erythema), inflammation, irritation (including burning), pain, itching

Common, may affect up to 1 in 10 people

• headache
• skin peeling (exfoliation)
• reactions at the application site

• bleeding, loss of the top skin layer (erosion), crusts

Uncommon, may affect up to 1 in 100 people

• dryness of the eyes, itching of the eyes, increased tear production (lacrimation)
• reactions at the application site

• skin inflammation (dermatitis), swelling (edema), ulcers

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Actikerall

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label and carton after EXP. The expiry date is the last day of the month stated.

Do not store above 25°C. Do not refrigerate or freeze.

Keep the bottle tightly closed to prevent the contents from drying out.

Do not use this medicine more than 3 months after opening the bottle.

Do not use this medicine if you notice the formation of crystals.

Warning: flammable product. Keep away from fire and do not use near flames, lit cigarettes, or some appliances (e.g., hair dryers).

Medicines should not be disposed of via wastewater or household waste. Place the empty packaging and any unused medicinal product in the SIGRE collection point at your pharmacy. If you have any further questions, ask your pharmacist how to dispose of the packaging and any unused medicinal product. This will help protect the environment.

6. Contents of the pack and further information

Composition of Actikerall

The active substances are fluorouracil and salicylic acid.

1 g (equivalent to 1.05 ml) of cutaneous solution contains 5 mg of fluorouracil and 100 mg of salicylic acid.

The other ingredients are: dimethyl sulfoxide; anhydrous ethanol; ethyl acetate; pyroxylin; poly(butyl methacrylate, methyl methacrylate).

Appearance and packaging

Actikerall is a clear, colorless to slightly orange cutaneous solution.

This medicine is packed in a brown glass bottle with a child-resistant polypropylene cap in a cardboard box. The bottle cap is attached to a brush that serves to apply the solution. The applicator brush is made of plastic (polyethylene) with nylon bristles attached to the rod with stainless steel (V2A).

Pack size: bottle with 25 ml of cutaneous solution.

Marketing authorization holder and manufacturer

Almirall Hermal GmbH

Scholtzstraße 3

21465 Reinbek

Germany

Local representative

Almirall, S.A.

General Mitre, 151

08022 Barcelona - Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet: October 2020

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es