Ameluz gel

Ameluz gel is used in combination with red light photodynamic therapy (PDT) to treat two skin conditions in adults:

• mild-to-moderate actinic keratosis (precancerous scaly spots found on sun-damaged skin) on the face and scalp. Ameluz can be used to treat single spots (lesion-directed treatment) or a whole affected area (field-directed treatment)
• superficial basal cell carcinoma (sBCC), a slow-growing form of skin cancer that stays in the top layer of the skin.

Ameluz is used with either the BF-RhodoLED lamp or the RhodoLED XL lamp. These are narrowband red light sources.

Ameluz contains aminolevulinic acid, a porphyrin precursor. After the gel is applied to the skin, aminolevulinic acid is taken up by skin cells and converted into a light-sensitive compound called protoporphyrin IX (PpIX). When the treated area is then exposed to red light from the lamp, the PpIX is activated. In the presence of oxygen, this forms reactive oxygen species, which damage cellular components and eventually destroy the targeted cells. Ameluz belongs to the drug class called topical photochemotherapeutics and it is also known as a porphyrin precursor.

Ameluz gained FDA approval for actinic keratosis on May 10, 2016. The FDA approved Ameluz for superficial basal cell carcinoma on September 90, 2026.

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Do not receive treatment with Ameluz if you have:

• a known allergy to porphyrins
• a known allergy to any ingredient in Ameluz, including soybean phosphatidylcholine
• porphyria, a genetic enzyme disorder affecting the skin or nervous system. Ameluz may cause uncontrolled phototoxic effects in people with porphyria
• photodermatoses, a group of conditions in which the skin reacts abnormally to light. Photodynamic therapy may make phototoxic or photoallergic reactions worse.

Before you receive Ameluz, tell your healthcare provider about all your medical conditions, including if:

• your skin is especially sensitive to light
• you have a blood-clotting problem
• you are pregnant or intending to become pregnant
• you are breastfeeding or intend to breastfeed
• you are taking medications that make your skin more sensitive to light, such as St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, and tetracyclines.

Pregnancy

Available data on the use of topical aminolevulinic acid with photodynamic therapy in pregnancy have not identified a risk of major birth defects, miscarriage, or other problems for the mother or baby. Animal reproduction studies have not been conducted. Very little aminolevulinic acid is absorbed into the body after Ameluz is applied to the skin, so the drug is not expected to reach an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Breastfeeding

It is not known whether aminolevulinic acid passes into breast milk or whether it affects a breastfed infant or milk production. Because so little of the drug is absorbed into the body, it is not expected to reach a breastfed infant. Ask a doctor if it is safe to breastfeed while using this medicine.

Children

The safety and effectiveness of Ameluz have not been established in children. Actinic keratosis and superficial basal cell carcinoma are not conditions usually seen in children.

Older adults

Of the 529 people given Ameluz in randomized clinical trials, 72% were aged 65 years or older. No overall differences in safety or effectiveness were seen between these people and younger adults, although greater sensitivity in some older people cannot be ruled out.

Ameluz is applied by a healthcare provider. It is for use on the skin only and is not for use in the eyes, mouth or vagina. It should not be used on the eyelid or around the eye.

Treatment with Ameluz involves several steps.

• Preparing the skin. Your healthcare provider wipes the lesions with an alcohol-soaked cotton pad to remove grease from the skin, then removes any scaling and crusts and gently roughens the lesion surfaces, taking care to avoid bleeding.
• Applying the gel. A layer of Ameluz about 1 mm thick is applied with gloved fingertips or a spatula. For actinic keratosis, the gel covers the lesions plus about 5 mm of surrounding healthy skin. For superficial basal cell carcinoma, it covers the lesions plus about 10 mm of surrounding healthy skin. The treatment area must not be larger than 60 cm2, and no more than 6 grams of Ameluz (3 tubes) may be used at one time. The gel is kept at least 10 mm away from the eyes, nostrils, mouth and ears.
• Covering the area for 3 hours. The gel is left to dry for about 10 minutes, then the area is covered with a light-blocking dressing. After 3 hours the dressing is removed and any remaining gel is wiped off.
• Light treatment. The area is illuminated straight away with the BF-RhodoLED or RhodoLED XL lamp. These lamps give off red light at around 635 nm and deliver a light dose of approximately 37 J/cm2. The lamp works out the illumination time automatically. You and any staff in the room must wear protective eyewear.

The light treatment has a low intensity and will not heat your skin. However, you may feel tingling, stinging, prickling, or burning where Ameluz was applied. This discomfort is usually temporary. Cooling the area with an air stream or a fine water mist may help reduce pain during the light treatment.

Healthy, untreated skin around the lesions does not need to be covered during the light treatment. If, for any reason, the lesions cannot be illuminated within 3 hours of the gel being applied, the gel is rinsed off with saline and water, and the treated skin must be protected from sunlight and strong light for 2 days.

You may need to be treated in separate sessions if you have lesions in more than one area.

How many treatments will I need?

For actinic keratosis, single lesions or a whole affected field can be treated in one session. Lesions that have not completely cleared are re-treated about 3 months after the first treatment.

For superficial basal cell carcinoma, treatment is given as two sessions spaced 1 to 2 weeks apart. About 3 months after the first treatment, any lesions that have not completely cleared are re-treated with two more sessions, again spaced 1 to 2 weeks apart. Your provider will check the treated area 4 to 6 weeks after each treatment cycle to confirm the lesions have gone, and will carry out routine skin examinations every 6 to 12 months.

What happens if I miss a dose?

In a medical setting, you are not likely to miss a dose. Call your doctor for instructions if you miss an appointment for your light treatment within the recommended time.

What happens if I overdose?

In a medical setting, an overdose would be treated quickly. Your healthcare provider should not treat an area of skin larger than 60 cm2, and a maximum of 3 Ameluz tubes (6 grams) may be used in one treatment session.

Ameluz has been studied in clinical trials for both of its approved uses.

In the actinic keratosis trials, 42% of people needed a second treatment because their lesions had not completely cleared 12 weeks after the first. Among those whose lesions did clear, some came back later. Recurrence rates across the three trials were 14%, 11%, and 25% at 6 months, and 40%, 22% and 37% at 12 months.

In the basal cell carcinoma trial, 22% of people in the Ameluz group looked clear to the eye at 12 weeks but still had cancer cells found on biopsy. This is why follow-up examinations are important.

Ameluz makes you more sensitive to light. Stay out of direct sunlight and avoid strong or prolonged light exposure, such as tanning beds and sun lamps, on the treated skin and surrounding area for approximately 48 hours after Ameluz is applied. Sunscreens will not protect you against this type of reaction. Wear a hat and clothing that covers your skin.

Do not get this medicine in your eyes, nose, mouth, or ears. If contact does occur, rinse with water.

Avoid using other medications on the areas treated with Ameluz unless your doctor tells you to.

Almost everyone treated with Ameluz gets some skin reaction where the gel was applied. In the actinic keratosis trials, local skin reactions occurred in about 99.5% of people treated. In the basal cell carcinoma trial, every person treated had at least one reaction at the application site.

The most common side effects happen where the gel has been applied. The table below shows how often each one was reported in clinical trials.

Most reactions start during the light treatment or shortly afterwards, are mild to moderate, and last 1 to 4 days. Sometimes they last 1 to 2 weeks or longer. Severe pain or burning occurred in up to 30% of people in the actinic keratosis trials that used one tube of gel on an area up to 20 cm2.

When a larger dose was used (three tubes, 6 g, on a 60 cm2 area), severe application site pain was reported in 41% of people, and 15% stopped the light treatment because of side effects. Peeling, itching, scabbing and skin erosion were also more common with the larger dose. Dry eyes, photosensitivity, and application site discoloration, dryness, papules and fissures were reported as well.

Serious side effects and warnings

Allergic reactions: Ameluz may cause allergic reactions, including severe reactions (anaphylaxis). Allergic reactions have been reported before the light treatment is given. If signs of an allergy such as a rash, redness or skin swelling occur, the gel should be washed off and appropriate treatment started. Get emergency medical help if you have signs of an allergic reaction such as hives, difficulty breathing, swelling of your face, lips, tongue or throat, a fast heartbeat, sweating, and loss of consciousness.

Temporary loss of memory: Transient amnestic episodes (temporary loss of memory) have been reported with Ameluz used in combination with photodynamic therapy. Contact your healthcare provider if memory loss, confusion or disorientation is noticed after treatment.

Risk of eye injury: The BF-RhodoLED and RhodoLED XL lamps may cause eye irritation, glare, blurred vision, visual impairment or eye injury. Eye exposure to the lamp light must be prevented. Protective eyewear must be worn by patients, healthcare providers, and anyone else present during the light treatment. Avoid staring directly into the light source.

Eye side effects: Eyelid swelling and dry eyes have occurred after photodynamic therapy with Ameluz. Avoid getting Ameluz in your eyes. Rinse your eyes with water if accidental contact occurs.

Increased sensitivity to light: Ameluz increases photosensitivity. Avoid sunlight and prolonged or intense light, such as tanning beds and sun lamps, on the treated lesions and surrounding skin for approximately 48 hours after treatment, whether or not the light treatment was given. Using Ameluz with other medicines that increase light sensitivity may raise the risk of a phototoxic reaction.

Risk of bleeding: Ameluz has not been tested in people with inherited or acquired coagulation disorders. Special care should be taken to avoid bleeding when the skin is prepared before treatment, and any bleeding must be stopped before the gel is applied.

Mucous membrane irritation: Ameluz can irritate mucous membranes and is for use on the skin only. Avoid direct contact with mucous membranes and rinse with water if accidental contact occurs.

Call your doctor at once if you have:

• eye problems such as eyelid swelling, dry eyes, double vision, red eyes or sensitivity to light
• severe skin pain or burning
• skin irritation that does not settle
• problems with memory, confusion, or disorientation

Side effects reported since Ameluz came on the market include allergic dermatitis, transient amnestic episodes, eye irritation, double vision, red eyes, sensitivity to light, and hypersensitivity reactions.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to Biofrontera Inc. at 1-844-829-7434 or to the FDA at 1-800-FDA-1088.

No formal drug interaction studies have been carried out with Ameluz. Tell your doctor about all your other medicines. Some drugs can make you more sensitive to light and may increase the phototoxic reaction to photodynamic therapy, especially:

• an antibiotic, including tetracyclines, quinolones or sulfa drugs
• griseofulvin, an antifungal
• a thiazide diuretic or "water pill"
• St. John's wort
• phenothiazines, used to treat nausea or vomiting and some mental health conditions such as schizophrenia
• sulfonylureas, an oral diabetes medicine.

This list is not complete. Other drugs may affect Ameluz, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Store Ameluz in a refrigerator at 2°C to 8°C (36°F to 46°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F).

After opening, Ameluz can be stored for up to 12 weeks in a refrigerator at 2°C to 8°C (36°F to 46°F) if the tube is tightly closed.

Ameluz is distributed by Biofrontera Inc., 660 Main Street, 1st Floor, Woburn, MA 01801, USA.

Active ingredient: aminolevulinic acid hydrochloride 100 mg per gram, equivalent to 78 mg aminolevulinic acid.

Inactive ingredients: xanthan gum, soybean phosphatidylcholine, polysorbate 80, medium-chain triglycerides, isopropyl alcohol, dibasic sodium phosphate, monobasic sodium phosphate, sodium benzoate and purified water.

Ameluz is a white-to-yellowish gel supplied in aluminum tubes with a white screw cap. Each tube contains 2 grams of gel. A maximum of 3 tubes (6 grams) may be used at each treatment session.