Aminolevulinic Acid Hydrochloride
FDA Drug Information • Also known as: Ameluz, Gleolan, Levulan Kerastick
- Brand Names
- Ameluz, Gleolan, Levulan Kerastick
- Route
- ORAL
- Dosage Form
- POWDER, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11. DESCRIPTION AMELUZ (aminolevulinic acid hydrochloride) topical gel, 10% is a non-sterile white-to-yellowish gel. The gel formulation contains a nanoemulsion. Aminolevulinic acid, a porphyrin precursor, is a white to off-white crystalline solid. It is readily soluble in water, methanol, and dimethylformamide. Its chemical name is 5-amino-4-oxo-pentanoic acid hydrochloride, molecular weight is 167.59 and molecular formula is C 5 H 9 NO 3 ·HCl. The structural formula of aminolevulinic acid hydrochloride is represented below: Each gram of AMELUZ contains 100 mg of aminolevulinic acid hydrochloride (equivalent to 78 mg aminolevulinic acid) as the active ingredient and the following inactive ingredients: xanthan gum, soybean phosphatidylcholine, polysorbate 80, medium-chain triglycerides, isopropyl alcohol, dibasic sodium phosphate, monobasic sodium phosphate, sodium benzoate and purified water. ALA.HCl - Structural Formula
What Is Aminolevulinic Acid Hydrochloride Used For?
1. INDICATIONS AND USAGE AMELUZ, in combination with photodynamic therapy (PDT) using BF-RhodoLED ® or RhodoLED ® XL lamp, a narrowband, red light illumination source, is indicated for lesion-directed and field-directed treatment of actinic keratoses (AKs) of mild-to-moderate severity on the face and scalp. AMELUZ, a porphyrin precursor, in combination with photodynamic therapy using BF-RhodoLED or RhodoLED XL lamp, is indicated for the lesion-directed and field-directed treatment of actinic keratoses (AK) of mild-to-moderate severity on the face and scalp ( 1 ).
Dosage and Administration
2. DOSAGE AND ADMINISTRATION Administer AMELUZ only by a health care provider ( 2.1 ). AMELUZ is for topical use only ( 2.1 ). Use AMELUZ in combination with red light photodynamic therapy (PDT). See BF-RhodoLED or RhodoLED XL user manual for detailed lamp safety and operating instructions ( 2.1 ). Photodynamic therapy with AMELUZ involves preparation of lesions, application of the product, occlusion and illumination with BF-RhodoLED or RhodoLED XL lamp ( 2.3 ). Apply an approximately 1 mm thick layer of AMELUZ to skin lesion(s). Cover individual lesions or the entire AK-field with AMELUZ. Include approximately 5 mm of the surrounding skin. Do not exceed an application area of 60 cm 2 . Do not use more than 6 grams of AMELUZ (3 tubes) at one time ( 2.2 ). Retreat lesions that have not completely resolved 3 months after the initial treatment ( 2.2 ). 2.1 Important Administration Information AMELUZ, in conjunction with lesion preparation, is only to be administered by a health care provider. AMELUZ is for topical use only. Not for ophthalmic, oral, or intravaginal use. Treat single lesions or an entire field affected by multiple lesions with AMELUZ, in combination with red light photodynamic therapy (PDT). PDT requires administration of both AMELUZ and BF-RhodoLED or RhodoLED XL light. Refer to BF-RhodoLED or RhodoLED XL user manual for detailed lamp safety and operating instructions. Adhere to all safety instructions for both patient and medical personnel while conducting the PDT. 2.2 Recommended Dosage Apply an approximately 1-mm thick layer of AMELUZ to skin lesion(s). Cover individual lesions or the entire AK-field with AMELUZ. Include approximately 5 mm of the surrounding skin. Do not exceed an application area of 60 cm 2 . Do not use more than 6 grams of AMELUZ (3 tubes) at one time. Retreat lesions that have not completely resolved after 3 months after the initial treatment. 2.3 Administration Instructions PDT is a multi-stage process: Step 1. Preparation of Lesions Before applying AMELUZ, carefully wipe all lesions with an ethanol or isopropanol-soaked cotton pad to ensure degreasing of the skin. Figure 1A: Degreasing the skin Thereafter, remove any scaling and crusts and gently roughen all lesion surfaces, taking care to avoid bleeding. Figure 1B: Removal of scales and crusts Step 2. Application of AMELUZ Apply AMELUZ using glove protected fingertips or a spatula. Use sufficient amount of gel to cover individual lesions or the entire field: Lesion-directed treatment: Apply gel approximately 1 mm thick to one or more individual AK lesions and include approximately 5 mm of the surrounding healthy skin. Field-directed treatment: Apply gel approximately 1 mm thick to the treatment field. Apply gel to the lesions and the skin in-between the lesions. Additionally, cover approximately 5 mm of the surrounding healthy area. Do not exceed an application area of 60 cm 2 and do not use more than 6 grams of AMELUZ (3 tubes) at one time. The gel can be...
Side Effects (Adverse Reactions)
6. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Hypersensitivity [ see Warnings and Precautions (5.1) ]. Transient Amnestic Episodes [ see Warnings and Precautions (5.2) ] . Risk of BF-RhodoLED or RhodoLED XL Lamp Induced Eye Injury [see Warnings and Precautions (5.3) ] . Ophthalmic Adverse Reactions [see Warnings and Precautions (5.4) ]. Increased Photosensitivity [see Warnings and Precautions (5.5) ] . Most common adverse reactions (≥10%) were application site erythema, pain/burning, irritation, edema, pruritus, exfoliation, scab, induration, and vesicles ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Biofrontera Inc. at 1-844-829-7434 or FDA at 1-800-332-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical program for AMELUZ included three double-blind and placebo-controlled phase 3 trials (Trials 1, 2, and 3), enrolling a total of 299 subjects that were treated with narrow band light. Trial subjects were adults greater than or equal to 49 years of age, and the majority had Fitzpatrick skin type I, II, or III. No subjects had Fitzpatrick skin type V or VI. Approximately 86% of subjects were male, and all subjects were White. For all three phase 3 trials, the enrolled subjects had mild to moderate AKs (Olsen grade 1 and 2) with 4 to 8 lesions on the face and scalp. Overall, 212 AMELUZ-treated subjects (n=32, n=55, and n=125) and 87 subjects receiving placebo (n=16, n=32, n=39) were illuminated with BF-RhodoLED or similar narrow spectrum lamps. For these trials, the maximal dose was one tube of AMELUZ (2 g) and the size of the application area was up to 20 cm 2 . Local skin reactions at the application site were observed in about 99.5% of subjects treated with AMELUZ and narrow spectrum lamps. The most frequent adverse reactions during and after PDT were application site erythema, pain, burning, irritation, edema, pruritus, exfoliation, scab, induration, and vesicles. Most adverse reactions occurred during illumination or shortly afterwards, were generally of mild or moderate intensity, and lasted for 1 to 4 days in most cases; in some cases, however, they persisted for 1 to 2 weeks or even longer. Severe pain/burning occurred in up to 30% of subjects. In one case, the adverse reactions required interruption or discontinuation of the illumination. Table 1 presents the incidence of common (≥1%, <10%) and very common (≥10%) adverse reactions at the application site in randomized, multicenter trials which evaluated a maximal dose of one tube of AMELUZ (2 g) and an application area up to 20 cm 2 . Table 1: Incidence of Adverse Reactions Occurring at ≥1% of the AMELUZ Group and More Frequently than the Vehicle Group in Actinic Keratosis Trials 1, 2, and 3 at the Application Site Adverse reaction Vehicle n=87 AMELUZ n=212 Adverse reactions at the application site Erythema Pain/Burning Irritation Edema Pruritus Exfoliation Scab Induration Vesicles Paresthesia Hyperalgesia Reaction Discomfort Erosion Discharge Bleeding Pustules 34 (39%) 26 (30%) 17 (20%) 3 (3%) 14 (16%) 4 (5%) 2 (2%) 0 (0%) 1 (1%) 2 (2%) 0 (0%) 2 (2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 195 (92%) 195 (92%) 153 (72%) 75 (35%) 72 (34%) 41 (19%) 41 (19%) 26 (12%) 25 (12%) 18 (9%) 13 (6%) 8 (4%) 7 (3%) 6 (3%) 4 (2%) 3 (1%) 3 (1%) Common (≥1%, <10%) adverse reactions not at the application site for AMELUZ maximal dose of one tube (2 g) and application area up to 20 cm 2 were headache, skin exfoliation, chills and eyelid edema. Less common (≥0.1%, <1%) adverse reactions at the application site for AMELUZ maximal dose of one tube (2 g) and application area up to 20 cm 2 were hemorrhage and swelling. The adverse...
Drug Interactions
7. DRUG INTERACTIONS There have been no formal studies of the interaction of AMELUZ with other drugs. It is possible that concomitant use of other known photosensitizing agents such as St. John’s wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines may enhance the phototoxic reaction to PDT [see Warnings and Precautions (5.3) ] . Concomitant use of the following medications may enhance the phototoxic reaction to photodynamic therapy: St. John’s wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones, and tetracyclines ( 7 ).
Contraindications
4. CONTRAINDICATIONS AMELUZ is contraindicated in patients with: Known hypersensitivity to porphyrins. Known hypersensitivity to any of the components of AMELUZ, which includes soybean phosphatidylcholine [see Warnings and Precautions (5.1) ] . Porphyria. AMELUZ use may cause uncontrolled phototoxic effects [see Warnings and Precautions (5.5) ] . Photodermatoses. PDT may worsen the phototoxic or photoallergic reactions [see Warnings and Precautions (5.5) ] . Known hypersensitivity to porphyrins ( 4 ). Known hypersensitivity to any component of AMELUZ, which includes soybean phosphatidylcholine ( 4 ). Porphyria ( 4 ). Photodermatoses ( 4 ).
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on AMELUZ use in pregnant women to inform a drug associated risk. Animal reproduction studies were not conducted with aminolevulinic acid. Systemic absorption of aminolevulinic acid in humans is negligible following topical administration of AMELUZ under maximal clinical use conditions [see Clinical Pharmacology (12.3) ] . It is not expected that maternal use of AMELUZ will result in fetal exposure to the drug. The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
How Supplied
16. HOW SUPPLIED/STORAGE AND HANDLING AMELUZ (aminolevulinic acid hydrochloride) topical gel, 10% is a white-to-yellowish gel. The drug product is supplied in an aluminum tube with a white, high density polyethylene (HDPE) screw cap. Each tube contains 2 g of gel. NDC 70621-101-01 2 g tube NDC 70621-101-10 Cardbox containing one 2 g tube NDC 70621-101-20 Cardbox containing ten 2 g tubes Store AMELUZ in a refrigerator, 2°C – 8°C (36°F – 46°F). Excursions permitted to 15°C – 30°C (59°F – 86°F). After opening, AMELUZ can be stored for up to 12 weeks in a refrigerator at 2°C – 8°C (36°F – 46°F) if the tube is tightly closed.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.