Data from FDA - Curated by EPG Health - Last updated 09 August 2018

Indication(s)

1. INDICATIONS AND USAGE AMELUZ® gel, in combination with photodynamic therapy (PDT) using BF-RhodoLED® 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 gel, a porphyrin precursor, in combination with photodynamic therapy using BF-RhodoLED lamp, is indicated for the lesion-directed and field-directed treatment of actinic keratoses of mild-to-moderate severity on the face and scalp (1).

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Advisory information

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. Porphyria. AMELUZ use may cause uncontrolled phototoxic effects [see Warnings and Precautions (5.3)]. Photodermatoses. PDT may worsen the phototoxic or photoallergic reactions [see Warnings and Precautions (5.3)]. Known hypersensitivity to porphyrins (4). Known hypersensitivity to any component of AMELUZ, which includes soybean phosphatidylcholine (4). Porphyria (4). Photodermatoses (4).
Adverse reactions
6. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Transient Amnestic Episodes [see Warnings and Precautions (5.1)]. Risk of BF-RhodoLED Lamp Induced Eye Injury [see Warnings and Precautions (5.2)]. Increased Photosensitivity [see Warnings and Precautions (5.3)]. Risk of Bleeding in Patients with Coagulation Disorders [see Warnings and Precautions (5.4)]. Ophthalmic Adverse Reactions [see Warnings and Precautions (5.5)]. Risk of Mucous Membrane Irritation [see Warnings and Precautions (5.6)]. 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 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 Caucasian. For all 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, 87 placebo-treated subjects (n=16, n=32, n=39) and 212 AMELUZ-treated subjects (n=32, n=55, and n=125) were illuminated with BF-RhodoLED or similar narrow spectrum lamps. 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. The incidence of common (≥1%, <10%) and very common (≥10%) adverse reactions in randomized, multicenter trials at the application site are presented in Table 1. Table 1: Incidence of Adverse Reactions Occurring at ≥1% of the AMELUZ Group and More Frequently than the Vehicle Group in the Actinic Keratosis Trials 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 were headache, skin exfoliation, chills and eyelid edema. Less common (≥0.1%, <1%) adverse reactions at the application site for AMELUZ were hemorrhage and swelling. The adverse reactions not at the application site were blister, feeling hot, pruritus, pyrexia, scab, nervousness, pain, petechiae, rash pustular, skin erosion and ulcer. In a clinical trial designed to investigate the sensitization potential of aminolevulinic acid with 216 healthy subjects, 13 subjects (6%) developed allergic contact dermatitis after continuous exposure for 21 days with doses of aminolevulinic acid that were higher than doses normally used in the treatment of AK. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of AMELUZ. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and subcutaneous tissue disorders: application site inflammation, application site discoloration. Eye disorders: eye irritation, diplopia, ocular hyperemia, photophobia, and blurred vision. General disorders and administration site conditions: fatigue. Nervous system disorders: dysaesthesia, transient amnestic episodes.

Usage information

Dosing and administration
2. DOSAGE AND ADMINISTRATION Administer AMELUZ only by a health care provider (2.1). AMELUZ is for topical use only (2.1). Photodynamic therapy with AMELUZ involves preparation of lesions, application of the product, occlusion and illumination with BF-RhodoLED (2.2). Retreat lesions that have not completely resolved 3 months after the initial treatment (2.1). See BF-RhodoLED user manual for detailed lamp safety and operating instructions (2.1). 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 light. Retreat lesions that have not completely resolved after 3 months after the initial treatment. Refer to BF-RhodoLED user manual for detailed lamp safety and operating instructions. Both patient and medical personnel conducting the PDT should adhere to all safety instructions. 2.2 Dosage and 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 crust Step 2. Application of AMELUZ Use glove protected fingertips or a spatula to apply AMELUZ. Apply gel approximately 1 mm thick and include approximately 5 mm of the surrounding skin. Use sufficient amount of gel to cover the single lesions or if multiple lesions, the entire area. Application area should not exceed 20 cm2 and no more than 2 grams of AMELUZ (one tube) should be used at one time. The gel can be applied to healthy skin around the lesions. Avoid application near mucous membranes such as the eyes, nostrils, mouth, and ears (keep a distance of 1 cm from these areas). In case of accidental contact with these areas, thoroughly rinse with water. Allow the gel to dry for approximately 10 minutes before applying occlusive dressing. Figure 2: Drug application Step 3. Occlusion for 3 Hours Cover the area where the gel has been applied with a light-blocking, occlusive dressing. Following 3 hours of occlusion, remove the dressing and wipe off any remaining gel. Figure 3: Occlusion Step 4. Illumination with Red Light During illumination, patient and medical personnel need to wear suitable protective eyewear. Immediately after removing occlusion and any remaining gel, illuminate the treatment area with BF-RhodoLED®, a red light source with a narrow spectrum around 635 nm that delivers a light dose of approximately 37 J/cm2 within 10 minutes. Calibration by the operator is not needed; the illumination time is calculated automatically. Position the lamp head 5-8 cm from the skin’s surface. When an area of 8 x 18 cm is illuminated, the effective treatment area is 6 x16 cm. Larger areas can be illuminated in several steps. Healthy untreated skin surrounding the AK lesions does not need protection during illumination. Figure 4: Illumination If for any reason, the lesions cannot be illuminated within 3 hours after AMELUZ application, rinse off the gel with saline and water. For 2 days, protect the lesion sites and surrounding skin from sunlight or prolonged or intense light (e.g., tanning beds, sun lamps). Figure 1A: Degreasing of the skin Figure 1B: Figure 1B: Removal of scales and crusts Figure 2: Drug application Figure 3: Occlusion Figure 4: Illumination
Use in special populations
8. USE IN SPECIFIC POPULATIONS 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 estimated 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. 8.2 Lactation Risk Summary No data are available regarding the presence of aminolevulinic acid in human milk, the effects of aminolevulinic acid on the breastfed infant or on milk production. However, breastfeeding is not expected to result in exposure of the child to the drug due to the negligible systemic absorption of aminolevulinic acid in humans following topical administration of AMELUZ under maximal clinical use conditions [see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AMELUZ and any potential adverse effects on the breastfeeding child from AMELUZ or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 have not been established. AK is not a condition generally seen in the pediatric population. 8.5 Geriatric Use Of the 384 subjects exposed to AMELUZ in randomized, multicenter clinical trials, 83% (318/384) of the subjects were 65 years old and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

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).

More information

Category Value
Authorisation number NDA208081
Agency product number V35KBM8JGR
Orphan designation No
Product NDC 70621-101
Date Last Revised 25-04-2018
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder Biofrontera Inc.