Notably, 5-ALA, the main component of Ameluz, is hydrophilic and has difficulty penetrating the outer layer of the epidermis, the stratum corneum, upon application. Past therapies that utilized ALA include Levulan (DUSA Pharmeceuticals, Inc.), an ALA in aqueous solution formulation, and Alacare (Spirig Pharma AG, Egerkingen, Switzerland), a patch containing ALA. Ameluz, a second-generation topical sensitizer used in conjunction with PDT, has been shown to have improved stability in aqueous solution. It uses a lecithin microemulsion as a transdermal delivery system that comes in a gel, which increases penetration of the stratum corneum by increasing the fluidity of lipids in the skin. This microemulsion medium sets Ameluz apart from other ALA photodynamic therapies. It increases the absorption of the drug and allows it to both reach deeper lesions and be distributed more uniformly throughout the lesion (Maisch, Santarelli, Schreml, Babilas, & Szeimies, 2010).
Moreover, it has been shown to be superior to other photodynamic therapies that utilize metabolites of ALA, including methyl-5-aminolevulinate formulations. Dirschka et al. conducted a multicentered, randomized, Phase III trial comparing nanoemulsion/noncolloidal ALA with methyl-5-aminolevulinate and found that it cleared more AKs than the latter (clearance = 78.2% vs. 64.2%, respectively, p < .05; Dirschka et al., 2012).
EFFICACY, DOSING, AND ADMINISTRATION
The results of the Phase III trial showed that Ameluz resulted in 90.9% complete clearance of AKs compared with the 21.9% clearance in the placebo group 12 weeks after the last PDT treatment. This showed that Ameluz was a statistically effective treatment (p < .0001). After only 12 weeks of the first PDT treatment, Ameluz treatment resulted in 61.8% clearance of AK compared with 9.4% for the placebo group. Most (90.7%) of the patients treated with Ameluz were satisfied with the treatment, and the number of patients with improved skin quality (measured by lack of roughness, dryness, and scales) increased from 14.8% before treatment to 63% after treatment (Reinhold et al., 2016).
Ameluz is applied topically only by a trained healthcare professional. First, the skin lesions need to be wiped with isopropanol or ethanol to decrease the normal lipid barrier of the skin allowing for better penetration and absorption of the medication. A 1-mm layer of Ameluz gel is then applied to the AK area with enough to cover a 5-mm border of surrounding skin. The Ameluz gel is applied to an area no larger than 20 mm2, and no more than 20 g of gel should be used for any one treatment area. Ameluz should not be applied to the eyes, mouth, nostrils, or inside of the ears (U.S. Food and Drug Administration [FDA], 2016).
The gel is then allowed to dry for 10 minutes before an occlusive dressing is applied to the application site. After 3 hours, the dressing is removed and the site is illuminated with red light around 635 nm from a BF-RhodoLED lamp. The lamp needs to deliver a radiation exposure dose of 37 J/cm2 to the skin at a distance of 5–8 cm from the skin surface for 10 minutes. The treated area should not be exposed to sunlight or UV light for 48 hours because Ameluz increases photosensitivity (FDA, 2016). Patients treated with Ameluz and phototherapy must be instructed to keep the treatment area covered with clothing or sunscreen and avoid UV light exposure for 48 hours.
During the Phase III trial, all patients given Ameluz reported at least one adverse effect. The adverse effects were all at the application site and included pruritus, erythema, exfoliation, scabs, vesicles, and pain. Most of these reactions were of mild intensity and resolved within 2 weeks (Reinhold et al., 2016). Other less common adverse reactions were headache and problems at the treatment site, including warmth, erosions, paresthesia, and hyperalgesia (Tzogani et al., 2014). Several methods have been developed to decrease the pain associated with this treatment. Although conventional topical anesthetics are used, newer techniques have also been developed, including cold air analgesia where a device that produces cold air cools the treatment area in PDT, such as a cold-air fan (Pagliaro, Elliot, Bulsara, King, & Vinciullo, 2004). Livopan (Linde Gas Therapeutics GmbH, Germany) is nitrous oxide/oxygen mixture that is used as an inhalation analgesia (Fink, Enk, & Gholam, 2015).
Ameluz was approved for the treatment of AKs of mild to moderate intensity (Olsen grades 1–2) appearing on the face and scalp. Treatment with Ameluz is done in conjunction with PDT using a BF-RhodoLED lamp (FDA, 2016).
Patients who are sensitive to porphyrins or have a history of porphyria/pseudoporphyria (either from a genetic defect or immune dysregulation that leads to accumulation of porphyrins or pathway metabolites) should not use Ameluz. In addition, Ameluz should not be used on patients who are hypersensitive to any of the ingredients in Ameluz or who have photodermatoses. There are no available data for the risks of using Ameluz in association with pregnancy (FDA, 2016).
As a healthcare provider, this therapy is important because it offers a convenient method for nursing staff to treat AKs in a few scheduled visits once a diagnosis and treatment plan has been established. A patient can simply check in and have the visit supervised by the nursing staff independently of a physician. This also offers benefits for patients who struggle with compliance with scheduled medications or AKs when treatment of the entire field is desired, such as topical creams. Patients can simply show up for a few visits and receive an equivalent treatment without the added stress of remembering when to apply their medications.
Ameluz is a great option for patients who have had negative experiences with alternative treatments, such as liquid nitrogen, 5-fluorouracil cream, or the more invasive electrodessication and curettage. Moreover, it is an additional option for patients with difficulty following rigorous treatment regimens. Overall, it is a safe and effective FDA-approved method of treating AKs in conjunction with PDT.
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Keywords:Copyright © 2017 by the Dermatology Nurses' Association.
Ameluz; Actinic Keratoses; 5-Aminolevulinic Acid; Photodynamic Therapy; Squamous Cell Carcinoma