Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, External, as hydrochloride:
Ameluz: 10% (2 g) [contains isopropyl alcohol, phosphatidylcholine, soy, polysorbate 80, propylene glycol, sodium benzoate]
Solution Reconstituted, External, as hydrochloride:
Levulan Kerastick: 20% (1 ea) [contains alcohol, usp, isopropyl alcohol, laureth, polyethylene glycol]
Pharmacology
Mechanism of Action
Aminolevulinic acid is a metabolic precursor of the photosensitizer protoporphyrin IX (PpIX). Photosensitization following local/topical application of aminolevulinic acid occurs through the metabolic conversion to PpIX. When exposed to light of appropriate wavelength and energy, accumulated PpIX produces a photodynamic reaction resulting in local cytotoxicity. Precancerous and cancerous cells exhibit a higher rate of porphyrin induction compared to normal cells.
Pharmacokinetics/Pharmacodynamics
Onset of Action
Peak fluorescence intensity of protoporphyrin IX (PpIX): Actinic keratosis: Solution: 11 hours ± 1 hour; Perilesional skin: 12 hours ± 1 hour
Time to Peak
Gel: 3 hours
Half-Life Elimination
Mean fluorescence clearance half-life of PpIX for lesions: Solution: 30 ± 10 hours
Use: Labeled Indications
Actinic keratoses:
Gel (Ameluz): Lesion-directed and field-directed topical treatment of mild to moderate actinic keratosis of the face and scalp; to be used in conjunction with photodynamic therapy with narrowband red light illumination (using BF-RhodoLED lamp).
Solution (Levulan Kerastick): Topical treatment of minimally to moderately thick actinic keratoses of the face, scalp, or upper extremities; to be used in conjunction with photodynamic therapy with blue light illumination (using BLU-U blue light).
Use: Off Label
Actinic cheilitisc
One very small study and 4 case reports indicate that topical aminolevulinic acid 20% solution and photodynamic therapy provide total clearance of symptoms in two-thirds to three-fourths of patients with actinic cheilitis, with a follow-up of 1 to 12 months. Aminolevulinic acid and photodynamic therapy was well tolerated; local stinging, burning, and erythema resolved 4 days posttreatment.Alexiades-Armenakas 2004, Kodama 2007, Stender 1996 A larger, controlled study with a long follow-up is needed to establish efficacy, safety, and long-term outcomes.
Basal cell skin cancer, superficial, low riskyes
Based on the International Society for Photodynamic Therapy in Dermatology Guidelines for treatment of nonmelanoma skin cancer with photodynamic therapy, topical aminolevulinic acid given for the management of low-risk superficial basal cell skin cancer is effective and recommended in this condition I-PDT [Braathen 2007].
Squamous cell skin cancer in situ, low risk (Bowen disease)yes
Based on the International Society for Photodynamic Therapy in Dermatology Guidelines for treatment of nonmelanoma skin cancer with photodynamic therapy, topical aminolevulinic acid given for the management of low-risk squamous cell skin cancer in situ (Bowen disease) is effective and recommended in this condition I-PDT [Braathen 2007].
Contraindications
Hypersensitivity to aminolevulinic acid or any component of the formulation; known allergy/hypersensitivity to porphyrins; known porphyria; hypersensitivity to soybean phosphatidylcholine (Ameluz); cutaneous photosensitivity at wavelengths of 400 to 450 nm (Levulan Kerastick); photodermatoses (Ameluz)
Dosage and Administration
Dosing: Adult
Note: Should only be applied by qualified medical personnel (not intended for application by patients).
Actinic keratoses: Topical:
Gel (Ameluz): Apply ~1 mm thick to actinic keratosis and to ~5 mm of surrounding skin; application area should not exceed 20 cm2 and a maximum of 2 g at one time. Cover with a light-blocking occlusive dressing and leave on for 3 hours. After 3 hours of occlusion, remove dressing, wipe off remaining gel, and follow with red light illumination. Lesions that have not completely resolved after 3 months following the initial treatment may be retreated.
Solution (Levulan Kerastick): Apply to actinic keratoses (not perilesional skin) followed by blue light illumination 3 hours (upper extremity lesions) or 14 to 18 hours (face or scalp lesions) later. Application/treatment may be repeated at a treatment region (once) after 8 weeks; multiple lesions can be treated within a treatment region but multiple treatment regions should not be treated simultaneously.
Actinic cheilitis (off-label use): Topical: Apply solution (20%) to lip lesion followed 2 to 3 hours later by photodynamic therapy. Application/treatment may be repeated as necessary once every 4 weeks or until complete clearing, for up to 3 treatment sessions (Alexiades-Armenakas 2004). Additional data may be necessary to further define the role of aminolevulinic acid in the treatment of this condition.
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Solution (Levulan Kerastick): Follow instructions on Kerastick Krusher or mix manually: Prepare solution by holding applicator tube with cap pointing up, applying finger pressure to "Position A" on cardboard sleeve to crush ampul containing solution vehicle. Apply finger pressure to "Position B" to crush ampul containing aminolevulinic acid powder. Shake gently for at least 30 seconds to dissolve; point applicator cap away from face while shaking tube. Remove cap; dab dry applicator tip on gauze pad until wet with solution.
Administration
For topical use only; not for ophthalmic, oral, or intravaginal use. During light treatment, both patients and health care personnel should wear appropriate eye protection.
Gel: Carefully wipe all lesions with an ethanol or isopropanol-soaked cotton pad (to degrease skin) and remove any scaling or crusts prior to application. Gently roughen lesion surfaces (avoid bleeding). Using a gloved fingertip or a spatula, apply gel ~1 mm thick and include ~5 mm of surrounding skin. Application area should not exceed 20 cm2 and no more than 2 g should be used at one time. May be applied to healthy skin around the lesion(s). Avoid mucous membranes (eyes, nostrils, mouth or ears); maintain a distance of 1 cm from these areas; rinse thoroughly if accidental contact with these areas occurs. Allow gel to dry ~10 minutes before covering with a light-blocking occlusive dressing. After 3 hours, remove dressing and wipe off residual gel. Immediately after removing dressing and residual gel, illuminate the treatment area with red light source. Position lamp 5 to 8 cm from patient's skin. Healthy untreated skin does not need protection during illumination.
After gel application, protect lesion sites and surrounding skin from sunlight or prolonged intense light (eg, tanning beds, sun lamps) for 2 days. If unable to perform red light illumination within 3 hours of gel application, rinse off gel with saline and water and protect lesion sites and surrounding skin from sunlight or prolonged intense light for 2 days.
Solution: Clean and dry lesion prior to application. Dab lesion gently with wet applicator tip (apply enough to uniformly wet lesion without excess running or dripping). Only apply to affected skin. Do not apply to periorbital area, ocular tissue, or mucosal surfaces. Allow to dry, then reapply to same lesion. Apply to either lesions on scalp, face, or upper extremities, but not to multiple regions simultaneously; lesions on the upper extremities should be occluded with low density polyethylene plastic wrap held in place with elastic net dressing until blue light therapy. Follow application with blue light exposure in 3 hours (upper extremity lesions) or in 14 to 18 hours (face or scalp lesions). Do not wash the application area during the time between application and during photosensitization; prior to blue light therapy, remove occlusive dressing (if applicable) and gently rinse actinic keratosis with water and pat dry. Stinging or burning may occur during blue light treatment. Following blue light treatment, the lesion will temporarily redden, swell and/or scale, which should resolve within 4 weeks after treatment.
After solution application, advise patient to avoid sunlight/bright light exposure to treated lesions (and wear a wide brimmed hat or other protective apparel) for at least 40 hours after application (burning/stinging sensation may still occur) even if blue light treatment is not performed, interrupted, or is stopped.
Storage
Gel: Store at 2°C to 8°C (36°F to 46°F); excursions permitted to 15°C to 30°C (59°F to 86°F). After opening, if the tubing is tightly closed, the gel may be stored for up to 12 weeks refrigerated at 2°C to 8°C (36°F to 46°F).
Solution: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Once prepared, the topical solution should be used immediately and application must be completed within 2 hours of solution preparation (if not completed within 2 hours, discard and prepare a new solution).
Drug Interactions
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination
Photosensitizing Agents: May enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Localized burning (≤92%; severe: ≤73%)
Dermatologic: Stinging of the skin (severe: ≤73%), crusted skin (≤71%; severe: ≤5%), desquamation (≤71%; severe: ≤22%), local dryness (≤65%; severe: ≤22%), hyperpigmentation (≤64%), hypopigmentation (≤36%), localized vesiculation (≤36%), exfoliation of skin (≤19%), skin erosion (≤14%; may be severe), dermatological disease (5% to 12%)
Local: Application site reaction (100%), application site erythema (65% to 99%), local pain (≤92%; severe: ≤30%), application site irritation (72%), localized edema (1% to 51%; may be severe), application site discharge (≤36%), application site pruritus (8% to 34%; severe: 1% to 7%), application site induration (12%)
1% to 10%:
Central nervous system: Paresthesia (9%), hyperalgesia (6%), local discomfort (3%), dysesthesia (≤2%), pain (≤1%), chills, headache
Dermatologic: Urticaria (1% to 7%; may be severe), pustules (1% to 4%), dermal ulcer (≤4%), excoriation (≤2%), pruritic rash (perilesional: <2%), skin blister (<2%)
Hematologic & oncologic: Squamous cell carcinoma (2% to <10%), squamous cell carcinoma of skin (2% to <10%), hemorrhage (≤4%)
Local: Localized tenderness (1% to 2%)
Ophthalmic: Eyelid edema
Respiratory: Sinusitis (2% to <10%)
<1%, postmarketing, and/or case reports: Blurred vision, diplopia, eye irritation, fatigue, feeling hot, fever, local inflammation, local swelling, nervousness, ocular hyperemia, petechia, photophobia, pruritus, pustular rash, skin discoloration, skin photosensitivity, temporary amnesia
Warnings/Precautions
Concerns related to adverse effects:
- Mucous membrane irritation: May cause irritation to mucous membranes; do not apply to mucous membranes; rinse with water if contact occurs.
- Ocular injury: Eyelid edema has been observed with topical aminolevulinic acid. Do not apply into eyes; rinse with water if eye contact occurs. Illumination light therapy may result in eye irritation, glare, or injury. During light treatment, patients, health care personnel, and any others present during illumination should wear appropriate eye protection. Avoid staring directly into the light source. Eye exposure to red light must be prevented.
- Photosensitivity: Treatment site will become photosensitive following topical application. Patients should be instructed to avoid exposure to sunlight, bright indoor lights, or tanning beds for 40 hours following application for blue light treatment or for 48 hours following application for red light treatment. Exposure may result in lesion burning, edema, erythema, and/or stinging. Sunscreen will not protect against visible light; head should be covered with light-opaque material or wide-brimmed hat. If unable to return for blue light treatment, continue to avoid sunlight/bright light exposure to treated lesions for at least 40 hours. If unable to perform red light illumination within 3 hours of gel application, protect lesion sites and surrounding skin from sunlight or prolonged intense light (eg, tanning beds, sun lamps) for 48 hours.
- Skin irritation: Excessive irritation may occur if solution (Levulan Kerastick) is applied under occlusion for >3 hours.
- Transient amnesia: Transient amnestic episodes have been reported with aminolevulinic acid in combination with photodynamic therapy (PDT). Advise patients to report amnesia that occurs after treatment.
Disease-related concerns:
- Coagulation defects: Has not been tested in individuals with coagulation defects (acquired or inherited). Avoid bleeding during lesion preparation in patients with coagulation defects; bleeding must be controlled prior to application.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions for more detailed information.
- Photosensitizing agents: Concomitant use of other known photosensitizing agents may increase the degree of photosensitivity reaction.
Other warnings/precautions:
- Appropriate use: For external use only. Do not apply to eyes or mucous membranes. Application of solution (Levulan Kerastick) should involve lesions on the scalp, face, or upper extremities, although not simultaneously; avoid application to perilesional skin. Should be applied by a qualified health professional.
Pregnancy
Pregnancy Considerations
Animal reproduction studies have not been conducted. Systemic absorption following topical application is negligible.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience chills or headache. Have patient report immediately to prescriber severe skin reaction, application site bleeding, eyelid swelling, skin discoloration, or trouble with memory (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
