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Aminolevulinic Acid (Topical)

Pronunciation

(a MEE noh lev yoo lin ik AS id)

Index Terms

  • 5-ALA
  • 5-Aminolevulinic Acid
  • ALA
  • Amino Levulinic Acid
  • Aminolevulinic Acid HCl
  • Aminolevulinic Acid Hydrochloride
  • Delta- Aminolevulinic Acid Hydrochloride

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]

Brand Names: U.S.

  • Ameluz
  • Levulan Kerastick

Pharmacologic Category

  • Photosensitizing Agent, Topical
  • Topical Skin Product

Pharmacology

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.

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 or scalp; to be used in conjunction with photodynamic therapy with blue light illumination (using BLU-U blue light).

Off Label Uses

Actinic cheilitis

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. 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 risk

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)

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)

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 an 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 14 to 18 hours later by blue light illumination. Application/treatment may be repeated at a treatment site (once) after 8 weeks.

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.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

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.

If unable to perform red light illumination within 3 hours of gel application, rinse off gel with saline and water. Protect lesion sites and surrounding skin from sunlight or prolonged intense light (eg, tanning beds, sun lamps) 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 scalp or facial lesions, but not to both simultaneously. Follow application with blue light exposure in 14 to 18 hours. Do not wash the application area during the time between application and photosensitization; after photosensitization, 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.

If unable to perform the blue light treatment after topical application or if treatment with the blue light is interrupted or stopped, 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).

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: Severe burning skin (≤50%; occurred during or shortly after illumination; most cases resolved in 1 to 4 days)

Dermatologic: Burning sensation of skin (≤92%), crusted skin (≤64% to 71%), desquamation (≤64% to 71%), stinging of the skin (severe: ≤50%), hyperpigmentation (≤22% to 36%), hypopigmentation (≤22% to 36%), exfoliation of skin (19%), scabbing (≤2% to 19%), skin erosion (2% to 14%), dermatological disease (5% to 12%), localized vesiculation (4% to 12%)

Endocrine & metabolic: Edematous lesion (35%)

Local: Applicaton site erythema (92% to 99%), local pain (≤1% to 92%; severe: ≤30%), application site irritation (72%), application site pruritus (14% to 34%), application site induration (12%)

1% to 10%:

Cardiovascular: Edema (≤1% to 35%)

Central nervous system: Paresthesia (9%), hyperalgesia (≤5%), local discomfort (3%), dysesthesia (≤2%), chills, headache

Dermatologic: Local flare (≤2% to 7%), urticaria (≤2% to 7%), dermal ulcer (2% to 4%), pustules (1% to ≤4%), excoriation (≤1%), oozing (≤1%)

Hematologic & oncologic: Hemorrhage (1% to 4%)

Local: Application site reaction (4%), application site discharge (2%), localized tenderness (1% to 2%)

<1% (Limited to important or life-threatening): Blurred vision, diplopia, eye irritation, eyelid edema, feeling hot, fever, local inflammation, local swelling, nervousness, ocular hyperemia, pain, petechia, photophobia, pruritus, pustular rash, skin blister, skin discoloration, ulcer

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 during the period prior to 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 the next day for blue light treatment, 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.

• Transient global amnesia: Photodynamic therapy (PTD) may rarely precipitate transient global amnesia; the risk for transient global amnesia may be due to the stress and pain associated with PDT. Discontinue PDT if amnesia is observed; 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 either scalp or face lesions, although not simultaneously; avoid application to perilesional skin. Should be applied by a qualified health professional.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Systemic absorption following topical application of the gel 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 edema, skin discoloration, or memory impairment (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.

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