Aminolevulinic acid

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Aminolevulinic acid may be confused with methyl aminolevulinate

U.S. BRAND NAMES — Levulan® Kerastick®

PHARMACOLOGIC CATEGORY
Photosensitizing Agent, Topical
Topical Skin Product

DOSING: ADULTS — Actinic keratoses: Topical: Apply to actinic keratoses (not perilesional skin) followed 14-18 hours later by blue light illumination. Application/treatment may be repeated at a treatment site (once) after 8 weeks.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Powder for topical solution:
Levulan® Kerastick®: 20% (1s, 6s) [2-component system containing aminolevulinic acid hydrochloride 354 mg (powder) and diluent containing ethanol 48% (1.5 mL) packaged together in an applicator tube]

DOSAGE FORMS: CONCISE
Powder for topical solution:
Levulan® Kerastick®: 20% (1s, 6s)

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — 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 14-18 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.

USE — Treatment of minimally to moderately thick actinic keratoses (grade 1 or 2) of the face or scalp; to be used in conjunction with blue light illumination

USE - UNLABELED / INVESTIGATIONAL — Photodynamic treatment of low-risk superficial basal cell skin cancer and low-risk squamous cell skin cancer in situ (Bowen's disease)

ADVERSE REACTIONS SIGNIFICANT — Transient stinging, burning, itching, erythema, and edema result from the photosensitizing properties of this agent. Symptoms subside between 1 minute and 24 hours after turning off the blue light illuminator. Severe stinging or burning was reported in at least 50% of patients from at least 1 lesional site during treatment.

>10%: Dermatologic: Stinging or burning (most patients; severe: ≥ 50%), erythema (99%), scaling/crusted skin (64% to 71%), hyper-/hypopigmentation (22% to 36%), edematous lesions (35%), itching (14% to 25%), erosion (2% to 14%), skin disorder (5% to 12%)

1% to 10%:
Central nervous system: Dysesthesia (≤ 2%)
Dermatologic: Vesiculation (4% to 5%), skin ulceration (2% to 4%), pustular drug eruption (≤ 4%)
Hematologic: Bleeding/hemorrhage (2% to 4%)
Local: Wheal/flare (2% to 7%), scabbing (≤ 2%), tenderness (1% to 2%), edema (≤ 1%), excoriation (≤ 1%), local pain (≤ 1%), oozing (≤ 1%)

CONTRAINDICATIONS — Hypersensitivity to aminolevulinic acid or any component of the formulation; individuals with cutaneous photosensitivity at wavelengths of 400-450 nm; porphyria; allergy to porphyrins

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Photosensitivity: Treatment site will become photosensitive following application. Patients should be instructed to avoid exposure to sunlight, bright indoor lights, or tanning beds during the period prior to blue 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. Skin irritation: Excessive irritation may occur if applied under occlusion.

Disease-related concerns: Coagulation defects: Has not been tested in individuals with coagulation defects (acquired or inherited).

Concurrent drug therapy issues: 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 should involve either scalp or face lesions, although not simultaneously. Should be applied by a qualified health professional to avoid application to perilesional skin.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted, and there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed.

LACTATION — Excretion in breast milk unknown/use caution

CANADIAN BRAND NAMES — Levulan® Kerastick®

INTERNATIONAL BRAND NAMES — Metvix (AR, AU, BE, BR, CH, CN, CZ, DE, DK, FI, GB, IE, NO, NZ, SE, SG)

MECHANISM OF ACTION — Aminolevulinic acid is a metabolic precursor of the photosensitizer protoporphyrin IX (PpIX). Photosensitization following local 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.

PHARMACODYNAMICS / KINETICS
Peak fluorescence intensity of protoporphyrin IX (PpIX): Actinic keratosis: 11 hours +/- 1 hour; Perilesional skin: 12 hours +/- 1 hour

Half-life elimination: Mean fluorescence clearance half-life of PpIX for lesions: 30 +/- 10 hours

PATIENT INFORMATION — Solution will be applied by prescriber. Once solution is applied, affected skin will be sensitive to light. Wear protective clothing when exposed to light and avoid bright lights (including tanning beds) and sunlight. Sunscreens will not prevent phototoxic reactions. Solution will be applied directly to lesions; blue light exposure should follow 14-18 hours later. Do not wash solution off skin during this time. If you are not able to return for blue light therapy, avoid sunlight and other bright light for at least 40 hours following application of solution.