Levulan

L

Generic Name: Aminolevulinic Acid Hydrochloride
Class: Skin and Mucous Membrane Agents, Miscellaneous
ATC Class: L01XD04
VA Class: DE350
Chemical Name: 5-Aminolevulinic acid hydrochloride
Molecular Formula: C5H9NO3•HCl
CAS Number: 5451-09-2

Introduction

Photosensitizer; hydrochloride salt of 5-aminolevulinic acid, an endogenous precursor of protoporphyrin IX.1 2

Uses for Levulan Nonhyperkeratotic Actinic Keratoses of Face or Scalp

Treatment of minimally to moderately thick (nonhyperkeratotic) actinic keratoses of the face or scalp, in conjunction with blue light illumination using the BLU-U Blue Light Photodynamic Therapy Illuminator (BLU-U).a

Levulan Dosage and Administration General

Topical solution should be applied only by qualified medical personnel.a

Apply topically to individual actinic keratosis lesions on either scalp or face, but not both simultaneously.a Do not apply in or around eyes or mucous membranes or to perilesional skin.a

Administration Topical Administration Preparation of the Applicator

With the applicator cap pointing up, sequentially break the 2 glass ampuls within the plastic applicator by applying finger pressure to appropriate position on the bottom ampul (vehicle solution), then the top ampul (powdered drug).a

With applicator cap pointed away from face, shake applicator gently for at least 3 minutes to completely dissolve the drug in the vehicle.a Do not press on end cap while shaking.a

Topical Application

Apply topically; use within 2 hours because of the instability of the activated product.a If application of the solution is not completed within 2 hours of activation, discard applicator and use a new one.1 a

Clean and dry lesions prior to application of solution.a

Gently dab target lesions directly with wet applicator tip, uniformly wetting lesion surface, including the edges, without excess running or dripping.a

Allow application to dry and then reapply one time in the same manner.a 7

Illumination of Treated Lesions

14–18 hours after application, gently rinse target lesions with water, pat dry, and photoactivate with blue light illumination from the BLU-U Blue Light Photodynamic Therapy Illuminator.a

Patients and medical personnel should use blue light-blocking protective eyewear during BLU-U illumination.a

Solution is not intended for use with any device other than the BLU-U Blue Light Photodynamic Illuminator.a

Dosage Adults Actinic Keratoses Topical

Apply solution to lesions as directed (See Topical Application under Dosage and Administration); allow to dry and reapply once.a 7 14–18 hours later, expose affected areas to BLU-U illumination for 1000 seconds [16 minutes, 40 seconds].a

After 8 weeks, apply solution a second time to lesions that have not completely resolved.a

Cautions for Levulan Contraindications

Known cutaneous photosensitivity at wavelengths of 400–450 nm.a

Known porphyria or known allergies to porphyrins.a

Known sensitivity to aminolevulinic acid or any ingredient in the formulation.a

Warnings/Precautions Warnings Topical Application Only

Solution contains alcohol; for topical use only.a Do not apply in or around the eyes or to mucous membranes.a May cause excessive irritation if applied under occlusion.a

General Precautions Application by Health Professional

Only qualified medical personnel should apply solution; application to perilesional area of face or scalp may result in photosensitivity.a

Photosensitivity Reactions

Sites will be photosensitive after topical application of solution; stinging and/or burning sensation, erythema, and/or edema of lesions may occur with exposure to bright light.a

Avoid exposure of treated sites to sunlight or bright indoor light (e.g., examination lamps, operating room lamps, tanning beds, lights at close proximity) prior to blue light photoactivation.a

Protect treated lesions from sun by wearing a wide-brimmed hat or similar head covering of light-opaque material, and keep lesions dry.a Sunscreens will not protect against photosensitivity reactions caused by visible light.a

Reduce exposure to light if stinging and/or burning occurs.a

Dermatologic Reactions

Following photoactivation with blue light, reddening, swelling, and scaling of treated actinic keratoses and surrounding skin may occur.a

Lesion changes usually resolve completely within 4 weeks after treatment.a

Delay in Receiving Blue Light Treatment

Patients should contact clinician if they cannot return for blue light treatment 14–18 hours after application of solution.a

Patients should continue to avoid exposure of photosensitized lesions to sunlight or prolonged or intense light for ?40 hours after solution application.a

Specific Populations Pregnancy

Category C.a

Lactation

Not known whether aminolevulinic acid is distributed into milk; use caution.a

Common Adverse Effects

Transient local stinging and/or burning, itching, erythema, edema, scaling/crusting,a itching,1 hypopigmentation/hyperpigmentaion,a erosion,a skin disorder (unspecified),a wheal/flare,a vesiculation.a a

Interactions for Levulan

No formal drug interaction studies performed.a No drug-specific interactions noted during controlled clinical trials.a

Other Known Photosensitizing Agents

Potential pharmacologic interaction (increased photosensitivity reaction) with other known photosensitizing agents (e.g., griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, tetracyclines).a

Levulan Pharmacokinetics Absorption Bioavailability

50-60% after a 128-mg oral dose of aminolevulinic acid hydrochloride (equivalent to 100 mg of aminolevulinic acid).a

Distribution Time to Peak Fluorescence

Peak fluorescence intensity for protoporphyrin IX (metabolite of aminolevulinic acid) reached at approximately 11 or 12 hours in actinic keratoses or perilesional skin, respectively.a

Elimination Half-life

0.83 or 0.7 hours with a 128-mg aminolevulinic acid hydrochloride IV or oral dose, respectively.a

Mean fluorescence half-life of 30 or 28 hours in lesions or perilesional skin, respectively.a

Stability Storage Topical Solution

20–25°C; excursions permitted to 15–30°C.a Discard reconstituted solution 2 hours after mixing.a

ActionsActions

Metabolism of aminolevulinic acid is first step in synthesis of heme,2 which is formed when iron (under action of ferrochelatase) is incorporated into protoporphyrin IX.2

Synthesis of endogenous aminolevulinic acid (ALA) tightly controlled by feedback inhibition of ALA synthetase, presumably by intracellular heme levels.a 2

Following topical application of aminolevulinic acid, it is converted into protoporphyrin IX (a photosensitizer), which accumulates in skin due to limited capacity of ferrochelatase to convert protoporphyrin IX into heme.a 2 6

When exposed to light of appropriate wavelength and energy, accumulated protoporphyrin IX produces a photodynamic reaction.a 3 5 6

Tissue-specific phototoxic effects result from generation of cytotoxic singlet oxygen atoms, which form superoxide and hydroxyl radicals.1 2 3 4 5 6

Advice to Patients

Aminolevulinic acid hydrochloride topical solution is not meant for application by patient.a Only qualified health professionals should apply drug.a

Importance of advising patient to keep lesions dry and out of bright light following application of the topical solution.a

Importance of informing patient of possible transient stinging and/or burning at treated lesion sites if exposed to bright light following topical solution application;a patient should reduce exposure to light if this occurs.a Importance of patient wearing light-protective clothing, such as a wide-brimmed hat or similar head covering of light-opaque material, before going into sunlight following topical solution application.a Importance of informing patient that sunscreens will not protect against photosensitivity reactions caused by visible light.a Importance of patient limiting exposure to bright indoor light following topical solution application.a

Importance of informing patient that transient tingling, stinging, prickling, and/or burning may occur at target lesion sites during period of blue light photoactivation.a

Importance of patient informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.a

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Aminolevulinic Acid Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

For solution

354 mg (for preparation of a 20% solution)

Levulan Kerastick (1.5 mL alcohol 48% v/v and isopropyl alcohol diluent)

DUSA

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. DUSA Pharmaceuticals, Inc. Levulan (aminolevulinic acid hydrochloride) topical solution prescribing information. Wilmington, MA; 1999 Dec.

2. Peng Q, Warloe T, Berg K et al. 5-Aminolevulinic acid-based photodynamic therapy. Cancer. 1997; 79:2282-2308. [IDIS 388777] [PubMed 9191516]

3. Stender IM, Wulf HC. Photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic cheilitis. Br J Dermatol. 1996; 135:454-6. [IDIS 373292] [PubMed 8949443]

4. Jeffes EW, McCullough JL, Weinstein GD et al. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. Arch Dermatol. 1997; 133:727-32. [IDIS 388720] [PubMed 9197826]

5. Fritsch C, Goerz G, Ruzicka T. Photodynamic therapy in dermatology. Arch Dermatol. 1998; 134:207-14. [PubMed 9487213]

6. Fritsch C, Lang K, Neuse W et al. Photodynamic diagnosis and therapy in dermatology. Skin Pharmacol Appl Skin Physiol. 1998; 11:358-73. [PubMed 10343206]

7. Manufacturer’s comments (personal observations).

a. DUSA Pharmaceuticals, Inc. Levulan (aminolevulinic acid hydrochloride) topical solution prescribing information. Wilmington, MA; revision F. Undated.

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