Levulan
Levulan - General Information
A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. It is used as a photochemotherapy for actinic keratosis. [PubChem]
Pharmacology of Levulan
The metabolism of aminolevulinic acid (ALA) is the first step in the biochemical pathway resulting in heme synthesis. Levulan is not a photosensitizer, but rather a metabolic precursor of protoporphyrin IX (PpIX), which is a photosensitizer. The synthesis of ALA is normally tightly controlled by feedback inhibition of the enzyme, ALA synthetase, presumably by intracellular heme levels. ALA, when provided to the cell, bypasses this control point and results in the accumulation of PpIX, which is converted into heme by ferrochelatase through the addition of iron to the PpIX nucleus.
Levulan for patients
LEVULAN Photodynamic Therapy for Actinic Keratoses
The first step in LEVULAN KERASTICK photodynamic therapy (PDT) for actinic keratoses is application of the LEVULAN KERASTICK for Topical Solution to actinic keratoses located on the patient's face or scalp. After LEVULAN KERASTICK for Topical Solution is applied to the actinic keratoses in the doctor's office, the patient will be told to return the next day. During this time the actinic keratoses will become sensitive to light (photosensitive). Care should be taken to keep the treated actinic keratoses dry and out of bright light. After LEVULAN KERASTICK Topical Solution is applied, it is important for the patient to wear light-protective clothing, such as a widebrimmed hat, when exposed to sunlight or sources of light. Fourteen to eighteen hours after application of LEVULAN KERASTICK Topical Solution the patient will return to the doctor's office to receive blue light treatment, which is the second and final step in the treatment. Prior to blue light treatment, the actinic keratoses will be rinsed with tap water. The patient will be given goggles to wear as eye protection during the blue light treatment. The blue light is of low intensity and will not heat the skin. However, during the light treatment, which lasts for approximately 17 minutes, the patient will experience sensations of tingling, stinging, prickling or burning of the treated lesions. These feelings of discomfort should improve at the end of the light treatment. Following treatment, the actinic keratoses and, to some degree, the surrounding skin, will redden, and swelling and scaling may also occur. However, these lesion changes are temporary and should completely resolve by 4 weeks after treatment.
Photosensitivity
After LEVULAN KERASTICK Topical Solution is applied to the actinic keratoses in the doctor's office, the patient should avoid exposure of the photosensitive actinic keratoses to sunlight or bright indoor light (e.g., from examination lamps, operating room lamps, tanning beds, or lights at close proximity) during the period prior to blue light treatment. If the patient feels stinging and/or burning on the actinic keratoses, exposure to light should be reduced. Before going into sunlight, the patient should protect treated lesions from the sun by wearing a wide-brimmed hat or similar head covering of light-opaque material. Sunscreens will not protect the patient against photosensitivity reactions.
If for any reason the patient cannot return for blue light treatment during the prescribed period after application of LEVULAN KERASTICK Topical Solution (14 to 18 hours), the patient should call the doctor. The patient should also continue to avoid exposure of the photosensitized lesions to sunlight or prolonged or intense light for at least 40 hours. If stinging and/or burning is noted, exposure to light should be reduced.
Levulan Interactions
There have been no formal studies of the interaction of LEVULAN KERASTICK for Topical Solution with any other drugs, and no drug-specific interactions were noted during any of the controlled clinical trials. It is, however, possible that concomitant use of other known photosensitizing agents such as griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides and tetracyclines might increase the photosensitivity reaction of actinic keratoses treated with the LEVULAN KERASTICK for Topical Solution.
Levulan Contraindications
The LEVULAN KERASTICK for Topical Solution plus blue light illumination using the BLU-U Blue Light Photodynamic Therapy Illuminator is contraindicated in patients with cutaneous photosensitivity at wavelengths of 400-450 nm, porphyria or known allergies to porphyrins, and in patients with known sensitivity to any of the components of the LEVULAN KERASTICK for Topical Solution.
Additional information about Levulan
Levulan Indication: Levulan plus blue light illumination using a blue light photodynamic therapy illuminator is indicated for the treatment of minimally to moderately thick actinic keratoses of the face or scalp.
Mechanism Of Action: According to the presumed mechanism of action, photosensitization following application of aminolevulinic acid (ALA) topical solution occurs through the metabolic conversion of ALA to protoporphyrin IX (PpIX), which accumulates in the skin to which aminolevulinic acid has been applied. When exposed to light of appropriate wavelength and energy, the accumulated PpIX produces a photodynamic reaction, a cytotoxic process dependent upon the simultaneous presence of light and oxygen. The absorption of light results in an excited state of the porphyrin molecule, and subsequent spin transfer from PpIX to molecular oxygen generates singlet oxygen, which can further react to form superoxide and hydroxyl radicals. Photosensitization of actinic (solar) keratosis lesions using aminolevulinic acid, plus illumination with the BLU-UTM Blue Light Photodynamic Therapy Illuminator (BLU-U), is the basis for aminolevulinic acid photodynamic therapy (PDT).
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Aminolevulinic acid
Synonyms: ALA; delta-Aminolevulinic acid; Aminolevulinate
Drug Category: Photosensitizing Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Aminolevulinic acid: Aladerm; Kerastick; Levulan; Levulan Kerastick;
Absorption: Oral bioavailability is 50-60%.
Toxicity (Overdose): Solution overdose have not been reported.
Protein Binding: Not Available
Biotransformation: Following topical administration, synthesis into protoporphyrin IX takes place in situ in the skin.
Half Life: Mean half-life is 0.70 ± 0.18 h after the oral dose and 0.83 ± 0.05 h after the intravenous dose.
Dosage Forms of Levulan: Powder, for solution Topical
Chemical IUPAC Name: 5-amino-4-oxopentanoic acid
Chemical Formula: C5H9NO3
Aminolevulinic acid on Wikipedia: https://en.wikipedia.org/wiki/Aminolevulinic_acid
Organisms Affected: Humans and other mammals
