Aminolevulinic Acid is a topically administered metabolic precursor of protoporphyrin IX. After topical administration, aminolevulinic acid (ALA) is converted to protoporphyrin IX (PpIX) which is a photosensitizer. When the proper wavelength of light activates protoporphyrin IX, singlet oxygen is produced, resulting in a local cytotoxic effect. (NCI04) Used in combination with blue light illumination for the treatment of minimally to moderately thick actinic keratosis of the face or scalp. It has a role as an antineoplastic agent, a photosensitizing agent, a dermatologic drug and a prodrug. It contains a 5-ammoniolevulinic acid.
Aminolevulinic Acid Hydrochloride is the hydrochloride salt form of aminolevulinic acid, an aminoketone, used for local photosensitizing therapy. Aminolevulinic acid (ALA) is a metabolic pro-drug that is converted into the photosensitizer protoporphyrin IX (PpIX), which accumulates intracellularly. Upon exposure to light of appropriate wavelength (red, or blue), PpIX catalyzes oxygen to singlet oxygen, an intracellular toxin, which can further react to form superoxide and hydroxyl radicals. This leads to cellular cytotoxic effects.
5-aminolevulinic acid is the simplest delta-amino acid in which the hydrogens at the gamma position are replaced by an oxo group. It is metabolized to protoporphyrin IX, a photoactive compound that accumulates in the skin. Used (in the form of the hydrochloride salt)in combination with blue light illumination for the treatment of minimally to moderately thick actinic keratosis of the face or scalp. It has a role as a photosensitizing agent, an antineoplastic agent, a dermatologic drug, a prodrug, a plant metabolite, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite, and a mouse metabolite. It is a delta-amino acid and a 4-oxo monocarboxylic acid. It is functionally related to a 4-oxopentanoic acid. It is a conjugate base of 5-aminolevulinic acid. It is a conjugate acid of a 5-aminolevulinate. It is a tautomer of a 5-aminolevulinate.
Mechanism of Action
According to the presumed mechanism of action, photosensitization following the 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 the 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).
Indications
- Aminolevulinic acid is a porphyrin precursor used to treat actinic keratosis of the face, scalp, and upper extremities, as well as to visualize a glioma.
- Aminolevulinic acid 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.
- Treatment of actinic keratosis of mild to moderate severity on the face and scalp and of field cancerization in adults. Treatment of superficial and/or nodular basal cell carcinoma is unsuitable for surgical treatment due to possible treatment-related morbidity and/or poor cosmetic outcome in adults.
- Gliolan is indicated in adult patients for visualization of malignant tissue during surgery for malignant glioma (World Health Organization grade III and IV).
- Actinic Cheilitis
- Actinic Keratoses of the face
- Actinic Keratoses of the scalp
- Actinic Keratosis (AK) of the Upper Extremity
- Basal Cell Carcinoma (BCC)
- Glioma
- Squamous Cell Carcinoma (SCC)
Use in Cancer
Aminolevulinic acid hydrochloride is approved to be used in photodynamic therapy to treat:
- Actinic keratosis.
Aminolevulinic acid hydrochloride is also being studied in the treatment of other conditions and types of cancer.
Contraindications
- are allergic to aminolevulinic acid, porphyrins, or any ingredients of the medication
- have porphyria (a group of conditions that result in the accumulation of porphyrins)
- your skin is sensitive to light at wavelengths of 400 nm to 450 nm
Dosage
- Application: Because this medication contains alcohol, it should not be applied to the eyes or mouth.
- Sensitivity to light: Between the time aminolevulinic acid has been applied to the skin and blue light treatment, your affected areas of skin will become more sensitive to light. During this time, you should avoid exposing the areas where the medication was applied to sunlight or any bright indoor light (e.g., examination lamps, unshaded light bulbs) at close distances.
- Aminolevulinic acid is usually given about 3 hours before surgery. A healthcare provider will prepare and give you aminolevulinic acid.
- For 24 hours before and after taking aminolevulinic acid, you will need to protect your skin from bright light. Avoid exposure to both sunlight and bright indoor light. Wear protective clothing and a wide-brimmed hat when you are outdoors. If you feel stinging or burning of the treated skin, reduce your exposure to light.
Side Effects
The Most Common
- tingling, stinging, prickling, or burning of lesions during blue light treatment (should get better within 24 hours)
- redness, swelling, and scaling of treated actinic keratoses and surrounding skin (should get better within 4 weeks)
- discoloration of the skin
- itching
- bleeding
- blistering
- pus under the skin
- hives
More Common
- crusting
- itching
- pain or tenderness
- peeling
- redness
- stinging, tingling, or burning
- swelling
Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.
Check with your doctor as soon as possible if any of the following side effects occur:
- blisters
- skin bleeding
- skin colour changes
- skin ulcers
Interactions
| DRUG | INTERACTION |
|---|---|
| Articaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Articaine. |
| Benzocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Benzocaine. |
| Benzyl alcohol | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Benzyl alcohol. |
| Bupivacaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Bupivacaine. |
| Butacaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Butacaine. |
| Butamben | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Butamben. |
| Capsaicin | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Capsaicin. |
| Chloroprocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Chloroprocaine. |
| Cinchocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Cinchocaine. |
| Cocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Cocaine. |
| Darbepoetin alfa | The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Aminolevulinic acid. |
| Diphenhydramine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Diphenhydramine. |
| Dyclonine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Dyclonine. |
| Erythropoietin | The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Aminolevulinic acid. |
| Ethyl chloride | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Ethyl chloride. |
| Etidocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Etidocaine. |
| Levobupivacaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Levobupivacaine. |
| Lidocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Lidocaine. |
| Meloxicam | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Meloxicam. |
| Mepivacaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Mepivacaine. |
| Methoxy polyethylene glycol-epoetin beta | The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Aminolevulinic acid. |
| Oxetacaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Oxetacaine. |
| Oxybuprocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Oxybuprocaine. |
| Padeliporfin | Aminolevulinic acid may increase the photosensitizing activities of Padeliporfin. |
| Peginesatide | The risk or severity of Thrombosis can be increased when Peginesatide is combined with Aminolevulinic acid. |
| Phenol | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Phenol. |
| Porfimer sodium | Aminolevulinic acid may increase the photosensitizing activities of Porfimer sodium. |
| Pramocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Pramocaine. |
| Prilocaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Prilocaine. |
| Procaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Procaine. |
| Proparacaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Proparacaine. |
| Propoxycaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Propoxycaine. |
| Ropivacaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Ropivacaine. |
| Tetracaine | The risk or severity of methemoglobinemia can be increased when Aminolevulinic acid is combined with Tetracaine. |
| Tretinoin | The adverse effects’ risk or severity can increase when Tretinoin is combined with Aminolevulinic acid. |
| Verteporfin | Aminolevulinic acid may increase the photosensitizing activities of Verteporfin. |
Pregnancy and Lactation
US FDA pregnancy category – C
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while using this medication, contact your doctor immediately.
Breast-feeding
It is not known if aminolevulinic acid passes into breast milk. If you are a breastfeeding mother and are using this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children and adolescents less than 18 years old.
What special precautions should I follow?
Before using aminolevulinic acid,
- tell your doctor and pharmacist if you are allergic to aminolevulinic acid, porphyrins, or any other medications.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antihistamines; diuretics (‘water pills’); griseofulvin (Fulvicin-U/F, Grifulvin V, Gris-PEG); medications for diabetes, mental illness, and nausea; sulfa antibiotics; and tetracycline antibiotics such as demeclocycline (Declomycin), doxycycline (Doryx, Vibramycin), minocycline (Dynacin, Minocin), and tetracycline (Sumycin). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have porphyria (a condition that causes sensitivity to light). Your doctor will probably tell you not to use aminolevulinic acid.
- tell your doctor if you have or have ever had any other medical conditions.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant during treatment with aminolevulinic acid, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are using aminolevulinic acid.
- you should know that aminolevulinic acid will make your skin very sensitive to sunlight (likely to get sunburn). Avoid exposure of treated skin to direct sunlight or bright indoor light (e.g. tanning salons, bright halogen lighting, close task lighting, and high power lighting used in operating rooms or dental offices) before exposure to blue light treatment. Before going outdoors in the sunlight, protect treated skin from the sun by wearing a wide-brimmed hat or other head covering that will shade the treated area or block the sun. Sunscreen will not protect you from sensitivity to sunlight. If you feel burning or stinging of the treated areas or see that they have become red or swollen, be sure that you are keeping the area protected from sunlight or bright light.
References
