Aminolevulinic acid

Summary

Aminolevulinic acid (ALA) is a naturally occurring, non-peptide amino acid used clinically as a photosensitizing prodrug. It is FDA-approved topically (as Ameluz and Levulan Kerastick) for actinic keratosis via photodynamic therapy (PDT), and orally (as Gleolan/Gliolan) for intraoperative fluorescence-guided resection of high-grade gliomas. Its selective accumulation as PpIX in dysplastic and malignant cells underpins both its photodynamic therapy and fluorescence imaging applications.

Mechanism of Action

Aminolevulinic acid (ALA) is a prodrug and endogenous precursor in the heme biosynthesis pathway. Exogenously administered ALA is taken up preferentially by rapidly proliferating or metabolically active cells, where it is converted to the photosensitizer protoporphyrin IX (PpIX). Upon activation by light of appropriate wavelength (~635 nm), PpIX generates reactive oxygen species (singlet oxygen), leading to selective cytotoxic and photodynamic effects in target tissue. It also causes fluorescent visualization of PpIX-rich tumor tissue.

Routes of Administration

Goals & Uses

• Bladder cancer detection (blue-light cystoscopy)Urology / OncologyHigh
• Photodynamic therapy of basal cell carcinomaDermatology / OncologyModerate
• Photodynamic therapy of actinic keratosisDermatology / OncologyHigh
• Fluorescence-guided resection of high-grade gliomaNeurosurgery / OncologyHigh
• PDT of field cancerization / photodamaged skinDermatologyModerate

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• PorphyriaMetabolic DisorderHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Photodermatoses or photosensitizing drug useDermatology / PharmacologyModerate
• Hypersensitivity to ALA or porphyrinsAllergy / ImmunologyHigh

Adverse Effects

• Nausea and vomitingGastrointestinalCommon
• Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers
• Phototoxic skin reactions (erythema, burning, stinging, edema)DermatologicCommon
• Transient hypotensionCardiovascularUncommon
• Crusting, vesiculation, pustulation at treatment siteDermatologicUncommon
• Photosensitivity / sunburn-like reactionDermatologicCommon

Drug Interactions

• Iron chelators (e.g., deferoxamine)Low
• Antioxidants (e.g., vitamin C, vitamin E, beta-carotene)Low
• Other photosensitizing agents (e.g., tetracyclines, fluoroquinolones, St. John's Wort, thiazides)Moderate

Population Constraints

• Pediatric patientsAgeRelative
• Breastfeeding womenReproductiveRelative
• Patients with hepatic impairmentOrgan FunctionRelative
• Pregnant womenReproductiveAbsolute
• Patients with known porphyriaMetabolicAbsolute

Regulatory Status

• European UnionApprovedApproved: Actinic keratosis (Ameluz, topical PDT), Superficial and nodular basal cell carcinoma (Ameluz, topical PDT), Fluorescence-guided resection of high-grade glioma (Gliolan, oral)EMA-approved; Ameluz has broader dermatology indications than in the US including BCC.
• United StatesApprovedApproved: Actinic keratosis of the face and scalp (Levulan Kerastick, topical PDT, 1999), Actinic keratosis (Ameluz 10% gel, topical PDT, 2016), Fluorescence-guided surgery of high-grade glioma (Gleolan oral solution, 2017)FDA-approved for multiple indications; Levulan and Ameluz are topical; Gleolan is oral.
• United KingdomApprovedApproved: Actinic keratosis (topical PDT), Superficial and nodular basal cell carcinoma (topical PDT), Fluorescence-guided surgery of high-grade glioma (oral)MHRA approved; largely aligned with EMA approvals post-Brexit via retained EU marketing authorizations.

FDA-approved: Levulan Kerastick (20% topical solution) for AK of the face/scalp (1999); Ameluz (10% gel) for AK (2016); Gleolan (oral solution, 1.5 g/vial) for fluorescence-guided surgery of high-grade gliomas (2017). EMA-approved: Gliolan (oral) for gliomas; Ameluz (topical) for AK and basal cell carcinoma.

Evidence & Sources

No sources recorded yet.