hexaminolevulinate

Action and Spectrum

Actions and Spectrum: 

hexaminolevulinate (HAL) is a prodrug of the photosensitizing agent 5-aminolevulinic acid (ALA). It is used in the diagnosis and treatment of certain types of cancer, such as bladder cancer, and pre-cancerous skin lesions (actinic keratosis). When applied topically or given intravenously, it is metabolized to ALA, which is then taken up by cells and converted to protoporphyrin IX (PpIX). PpIX is then concentrated in cancerous or abnormal cells, which when exposed to a specific wavelength of light causes the cells to die via a process called photodynamic therapy (PDT). This is a non-invasive procedure and target the affected cells without damaging the surrounding healthy tissue. In addition to photodynamic therapy, PpIX can be used as a diagnostic tool, since it fluoresces in the presence of light, making it easier to identify cancerous or abnormal cells. 

Drug Interaction

Adverse Reaction

Frequency Defined  

1-10%   

Headache  

Hematuria  

Pain  

Spasm  

Dysuria  

Urinary retention  

Black Box Warning

Black Box Warning 

The Black Box Warning, which is the highest level of warning issued by the US Food and Drug Administration (FDA), due to the risk of severe and potentially life-threatening reactions. 

The warning states that HAL can cause severe skin reactions, including burns and blisters, as well as eye and respiratory irritation. These reactions can occur both during and after treatment. HAL may also cause a condition known as methemoglobinemia, which is a buildup of a certain type of hemoglobin in the blood that can lead to low oxygen levels in the body and potentially death. 

Contraindication / Caution

Contraindication/Caution: 

hexaminolevulinate is contraindicated in individuals with known hypersensitivity to hexaminolevulinate or any of its components. 

Caution should be used in individuals with porphyria or a history of porphyria, as hexaminolevulinate can exacerbate the condition. It should also be used with caution in individuals with liver or kidney dysfunction, as it may not be metabolized or eliminated as efficiently. 

Additionally, individuals with a history of photosensitivity or skin reactions should use hexaminolevulinate with caution, as it may increase the risk of such reactions. Consultation with a healthcare professional is recommended for individuals with these or any other underlying medical conditions before using hexaminolevulinate. 

Pregnancy / Lactation

Pregnancy warnings:     

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is known.  

Pregnancy Categories:         

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.    

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.     

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.     

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.     

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology:  

hexaminolevulinate (HAL) is a prodrug of hexaminolevulinate hydrochloride (HAL-HCL) which is a photosensitizer used in photodynamic therapy (PDT). When administered, HAL is converted into its active form, HAL-HCL, which is selectively accumulated in malignant cells and tissues. When exposed to light of a specific wavelength, HAL-HCL generates reactive oxygen species that can damage or destroy the targeted cells. Pharmacodynamics:  

When HAL is administered, it is rapidly converted to 5-ALA by hydrolysis in the body. 5-ALA is then taken up by cells, where it is converted to PpIX by the enzyme ALA synthase. PpIX accumulates in cells, especially in malignant cells, and is subsequently activated by light to produce reactive oxygen species (ROS) that damage cellular components and cause cell death.  

Pharmacokinetics:  

Absorption  

HAL is rapidly and completely absorbed following bladder instillation, reaching peak plasma concentrations within 1 to 2 hours.  

Distribution  

HAL is widely distributed throughout the body and is found in high concentrations in the liver, kidney, and bladder.  

Metabolism  

HAL is rapidly metabolized in the liver and kidneys by the enzyme δ-aminolevulinate dehydratase (ALA-D) to PpIX. PpIX is then excreted in the urine.  

Elimination and excretion  

The majority of PpIX is excreted in the urine within 24 hours of HAL administration. Some PpIX is also excreted in the feces.

Adminstartion

Administration:  

Instillation of a bladder 

Reconstitute the powder with 50 mL of the provided diluent for a 2 mg/mL concentration.  

After reconstitution, use the solution right away; otherwise, keep it refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for up to two hours. 

After bladder instillation, hold for at least one hour (but no longer than three hours) before removing and doing a cystoscopic evaluation 

Patient Information Leaflet

Patient information leaflet 

Generic Name: hexaminolevulinate  

Why do we use hexaminolevulinate? 

The imaging agent hexaminolevulinate is utilised during the bladder procedure known as cystoscopy. 

Body parts, including the bladder, can be visualised as images or pictures thanks to imaging agents. 

To examine the bladder for cancer cells, hexaminolevulinate is employed.