trioxsalen

Action and Spectrum

Actions and Spectrum: 

trioxsalen is a drug used with UVA (ultraviolet A) light therapy, a treatment known as PUVA therapy, primarily used to treat certain skin disorders, particularly psoriasis, and vitiligo. The mechanism of action of trioxsalen involves its ability to sensitize the skin to UVA light, making the skin more responsive to the effects of UVA radiation. 

trioxsalen’s spectrum of activity is limited to treating certain skin disorders and is not used for systemic conditions. Its main indications include: 

• Psoriasis: trioxsalen with UVA light therapy is used to treat plaque psoriasis, a chronic skin condition characterized by red, raised, and scaly patches on the skin. 
• Vitiligo: trioxsalen combined with UVA light therapy can treat vitiligo. In this condition, the skin loses its natural pigmentation, resulting in white patches on various body parts. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Irritation 

Blistering 

Rash  

Dizziness 

Depression 

Itching 

Nausea 

Redness 

Swelling 

Headache 

Nervousness 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: trioxsalen should not be used in individuals with known hypersensitivity or allergy to the drug or its components. 
• History of Melanoma or Other Skin Cancers: trioxsalen, combined with UVA light therapy, may increase the risk of skin cancer, especially in individuals with a history of melanoma or other skin cancers. 
• Light-Sensitive Conditions: trioxsalen sensitizes the skin to light, and thus, it should be avoided in individuals with conditions that make them highly sensitive to light (phototoxic reactions) or those who have certain light-sensitive disorders like systemic lupus erythematosus (SLE) or porphyria. 
• Photosensitivity: trioxsalen should not be used in individuals who are photosensitive or prone to severe sunburn. 
• Liver and Kidney Dysfunction: trioxsalen is metabolized in the liver, and its excretion occurs through the kidneys. It should be used cautiously or avoided in individuals with severe liver or kidney dysfunction. 
• Children: trioxsalen should only be used in children with the specific recommendation and close supervision of a healthcare professional. 
• Cataracts: trioxsalen may worsen cataracts or increase the risk of developing them. Therefore, caution is advised in individuals with existing cataracts. 

Caution: 

• Sun Exposure: trioxsalen makes the skin more sensitive to sunlight and UVA radiation. Therefore, during treatment and afterward, it’s essential to avoid prolonged exposure to natural or artificial sunlight, as it can lead to severe sunburn and phototoxic reactions. 
• Eye Protection: The eyes are susceptible to UVA light and may be at risk of damage during PUVA therapy. Proper eye protection, such as UVA-blocking goggles, should be worn during treatment to prevent eye damage or cataract formation. 
• Photosensitivity: Individuals taking trioxsalen should avoid other medications or substances that can cause photosensitivity, as combining them may increase the risk of severe sunburn or skin reactions. 
• Liver and Kidney Function: trioxsalen is metabolized in the liver and excreted through the kidneys. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

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 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: 

trioxsalen is a naturally occurring psoralen compound with photoactive properties. Its pharmacology mainly revolves around its ability to interact with ultraviolet A (UVA) radiation to treat certain skin disorders when used in PUVA therapy (psoralen and UVA). 

• Photosensitization: trioxsalen is a photosensitizing agent, increasing the skin’s sensitivity to UVA light.  
• Absorption of UVA Light: After trioxsalen is absorbed into the skin cells, it can intercalate into the DNA strands within the nucleus. Upon exposure to UVA radiation, trioxsalen becomes activated and forms cross-links between adjacent DNA strands, leading to DNA damage. 
• Modulation of Cell Division: trioxsalen’s cross-linking of DNA affects the ability of the cell to divide and proliferate. This is particularly useful in treating conditions like psoriasis, where skin cells are overgrowth. 
• Treatment of Skin Disorders: The combined effect of trioxsalen’s photosensitization and UVA radiation helps slow down the abnormal growth of skin cells in conditions like psoriasis. It also stimulates melanocytes in the skin, leading to repigmentation in areas affected by vitiligo. 

Pharmacodynamics:  

trioxsalen’s pharmacodynamics are closely related to its ability to sensitize the skin to ultraviolet A (UVA) radiation and its impact on cell division and DNA. 

• Photosensitization: trioxsalen is a photosensitizing agent, enhancing the skin’s sensitivity to UVA light. After being absorbed into the skin cells, trioxsalen undergoes a chemical transformation when exposed to UVA radiation, becoming an activated form of the compound. 
• DNA Cross-linking: The activated form of trioxsalen forms cross-links between adjacent DNA strands within the cell nucleus. This process, known as photochemical cross-linking, results in the formation of covalent bonds between DNA bases. The cross-linking can occur between two pyrimidine bases, typically thymine, or between a pyrimidine base and a neighboring protein or another cellular component. 
• Inhibition of DNA Replication and Cell Division: The cross-linking of DNA interferes with the normal processes of DNA replication and cell division. Cells with cross-linked DNA become less able to divide and increase, which can be beneficial in conditions characterized by excessive cell growth, such as psoriasis. 
• Melanocyte Stimulation: trioxsalen, in combination with UVA radiation, also stimulates melanocytes, the cells responsible for producing melanin (skin pigment). This effect is essential in treating vitiligo, where skin pigmentation is lost in certain areas.

Pharmacokinetics: 

Absorption 

trioxsalen is administered orally in the form of capsules or tablets. After oral administration, it is absorbed from the gastrointestinal tract into the bloodstream. The rate and extent of absorption may vary among individuals but are generally relatively slow. 

Distribution 

trioxsalen is distributed throughout the body, including the skin, where it exerts its therapeutic effects in PUVA therapy. It can also cross the blood-brain barrier, which may contribute to its central nervous system effects. 

Metabolism 

trioxsalen is extensively metabolized in the liver through a process called biotransformation. The primary metabolic pathway involves the formation of reactive intermediates that can bind to cellular components, including DNA, leading to photosensitizing effects. The exact details of its metabolic pathways may vary among individuals. 

Elimination and Excretion 

The metabolites of trioxsalen are excreted primarily through the urine, with a smaller portion being eliminated in the feces. The excretion process ensures that trioxsalen and its metabolites are eliminated from the body over time. 

Adminstartion

Administration: 

Oral administration 

trioxsalen is given orally, usually in the form of capsules or tablets. The dose and duration of treatment will depend on the specific skin condition and the individual’s response to the therapy. The medication is typically taken with a meal or milk to improve absorption. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: trioxsalen 

Why do we use trioxsalen? 

trioxsalen is primarily used with UVA (ultraviolet A) light therapy in a treatment known as PUVA therapy (psoralen and UVA therapy). This treatment is used to manage certain skin disorders, mainly: 

• Psoriasis: trioxsalen with UVA light therapy is used to treat plaque psoriasis, a chronic skin condition characterized by red, raised, and scaly patches on the skin. PUVA therapy helps to slow down the excessive growth of skin cells seen in psoriasis and reduce inflammation. 
• Vitiligo: trioxsalen combined with UVA light therapy can treat vitiligo, a condition where the skin loses its natural pigmentation, resulting in white patches on various body parts. PUVA therapy helps to stimulate melanocytes and promote repigmentation in the affected areas.