Usage
- Trioxasalen is prescribed for the treatment of vitiligo (a skin condition characterized by loss of pigmentation) in conjunction with ultraviolet A (UVA) light therapy (PUVA). It is also used to increase the skin’s tolerance to sunlight in individuals with photosensitivity.
- Pharmacological Classification: Photosensitizing agent, Psoralen.
- Mechanism of Action: Trioxasalen works by increasing the skin’s sensitivity to UVA light. When activated by UVA, it binds to DNA, forming crosslinks that can inhibit DNA replication and lead to cell death. This effect is used therapeutically to destroy melanocytes in vitiligo or to increase melanin production.
Alternate Names
How It Works
- Pharmacodynamics: Trioxasalen enhances the effects of UVA radiation on the skin, leading to increased melanin production and melanocyte proliferation. The extent of these effects depends upon the dose of trioxasalen and the amount of UVA exposure.
- Pharmacokinetics: Trioxasalen is administered orally and is well-absorbed from the gastrointestinal tract. It is metabolized primarily in the liver, and its metabolites are excreted mainly through the kidneys. CYP enzymes are involved in its metabolism.
- Mode of Action: Trioxasalen intercalates into DNA and, upon UVA irradiation, forms covalent bonds with pyrimidine bases, creating monoadducts and crosslinks. This DNA damage can induce apoptosis (programmed cell death) in melanocytes and other skin cells.
- Elimination Pathways: Primarily renal excretion of metabolites after hepatic metabolism.
Dosage
Standard Dosage
Adults:
- 20 to 40 mg taken orally two to four hours before UVA exposure for vitiligo.
- 20 to 40 mg taken orally two hours before UVA exposure for increasing tolerance to sunlight.
- Administer two or three times per week, with at least 48 hours between treatments.
Children:
- Dosage must be determined by a physician and is based on weight or age.
- Pediatric safety needs careful evaluation, as long-term effects are not fully understood.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary based on renal and hepatic function.
- Patients with Renal Impairment: Dose modifications are needed based on creatinine clearance.
- Patients with Hepatic Dysfunction: Dose reduction is usually required due to impaired metabolism.
- Patients with Comorbid Conditions: Careful assessment and dose adjustments may be needed in patients with cardiovascular disease, diabetes, or other relevant conditions.
Clinical Use Cases
Trioxasalen is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its primary use is limited to dermatological conditions with UVA light therapy.
Dosage Adjustments
Dosage adjustments may be required based on individual patient response, renal/hepatic function, and concomitant medications.
Side Effects
Common Side Effects
- Nausea
- Itching or burning sensation
- Skin redness (erythema)
- Blistering
Rare but Serious Side Effects
- Severe burns
- Skin cancer (with prolonged use)
- Cataracts (with prolonged use)
- Premature skin aging
Long-Term Effects
- Increased risk of skin cancer
- Premature aging of the skin
- Cataracts
Adverse Drug Reactions (ADR)
- Severe skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome)
Contraindications
- Porphyria
- Lupus erythematosus
- Melanoma or other types of skin cancer
- Cataracts
- Hypersensitivity to trioxasalen
- Xeroderma pigmentosum
Drug Interactions
- Other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines)
- Drugs metabolized by CYP enzymes (e.g., some antidepressants, antipsychotics)
- Foods containing furanocoumarins (e.g., limes, figs, parsley) can increase photosensitivity
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Animal studies show adverse effects, but no adequate studies in humans). Use only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Safety not established. Avoid use or discontinue breastfeeding.
Drug Profile Summary
- Mechanism of Action: Photosensitizes skin, increasing UVA absorption.
- Side Effects: Nausea, itching, skin redness, blistering, increased risk of skin cancer and cataracts with prolonged use.
- Contraindications: Porphyria, lupus, melanoma, cataracts, hypersensitivity.
- Drug Interactions: Other photosensitizers, CYP-metabolized drugs.
- Pregnancy & Breastfeeding: Category C; not recommended.
- Dosage: 20–40 mg 2–4 hours before UVA; adjustments as needed.
- Monitoring Parameters: Skin reactions, eye exams.
Popular Combinations
Trioxasalen is generally used alone with UVA therapy. No other drug combinations are routinely recommended.
Precautions
- Protect eyes and skin from excessive sunlight during and after treatment.
- Monitor for signs of skin burns or other adverse reactions.
- Evaluate renal and hepatic function before and during treatment, especially in elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Trioxasalen?
A: Adults: 20-40 mg 2-4 hours before UVA. Children: Dose determined by a physician.
Q2: What are the common side effects?
A: Nausea, itching, skin redness, and blistering.
Q3: How does Trioxasalen work?
A: Increases skin’s sensitivity to UVA light, leading to DNA damage and cell death/increased melanin production.
Q4: What are the contraindications for Trioxasalen?
A: Porphyria, lupus, melanoma, cataracts, and hypersensitivity to the drug.
Q5: Can Trioxasalen be used during pregnancy?
A: Category C; use only if the potential benefit outweighs the risk.
Q6: How often should Trioxasalen be administered?
A: Two to three times a week, with at least 48 hours between treatments.
Q7: What precautions should be taken during treatment?
A: Protect eyes and skin from sunlight, monitor skin reactions.
Q8: Does Trioxasalen interact with other medications?
A: Yes, it can interact with other photosensitizing agents and drugs metabolized by CYP enzymes.
Q9: What is the long-term risk of Trioxasalen use?
A: Increased risk of skin cancer, premature skin aging, and cataracts.
