TRISORALEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRISORALEN (TRISORALEN).

How it works

Psoralen (trisoralen) intercalates into DNA and, upon UVA irradiation, forms covalent cross-links between pyrimidine bases, inhibiting DNA replication and cell division. It also suppresses DNA synthesis and epidermal cell proliferation.

What the body does with it

Metabolism	Metabolized extensively in the liver via cytochrome P450 enzymes (primarily CYP1A2 and CYP2A6) to inactive metabolites; undergoes enterohepatic recirculation.
Excretion	Primarily renal elimination of metabolites; less than 5% excreted unchanged in urine. Approximately 90% of a radiolabeled dose is recovered in urine within 24 hours, with less than 5% in feces.
Half-life	Terminal elimination half-life is approximately 2 hours (range 1.1–2.5 h) for trioxsalen after oral administration; clinical phototoxic effect peaks at 2–4 hours post-dose.
Protein binding	Approximately 90–95% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is approximately 0.2–0.3 L/kg, indicating limited extravascular distribution; clinically suggests low tissue accumulation.
Bioavailability	Oral bioavailability is highly variable, reported at approximately 40–60% due to extensive first-pass metabolism; topical absorption is minimal but varies with formulation and skin integrity.
Onset of Action	Oral: Phototoxic effect begins approximately 2–3 hours after ingestion when combined with UVA exposure; topical: within 1–2 hours after application and UVA exposure.
Duration of Action	Oral: Phototoxic effect lasts 8–12 hours, corresponding to drug presence in skin; topical: effect may persist 12–24 hours due to cutaneous drug retention.

Classification & Brands

Dosing & administration

10-70 mg orally 2 hours before UVA exposure, given 2-3 times per week, with dose based on body weight (0.6 mg/kg).

Dosage form	TABLET
Renal impairment	No specific dose adjustments recommended; use with caution in severe renal impairment due to lack of data.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild-moderate impairment (Child-Pugh A or B), reduce dose by 50% and monitor liver function.
Pediatric use	0.6 mg/kg orally 2 hours before UVA exposure (maximum 70 mg per dose). Not recommended in children under 12 years due to safety concerns in clinical trials.
Geriatric use	No specific adjustment; start at low end of adult dose (10-20 mg) and titrate cautiously due to increased risk of photosensitivity and reduced renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRISORALEN (TRISORALEN).

Breastfeeding	Excretion in human milk is unknown. Given the potential for phototoxicity and DNA damage, breastfeeding is not recommended during treatment. M/P ratio not available.
Teratogenic Risk	Trisoralen (trioxsalen) is a psoralen derivative. Based on animal studies, it is teratogenic (skeletal and visceral malformations) and embryotoxic. Human data are limited, but due to DNA intercalation and phototoxicity, use is contraindicated in all trimesters. Risk cannot be ruled out.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Trisoralen with UVA therapy (PUVA) is carcinogenic; may increase risk of skin cancer (squamous cell carcinoma, melanoma) and cataract formation. Use only under direct supervision of a physician experienced in photochemotherapy.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to psoralens or any component of formulation","Aphakia (absence of lens) due to increased risk of retinal damage","Melanoma or history of melanoma","Invasive squamous cell carcinoma","Lupus erythematosus, porphyria, xeroderma pigmentosum, albinism","Severe hepatic or renal impairment","Pregnancy and breastfeeding"]

Clinical Precautions

Precautions

["Skin cancer risk: cumulative PUVA exposure increases risk of squamous cell carcinoma and melanoma; monitor skin regularly.","Cataract formation: patients must wear UVA-blocking eye protection during and 24 hours after treatment; avoid sun exposure.","Photosensitivity: severe burns may occur if additional UV exposure occurs within 24 hours of therapy.","Hepatic impairment: use with caution; monitor liver function.","Pregnancy: avoid unless benefit outweighs risk; excreted in breast milk."]

Clinical Tips & Counseling

Drug interactions

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TRISORALEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRISORALEN (TRISORALEN).

How it works

What the body does with it

Metabolism	Metabolized extensively in the liver via cytochrome P450 enzymes (primarily CYP1A2 and CYP2A6) to inactive metabolites; undergoes enterohepatic recirculation.
Excretion	Primarily renal elimination of metabolites; less than 5% excreted unchanged in urine. Approximately 90% of a radiolabeled dose is recovered in urine within 24 hours, with less than 5% in feces.
Half-life	Terminal elimination half-life is approximately 2 hours (range 1.1–2.5 h) for trioxsalen after oral administration; clinical phototoxic effect peaks at 2–4 hours post-dose.
Protein binding	Approximately 90–95% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is approximately 0.2–0.3 L/kg, indicating limited extravascular distribution; clinically suggests low tissue accumulation.
Bioavailability	Oral bioavailability is highly variable, reported at approximately 40–60% due to extensive first-pass metabolism; topical absorption is minimal but varies with formulation and skin integrity.
Onset of Action	Oral: Phototoxic effect begins approximately 2–3 hours after ingestion when combined with UVA exposure; topical: within 1–2 hours after application and UVA exposure.
Duration of Action	Oral: Phototoxic effect lasts 8–12 hours, corresponding to drug presence in skin; topical: effect may persist 12–24 hours due to cutaneous drug retention.

Classification & Brands

Dosing & administration

10-70 mg orally 2 hours before UVA exposure, given 2-3 times per week, with dose based on body weight (0.6 mg/kg).

Dosage form	TABLET
Renal impairment	No specific dose adjustments recommended; use with caution in severe renal impairment due to lack of data.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild-moderate impairment (Child-Pugh A or B), reduce dose by 50% and monitor liver function.
Pediatric use	0.6 mg/kg orally 2 hours before UVA exposure (maximum 70 mg per dose). Not recommended in children under 12 years due to safety concerns in clinical trials.
Geriatric use	No specific adjustment; start at low end of adult dose (10-20 mg) and titrate cautiously due to increased risk of photosensitivity and reduced renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRISORALEN (TRISORALEN).

Breastfeeding	Excretion in human milk is unknown. Given the potential for phototoxicity and DNA damage, breastfeeding is not recommended during treatment. M/P ratio not available.
Teratogenic Risk	Trisoralen (trioxsalen) is a psoralen derivative. Based on animal studies, it is teratogenic (skeletal and visceral malformations) and embryotoxic. Human data are limited, but due to DNA intercalation and phototoxicity, use is contraindicated in all trimesters. Risk cannot be ruled out.
Fetal Monitoring