TRISORALEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRISORALEN (TRISORALEN).
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.
| 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. |
| Molecular Weight | 300.35 |
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. |
| 1st trimester | Contraindicated due to teratogenic effects observed in animal studies and potential for DNA damage. Use only if benefit outweighs risk, with strict photoprotection. |
| 2nd trimester | Contraindicated; avoid use due to risk of fetal phototoxicity and potential for growth retardation. Limited human data suggest safety concerns. |
| 3rd trimester | Contraindicated; may cause neonatal phototoxicity and premature closure of ductus arteriosus. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for TRISORALEN (TRISORALEN).
| Placental transfer | Crosses placenta in animals; human data limited. Theoretical risk of fetal phototoxicity and DNA binding. |
| Breastfeeding | Excreted in breast milk in unknown amounts. Potential for phototoxicity in nursing infant. Avoid breastfeeding during therapy and for 24 hours after last dose. Consider alternative treatments. |
■ 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.
| Serious Effects |
PregnancyLactationSevere hepatic impairmentPhotosensitivity disorders (e.g., lupus erythematosus, porphyria)Prior sensitivity to psoralensMalignant melanomaInvasive squamous cell carcinomaAphakia (due to increased retinal light exposure)
| 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. |
| Food/Dietary | Take with food or milk to reduce GI side effects. Avoid foods containing natural psoralens (e.g., celery, figs, limes, parsley, parsnips, cilantro) in large quantities during therapy as they may increase photosensitivity risk. Grapefruit juice may alter metabolism; avoid excessive consumption. |
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| Lactation Rating | L4 (Hazardous) |
| 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 | No specific fetal monitoring required, but pregnancy status should be confirmed before initiating therapy. Monitor for maternal hepatotoxicity, photosensitivity, and skin reactions. |
| Fertility Effects | Based on animal studies, trioxsalen may impair fertility due to DNA crosslinking and ovarian toxicity. Human data are insufficient. |
| Clinical Pearls | Trisoralen (trioxsalen) is a photosensitizing agent used in combination with UVA radiation (PUVA therapy) for repigmentation in vitiligo. Monitor ocular lens for cataract formation due to psoralen binding to DNA in lens. Avoid concomitant use with other photosensitizing drugs. Dose depends on patient weight and skin type; therapy requires precise UVA dosimetry. May cause severe burns if UVA exposure is excessive. |
| Patient Advice | Take trisoralen with food or milk to reduce gastrointestinal upset. · Avoid sunlight and UV light exposure for 24-48 hours after treatment to prevent severe sunburn. · Wear UVA-protective sunglasses for 24 hours after each dose to protect eyes. · Do not use any other photosensitizing medications or topical agents without consulting your doctor. · Report any blistering, severe redness, or eye pain immediately. · Pregnancy and breastfeeding: not recommended; use effective contraception. · You will need regular eye exams to monitor for cataract formation. |