METHOXSALEN
Clinical safety rating: avoid
Contraindicated (not allowed)
Methoxsalen is a psoralen that intercalates DNA, and upon UVA activation, forms covalent cross-links with pyrimidine bases, inhibiting DNA synthesis and cell division.
| Metabolism | Extensively metabolized by cytochrome P450 enzymes, primarily CYP1A2 and CYP2A6. |
| Excretion | Renal: 95% as metabolites (glucuronides); fecal: 4%; <0.1% unchanged in urine |
| Half-life | 2 hours (range 1-3 h); terminal half-life is 2 h after oral administration; no accumulation with once-daily dosing |
| Protein binding | 88-91% bound to albumin |
| Volume of Distribution | 1.2 L/kg (indicates extensive tissue distribution; high binding to skin and melanocytes) |
| Bioavailability | Oral: 70-80% (variable, affected by food; high-fat meals increase absorption) |
| Onset of Action | Oral: 2-4 hours (psoralen-UVA photochemotherapy effect); Topical: 1-2 hours |
| Duration of Action | Oral: 8-12 hours (photosensitivity persists); Topical: 12-24 hours (variable with skin site and UVA dose) |
Oral: 0.4–0.6 mg/kg taken 1.5–2 hours before UVA exposure; typical dose range 10–70 mg. Topical: 0.1% lotion applied 1 hour before UVA.
| Dosage form | CAPSULE |
| Renal impairment | No formal guidelines; use caution with severe renal impairment (CrCl <30 mL/min) due to lack of safety data; consider dose reduction or alternative. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 12 years and older: 0.4–0.6 mg/kg orally 1.5–2 hours before UVA; under 12 years: safety not established. |
| Geriatric use | Start at lowest adult dose (0.4 mg/kg); monitor renal and hepatic function; cautious due to increased risk of photosensitivity and skin aging. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Many drugs are photosensitizing (eg tetracyclines) Can cause severe phototoxic reactions and increased risk of skin cancer.
| Breastfeeding | Unknown if excreted in human milk. M/P ratio not available. Avoid breastfeeding due to potential for infant photosensitivity and carcinogenicity. Consider alternative therapies. |
| Teratogenic Risk | Pregnancy category C. Teratogenic in animal studies at high doses; human data limited. Risk of fetal harm cannot be ruled out. Avoid first trimester due to theoretical risk of folate antagonism and photosensitivity. Second/third trimester: use only if benefit outweighs risk; monitor fetal growth and amniotic fluid. |
■ FDA Black Box Warning
Methoxsalen with UVA therapy (PUVA) significantly increases the risk of skin cancer, including melanoma and squamous cell carcinoma. Strict sun protection and regular skin monitoring are required.
| Common Effects | vitiligo (with UVA) |
| Serious Effects |
["Hypersensitivity to methoxsalen or any psoralen","Porphyria","History of melanoma or invasive squamous cell carcinoma","Cataracts or aphakia","Severe hepatic or renal impairment","Pregnancy and lactation"]
| Precautions | ["Carcinogenicity: Increased risk of skin cancer with PUVA therapy","Photosensitivity: Severe burns and ocular damage if exposed to sunlight or UV light","Hepatotoxicity: Monitor liver function due to potential liver damage","Immunosuppression: May increase risk of infections","Pregnancy: Avoid use due to teratogenicity"] |
Loading safety data…
| Fetal Monitoring |
| Baseline and periodic liver function tests, renal function, complete blood count. Monitor for phototoxicity in mother. Fetal ultrasound for growth and amniotic fluid volume if used during pregnancy. |
| Fertility Effects | No known direct effects on fertility in humans. Animal studies show no impairment at therapeutic doses. Theoretical risk of ovarian toxicity at high cumulative doses, but not well documented. |