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) |
| Molecular Weight | 216.19 |
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 | Contraindicated. Methoxsalen is a photosensitizer and potential teratogen. Exposure during organogenesis may increase risk of fetal anomalies. |
| 2nd trimester | Contraindicated. Avoid use due to lack of safety data and potential for phototoxicity and DNA damage. |
| 3rd trimester | Contraindicated. Use only if benefit outweighs risk; limited data, but theoretical risk of neonatal phototoxicity. |
Clinical note
Many drugs are photosensitizing (eg tetracyclines) Can cause severe phototoxic reactions and increased risk of skin cancer.
| Placental transfer | Methoxsalen is known to cross the placenta in animals; human data are lacking but molecular weight suggests transfer is likely. |
| Breastfeeding | Methoxsalen is excreted into breast milk. It may cause phototoxicity in the nursing infant. Avoid breastfeeding during therapy and for at least 24 hours after the last dose. |
■ 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 |
Known hypersensitivity to methoxsalen or related psoralensPorphyria cutanea tardaSystemic lupus erythematosusHistory of melanomaXeroderma pigmentosumPrior exposure to ionizing radiation or arsenic therapySevere hepatic or renal impairmentPregnancy
| 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 |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
| Avoid foods high in psoralens (e.g., figs, celery, parsley, limes, parsnips) as they may increase photosensitivity. Grapefruit and grapefruit juice may alter drug metabolism; avoid concurrent use. Methoxsalen should be taken with food to reduce gastrointestinal irritation. |
| Clinical Pearls | Methoxsalen is a photosensitizing agent used in PUVA therapy for psoriasis, vitiligo, and cutaneous T-cell lymphoma. Administer with food to reduce nausea. Avoid sun exposure for 24-48 hours after dose. Monitor liver function and eye exams (cataract risk). Dose adjustments needed in hepatic impairment. |
| Patient Advice | Take methoxsalen with a meal or milk to prevent stomach upset. · Avoid sunlight and tanning beds for at least 24-48 hours after taking the medication. · Wear UVA-blocking sunglasses during PUVA treatment to protect eyes. · Inform your doctor immediately if you develop severe sunburn, blisters, or skin pain. · Do not use other photosensitizing medications (e.g., tetracyclines, thiazides) without consulting your doctor. · Report vision changes or eye pain promptly. · Avoid alcohol, which can increase photosensitivity. · Use sunscreen on uncovered skin even on cloudy days. |