Methoxsalen (Hipprex) Dosing and Administration for PUVA Therapy
Oral Methoxsalen Dosing
For oral PUVA therapy, methoxsalen capsules should be taken 1.5 to 2 hours before UVA exposure with low-fat food or milk, dosed according to body weight. 1
Weight-Based Dosing Table
- <30 kg (<66 lbs): 10 mg
- 30-50 kg (66-110 lbs): 20 mg
- 51-65 kg (112-143 lbs): 30 mg
- 66-80 kg (146-176 lbs): 40 mg
- 81-90 kg (179-198 lbs): 50 mg
- 91-115 kg (201-254 lbs): 60 mg
- >115 kg (>254 lbs): 70 mg 1
Critical Timing Considerations
The newer soft gelatin capsule formulation (Oxsoralen-Ultra) reaches peak photosensitivity at 1.5-2.1 hours post-ingestion, significantly earlier than older hard gelatin formulations (3.9-4.25 hours). 1 This formulation achieves twice the serum levels of hard gelatin capsules and requires substantially lower UVA doses. 1
An alternative formulation, 8-methoxypsoralen (8-MOP), requires 2 hours before UVA exposure. 2
Food Interaction Management
While it is preferred to avoid food for 1 hour before and after dosing (as food decreases absorption), if nausea necessitates food intake, maintain consistent timing and type of food with each dose to minimize pharmacokinetic variability. 2 Taking methoxsalen with milk or crackers can reduce nausea. 2
Initial UVA Exposure Protocol
Starting UVA doses are determined by Fitzpatrick skin type, NOT by arbitrary fixed doses. 1
Skin Type-Based Initial Dosing
- Type I (Always burn, never tan; includes erythrodermic psoriasis): 0.5 J/cm²
- Type II (Always burn, sometimes tan): 1.0 J/cm²
- Type III (Sometimes burn, always tan): 1.5 J/cm²
- Type IV (Never burn, always tan): 2.0 J/cm²
- Type V (Moderately pigmented): 2.5 J/cm²
- Type VI (Black skin): 3.0 J/cm² 1
If minimal phototoxic dose (MPD) testing is performed, start at ½ MPD. 1
Treatment Frequency and Escalation
Treatments should be administered 2-3 times weekly with at least 48 hours between sessions, as full phototoxic reactions may not manifest until 48 hours post-exposure. 2, 1
Clearance Phase Dose Escalation
For Skin Types I, II, III:
- Increase UVA by up to 1.0 J/cm² per treatment based on response
- Hold dose constant if erythema develops until resolution 1
For Skin Types IV, V, VI:
- Increase UVA by up to 1.5 J/cm² per treatment unless erythema occurs
- If erythema develops, follow Type I-III protocols 1
For Erythrodermic Psoriasis:
- Treat as Type I patient (maximum 1.0 J/cm² increases) due to difficulty assessing treatment-related erythema against baseline erythema 1
Non-Response Protocol
After 10 treatments without response: Increase UVA by an additional 0.5-1.0 J/cm² above the standard incremental increases. 1
After 15 treatments with minimal/no response: Increase methoxsalen dose by 10 mg (one-time only). This increased dose may continue for the remainder of treatment but should not be exceeded. 1
Missed Treatment Adjustments
- One missed treatment: Do not increase UVA exposure at next session
- Multiple missed treatments: Reduce exposure by 0.5 J/cm² for each treatment missed 1
Topical PUVA Alternatives
Topical Application Method
For palmar-plantar psoriasis: Apply 0.1% 8-methoxypsoralen in emollient 30 minutes before UVA, treating 2-3 times weekly. Start at 0.25-0.5 J/cm² and increase by 0.25-0.5 J/cm² per session. 2
Bath PUVA Method
For generalized psoriasis (adults and children): Use 50 mg of 8-methoxypsoralen in 100 L of water with 20-30 minute pre-exposure immersion. Follow similar scheduling to oral PUVA. 2
A higher concentration (5 mg/L methoxsalen) is substantially more effective than 1 mg/L, achieving 87% reduction in PASI scores versus 72%, with median cumulative UVA dose of 25.4 J/cm² versus 71.9 J/cm² respectively. 3 However, mild-to-moderate adverse events are more common with the higher concentration. 3
Maintenance Phase Protocol
Once 95% clearing (Grade 4 response) is achieved, transition to sequential maintenance schedules:
- M1: Once weekly
- M2: Once every 2 weeks
- M3: Once every 3 weeks
- M4: As needed for flares 1
Each maintenance schedule should be maintained for at least 2 treatments before advancing. 1 Remission times typically range from 3-12 months. 2
Maximum Maintenance Doses by Skin Type
To prevent cumulative photocarcinogenesis risk, maximum UVA dosages during maintenance should not exceed:
- Type I: 12 J/cm²/treatment
- Type II: 14 J/cm²/treatment
- Type III: 18 J/cm²/treatment
- Type IV: 22 J/cm²/treatment 1
Critical Safety Monitoring
Absolute Contraindications
Do not use PUVA in patients with:
- Lupus erythematosus
- Porphyria
- Xeroderma pigmentosum 2
High-Risk Populations Requiring Extreme Caution
- Skin types I-II (burn easily)
- History of arsenic exposure or ionizing radiation
- History of melanoma or multiple non-melanoma skin cancers
- Severe liver disease (risk of toxic psoralen levels)
- Prior cyclosporine or methotrexate treatment
- Pregnancy or nursing 2
Photocarcinogenesis Risk
Caucasians with skin types I-III face significantly increased risk of squamous cell carcinoma after 200 treatments or 2000 J/cm² cumulative exposure. 2 A 14-fold increased incidence of SCC occurs with high-dose PUVA (≥200 treatments) compared to low-dose (<100 treatments). 2 This risk is not present in non-Caucasian populations. 2
Male genitalia require shielding during all treatments due to particularly elevated SCC risk in this area. 2
Drug Interactions
If oral retinoids are initiated during PUVA therapy, decrease UVA dose by one-third. 2 Exercise caution with any photosensitizing medications. 2
Eye Protection Requirements
Patients must wear UVA-blocking eyewear during treatment and for the remainder of the day after psoralen ingestion. 2 However, a 25-year prospective study found no increased risk of cataract formation with proper eye protection compliance. 2
Nursing is contraindicated for 24 hours after psoralen ingestion. 2
Expected Treatment Course
Typical response occurs within 1 month of treatment initiation. 2 A single course usually requires 30-40 treatments for clearance, though noticeable response may take 30 treatments. 2 Historical data from 1,308 patients showed 88% clearance rate with oral PUVA. 4