Usage
Psoralen, combined with ultraviolet A (UVA) light (PUVA therapy), is prescribed for treating:
- Psoriasis: A chronic skin condition causing red, scaly patches.
- Vitiligo: A skin disease resulting in loss of skin color (depigmentation).
- Cutaneous T-cell lymphoma (CTCL): A type of non-Hodgkin lymphoma affecting the skin.
- Eczema: (Atopic Dermatitis) A condition that makes skin red and itchy.
- Other skin conditions: Such as scleroderma, and some types of dermatitis.
Pharmacological Classification: Photosensitizing medication.
Mechanism of Action: Psoralen increases the skin’s sensitivity to UVA light. When activated by UVA exposure, psoralen interacts with DNA, leading to cross-linking and cell damage. This initiates an inflammatory response and increases melanin production, darkening the skin and thickening the stratum corneum (outermost skin layer).
Alternate Names
- Methoxsalen (most common alternate name and active ingredient in many formulations)
- 8-Methoxypsoralen (8-MOP)
- Furocoumarin (chemical class)
Brand Names:
- Oxsoralen-Ultra
- Uvadex
- 8-MOP (generic)
- Chromalin 10
- Meladerm
- Melanocyl
- Melcyl
- Melonil
- Manaderm
How It Works
Pharmacodynamics: Psoralen enhances the effects of UVA radiation on the skin, inducing phototoxic reactions that modify immune responses, cell growth, and pigmentation.
Pharmacokinetics:
- Absorption: Oral psoralen is absorbed from the gastrointestinal tract. Topical absorption depends on the formulation and application site.
- Metabolism: Primarily hepatic metabolism via cytochrome P450 enzymes.
- Elimination: Mainly renal excretion.
Mode of Action: Psoralen intercalates into DNA. Upon UVA exposure, it forms covalent bonds with pyrimidine bases (thymine and cytosine), creating DNA cross-links. This disrupts DNA replication and transcription, leading to cell cycle arrest and apoptosis (programmed cell death) in rapidly dividing cells like those in psoriatic plaques or malignant T-cells.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: The primary mechanism is not receptor-mediated, enzyme inhibition, or neurotransmitter modulation. Instead, psoralen acts directly on DNA by forming cross-links.
Elimination Pathways: Predominantly renal excretion, along with some hepatic metabolism by CYP450 enzymes.
Dosage
Standard Dosage
Adults:
- Oral (for psoriasis, CTCL, vitiligo): Methoxsalen: 0.6 mg/kg (for hard gelatin capsules) or 0.4 mg/kg (for soft gelatin capsules) taken 1.5-4 hours before UVA exposure, 2-3 times per week, with at least 48 hours between treatments. For vitiligo: 20 mg taken 2-4 hours before UVA exposure. Dosage can be adjusted based on skin type, body surface area, and individual response. Dosing for mycosis fungoides is 0.6 mg/kg.
- Topical (for vitiligo): Apply to affected skin 1-2 minutes before, and then again 2-2.5 hours before UVA exposure.
Children:
- Dosing must be determined by a doctor and depends on body weight, age, and condition.
Special Cases:
- Elderly Patients: Close monitoring is recommended. Dosage adjustments might be necessary due to age-related changes in organ function.
- Patients with Renal Impairment: Dose adjustments are required based on creatinine clearance.
- Patients with Hepatic Dysfunction: Careful monitoring and dose reduction may be necessary.
- Patients with Comorbid Conditions: Individualized dosing is required, especially for patients with conditions affecting drug metabolism or photosensitivity.
Clinical Use Cases:
Psoralen’s clinical use is primarily centered around photochemotherapy (PUVA) or photopheresis. It is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations.
Dosage Adjustments:
Dosage adjustments are individualized based on the patient’s weight, body surface area, skin type, response to treatment, concurrent medications, and any existing renal or hepatic impairment.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Itching (pruritus)
- Skin burning
- Redness (erythema)
- Skin tanning or darkening
- Headaches
- Dizziness
Rare but Serious Side Effects:
- Severe sunburn and blistering
- Premature skin aging (photoaging)
- Cataracts
- Increased risk of skin cancer (squamous cell carcinoma, melanoma, basal cell carcinoma)
- Eye damage (conjunctival changes)
Long-Term Effects:
- Increased risk of skin cancer with prolonged PUVA therapy
- Photoaging
Adverse Drug Reactions (ADR):
- Severe skin reactions, burns and blistering
- Allergic reactions
- Ocular toxicity
Contraindications
- Absolute: Known hypersensitivity to psoralen, history of melanoma or other skin cancers, photosensitivity disorders (e.g., lupus, porphyria, xeroderma pigmentosum, albinism), aphakia (absence of the eye lens). In neonates, it is contraindicated with phototherapy devices emitting peak energy wavelength <425nm or lower bound of emission bandwidth <375nm.
- Relative: Cardiac, liver, or renal disease, family history of melanoma, young children (long-term safety not established), pregnancy, breastfeeding.
Drug Interactions
- Photosensitizing medications: Tetracyclines, sulfonamides, phenothiazines – may increase risk of sunburn.
- CYP450 enzyme inducers/inhibitors: Phenytoin, warfarin, cyclosporine, calcium channel blockers, some antifungals and antibiotics – may affect psoralen metabolism.
- Other: Anagrelide and tegafur – avoid concomitant use.
- Herbal supplements: St. John’s wort - may increase the risk of photosensitivity.
- Food and Lifestyle: Alcohol may increase the risk of side effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (oral), Not established (topical)
- Fetal Risks: Psoralen is considered teratogenic in animal studies, but limited data exists for humans. Its use is generally contraindicated during pregnancy due to the potential for birth defects and developmental issues.
- Breastfeeding: Psoralen is excreted in breast milk and may cause photosensitivity in infants. Breastfeeding is contraindicated during PUVA therapy.
Drug Profile Summary
- Mechanism of Action: Increases skin sensitivity to UVA light, causing DNA cross-linking and cell damage.
- Side Effects: Nausea, itching, sunburn, increased risk of skin cancer.
- Contraindications: Skin cancer, photosensitivity disorders, pregnancy.
- Drug Interactions: Photosensitizing drugs, CYP450 inducers/inhibitors.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Weight-based dosing before UVA exposure.
- Monitoring Parameters: Skin reactions, eye exams, liver and kidney function.
Popular Combinations:
Psoralen is typically used in combination with UVA light (PUVA therapy). No other drug combinations are typically used alongside PUVA.
Precautions
- General Precautions: Screen for contraindications, monitor for side effects, protect eyes during and after UVA exposure, avoid excessive sun exposure.
- Specific Populations: Pregnant/breastfeeding women (contraindicated), children (use with caution), elderly (close monitoring).
- Lifestyle Considerations: Avoid alcohol, protect skin from sunlight.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Psoralen?
A: Oral dosage depends on weight, condition, and psoralen formulation. For adults with psoriasis: 0.6 mg/kg (hard capsules) or 0.4 mg/kg (soft capsules) 1.5-2 hours before UVA. For vitiligo: 20 mg 2-4 hrs before UVA. Pediatric and special case dosing should be determined by a physician.
Q2: How does PUVA therapy work?
A: Psoralen enhances UVA light’s effect on skin cells, causing DNA cross-linking, inhibiting cell growth, and promoting an inflammatory response.
Q3: What are the most common side effects of Psoralen?
A: Nausea, itching, skin burning/redness, and increased sun sensitivity are common.
Q4: What are the serious side effects of long-term PUVA therapy?
A: Premature skin aging and increased risk of skin cancers are potential long-term complications.
Q5: Who should not take Psoralen?
A: Patients with skin cancer, photosensitivity disorders, or pregnant/breastfeeding women should not use psoralen.
Q6: Are there any drug interactions with Psoralen?
A: Yes, psoralen can interact with other photosensitizing medications, CYP450 enzyme inducers/inhibitors, and certain other drugs (e.g. anagrelide, tegafur). Consult a drug interaction checker for a full list.
Q7: Can Psoralen be used during pregnancy?
A: No. Psoralen is contraindicated during pregnancy due to potential teratogenic effects.
Q8: Can Psoralen be used while breastfeeding?
A: No. Psoralen is excreted in breast milk and may cause photosensitivity in infants.
Q9: What precautions should be taken during PUVA therapy?
A: Wear protective eyewear during and after UVA exposure, avoid excessive sun exposure, and monitor for side effects. Report any unusual skin reactions or eye changes to your physician immediately.
Q10: How frequently is PUVA therapy administered?
A: Typically, PUVA is administered 2-3 times a week, with a minimum of 48 hours between treatments. This allows the skin to recover and minimizes the cumulative effects of UVA exposure.
