methoxsalen

Action and Spectrum

Actions and spectrum: 

methoxsalen is a medication that belongs to the class of psoralens. Psoralens are a group of naturally occurring or synthetic compounds that have the ability to sensitize the skin to the effects of ultraviolet light.

methoxsalen works by increasing the skin’s sensitivity to UV radiation, which is why it is used in phototherapy to treat skin disorders such as psoriasis, vitiligo, and mycosis fungoides.

methoxsalen binds to DNA in the skin cells and, when activated by UV radiation, causes cross-linking of the DNA strands, resulting in inhibition of cell division and proliferation. 

Drug Interaction

Adverse Reaction

Frequency defined 

All Patients 

erythema for 24-48 hrs mild-moderate 

1-10% 

Pruritis 

Nausea  

Frequency not defined 

Dizziness 

Malaise 

Hypopigmentation 

Rash 

Urticaria 

Leg cramps 

Extension of psoriasis 

Edema 

Headache 

Depression 

Bullae formation 

Herpes simplex 

GI disturbances 

Hypotension  

Post marketing Reports 

Allergic reaction 

Nausea 

Rash 

Pyrexia 

Dysgeusia 

Black Box Warning

Black Box Warning: 

methoxsalen carries a black box warning that it may have an increased risk of developing cataracts and skin cancer, which can lead to blindness. Therefore, methoxsalen should only be used in patients with severe, disabling psoriasis or vitiligo that cannot be treated with other therapies.

The risks and benefits of methoxsalen therapy should be carefully evaluated in each patient. Patients receiving methoxsalen should be advised to avoid excessive exposure to sunlight or artificial UV radiation. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity to methoxsalen or any component of the formulation 
• Known sensitivity to sunlight or other UV radiation 
• Ocular cataracts 
• squamous cell carcinoma or basal cells of the skin 
• Melanoma or any type of skin cancer 
• Pregnancy and lactation 
• Hepatic or renal impairment 
• Porphyria

Caution: 

• Photosensitivity disorders 
• Liver disease 
• Renal impairment 
• History of skin cancer 
• History of melanoma 
• Co-treatment with other psoralens 
• Patients who are receiving immunosuppressive therapy 
• Patients with a history of radiation therapy 
• Pregnant or lactating women 
• Children and elderly patients.

Comorbidities: 

methoxsalen is primarily used in the treatment of skin conditions such as vitiligo, eczema and psoriasis. The use of methoxsalen is contraindicated in patients with a history of basal cell, melanoma or squamous cell skin cancer.

Caution is required when using methoxsalen in patients with a history of liver or kidney disease, photosensitivity disorders, and those with a history of prolonged exposure to sunlight or ultraviolet light.

methoxsalen may exacerbate these conditions or increase the risk of skin cancer. Patients who are immunocompromised or taking immunosuppressive drugs may also be at increased risk for skin cancer with the use of methoxsalen. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category: C 

Lactation: methoxsalen is not recommended for use in lactating women.  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

methoxsalen is a photosensitizing agent that works by intercalating with DNA and crosslinking of pyrimidine bases when exposed to UVA radiation. It is a psoralen derivative that belongs to the class of furanocoumarins. methoxsalen is absorbed through the skin, gastrointestinal tract, and lung. It can be found in the skin, plasma, and urine. 

Once inside the body, methoxsalen is rapidly metabolized in the liver to its active metabolite, 8-methoxypsoralen (8-MOP), by demethylation. It has a short half-life of about 1 hour, and its elimination is primarily through the urine, with a small amount of elimination through the feces. methoxsalen also induces the synthesis of melanin in the skin, which protects against further UV damage.  

Pharmacodynamics: 

methoxsalen is a psoralen derivative that is primarily used for its photochemotherapeutic properties. It acts as a photosensitizer that binds to DNA upon activation by UV-A light (320-400 nm) and induces cross-linking between pyrimidine bases, which in turn results in inhibition of DNA synthesis and cellular proliferation. 

methoxsalen also has immunomodulatory effects, including inhibition of lymphocyte proliferation and cytokine production, and upregulation of regulatory T cells. These effects may contribute to its therapeutic activity in certain autoimmune and inflammatory conditions.  

Pharmacokinetics: 

Absorption 

methoxsalen can be administered orally or topically. Oral administration leads to almost complete absorption in the gastrointestinal tract, with peak plasma concentrations observed between 1 and 2 hours after administration. Absorption is delayed and reduced when methoxsalen is taken with food or milk. Topical administration leads to lower systemic exposure, with variable absorption depending on the vehicle used. 

Distribution 

methoxsalen is highly lipophilic and has a high affinity for melanin-containing tissues, including skin and the retinal pigment epithelium. It is distributed extensively throughout the body, with a volume of distribution of approximately 1-2 L/kg. methoxsalen readily crosses the placenta and is excreted in breast milk. It is also known to cross the blood-brain barrier. 

Metabolism 

methoxsalen is metabolized in the liver by cytochrome P450 enzymes (CYPs) including CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. The primary metabolite of methoxsalen is 8-hydroxy methoxsalen (8-HOM), which has minimal photo reactivity. Another minor metabolite is 5-methoxypsoralen. The metabolites are excreted in the urine within 24 hours of administration. 

Elimination and excretion 

methoxsalen is primarily metabolized in the liver and excreted mainly in the urine. Only a small fraction of the drug is excreted unchanged in the urine. The half-life of methoxsalen in plasma is approximately 1-2 hours. 

Adminstartion

Administration: 

• Oral: methoxsalen is available in an oral tablet form that is taken by mouth. 
• Topical: methoxsalen is available as a topical solution that can be applied to the skin. 
• Bath: methoxsalen can also be administered through a bath, where the solution is added to a bath. 
• Intravenous: methoxsalen can be administered through intravenous infusion. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: methoxsalen 

Pronounced: [ meth-ox-a-len ]  

Why do we use methoxsalen? 

methoxsalen is primarily used in combination with ultraviolet A (UVA) radiation (PUVA therapy) for the treatment of various skin conditions such as psoriasis, vitiligo, and cutaneous T-cell lymphoma.

It is used in the treatment of some types of lymphoma and as a prophylaxis for graft-versus-host disease in patients undergoing bone marrow transplantation. Additionally, methoxsalen is used for the treatment of a rare genetic skin condition called xeroderma pigmentosum.