Methoxsalen (Oxsoralen) tablets belong to the class of drugs called psoralens. It is used in combination with PUVA therapy for the treatment of vitiligo, psoriasis, and skin manifestations of cutaneous T-cell lymphoma.

Methoxsalen (Oxsoralen) Tablets Uses:

• The oral formulation is used for:
  • Vitiligo idiopathic repigmentation
  • The symptomatic management of severe, refractory, and incapacitating psoriasis,
  • Skin symptoms of cutaneous T-cell lymphoma receiving palliative care (CTCL)
• Extracorporeal administration:
  • When other treatments fail to control the cutaneous signs of CTCL, it is used as a palliative measure.

Details of Topical Methoxsalen can be read here: Topical Methoxsalen (Uvadex, Oxsoralen) lotion for Vitiligo.

Methoxsalen (Oxsoralen) Dose in Adults:

Methoxsalen (Oxsoralen) Dose in the treatment of Psoriasis:

• At first, take 10 to 70 mg 1.5–2 hours (Oxsoralen Ultra) or 2 hours (8-MOP) before being exposed to UVA rays.
• Depending on the exposure to UVA, the dose may be repeated 2 to 3 times in a week.
• The dosage depends on the patient's body weight and skin type and must be administered over a minimum of 48 hours:
  • 81 to 90 kg: 50 mg
  • 91 to 115 kg: 60 mg
  • <30 kg: 10 mg
  • 66 to 80 kg: 40 mg
  • >115 kg: 70 mg
  • 30 to 50 kg: 20 mg
  • 51 to 65 kg: 30 mg

Note: After the fifteenth treatment, the dosage may be raised (once) by 10 mg if no improvement is shown (if no response or minimal response is noted).

• Maintenance treatment:
  • Treatment is then administered as needed to maintain response and reduce UVA exposure.
  • After psoriasis has cleared up to 95% of the skin, you can start one treatment every week for at least two treatments, then one treatment every two weeks for at least two treatments, and finally one treatment every three weeks for at least two treatments 

Methoxsalen (Oxsoralen) Dose in the treatment of Vitiligo:

• Oral (8-MOP):
  • On the basis of erythema and skin discomfort, the dose may be repeated.
  • 20 mg two to four hours before UVA exposure
  • Avoid receiving treatment on two consecutive days.

Methoxsalen (Oxsoralen) Dose in the treatment of Cutaneous T-cell lymphoma (CTCL):

• Extracorporeal (Uvadex):

  • Treatment volume determines the dosage, and the following equation may be used to predict how much Uvadex is required for each treatment: 
    • Uvadex is required in mL (treatment volume x 0.017). 
  • Utilizing a UVAR XTS or CELLEX photopheresis system, inject this quantity into the recirculation bag before the photoactivation phase (see to the user's manual for further information).

• Treatment schedule:

  • For a minimum of seven treatment cycles, two consecutive days were required every four weeks (6 months). 
  • The fourth treatment cycle (about the third month) is when the skin score is examined, and if it worsens (rises over the baseline), the therapy may be expedited to two consecutive days given every two weeks. 
  • After the fourth consecutive week of accelerated therapy, the standard treatment cycle may be continued if the skin score has improved by 25% or more. 
  • A maximum of twenty accelerated therapy cycles may be given to patients who are maintained on accelerated therapy.
  • Use for more than six months or using a different treatment schedule has not been studied and may not be of additional benefit.

Use in children:

It is not indicated for use in children.

Methoxsalen (Oxsoralen) Pregnancy Risk Category: D

• Reproductively-potent females should be advised not to get pregnant and to use effective contraception. Animal studies have shown adverse outcomes for fetuses.

Methoxsalen use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• The manufacturer suggests that lactating mothers use the drug with caution.

Methoxsalen (Oxsoralen) Dose in Kidney Disease:

In the manufacturer’s labeling, adjustments in the dose have not been recommended.

Methoxsalen (Oxsoralen) Dose in Liver disease:

• In the manufacturer’s labeling, dose adjustment has not been suggested.
• However, use it with caution as it is metabolized in the liver.

Side Effects of Methoxsalen (Oxsoralen):

• Dermatologic:

  • Pruritus

• Gastrointestinal:

  • Nausea

Uncommon Side effects of Methoxsalen (Oxsoralen):

• Central nervous system:

  • Insomnia
  • Malaise
  • Nervousness
  • Vertigo
  • Depression
  • Dizziness
  • Headache
•  

• Cardiovascular:

  • Edema
  • Hypotension (due to photopheresis)

• Infection:

  • Infection (due to vascular access for photopheresis)

• Dermatologic:

  • Erythema
  • Exfoliation of skin
  • Skin neoplasm
  • Skin rash
  • Bulla
  • Burning sensation of skin
  • Dermatological disease (premature aging)
  • Ephelis
  • Skin tenderness
  • Skin vesicle
  • Urticaria
  • Folliculitis
  • Hypopigmentation
  • Miliaria
  • Skin blister (painful)

• Ophthalmic:

  • Cataract

Contraindications to Methoxsalen (Oxsoralen):

• Allergy reactions to the drug (psoralens or any component thereof)
• Photosensitive skin conditions include albinism, Systemic Lupus Erythematosus and porphyrias such as erythropoietic and variegate porphyria.
• Aphakia
• Contraindications to photopheresis
• Cardiac disease severe
• Severe anaemia
• WBC counts exceeding 25,000/mm3
• Patients who had splenectomy or coagulation disorders
• Basal cell carcinoma
• A history of melanoma and coexistence
• Squamous cell carcinoma

Warnings and precautions

• Actinic degeneration:

  • Patients may age prematurely if they are exposed to sunshine or UV radiation.

• Burns

  • Patients who are exposed to UV rays or sunlight for longer than is safe may get serious burns.
  • Patients should stay out of the sun for 24 hours after their therapy.

• Cataracts

  • To prevent cataract formation, patients should keep their eyes protected from direct and indirect sunlight for at least 24 hours following methoxsalen treatment.
  • Cataract formation is caused by the drug concentration in the lens.

• Photosensitivity

  • After the administration of the drug, patients should not expose themselves to sunlight for at least 24 hours.
  • After receiving combined methoxsalen/ UVA therapy, patients should wear protective clothing, sunscreen, eyewear, and sunglasses for at least 24 hours.
  • Sunscreen should not apply to areas with psoriasis.
  • Sunburn patients should be fully healed before starting therapy.
  • It may be difficult to evaluate patients suffering from sunburns.
  • Patients are advised not to sunbathe for 24 hours prior to and 48 hours following treatment.
  • Patients who are exposed to the sun a lot (due to their occupation) should not use this drug.

• Skin cancer:

  • Treatment may increase the risk of developing skin cancers such as basal cell carcinoma, melanomas, and squamous cell carcinoma.
  • Patients with fair skin, patients who have been exposed to long-term tar and UVB treatment, arsenic, or those exposed to ionizing radiation, are at greater risk for developing skin cancers.

• Events that are thromboembolic:

  • Patients with graft-versus-host disease have had thromboembolic problems, including deep vein thrombosis or pulmonary embolism.
  • It has not been approved by the FDA for treatment of GVHD (graft versus Host Disease).

• Basal cell carcinoma

  • The medication should only be taken with caution in patients who have basal cell carcinoma or a prior history of basal cancer and should be regularly monitored.

• Cardiovascular disease

  • Patients suffering from cardiovascular disease may be unable to stand for long periods of time or heat stress during UVA treatment.
  • Patients with heart disease should use caution.

• Hepatic impairment

  • Patients with liver disease should not use it as it is metabolized by the liver.

Methoxsalen (systemic): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Antinuclear antibodies at baseline and every 6-12 months thereafter
• Ophthalmic exam before initiating treatment and yearly thereafter
• CBC with differential counts at baseline and every 6-12 months thereafter
• Observe for the signs and symptoms of skin cancer, burns, and photosensitivity
• Liver and renal function tests at baseline and every 6-12 months thereafter

How to administer Methoxsalen (Oxsoralen)?

Oral formulation:

• It is administered orally.
• Administered the capsule with food or milk to avoid gastrointestinal upset such as nausea and vomiting.

Extracorporeal:

• The solution should not be injected directly.
• After being pulled into the syringe, immediately inject the vial's contents into the photoactivation bag of the UVAR XTS or CELLEX Photopheresis System.
• Plastics and PVC can absorb the solution.
• To administer the solution, only UVAR XTS or CELLEX photopheresis procedure kits should be utilised (the kit is supplied with the drug).

Mechanism of action of Methoxsalen:

• It causes cellular replication to be inhibited by covalent bonds with DNA nucleotide bases pyrimidine nucleotide.
• This results in inhibition of DNA synthesis.
• It results in thickening the stratum corneum, increased pigmentation and an increase in melanocyte production.
• The methoxsalen molecular is stimulated by sunburn and ultraviolet rays to create a "triplet electronic condition" in the skin. 
• The skin's reaction to this exciting molecule is photosensitization and an inflammatory reaction.
• Following the erythematous reaction, skin repair takes place over several days or weeks.
• This results in melanocyte production as well as hardening of skin (stratum corneum).

Protein binding:

• It reversibly binds to albumin

Metabolism:

• The liver transforms it into metabolites. 

Half-life elimination:

• about 2 hours

Bioavailability:

• Soft-gelatin capsules (Oxsoralen-Ultra) provide a higher bioavailability of the oral medication than hard-gelatin capsules (8-MOP)
• Compared to oral methoxsalen administration, exposure using Uvadex with the UVAR photopheresis system is about 200 times less.

Time to peak serum concentration:

• Oxsoralen Ultra soft-gel capsules: 0.5 to 4 hours (peak photosensitivity: 1.5 to 2 hours)
• 8-MOP hard-gel capsules: 1.5 to 6 hours (peak photosensitivity: about 4 hours)

Excretion:

• It is excreted in urine (about 95% as metabolites)

International Brands of Methoxsalen:

• 8-Mop
• Oxsoralen Ultra
• Uvadex
• Oxsoralen
• Delsoralen
• Lukodermine
• Meladerm
• Meladinina
• Meladinine
• Melanocyl
• Metoxaleno
• Mopsalem
• Mopsoralen
• Neo-Medanine
• Neomeladinine
• Oxsoralen
• Oxsoralen Ultra
• Sorialen
• Ultra-Medanine

Methoxsalen Brand Names in Pakistan