OCTAMOP Tablets (PHOTOSENSITIZING AGENT )

COMPOSITION :
OCTAMOP TABLETS (each tab contains)
Methoxsalen (8-methoxy psoralen)           10mg
Molecular formula.
OCTAMOP                                                   C12H8O4

CLINICAL PHARMACOLOGY :
The combination treatment regimen of psoralen(P) and ultra violet radiation of 320-400nm. wavelength commonly referred to as UVA is known by the acronym, PUVA. Skin reactivity to UVA (320-400nm) radiation is markedly enhanced by the ingestion of methoxsalen. The drug reaches its maximum bioavailability 1(1/2) –3 hours after oral administration and may last for upto 8 hours. Methoxsalen is reversibly bound to serum albumin and is also preferentially taken up by epidermal cells.
Mechanism of action :
The exact mechanism of action of methoxsalen with the epidermal melanocytes and keratinocytes is not known. The best known biochemical reaction of methoxsalen is with DNA(forms covalent bonds with DNA).
(A)OCTAMOP in vitiligo :
OCTAMOP along with UVA penetrates the skin and causes cell injury. If sufficient cell injury occurs in the skin, an inflammatory reaction occurs. This is manifested as delayed erythema, which peaks at 48 – 72 hours. The inflammation is followed, over several days to weeks, by repair which is manifested by increased melanization of the epidermis, and thickening of the stratum corneum . The mechanisms of therapy are not known. In the treatment of vitiligo , it has been suggested that melanocytes in the hair follicle are stimulated to move up the follicle and to repopulate the epidermis.
(B)OCTAMOP in Psoriasis :
In the treatment of Psoriasis, the mechanism is most often assumed to be DNA photodamage and resulting decrease in cell proliferation (of conneocytes), thereby stabilizing the psoriatic epidermis.

INDICATIONS :
OCTAMOP (as a part of PUVA therapy) is indicated for
1. Repigmentation of idiopathic vitiligo.
2.Symptomatic control of severe, recalcitrant, disabling psoriasis not adequately responsive to other forms of therapy.

DOSAGE AND ADMINISTRATION :
The following is the guidline only. The treating physician would decide for a particular patient.

(A) VITILIGO THERAPY :
1. Drug Dosage : Two tablets(10 mg each) in one dose taken with milk or in food two to four hours before ultraviolet light exposure
1. Drug Dosage : The exposure to Sunlight should comply with the following guide.

BASIC Skin Colour
  Light Medium Dark
Initial Exposure 15min 20min 25min
Second Exposure 20min 25min 30min
Third Exposure 25min 30min 35min
Fourth Exposure 30min 35min 40min


Subsequent Exposure: Gradually increase exposure based on erythema and tenderness of the amelanotic skin. Therapy should be on alternate days and never two consecutive days.
(B) PSORIASIS THERAPY
1. Drug Dosage: OCTAMOP should be taken 2 hours before UVA exposure with some food according to the following Dosage Schedule:

Weight of patients Methoxsalen in mgs. No.of tablets (10mg)
Less than 30kgs 10 1
30-50kgs 20 2
51-65kgs 30 3
66-80kgs 40 4
More than 80kgs as per dose of 0.6 mg/kg body weight.


The recommended dose is 0.6 mg/ kg body wt.
2. Sunlight Exposure Schedule in Psoriasis:

No .of exposure    Day     Exposure to sunlight inminutes
            1                    1                          5
            2                    4                          10
            3                    6                          15
            4                    8                          20
            5                   10                         25
            6                   12                         30
            7                   14                         30
            8                   16                         30
            9                   18                         30
           10                  20                         30
Treatment may be continued up to the recommended number of exposures or till complete remission. For solar radiation, the best exposure time is when the sun is at the zenith. The position of the patient should be lying down.
3. Maintenance Therapy for Psoriasis: Psoriatic patients should be given one exposure per week and gradually frequency of exposure should be reduced. Those patients who develop recurrences during maintenance treatment should be put on initial treatment again.

CONTRAINDICATIONS :
1. Patients exhibiting idiosyncratic reactions to psoralen compound.
2. Patients possessing a specific history of height sensitive disease should not initiate
3. methoxsalen therapy.
4. Patients exhibiting melanoma or possessing a history of melanoma.
5. Patients exhibiting invasive squamous cell carcinoma.
6. Patients with aphakia, because of the significantly increased risk of retinal damage due to the absence of lenses.
7. Children less than12 years (unless absolutely required)
WARNINGS :
1. Skin burning:
Serious burns from either UVA or sunlight can result if the recommended dose of the drug and/or exposure schedules are not maintained.
2. Carcinogenecity:
Risks of squamous cell carcinoma, basal cell carcinoma, melanoma, keratoses.
3. Cataractogenecity: Exposure to large doses of UVA increases risks of cataract.
4. Actinic degeneration: Exposure to sunlight and / or UV radiation may result in “premature aging” of the skin.
5. Radiation & Arsenic therapy: Patients having a previous history of x-ray therapy, grenz ray therapy or signs of carcinoma.
6. Hepatic Diseases : Patients with hepatic insufficiency should be treated with caution since hepatic biotransformation is necessary for drug urinary excretion.
7. Concomitant Therapy : Special care should be exercised in treating patients who are receiving concomitant therapy (either topically or systematically) with known photosensitizing agents such as anthralin, coal tar or coal tar derivatives, griseofulvin, phenothiazines, nalidixic acid, sulfonamides, tetracyclines, thiazides, and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal, and methylorange.

PRECAUTIONS :
1. (i) Before Methoxsalen Ingestion : Patients must not sunbathe during the 24 hours prior to Methoxsalen ingestion and UV exposure. The presence of sunburn may prevent an accurate evaluation of the patients response to photochemotherapy.
(ii) After Methoxsalen Ingestion : (a) UVA – absorbing wraparound sunglass should be worn during daylight for 24 hours after methoxsalen ingestion. The protective eyewear is used to prevent the irreversible binding of methoxsalen to the proteins and DNA components of the lens. (b) Patients must avoid sunexposure, even through window glass or cloud cover, for at least 8 hours after methoxsalen ingestion. If sunexposure cannot be avoided, the patients should wear protective devices such as hat and gloves, and/or apply sunscreens which can filter out UVA radiation. Patients should not sunbathe for 48 hours after therapy.
(iii) Vitiligo Therapy : The dosage of methoxsalen should not be increased above 0.6 mg/Kg since over dosage may result in serious burning of the skin.
Pregnancy :
Methoxsalen should be given to a woman only if clearly needed.
Nursing mothers :
It is not known whether this drug is excreted in human milk. Caution should be exercised when Methoxsalen is administered to a nursing woman.

ADVERSE REACTIONS :
A) Methoxsalen: Most common side effects is nausea, which can be avoided or minimised when the drug is taken with food.
B) Combined Methoxsalen/ UVA Therapy: Pruritus, Erythema.

STORAGE INSTRUCTIONS :
Protect from light. Store in a cool, dry dark place.