Midothal Capsul

Multiple Myeloma: Thalidomide in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma (MM).

Erythema Nodosum Leprosum: Thalidomide is indicated for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Thalidomide is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. Thalidomide is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence

Thalidomide is a synthetic glutamic acid derivative immunomodulator with anti-inflammatory, antiangiogenetic, sedative and hypnotic activity.

In patients with erythema nodosum leprosum (ENL) the mechanism of action is not fully understood. Available data from in vitro studies and preliminary clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-a) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-a in patients with ENL, however, it has also been shown to increase plasma TNF-a levels in HIV-seropositive patients. As a cancer treatment, the drug may act as a VEGF inhibitor.

Multiple Myeloma: Thalidomide is administered in combination with dexamethasone in 28-day treatment cycles. The dose of Thalidomide is 200 mg administered orally once daily with water, preferably at bedtime and at least 1 hour after the evening meal. The dose of dexamethasone is 40 mg daily administered orally on days 1-4, 9-12, and 17-20 every 28 days.

Patients who develop adverse reactions such as constipation, somnolence, or peripheral neuropathy may benefit by either temporarily discontinuing the drug or continuing at a lower dose. With the abatement of these adverse reactions, the drug may be started at a lower dose or at the previous dose based on clinical judgment.

Erythema Nodosum Leprosum: For an episode of cutaneous ENL, Thalidomide dosing should be initiated at 100 to 300 mg/day, administered once daily with water, preferably at bedtime and at least 1 hour after the evening meal. Patients weighing less than 50 kilograms should be started at the low end of the dose range.

In patients with a severe cutaneous ENL reaction, or in those who have previously required higher doses to control the reaction, Thalidomide dosing may be initiated at higher doses up to 400 mg/day once daily at bedtime or in divided doses with water, at least 1 hour after meals.

In patients with moderate to severe neuritis associated with a severe ENL reaction, corticosteroids may be started concomitantly with Thalidomide. Steroid usage can be tapered and discontinued when the neuritis has ameliorated.

Dosing with Thalidomide should usually continue until signs and symptoms of active reaction have subsided, usually a period of at least 2 weeks. Patients may then be tapered off medication in 50 mg decrements every 2 to 4 weeks.

Patients who have a documented history of requiring prolonged maintenance treatment to prevent the recurrence of cutaneous ENL or who flare during tapering should be maintained on the minimum dose necessary to control the reaction. Tapering off medication should be attempted every 3 to 6 months, in decrements of 50 mg every 2 to 4 weeks.

Thalidomide enhances sedative activity of barbiturates, alcohol, chlorpromazine and reserpine. Avoid use of other drugs that have the potential to cause peripheral neuropathy. Increased risk of thromboembolic events with darbepoetin-alfa and doxorubicin.

Pregnancy and lactation.

Severe and irreversible peripheral neuropathy, constipation, dizziness, orthostatic hypotension, drowsiness, somnolence, bradycardia, increase of viral load in HIV-infected patients, hypersensitivity reaction.

Pregnancy Category X. Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

All females of childbearing potential must use 2 reliable forms of contraception simultaneously 4 wk before starting therapy, during and 4 wk after therapy is discontinued. Therapy to be stopped immediately if pregnancy occurs. Male: Use of barrier methods of contraception if partner is of child-bearing potential. Do not donate blood or sperm during therapy. Patient should not drive or operate machinery. Discontinue therapy if any skin rash develops. Do not resume therapy if the rash is exfoliative, purpuric, or bullous, or if Stevens-Johnson syndrome or toxic epidermal necrolysis suspected.

Anti-Leprotic drugs, Immunosuppressant.