Thelobenz

Uses

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

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

Thelobenz is also used to associated treatment for these conditions: Chronic Graft Versus Host Disease, Multiple Myeloma (MM), Stomatitis, Aphthous, Uremic Pruritus, Waldenström's Macroglobulinemia (WM), Advanced Systemic light chain amyloidosis, Moderate Erythema nodosum leprosum, Refractory Graft versus host disease, Severe Erythema nodosum leprosum, Treatment naive multiple myeloma

How Thelobenz works

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.

Dosage

Thelobenz dosage

Multiple Myeloma: Thelobenz is administered in combination with dexamethasone in 28-day treatment cycles. The dose of Thelobenz 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, Thelobenz 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, Thelobenz 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 Thelobenz. Steroid usage can be tapered and discontinued when the neuritis has ameliorated.

Dosing with Thelobenz 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.

Side Effects

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

Toxicity

The R-configuration and the S-configuration are more toxic individually than the racemic mixture. The LD₅₀ could not be established in mice for racemic thalidomide, whereas LD₅₀ values for the R and S configurations are reported to be 0.4 to 0.7 g/kg and 0.5 to 1.5 g/kg, respectively.

Precaution

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

Interaction

Thelobenz 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.

Food Interaction

• Avoid alcohol. Ingesting alcohol may increase the drowsiness caused by thalidomide.
• Take after a meal. Wait at least 1 hour after eating before taking thalidomide.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Thelobenz Drug Interaction

Moderate: aripiprazole, pamidronate, buspirone, prochlorperazine, ethanol, tramadol, bortezomib, ondansetron, zoledronic acidUnknown: aspirin, amphetamine / dextroamphetamine, aspirin, sulfamethoxazole / trimethoprim, ubiquinone, albuterol / ipratropium, warfarin, furosemide, levothyroxine, cyanocobalamin, cholecalciferol

Thelobenz Disease Interaction

Moderate: seizures, HIV infection, hypotension, neutropenia, peripheral neuropathy

Elimination Route

The absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. In studies of both healthy volunteers and subjects with Hansen’s disease, the mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours indicating that thalidomide is slowly absorbed from the gastrointestinal tract.

Half Life

The mean half-life of elimination ranges from approximately 5 to 7 hours following a single dose and is not altered upon multiple dosing.

Elimination Route

Thelobenz itself has less than 0.7% of the dose excreted in the urine as unchanged drug.

Pregnancy & Breastfeeding use

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.

Contraindication

Pregnancy and lactation.

Innovators Monograph

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