Thalidomide

What it is and how it works

Mechanism of Action The mechanism of action of THALOMID is not fully understood. Cellular activities of thalidomide are mediated through its target cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex. THALOMID possesses immunomodulatory, anti-inflammatory and antiangiogenic properties. Available data from in vitro studies and 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-α) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration.

Indications

• THALOMID in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma (MM). • THALOMID is indicated for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). THALOMID is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. THALOMID is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence. Multiple Myeloma THALOMID in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma (MM) . Erythema Nodosum Leprosum THALOMID is indicated for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). THALOMID is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. THALOMID is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence .

Dosage and administration (summary)

• MM: 200 mg orally once daily. The recommended dose of dexamethasone is 40 mg/day on days 1-4, 9-12, and 17-20 every 28 days. • ENL: 100 to 300 mg/day for an episode of cutaneous ENL. Up to 400 mg/day for severe cutaneous ENL. Required Baseline Testing Drug prescribing to females of reproductive potential is contingent upon initial and continued negative results of pregnancy testing . THALOMID must only be administered in compliance with all of the terms outlined in the THALOMID REMS program. THALOMID may only be prescribed by prescribers certified with the THALOMID REMS program and may only be dispensed by pharmacists certified with the THALOMID REMS program.

Contraindications

• Pregnancy ( Boxed Warning , 4.1 , 5.1 , 5.2 , 8.1 , 17 ) • Demonstrated hypersensitivity to the drug or its components ( 4.2 , 5.16 , 6.2 ) Pregnancy THALOMID is contraindicated in females who are pregnant. THALOMID can cause fetal harm when administered to a pregnant female . THALOMID is a powerful human teratogen, inducing a high frequency of severe and life-threatening birth defects, even after a single dose . Mortality at or shortly after birth has been reported in about 40% of infants.

Warnings and precautions

• Ischemic heart disease (including myocardial infarction) and stroke have been observed in patients treated with THALOMID in combination with dexamethasone. • Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue. • Drowsiness and Somnolence: Instruct patients to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness. • Peripheral Neuropathy: Monitor patients for signs or symptoms of peripheral neuropathy during treatment.

Pregnancy

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to THALOMID during pregnancy as well as female partners of male patients who are exposed to THALOMID. This registry is also used to understand the root cause for the pregnancy.

Storage and supply

Storage This drug must not be repackaged. Store at 20°C- 25°C (68°F -77°F); excursions permitted to 15-30º C (59-86º F). . Protect from light.

Source: Thalidomide (Thalomid) — US FDA prescribing information, 2023-03-24, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.