Thalidomide (2 brand names, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- THALIDOMIDE
- THALOMID
Adverse Reactions
The following clinically significant adverse reactions are described in detail in other labeling sections: •Teratogenicity [see Boxed Warning, Warnings and Precautions (5.1, 5.2), and Patient Counseling Information (17)] •Venous and Arterial Thromboembolism [see Boxed Warning, Warnings and Precautions (5.3), and Patient Counseling Information (17)] •Increased Mortality in Patients with MM When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4)] •Drowsiness and Somnolence [see Warnings and Precautions (5.5)] •Peripheral Neuropathy [see Warnings and Precautions (5.6)] •Dizziness and Orthostatic Hypotension [see Warnings and Precautions (5.7)] •Neutropenia [see Warnings and Precautions (5.8)] •Thrombocytopenia [see Warnings and Precautions (5.9)] •Increased HIV Viral Load [see Warnings and Precautions (5.10)] •Bradycardia [see Warnings and Precautions (5.11)] •Severe Cutaneous Reactions [see Warnings and Precautions (5.12)] •Seizures [see Warnings and Precautions (5.13)] •Tumor Lysis Syndrome [see Warnings and Precautions (5.14)] •Hypersensitivity [see Warnings and Precautions (5.16)]
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. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-α in patients with erythema nodosum leprosum (ENL); however, it has also been shown to increase plasma TNF-α levels in HIV-seropositive patients. Other anti-inflammatory and immunomodulatory properties of thalidomide may include suppression of macrophage involvement in prostaglandin synthesis, and modulation of interleukin-10 and interleukin-12 production by peripheral blood mononuclear cells. Thalidomide treatment of multiple myeloma patients is accompanied by an increase in the number of circulating natural killer cells, and an increase in plasma levels of interleukin-2 and interferon-gamma (T cell-derived cytokines associated with cytotoxic activity). Thalidomide was found to inhibit angiogenesis in a human umbilical artery explant model in vitro. The cellular processes of angiogenesis inhibited by thalidomide may include the proliferation of endothelial cells.
Overdosage
There is no specific antidote for a THALOMID overdose. In the event of an overdose, the patient’s vital signs should be monitored and appropriate supportive care given to maintain blood pressure and respiratory status.