Drug General Information (ID: DDISQNVWB8)
Drug Name			Letrozole		Drug Info		Thalidomide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antineoplastics				Immunosuppressive Agents
Structure

Mechanism of Letrozole-Thalidomide Interaction (Severity Level: Major)
Additive thrombogenic effects Click to Show/Hide Mechanism Graph
Drug Name		Letrozole				Thalidomide
Mechanism		Thrombogenic effects				Thrombogenic effects
Key Mechanism Factor 1
		Factor Name		Thrombogenic effects
		Factor Description		Drug-induced thrombosis disrupts the balance between thrombogenic factors and protective mechanisms and tends to produce thrombosis. Drug-induced thrombosis usually causes venous thrombotic events, and arterial thrombotic events are also noted as a result of drug administration
Mechanism Description		Additive thrombogenic effects by the combination of Letrozole and Thalidomide

Recommended Action
Management		Close monitoring for DVT or pulmonary embolism is recommended in patients who require thalidomide therapy in combination with glucocorticoids and/or cytotoxic agents. Patients should be advised to seek medical attention if they develop potential signs and symptoms of thromboembolism such as chest pain, shortness of breath, and pain or swelling in the arms or legs. Prophylaxis with anticoagulants such as low-molecular weight heparins or warfarin may be appropriate, but the decision to take thromboprophylactic measures should be made after careful assessment of underlying risk factors. If a thromboembolic event occurs during therapy with thalidomide, treatment must be discontinued and standard anticoagulation therapy started. Once anticoagulation is stabilized and complications of the thromboembolic event under control, thalidomide may be restarted at the original dose if benefit is deemed to outweigh the risks.

References
1	Bennett CL, Nebeker JR, Samore MH, et al "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA 293 (2005): 2131-40. [PMID: 15870417]
2	Bennett CL, Schumock GT, Desai AA, et al "Thalidomide-associated deep vein thrombosis and pulmonary embolism." Am J Med 113 (2002): 603-6. [PMID: 12459408]
3	Cavo M, Zamagni E, Cellini C, et al. "Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy." Blood 100 (2002): 2272-3. [PMID: 12229885]
4	Escudier B, Lassau N, Leborgne S, Angevin E, Laplanche A "Thalidomide and venous thrombosis." Ann Intern Med 136 (2002): 711. [PMID: 11992318]
5	Figg WD, Arlen P, Gulley J, et al. "A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer." Semin Oncol 28(4 Suppl 15) (2001): 62-6. [PMID: 11685731]
6	Fine HA, Wen PY, Maher EA, et al. "Phase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas." J Clin Oncol 21 (2003): 2299-304. [PMID: 12805330]
7	Lee CK, Barlogie B, Munshi N, et al "DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma." J Clin Oncol 21 (2003): 2732-9. [PMID: 12860952]
8	Osman K, Comenzo R, Rajkumar SV "Deep venous thrombosis and thalidomide therapy for multiple myeloma." N Engl J Med 344 (2001): 1951-2. [PMID: 11419443]
9	Product Information. Thalomid (thalidomide). Celgene Corporation, Warren, NJ.
10	Rajkumar SV, Hayman S, Gertz MA, et al. "Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma." J Clin Oncol 20 (2002): 4319-23. [PMID: 12409330]
11	Urbauer E, Kaufmann H, Nosslinger T, Raderer M, Drach J "Thromboembolic events during treatment with thalidomide." Blood 99 (2002): 4247-8. [PMID: 12043695]
12	Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R "Thalidomide alone or with dexamethasone for previously untreated multiple myeloma." J Clin Oncol 21 (2003): 16-9. [PMID: 12506164]
13	Zangari M, Anaissie E, Barlogie B, et al "Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy." Blood 98 (2001): 1614-5. [PMID: 11520815]
14	Zangari M, Barlogie B, Anaissie E, et al "Deep vein thrombosis in patients with mutiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation." Br J Haematol 126 (2004): 715-21. [PMID: 15327525]
15	Zangari M, Siegel E, Barlogie B, et al "Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy." Blood 100 (2002): 1168-71. [PMID: 12149193]
16	Desai AA, Vogelzang NJ, Rini BI, Ansari R, Krauss S, Stadler WM "A high rate of venous thromboembolism in a multi-institutional Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil and daily thalidomide in patients with metastatic renal cell carcinoma." Cancer 95 (2002): 1629-36. [PMID: 12365009]