Temsirolimus

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 Generic Name : Temsirolimus

Synonyms :

• CCI-779


• temsirolimus

Category :

• Antineoplastic Agents


• Protein Kinase Inhibitors

Description : Temsirolimus is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the FDA in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007. It is a derivative of sirolimus and is sold as Torisel.

Indication : For the treatment of renal cell carcinoma (RCC). Also investigated for use/treatment in breast cancer, lymphoma (unspecified), rheumatoid arthritis, and multiple myeloma.

State : Solid

Mechanism of Action : Temsirolimus is an inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein (FKBP-12), and the protein-drug complex inhibits the activity of mTOR that controls cell division. Inhibition of mTOR activity resulted in a G1 growth arrest in treated tumor cells. When mTOR was inhibited, its ability to phosphorylate p70S6k and S6 ribosomal protein, which are downstream of mTOR in the PI3 kinase/AKT pathway was blocked. In in vitro studies using renal cell carcinoma cell lines, temsirolimus inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha, and the vascular endothelial growth factor.

Drug-Drug Interaction :

• Aminoglutethimide Aminoglutethimide may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Amprenavir Amprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Atazanavir Atazanavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Bosentan Bosentan may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Carbamazepine Carbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Clarithromycin Clarithromycin may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Conivaptan Conivaptan may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Darunavir Darunavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Delavirdine Delavirdine may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Dexamethasone Dexamethasone may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Efavirenz Efavirenz may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Fluorouracil Co-administration of Temsirolimus and Fluorouracil may result in serious adverse drug reactions.


• Fosamprenavir Fosamprenavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Fosphenytoin Fosphenytoin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Gemcitabine Co-administration of Temsirolimus and Gemcitabine may result in serious adverse drug reactions.


• Imatinib Imatinib may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Indinavir Indinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Isoniazid Isoniazid may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Itraconazole Itraconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Ketoconazole Ketoconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Lopinavir Lopinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Miconazole Miconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Nafcillin Nafcillin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Natalizumab Temsirolimus may increase the toxicity of Natalizumab. Concomitant therapy should be avoided.


• Nefazodone Nefazodone may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Nelfinavir Nelfinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Nevirapine Nevirapine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Nicardipine Nicardipine may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Oxcarbazepine Oxcarbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Pentobarbital Pentobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Phenobarbital Phenobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Phenytoin Phenytoin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Posaconazole Posaconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Primidone Primidone may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Quinidine Quinidine may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Rifabutin Rifabutin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Rifampin Rifampin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Rifapentine Rifapentine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Ritonavir Ritonavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Saquinavir Saquinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• St. John's Wort St. John's Wort may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.


• Sunitinib Co-administration of Temsirolimus and Sunitinib may result in serious adverse drug reactions.


• Telithromycin Telithromycin may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.


• Voriconazole Voriconzole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.

Half Life : Temsirolimus exhibits a bi-exponential decline in whole blood concentrations and the mean half-lives of temsirolimus and sirolimus were 17.3 hr and 54.6 hr, respectively.

Toxicity : Temsirolimus has been administered to patients with cancer in phase 1 and 2 trials with repeated intravenous doses as high as 220 mg/m2. The risk of several serious adverse events, including thrombosis, bowel perforation, interstitial lung disease (ILD), seizure, and psychosis, is increased with doses of temsirolimus greater than 25 mg.

Dosage Form : SolutionIntravenous

Brands : Torisel