Temsirolimus (2 brand names, 1 dosage form, 1 route)
Available dosage forms: SOLUTION.
Routes of administration: INTRAVENOUS.
Brand Names
- TEMSIROLIMUS
- TORISEL
Indications and Usage
TORISEL is indicated for the treatment of advanced renal cell carcinoma.
Contraindications
TORISEL is contraindicated in patients with bilirubin >1.5×ULN [see Warnings and Precautions (5.2)].
Adverse Reactions
The following serious adverse reactions have been associated with TORISEL in clinical trials and are discussed in greater detail in other sections of the label [see Warnings and Precautions (5)]. •Hypersensitivity/Infusion Reactions [see Warnings and Precautions (5.1)] •Hepatic Impairment [see Warnings and Precautions (5.2)] •Hyperglycemia/Glucose Intolerance [see Warnings and Precautions (5.3)] •Infections [see Warnings and Precautions (5.4)] •Interstitial Lung Disease [see Warnings and Precautions (5.5)] •Hyperlipidemia [see Warnings and Precautions (5.6)] •Bowel Perforation [see Warnings and Precautions (5.7)] •Renal Failure [see Warnings and Precautions (5.8)] •Wound Healing Complications [see Warnings and Precautions (5.9)] •Intracerebral Hemorrhage [see Warnings and Precautions (5.10)] The most common (≥30%) adverse reactions observed with TORISEL are rash, asthenia, mucositis, nausea, edema, and anorexia. The most common (≥30%) laboratory abnormalities observed with TORISEL are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, lymphopenia, elevated alkaline phosphatase, elevated serum creatinine, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.
Drug Interactions
Drug Interactions
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.
Overdosage
There is no specific treatment for TORISEL intravenous overdose. TORISEL 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 TORISEL greater than 25 mg.