TORISEL(temsirolimus) injection
TORISEL is the first mTOR inhibitor approved for the treatment of patients with advanced renal cell carcinoma (RCC). Learn more about the TORISEL mechanism of action. TORISEL provides significantly higher median overall survival and progression-free survival compared with interferon-alpha (IFN-α).1 Learn more about the efficacy of TORISEL. The TORISEL safety profile has been eva luated in clinical trials.
Learn more about the adverse events profile of TORISEL in patients with advanced RCC.
The recommended dose of TORISEL for advanced RCC is 25 mg infused over 30 to 60 minutes once
weekly.
Learn more about TORISEL dosage and administration.
Important Safety Information
Hypersensitivity reactions manifested by symptoms, including, but not limited to anaphylaxis, dyspnea, flushing, and chest pain have been observed with TORISEL. Serum glucose, serum cholesterol, and triglycerides should be tested before and during treatment with TORISEL.
The use of TORISEL is likely to result in hyperglycemia and hyperlipemia. This may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycemic agent therapy and/or lipid-lowering agents, respectively.
The use of TORISEL may result in immunosuppression. Patients should be carefully observed for the occurrence of infections, including opportunistic infections. Cases of interstitial lung disease, some resulting in death, have occurred. Some patients were asymptomatic and others presented with symptoms. Some patients required discontinuation of TORISEL and/or treatment with corticosteroids and/or antibiotics. Cases of fatal bowel perforation occurred with TORISEL.
These patients presented with fever, abdominal pain, metabolic acidosis, bloody stools, diarrhea, and/or acute abdomen.
Cases of rapidly progressive and sometimes fatal acute renal failure not clearly related to disease progression occurred in patients who received TORISEL. Due to abnormal wound healing, use TORISEL with caution in the perioperative period. Patients with central nervous
system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving TORISEL.
Live vaccinations and close contact with those who received live vaccines should be avoided. Patients and their partners should be advised to avoid pregnancy throughout treatment and for 3 months after TORISEL therapy has stopped. The most common (incidence ≥30%) adverse reactions observed with TORISEL are: rash (47%), asthenia(51%), mucositis (41%), nausea (37%), edema (35%), and anorexia(32%). The most common laboratory abnormalities (incidence ≥30%) are anemia (94%), hyperglycemia (89%), hyperlipemia (87%), hypertriglyceridemia (83%), elevated alkaline phosphatase (68%), elevated serum creatinine (57%), lymphopenia (53%), hypophosphatemia(49%), thrombocytopenia (40%), elevated AST (38%), and leukopenia
(32%).
Most common grades 3/4 adverse events included asthenia(11%), dyspnea (9%), hemoglobin decreased (20%), lymphocytes decreased (16%), glucose increased (16%), phosphorus decreased
(18%), and triglycerides increased (44%). Strong inducers of CYP3A4/5 (eg, dexamethasone, rifampin) and strong inhibitors of CYP3A4 (eg, ketoconazole, atazanavir) may decrease and increase concentrations of the major metabolite of TORISEL, respectively.
If alternatives cannot be used, dose modifications of TORISEL are recommended. St. John’s Wort may decrease TORISEL plasma concentrations, and grapefruit juice may increase plasma
concentrations of the major metabolite of TORISEL, and therefore both should be avoided. The combination of TORISEL and sunitinib resulted in dose-limiting toxicity.
Company: Wyeth
Pharmacologic class: Antineoplastic (mTOR kinase inhibitor) Active ingredient: Temsirolimus 25mg/mL; ethanolic soln for IV infusion after two dilutions (first w. supplied diluent); contains alcohol, polysorbate 80.
Indication:
Advanced renal cell carcinoma.
Pharmacology:
Temsirolimus binds to an intracellular protein, and the resulting protein-drug complex inhibits the activity of an intracellular target called mTOR kinase, a cellular enzyme that regulates cell proliferation, cell growth and cell survival. In vitro studies show that inhibiting mTOR interferes with the translation of genes that regulate the cell cycle.
It also resulted in reduced levels of certain cell growth factors involved in the development of new blood vessels, such as vascular endothelial growth factor.
Clinical trials:
In a study conducted in 626 previously untreated patients with advanced renal cell carcinoma, treatment with temsirolimus was compared to temsirolimus + interferon-α and to interferon-α alone.
There was a statistically significant improvement in overall survival in the patients given temsirolimus (10.9 months) compared to those given interferon-α (7.3 months).
Adults:
25mg once weekly. Infuse IV over 30?0min, using an infusion pump.
Continue until disease progression or unacceptable toxicity occurs.
Premedicate with IV antihistamine (eg, diphenydramine). Hold dose if ANC <1000/mm3, platelets <75000/mm3, or NCI CTCAE ≥grade 3 adverse reaction occurs; may restart at a dose reduced by 5mg/week (no lower than 15mg/wk) if adverse reactions resolve to ≤grade 2. See
Interactions.
Children:
Not recommended.
Precautions:
Sirolimus or related allergy. Hepatic insufficiency. Perioperative period (may interfere with wound healing). CNS tumors. Monitor CBCs weekly and chemistry panels every 2 weeks, blood glucose, lipids, renal function, and for worsening respiratory or GI symptoms (eg,
acute abdomen, blood in stool). Elderly. Pregnancy (Cat.D) (avoid pregnancy during and for 3 months after therapy, male patients should use appropriate contraception), nursing mothers: not recommended.
Interactions:
Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice); if used, consider reducing temsirolimus dose to 12.5mg/week(allow 1 week after discontinuing CYP3A4 inhibitor before readjusting temsirolimus dose). Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin,rifabutin,rifampicin, phenobarbital, St. John's Wort); if used, consider increasing temsirolimus dose to 50mg/week. Avoid live vaccines, close contact with vaccinees. Additive toxicity with sunitinib(rash, gout/cellulitis), anticoagulants (intracerebral bleeding).
Adverse reactions:
Rash, asthenia, mucositis, nausea, edema, anorexia, infection, pain, anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, leukopenia; hypersensitivity/infusion reactions (anaphylaxis, dyspnea, flushing, chest pain), immunosuppression, interstitial lung disease, bowel perforation, acute renal failure, abnormal wound healing; others (see literature).
How supplied:
Kit (vial + diluent)
TORISEL (TEMSIROLIMUS)25MG/ML+1.8ML DILU KIT
