IV DOSE DELIVERY

IV offers management opportunities

Ability to control and verify drug delivery

• TORISEL is administered as a weekly 25 mg IV infusion over 30-60 minutes¹
• TORISEL typically reaches peak exposure and 100% bioavailability by the end of the infusion (30-60 minutes)^1,2*
• Bioavailability not affected by gastrointestinal function²
• In a phase 1 study, concentrations of temsirolimus and its metabolite sirolimus were increased in patients with elevated AST or bilirubin.¹ Please see Important Safety Information below regarding the contraindication and dose adjustments for patients with hepatic impairment

Opportunities for patient management and monitoring

• Enables regular monitoring of dose adherence and adverse events
• Hypersensitivity reactions manifested by symptoms, including, but not limited to anaphylaxis, dyspnea, flushing, and chest pain have been observed with TORISEL.

CYP3A interactions

• 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.¹
• 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.¹

Hypersensitivity information

• In the phase 3 study, all hypersensitivity reactions experienced by patients receiving TORISEL alone were of Grade 1 or 2 severity³
  • 5% of patients experienced a hypersensitivity reaction(s) on the same day as dosing, despite receiving premedication with an antihistamine³
  • A total of 9% of patients experienced allergic or hypersensitivity reactions¹
• If a patient develops a hypersensitivity reaction, stop the infusion and observe for at least 30 to 60 minutes. At the physician's discretion, treat with an H₁ antagonist, if not previously administered, and /or an H₂ antagonist. The infusion may then be resumed at a slower rate (up to 60 minutes)¹
• Hypersensitivity reactions, some life-threatening, can occur early in the first infusion, or during subsequent infusions³
• Patients should be monitored early during the infusion and appropriate supportive care should be available

Please see Section 2 of the full Prescribing Information for complete Dosage and Administration information.

Important Safety Information

• TORISEL is contraindicated in patients with bilirubin >1.5 x ULN and should be used with caution when treating patients with mild hepatic impairment (bilirubin >1 - 1.5 x ULN or AST > ULN but bilirubin ≤ ULN). If TORISEL must be given to patients with mild hepatic impairment, reduce the dose of TORISEL to 15 mg/week. In a phase 1 study, the overall frequency of ≥ grade 3 adverse reactions and deaths, including deaths due to progressive disease, was greater in patients with baseline bilirubin > 1.5 x ULN.
• Hypersensitivity/infusion reactions, including flushing, chest pain, dyspnea, hypotension, apnea, loss of consciousness, hypersensitivity and anaphylaxis, may occur very early in the first infusion or with subsequent infusions. Pretreat with an H1 antihistamine. TORISEL infusion should be interrupted in patients with infusion reactions and appropriate therapy given.
• Serum glucose, serum cholesterol, and triglycerides should be tested before and during TORISEL treatment.
• 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.
• 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 or had minimal symptoms. Patients should undergo baseline radiography prior to TORISEL therapy and periodically thereafter, even in the absence of clinical respiratory symptoms. Follow patients closely and, if clinically significant respiratory symptoms develop, consider withholding TORISEL until recovery of symptoms and radiographic improvement of pneumonitis findings. Some patients required TORISEL discontinuation 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.
• TORISEL may cause fetal harm. Patients and their partners should be advised to avoid pregnancy throughout treatment and for 3 months after TORISEL therapy has stopped.
• Elderly patients may be more likely to experience certain adverse reactions including diarrhea, edema and pneumonia.
• 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 and laboratory abnormalities included asthenia (11%), dyspnea (9%), hemoglobin decreased (20%), lymphocytes decreased (16%), glucose increased (16%), phosphorus decreased (18%), and triglycerides increased (44%).
• Pleural effusion, hemodynamically significant pericardial effusions requiring intervention, convulsions, rhabdomyolysis, Stevens-Johnson Syndrome, complex regional pain syndrome and extravasations have been reported during postmarketing use.
• 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.
• Avoid St. John's Wort which may decrease TORISEL plasma concentrations, and grapefruit juice which may increase plasma concentrations of the major metabolite of TORISEL.
• The combination of TORISEL and sunitinib resulted in dose-limiting toxicity (Grade 3/4 erythematous maculopapular rash, and gout/cellulitis requiring hospitalization).

Please see the full Prescribing Information for TORISEL.