Warnings and Precautions

Specific Populations¹

• Pregnancy Category D
  • Women of childbearing age should be advised of the potential hazard to the fetus and to avoid becoming pregnant.
  • Women and men of childbearing age or potential should use contraception during treatment and up to 3 months after the last dose of TORISEL.
• Geriatric Use
  • Clinical studies of TORISEL did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.
• Hepatic elimination: predominant pathway
• No data is available about the influence of hepatic dysfunction on temsirolimus disposition.
• Renal impairment
• No dose adjustment recommended for patients with impaired renal function.
• Renal impairment is not expected to markedly influence drug exposure

Hypersensitivity reactions¹

Hypersensitivity reactions manifested by symptoms including, but not limited to, anaphylaxis, dyspnea, flushing, and chest pain have been observed with TORISEL.

• In post-marketing surveillance, hypersensitivity reactions include some life-threatening and rare fatal reactions, which can occur very early in the first infusion of TORISEL, but may also occur with subsequent infusions.² Patients should be monitored early during the infusion and appropriate supportive care should be available.

An H₁ antihistamine should be administered to patients before the start of the intravenous temsirolimus infusion. TORISEL should be used with caution in patients with known hypersensitivity to an antihistamine, or patients who cannot receive an antihistamine for other medical reasons.

Hyperglycemia/glucose intolerance¹

The use of TORISEL is likely to result in increases in serum glucose. This may result in the need for an increase in the dose, or initiation, of insulin and/or oral hypoglycemic agent therapy. Serum glucose should be tested before and during treatment with TORISEL. Patients should be advised to report excessive thirst or any increase in the volume or frequency of urination.

Infections¹

The use of TORISEL may result in immunosuppression.  Patients should be carefully observed for the occurrence of infections, including opportunistic infections.

Interstitial lung disease¹

Cases of interstitial lung disease, some resulting in death, occurred in patients who received TORISEL. Patients should be advised to report promptly any new or worsening respiratory symptoms.

Hyperlipemia¹

The use of TORISEL is likely to result in increases in serum triglycerides and cholesterol. This may require initiation, or increase in the dose, of lipid-lowering agents. Serum cholesterol and triglycerides should be tested before and during treatment with TORISEL.

Bowel perforation¹

Cases of fatal bowel perforation occurred in patients who received TORISEL. Patients should be advised to report promptly any new or worsening abdominal pain or blood in their stool.

Renal failure¹

Cases of rapidly progressive and sometimes fatal acute renal failure not clearly related to disease progression occurred in patients who received TORISEL. Some of these cases were not responsive to dialysis.

Wound healing complications¹

Use of TORISEL has been associated with abnormal wound healing. Therefore, caution should be exercised with the use of TORISEL in the perioperative period.

Intracerebral hemorrhage¹

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.

Concomitant use of TORISEL with sunitinib¹

The combination of TORISEL and sunitinib resulted in dose-limiting toxicity. Dose-limiting
toxicities (Grade 3/4 erythematous maculopapular rash, and gout/cellulitis requiring
hospitalization) were observed in two out of three patients treated in the first cohort of a phase 1
study at doses of TORISEL 15 mg IV per week and sunitinib 25 mg oral per day (Days 1-28
followed by a 2-week rest).

Vaccinations¹

The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with TORISEL. Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.

For information on managing TORISEL side effects, see Managing Side Effects in the Nurses' Guide.

For more details on TORISEL safety, download the full Prescribing Information.

242252-01