Generic Name and Formulations:
Temsirolimus 25mg/mL; ethanolic soln for IV infusion after two dilutions (first w. supplied diluent); contains alcohol, polysorbate 80.
Indications for TORISEL:
Advanced renal cell carcinoma.
Give by IV infusion over 30–60mins, using an infusion pump. Premedicate with IV antihistamine (eg, diphenydramine) 30mins prior to each dose. 25mg once weekly until disease progression or unacceptable toxicity. 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/week) if adverse reactions resolve to ≤Grade 2. Hepatic impairment: bilirubin >1–1.5xULN or AST > ULN but bilirubin ≤ ULN: reduce to 15mg/week; >1.5xULN: contraindicated. Concomitant strong CYP3A4 inhibitors: if unavoidable, consider reducing to 12.5mg/week (allow 1 week after discontinuing inhibitor before readjusting temsirolimus dose). Concomitant CYP3A4 inducers: if unavoidable, consider increasing up to 50mg/week.
Sirolimus or antihistamine allergy. Perioperative period (may interfere with wound healing). CNS tumors. Monitor for infections; consider prophylaxis for pneumocystis jiroveci pneumonia (PJP) when concomitant corticosteroids, other immunosuppresives required. Perform baseline lung/chest radiographic assessment prior to initiation. Monitor for respiratory symptoms or radiographic changes of interstitial lung disease (ILD); discontinue and consider steroid/antibiotic use if ILD is suspected. Monitor blood glucose, lipids, renal function, urine protein, AST, bilirubin prior to initiation and periodically during treatment. Hepatic impairment. Elderly. Embryo-fetal toxicity. Pregnancy; avoid. Females of reproductive potential and males (w. female partners) must use effective contraception during and for 3 months after last dose. Nursing mothers: not recommended (during and for 3 weeks after last dose).
Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit juice; see Adults. Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital); see Adults. Avoid live vaccines, close contact with vaccinees. Additive toxicity with sunitinib (rash, gout/cellulitis), anticoagulants (intracerebral bleeding). Angioedema when concomitant with ACEIs (eg, ramipril) or CCBs (eg, amlodipine); monitor. Avoid concomitant St. John's Wort or pH-modifying drugs. May need to initiate or increase dose of insulin and/or hypoglycemic agents, or lipid-lowering drugs.
mTOR kinase inhibitor.
Rash, asthenia, mucositis, nausea, edema, anorexia, anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, leukopenia; hypersensitivity/infusion reactions (monitor), immunosuppression, infections, ILD, bowel perforation, acute renal failure, abnormal wound healing, proteinuria, nephrotic syndrome (discontinue if occurs).
Kit (vial + diluent)—1