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-a and to interferon-a alone. There was a statistically significant improvement in overall survival in the patients given temsirolimus (10.9 months) compared to those given interferon-a (7.3 months).
ADULTS: 25mg once weekly. Infuse IV over 30–60min, 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/week) 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, males 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 be-fore 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, anticoagulants.
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 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)—1
For more information call (800) 934-5556 or visit www.Torisel.com