Torisel (temsirolimus)

Concomitant use of temsirolimus with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice) should be avoided. If patients must be administered a strong CYP3A4 inhibitor, consider a dosage reduction of temsirolimus to 12.5 mg weekly. If the strong CYP3A4 inhibitor is discontinued, allow a washout period of approximately 1 week before temsirolimus is adjusted back to the dosage used prior to initiation of the CYP3A4 inhibitor.

Concomitant use with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital) should be avoided. If patients must be administered a strong CYP3A4 inducer, consider a dosage increase of temsirolimus from 25 mg weekly to 50 mg weekly. If the strong inducer is discontinued, adjust temsirolimus dosage back to the dosage used prior to initiation of the strong CYP3A4 inducer.

Therapy should be temporarily interrupted if hematologic toxicities (e.g., absolute neutrophil count less than 1000/mm3, platelet count less than 75,000/mm3) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or greater toxicity occurs.

Following resolution of toxicity to grade 2 or less, temsirolimus may be restarted at a reduced weekly dosage that is 5 mg less than the previous dosage, but not less than 15 mg weekly.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

Patients should avoid concomitant use of temsirolimus with strong inhibitors or inducers of cytochrome P-450 (CYP) isoenzyme 3A; if alternative treatment cannot be given, adjustment of temsirolimus dosage is recommended.

Concomitant use of temsirolimus and sunitinib has resulted in dose-limiting toxicity.

Both temsirolimus and its principal active metabolite, sirolimus, are metabolized by cytochrome P-450 (CYP) isoenzyme 3A4. In vitro studies using human liver microsomes indicate that temsirolimus inhibits CYP isoenzymes 2D6 and 3A4.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Patients with bilirubin >1.5 times upper limit of normal (ULN).

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most common adverse reactions (>=30%) reported with temsirolimus are rash, asthenia, mucositis, nausea, edema, and anorexia. The most common laboratory abnormalities (>=30%) are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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There is limited information on the use of temsirolimus in pediatric patients. Effectiveness of the drug in pediatric patients with advanced recurrent/refractory solid tumors has not been established. In a clinical study that included 59 pediatric patients ages 1-17 years of age, temsirolimus 10 mg/m2 to 150 mg/m2 was given in 3 week cycles for treatment of advanced recurrent/refractory solid tumors to explore safety and pharmacodynamics. In a later study, 52 pediatric patients with recurrent/relapsed neruoblastoma, rhabdomyosarcoma, or high grade glioma received temsirolimus 75 mg/m2 weekly. One patient with neuroblastoma had a partial response; no objective responses were observed with the other indications for use.

Adverse reactions associated with temsirolimus in the pediatric population were similar to adults. The most common reactions (>=20%) in pediatric patients receiving the temsirolimus 75 mg/m2 weekly dosage included thrombocytopenia, infections, asthenia/fatigue, fever, pain, leukopenia, rash, anemia, hyperlipidemia, increased cough, stomatitis, anorexia, increased plasma levels of alanine aminotransferase and aspartate aminotransferase, hypercholesterolemia, hyperglycemia, abdominal pain, headache, arthralgia, upper respiratory infection, nausea and vomiting, neutropenia, hypokalemia, and hypophosphatemia.

Temsirolimus may cause fetal harm. Animal studies indicate adverse effects on embryofetal development. Advise pregnant women and females of reproductive potential of the potential risk to the fetus.

Not known whether temsirolimus is distributed into milk or the effects on the breastfed child or milk production. Advise lactating females not to breastfeed during treatment with temsirolimus and for 3 weeks after the final dose.

The manufacturer makes no specific geriatric dosage recommendations at this time.

Older adults are more likely to experience certain adverse reactions with temsirolimus (e.g., diarrhea, edema, pneumonia).

There is insufficient experience in patients 65 years of age or older to determine whether geriatric patients respond differently than younger adults. Elderly patients may be more likely to experience adverse reactions of temsirolimus such as diarrhea, edema, and pneumonia.