Class: Protein-tyrosine kinase inhibitor
- Injection, solution, concentrate 25 mg/mL
Binds to an intracellular protein, and the protein-drug complex inhibits the activity of mammalian target of rapamycin that controls cell division.
Mean C max in whole blood is 585 ng/mL following a single 25 mg dose in cancer patients. Mean AUC is 1,627 ng•h/mL.
Following a single 25 mg IV dose, mean steady-state Vd in whole blood is 172 L.
The major isozyme responsible for temsirolimus metabolism is CYP3A4. Sirolimus, an active metabolite of temsirolimus, is the principal metabolite following IV treatment.
Mean t ½ is 17.3 h. Mean systemic Cl is 16.2 L/h. Elimination is primarily via the feces.
Indications and Usage
Treatment of advanced renal cell carcinoma.
Dosage and AdministrationAdvanced Renal Cell Carcinoma
IV 25 mg infused over a 30- to 60-min period once a wk. Continue treatment until disease progression or unacceptable toxicity occurs. Withhold drug for absolute neutrophil count less than 1,000/mm 3 , platelet count less than 75,000/mm 3 , or National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or greater adverse reactions. Once toxicities have resolved to grade 2 or less, reinstate treatment with the temsirolimus dose reduced by 5 mg/wk, but no lower than 15 mg/wk.Dose Modification
IVCoadministration of a strong CYP3A4 inhibitor (eg, indinavir, ketoconazole, telithromycin, voriconazole)
If a strong CYP3A4 inhibitor must be coadministered, consider reducing the temsirolimus dose to 12.5 mg/wk. If the inhibitor is discontinued, allow 1 wk before adjusting the temsirolimus dose back to the amount given prior to starting the CYP3A4 inhibitor.Coadministration of a strong CYP3A4 inducer (eg, carbamazepine, phenytoin, rifampin)
If a strong CYP3A4 inducer must be coadministered, consider increasing the temsirolimus dose to 50 mg/wk. If the inducer is discontinued, return the temsirolimus dose to the amount given prior to starting the inducer.
- Premedicate patients prophylactically with an IV antihistamine (eg, diphenhydramine 25 to 50 mg) approximately 30 min prior to start of each temsirolimus dose.
- Visually inspect product for particulate matter and discoloration prior to administration.
- The final temsirolimus dilution for infusion should be stored in bottles (ie, glass, polypropylene) or plastic bags (eg, polyolefin, polypropylene) and administered through polyethylene-lined administration sets.
- To prevent precipitation of drug, do not add directly to aqueous infusion solutions. Always combine temsirolimus with the diluent before adding to infusion solutions.
- Administer in sodium chloride 0.9% injection after combining with diluent. Administration of a final diluted infusion solution should be completed within 6 h.
Store under refrigeration at 36° to 46°F. Protect from light.
Drug InteractionsAnticoagulant therapy (eg, warfarin)
Risk of developing life-threatening intracerebral bleeding may be increased.CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin)
Plasma concentration of a major metabolite of temsirolimus, sirolimus, may be reduced, decreasing the therapeutic effects.CYP3A4 inhibitors (eg, atazanavir, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
Plasma concentration of a major metabolite of temsirolimus, sirolimus, may be elevated, increasing the risk of adverse reactions.Grapefruit
Grapefruit juice should be avoided. Plasma concentration of a major metabolite of temsirolimus, sirolimus, may be elevated, increasing the risk of adverse reactions.Sunitinib
Increased risk of developing dose-limiting toxicity (eg, grade 3/4 erythematous maculopapular rash).Vaccinations
Vaccinations may be less effective.
Laboratory Test Interactions
None well documented.
Hypertension (7%); venous thromboembolism (2%); thrombophlebitis (1%).
Pyrexia (24%); dysgeusia (20%); headache (15%); insomnia (12%); depression (4%).
Rash (47%; pruritus (19%); nail disorder (14%); dry skin (11%); acne (10%).
Epistaxis, pharyngitis (12%); rhinitis (10%); conjunctivitis (7%).
Mucositis (41%); nausea (37%); anorexia (32%); diarrhea (27%); abdominal pain (21%); constipation (20%); vomiting (19%); fatal bowel perforation (1%).
Decreased hemoglobin (94%); increased glucose (89%); increased total cholesterol (87%); increased triglycerides (83%); increased alkaline phosphatase (68%); increased creatinine (57%); decreased lymphocytes (53%); decreased phosphorus (49%); decreased platelets (40%); increased AST (38%); decreased leukocytes (32%); decreased potassium (21%); decreased neutrophils (19%); increased total bilirubin (8%).
Impaired wound healing (1%).
Weight loss (19%).
Back pain (20%); arthralgia (18%); myalgia (8%).
Dyspnea (28%); cough (26%); pneumonia (8%); upper respiratory tract infection (7%); interstitial lung disease (2%).
Asthenia (51%); edema (35%); pain (28%); infections (20%); chest pain (16%); allergic/hypersensitivity reactions (9%); chills (8%).
Serum glucose, cholesterol, and triglycerides should be measured before and during treatment. Chemistry panels and CBC may need to be performed at the health care provider's discretion.
Category D .
Safety and efficacy not established.
Studies did not include sufficient numbers of subjects 65 yr of age and older to determine if they respond differently from younger subjects.
Rapidly progressive and sometimes fatal acute renal failure can occur. Renal function impairment is not expected to influence drug exposure and no dosage adjustment is recommended.
No data are available; however, temsirolimus is predominantly cleared by the liver.
Fatal bowel perforation can occur.
Increased serum glucose, requiring an increase in dose of, or initiation of, insulin and/or oral hypoglycemic agents, can occur.
Increases in serum triglycerides and cholesterol are likely to occur, which may require the initiation, or increase in the dose, of lipid-lowering agents.
Hypersensitivity reactions, including symptoms of anaphylaxis, dyspnea, flushing, and chest pain, can occur.
Immunosuppression can occur, increasing the risk of infection and opportunistic infections.
Interstitial lung disease
Can occur and may result in death.
Patients with CNS tumors and/or who are receiving anticoagulant therapy may be at increased risk of developing life-threatening intracerebral bleeding.
Wound healing complications
Use with caution in the perioperative period; abnormal would healing can occur.
Use of live vaccines and contact with individuals who have received live vaccines should be avoided.
Risk of bowel perforation, interstitial lung disease, psychosis, seizures, and thrombosis is increased.
- Advise patients to immediately report to health care provider any facial swelling, difficulty in breathing, new or worsening of respiratory symptoms, new or worsening abdominal pain or blood in stools, or excessive thirst or frequency of urination.
- Inform patients that they may be more susceptible to developing or experiencing infection, abnormal wound healing, interstitial lung disease, bowel perforation, renal failure, or elevated triglycerides and/or cholesterol while taking temsirolimus.
- Inform patients with CNS tumors and/or who are receiving anticoagulant therapy that the risk of developing intracerebral bleeding may be increased.
- Advise patients that vaccinations may be less effective while receiving this product and to avoid use of live vaccines and close contact with individuals who have received live vaccines.
- Advise women of childbearing potential to avoid becoming pregnant throughout treatment and for 3 months after receiving this product. Men with partners of childbearing potential should use reliable contraception throughout treatment and for 3 months after the last dose.
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