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TORISEL Kit (temsirolimus) injection
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TORISEL ® safely and effectively. See full prescribing information for TORISEL.
TORISEL Kit (temsirolimus) injection, for intravenous infusion only
Initial U.S. Approval: 2007
RECENT MAJOR CHANGES
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Warnings and Precautions, Infections (5.4) |
4/2014 |
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Warnings and Precautions, Interstitial Lung Disease (5.5) |
4/2014 |
INDICATIONS AND USAGE
TORISEL® is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. (1)
DOSAGE AND ADMINISTRATION
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The recommended dose of TORISEL is 25 mg infused over a 30–60 minute period once a week. Treat until disease progression or unacceptable toxicity. (2.1)
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Antihistamine pre-treatment is recommended. (2.2)
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Dose reduction is required in patients with mild hepatic impairment. (2.4)
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TORISEL (temsirolimus) injection vial contents must first be diluted with the enclosed diluent before diluting the resultant solution with 250 mL of 0.9% Sodium Chloride Injection. (2.5)
DOSAGE FORMS AND STRENGTHS
TORISEL injection, 25 mg/mL supplied with DILUENT for TORISEL. (3)
CONTRAINDICATIONS
TORISEL is contraindicated in patients with bilirubin > 1.5×ULN. (4)
WARNINGS AND PRECAUTIONS
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Hypersensitivity/Infusion Reactions (including some life-threatening and rare fatal reactions) can occur early in the first infusion of TORISEL. Patients should be monitored throughout the infusion. (5.1)
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To treat hypersensitivity reactions, stop TORISEL and treat with an antihistamine. TORISEL may be restarted at physician discretion at a slower rate. (5.1)
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Hepatic Impairment: Use caution when treating patients with mild hepatic impairment and reduce dose. (2.4, 5.2)
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Hyperglycemia and hyperlipemia are likely and may require treatment. Monitor glucose and lipid profiles. (5.3, 5.6)
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Infections may result from immunosuppression. (5.4)
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Monitor for symptoms or radiographic changes of interstitial lung disease (ILD). If ILD is suspected, discontinue TORISEL, and consider use of corticosteroids and/or antibiotics. (5.5)
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Bowel perforation may occur. eva luate fever, abdominal pain, bloody stools, and/or acute abdomen promptly. (5.7)
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Renal failure, sometimes fatal, has occurred. Monitor renal function at baseline and while on TORISEL. (5.8)
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Due to abnormal wound healing, use TORISEL with caution in the perioperative period. (5.9)
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Live vaccinations and close contact with those who received live vaccines should be avoided. (5.13)
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Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant. (5.14)
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Elderly patients may be more likely to experience certain adverse reactions, including diarrhea, edema and pneumonia. (5.15)
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥30%) are rash, asthenia, mucositis, nausea, edema, and anorexia. The most common laboratory abnormalities (incidence ≥30%) are anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Wyeth Pharmaceuticals Inc. at 1-800-934-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
DRUG INTERACTIONS
Strong inducers of CYP3A4/5 and inhibitors of CYP3A4 may affect concentrations of the primary metabolite of TORISEL. If alternatives cannot be used, dose modifications of TORISEL are recommended. (7.1, 7.2)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 2/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
TORISEL is indicated for the treatment of advanced renal cell carcinoma.
2 DOSAGE AND ADMINISTRATION
2.1 Advanced Renal Cell Carcinoma
The recommended dose of TORISEL for advanced renal cell carcinoma is 25 mg infused over a 30 – 60 minute period once a week.
Treatment should continue until disease progression or unacceptable toxicity occurs.
2.2 Premedication
Patients should receive prophylactic intravenous diphenhydramine 25 to 50 mg (or similar antihistamine) approximately 30 minutes before the start of each dose of TORISEL [see Warnings and Precautions (5.1)].
2.3 Dosage Interruption/Adjustment
TORISEL should be held for absolute neutrophil count (ANC) <1,000/mm3, platelet count <75,000/mm3, or NCI CTCAE grade 3 or greater adverse reactions. Once toxicities have resolved to grade 2 or less, TORISEL may be restarted with the dose reduced by 5 mg/week to a dose no lower than 15 mg/week.
2.4 Dose Modification Guidelines
Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors should be avoided (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Grapefruit juice may also increase plasma concentrations of sirolimus (a major metabolite of temsirolimus) and should be avoided. If patients must be co-administered a strong CYP3A4 inhibitor, based on pharmacokinetic studies, a TORISEL dose reduction to 12.5 mg/week should be considered. This dose of TORISEL is predicted to adjust the AUC to the range observed without inhibitors. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inhibitors. If the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed before the TORISEL dose is adjusted back to the dose used prior to initiation of the strong CYP3A4 inhibitor [see Warnings and Precautions (5.11) and Drug Interactions (7.2)].
Concomitant Strong CYP3A4 Inducers: The use of concomitant strong CYP3A4 inducers should be avoided (e.g. dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampacin, phenobarbital). If patients must be co-administered a strong CYP3A4 inducer, based on pharmacokinetic studies, a TORISEL dose increase from 25 mg/week up to 50 mg/week should be considered. This dose of TORISEL is predicted to adjust the AUC to the range observed without inducers. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers. If the strong inducer is discontinued the temsirolimus dose should be returned to the dose used prior to initiation of the strong CYP3A4 inducer [see Warnings and Precautions (5.11) and Drug Interactions (7.1)].
2.5 Instructions for Preparation
TORISEL must be stored under refrigeration at 2°–8°C (36°–46°F) and protected from light. During handling and preparation of admixtures, TORISEL should be protected from excessive room light and sunlight. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
In order to minimize the patient exposure to the plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, the final TORISEL dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.
TORISEL 25 mg/mL injection must be diluted with the supplied diluent before further dilution in 0.9% Sodium Chloride Injection, USP.
Please note that both the TORISEL injection and diluent vials contain an overfill to ensure the recommended volume can be withdrawn.
Follow this two-step dilution process in an aseptic manner.
Step 1:
DILUTION OF TORISEL INJECTION 25 MG/ML WITH SUPPLIED DILUENT
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Each Vial of Torisel (temsirolimus) must first be mixed with 1.8 mL of the enclosed diluent. The resultant solution contains 30 mg/3 mL (10 mg/mL).
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Mix well by inversion of the vial. Allow sufficient time for the air bubbles to subside. The solution should be clear to slightly turbid, colorless to light-yellow solution, essentially free from visual particulates.
The concentrate-diluent mixture is stable below 25ºC for up to 24 hours.
Step 2:
DILUTION OF CONCENTRATE-DILUENT MIXTURE WITH 0.9% SODIUM CHLORIDE INJECTION, USP
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Withdraw precisely the required amount of concentrate-diluent mixture containing temsirolimus 10 mg/mL as prepared in Step 1 from the vial (i.e., 2.5 mL for a temsirolimus dose of 25 mg) and further dilute into an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection, USP.
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Mix by inversion of the bag or bottle, avoiding excessive shaking, as this may cause foaming.
The resulting solution should be inspected visually for particulate matte |
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