TEMSIROLIMUS kit

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TEMSIROLIMUS (UNII: 624KN6GM2T) (TEMSIROLIMUS - UNII:624KN6GM2T)

Available from:

Accord Healthcare Inc.

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Temsirolimus injection is indicated for the treatment of advanced renal cell carcinoma. Temsirolimus injection is contraindicated in patients with bilirubin >1.5 x ULN [ see Warnings and Precautions ( 5.2 )]. Risk Summary Based on findings in animal studies and its mechanism of action, temsirolimus can cause fetal harm when administered to a pregnant woman [ see Clinical Pharmacology ( 12.1) ]. Although there are no data on the use of temsirolimus in pregnant women, there are limited data on the use of sirolimus, the active metabolite of temsirolimus, during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal reproductive studies, oral daily administration of temsirolimus to pregnant rats and rabbits during organogenesis caused adverse embryo-fetal effects at approximately 0.04 and 0.12 times the AUC in patients at the recommended dose, respectively ( see Data ). Advise pregnant women of the potential hazard to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Temsirolimus administered daily as an oral formulation throughout organogenesis caused adverse embryo-fetal effects in rats and rabbits at human sub-therapeutic exposures. Embryo-fetal adverse effects in rats consisted of reduced fetal weight and reduced ossifications, and in rabbits included reduced fetal weight, omphalocele, bifurcated sternabrae, notched ribs, and incomplete ossifications. In rats, the adverse embryo-fetal effects were observed at the oral dose of 2.7 mg/m2/day (approximately 0.04-fold the AUC in patients with cancer at the human recommended dose). In rabbits, the adverse embryo-fetal effects were observed at the oral dose of ≥7.2 mg/m2/day (approximately 0.12-fold the AUC in patients with cancer at the recommended human dose). Risk Summary There is no information regarding the presence of temsirolimus or its metabolites in human milk, or their effects on the breastfed child or milk production. Trace amounts of sirolimus, the active metabolite of temsirolimus, were present in milk from lactating rats administered sirolimus. Because of the potential for serious adverse reactions in a breastfed child from temsirolimus, advise a lactating woman not to breastfeed during treatment with Temsirolimus injection and for 3 weeks after the final dose. Contraception Females Temsirolimus can cause fetal harm when administered to a pregnant woman [ see Use in Specific Population ( 8.1)] . Advise females of reproductive potential to use effective contraception during treatment with Temsirolimus injection and for 3 months after the last dose. Males Advise males with partners of reproductive potential to use effective contraception during treatment with Temsirolimus injection and for 3 months after the last dose [ see Nonclinical Toxicology ( 13.1)] . Infertility Based on the findings in animal fertility studies, male and female fertility may be compromised by the treatment with Temsirolimus injection. It is not known if the effects on fertility in animal studies were reversible [ see Nonclinical Toxicology ( 13.1)] . Limited data are available on the use of temsirolimus in pediatric patients. The effectiveness of temsirolimus in pediatric patients with advanced recurrent/refractory solid tumors has not been established. Temsirolimus injection was studied in 71 patients (59 patients ages 1 to 17 years and 12 patients ages 18 to 21 years) with relapsed/refractory solid tumors in a phase 1-2 safety and exploratory pharmacodynamic study. In phase 1, 19 pediatric patients with advanced recurrent/refractory solid tumors received Temsirolimus injection at doses ranging from 10 mg/m 2 to 150 mg/m 2 as a 60-minute intravenous infusion once weekly in three-week cycles. In phase 2, 52 pediatric patients with recurrent/relapsed neuroblastoma, rhabdomyosarcoma, or high grade glioma received Temsirolimus injection at a weekly dose of 75 mg/m 2 . One of 19 patients with neuroblastoma achieved a partial response. There were no objective responses in pediatric patients with recurrent/relapsed rhabdomyosarcoma or high grade glioma. Adverse reactions associated with Temsirolimus injection were similar to those observed in adults. The most common adverse reactions (≥20%) in pediatric patients receiving the 75 mg/m 2 dose 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. Pharmacokinetics: In phase 1 of the above mentioned pediatric trial, the single dose and multiple dose total systemic exposure (AUC) of temsirolimus and sirolimus were less than dose-proportional over the dose range of 10 to 150 mg/m 2 . In the phase 2 portion, the multiple dose (Day 1, Cycle 2) pharmacokinetics of Temsirolimus injection 75 mg/m 2 were characterized in an additional 35 patients ages 28 days to 21 years (median age of 8 years). The geometric mean body surface adjusted clearance of temsirolimus and sirolimus was 9.45 L/h/m 2 and 9.26 L/h/m 2 , respectively. The mean elimination half-life of temsirolimus and sirolimus was 31 hours and 44 hours, respectively. The exposure (AUCss) to temsirolimus and sirolimus was approximately 6-fold and 2-fold higher, respectively than the exposure in adult patients receiving a 25 mg intravenous infusion. Clinical studies of Temsirolimus injection did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Based on the results of a phase 3 study, elderly patients may be more likely to experience certain adverse reactions including diarrhea, edema, and pneumonia [ see Warnings and Precautions ( 5.16) ]. No clinical studies were conducted with Temsirolimus injection in patients with decreased renal function. Less than 5% of total radioactivity was excreted in the urine following a 25 mg intravenous dose of [ 14 C]-labeled temsirolimus in healthy subjects. Renal impairment is not expected to markedly influence drug exposure, and no dosage adjustment of Temsirolimus injection is recommended in patients with renal impairment. Temsirolimus injection has not been studied in patients undergoing hemodialysis. Temsirolimus injection was evaluated in a dose escalation phase 1 study in 110 patients with normal or varying degrees of hepatic impairment as defined by AST and bilirubin levels and patients with liver transplant ( Table 3). Patients with moderate and severe hepatic impairment had increased rates of adverse reactions and deaths, including deaths due to progressive disease, during the study ( Table 3). Temsirolimus injection is contraindicated in patients with bilirubin >1.5 x ULN [ see Contraindications ( 4 ) , and Warnings and Precautions ( 5.2 ) ]. Use caution when treating patients with mild hepatic impairment. If Temsirolimus injection must be given in patients with mild hepatic impairment (bilirubin >1 – 1.5 x ULN or AST > ULN but bilirubin ≤ULN), reduce the dose of Temsirolimus injection to 15 mg/week [ see Dosage and Administration ( 2.4 ) ]. Because there is a need for dosage adjustment based upon hepatic function, assessment of AST and bilirubin levels is recommended before initiation of Temsirolimus injection and periodically thereafter.

Product summary:

NDC 16729-223-61 Temsirolimus injection, 25 mg/mL. Each kit is supplied in a single carton containing one single-dose vial of 25 mg/mL of temsirolimus and one Diluent vial which includes a deliverable volume of 1.8 mL, and must be stored at 2°-8°C (36°-46°F). Protect from light. Temsirolimus Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures 1 .

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

TEMSIROLIMUS- TEMSIROLIMUS
ACCORD HEALTHCARE INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TEMSIROLIMUS INJECTION
SAFELY AND EFFECTIVELY.
SEE FULL PRESCRIBING INFORMATION FOR TEMSIROLIMUS INJECTION.
TEMSIROLIMUS INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2007
RECENT MAJOR CHANGES
Warnings and Precautions, Proteinuria and Nephrotic Syndrome ( 5.11)
3/2018
Warnings and Precautions, Embryo-Fetal Toxicity (
5.15) 3/2018
INDICATIONS AND USAGE
Temsirolimus injection is a kinase inhibitor indicated for the
treatment of advanced renal cell carcinoma. (
1)
DOSAGE AND ADMINISTRATION
The recommended dose of Temsirolimus injection is 25 mg administered
as an intravenous infusion
over a 30-60 minute period once a week. Treat until disease
progression or unacceptable toxicity. ( 2.1)
Antihistamine pre-treatment is recommended. ( 2.2)
Dose reduction is required in patients with mild hepatic impairment. (
2.4)
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
Temsirolimus injection, 25 mg/mL supplied with Diluent for
Temsirolimus injection. ( 3)
CONTRAINDICATIONS
Temsirolimus injection is contraindicated in patients with bilirubin
>1.5 x ULN. ( 4)
WARNINGS AND PRECAUTIONS
Hypersensitivity/Infusion Reactions (including some life-threatening
and rare fatal reactions) can occur
early in the first infusion of Temsirolimus injection. Patients should
be monitored throughout the
infusion. ( 5.1)
To treat hypersensitivity reactions, stop Temsirolimus injection and
treat with an antihistamine.
Temsirolimus injection may be restarted at physician discretion at a
slower rate. ( 5.1)
Hepatic Impairment: Use caution when treating patients with mild
hepatic impairment and reduce dose
( 2.4, 5.2)
Hyperglycemia and hyperlipidemia are likely and may require treatment.
Monitor glucose and lipid
profiles. ( 5.3,