BORTEZOMIB injection, powder, lyophilized, for solution

Země: Spojené státy

Jazyk: angličtina

Zdroj: NLM (National Library of Medicine)

Aktivní složka:

BORTEZOMIB (UNII: 69G8BD63PP) (BORTEZOMIB - UNII:69G8BD63PP)

Dostupné s:

BluePoint Laboratories

Podání:

INTRAVENOUS

Druh předpisu:

PRESCRIPTION DRUG

Terapeutické indikace:

Bortezomib for Injection is indicated for the treatment of adult patients with multiple myeloma. Bortezomib for Injection is indicated for the treatment of adult patients with mantle cell lymphoma. Bortezomib for Injection is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol. Reactions have included anaphylactic reactions [see Adverse Reactions (6.1)] . Bortezomib for Injection is contraindicated for intrathecal administration. Fatal events have occurred with intrathecal administration of Bortezomib for Injection. Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1)] and findings in animals, Bortezomib for Injection can cause fetal harm when administered to a pregnant woman. There are no studies with the use of Bortezomib for Injection in pregnant women to inform drug-associated risks. Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Error! Hyperlink reference not valid. ) . Advise pregnant women of the potential risk to the fetus. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Bortezomib was not teratogenic in nonclinical developmental toxicity studies in rats and rabbits at the highest dose tested (0.075 mg/kg; 0.5 mg/m 2 in the rat and 0.05 mg/kg; 0.6 mg/m 2 in the rabbit) when administered during organogenesis. These dosages are approximately 0.5 times the clinical dose of 1.3 mg/m 2 based on body surface area. Bortezomib caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (approximately 0.5 times the clinical dose of 1.3 mg/m 2 based on body surface area). Pregnant rabbits given bortezomib during organogenesis at a dose of 0.05 mg/kg (0.6 mg/m 2 ) experienced significant postimplantation loss and decreased number of live fetuses. Live fetuses from these litters also showed significant decreases in fetal weight. Risk Summary There are no data on the presence of bortezomib or its metabolites in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. Because many drugs are excreted in human milk and because the potential for serious adverse reactions in a breastfed child from Bortezomib for Injection is unknown, advise nursing women not to breastfeed during treatment with Bortezomib for Injection and for two months after treatment. Based on its mechanism of action and findings in animals, Bortezomib for Injection can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Pregnancy Testing Conduct pregnancy testing in females of reproductive potential prior to initiating Bortezomib for Injection treatment. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Bortezomib for Injection and for seven months after the last dose. Males Males with female partners of reproductive potential should use effective contraception during treatment with Bortezomib for Injection and for four months after the last dose. Infertility Based on the mechanism of action and findings in animals, Bortezomib for Injection may have an effect on either male or female fertility [see Nonclinical Toxicology (13.1)] . Safety and effectiveness have not been established in pediatric patients. The activity and safety of Bortezomib for Injection in combination with intensive reinduction chemotherapy was evaluated in pediatric and young adult patients with lymphoid malignancies (pre-B cell ALL 77%, 16% with T-cell ALL, and 7% T-cell lymphoblastic lymphoma (LL)), all of whom relapsed within 36 months of initial diagnosis in a single-arm multicenter, nonrandomized cooperative group trial. An effective reinduction multiagent chemotherapy regimen was administered in three blocks. Block 1 included vincristine, prednisone, doxorubicin and pegaspargase; Block 2 included cyclophosphamide, etoposide and methotrexate; Block 3 included high-dose cytosine arabinoside and asparaginase. Bortezomib for Injection was administered at a dose of 1.3 mg/m 2 as a bolus intravenous injection on Days 1, 4, 8, and 11 of Block 1 and Days 1, 4, and 8 of Block 2. There were 140 patients with ALL or LL enrolled and evaluated for safety. The median age was ten years (range: 1 to 26), 57% were male, 70% were white, 14% were black, 4% were Asian, 2% were American Indian/Alaska Native, 1% were Pacific Islander. The activity was evaluated in a prespecified subset of the first 60 evaluable patients enrolled on the study with pre-B ALL ≤21 years and relapsed <36 months from diagnosis. The complete remission (CR) rate at day 36 was compared to that in a historical control set of patients who had received the identical backbone therapy without Bortezomib for Injection. There was no evidence that the addition of Bortezomib for Injection had any impact on the CR rate. No new safety concerns were observed when Bortezomib for Injection was added to a chemotherapy backbone regimen as compared with a historical control group in which the backbone regimen was given without Bortezomib for Injection. The BSA-normalized clearance of bortezomib in pediatric patients was similar to that observed in adults. Of the 669 patients enrolled in the relapsed multiple myeloma study, 245 (37%) were 65 years of age or older: 125 (38%) on the Bortezomib for Injection arm and 120 (36%) on the dexamethasone arm. Median time to progression and median duration of response for patients ≥65 were longer on Bortezomib for Injection compared to dexamethasone [5.5 mo vs 4.3 mo, and 8.0 mo vs 4.9 mo, respectively]. On the Bortezomib for Injection arm, 40% (n=46) of evaluable patients aged ≥65 experienced response (CR + PR) vs 18% (n=21) on the dexamethasone arm. The incidence of Grade 3 and 4 events was 64%, 78% and 75% for Bortezomib for Injection patients ≤50, 51 to 64 and ≥65 years old, respectively [see Adverse Reactions (6.1), Clinical Studies (14.1)] . No overall differences in safety or effectiveness were observed between patients ≥age 65 and younger patients receiving Bortezomib for Injection; but greater sensitivity of some older individuals cannot be ruled out. No starting dosage adjustment of Bortezomib for Injection is recommended for patients with renal impairment. In patients requiring dialysis, Bortezomib for Injection should be administered after the dialysis procedure [see Clinical Pharmacology (12.3)] . No starting dosage adjustment of Bortezomib for Injection is recommended for patients with mild hepatic impairment (total bilirubin ≤1× ULN and AST >ULN, or total bilirubin >1 to 1.5× ULN and any AST). The exposure of bortezomib is increased in patients with moderate (total bilirubin ≥1.5 to 3× ULN and any AST) and severe (total bilirubin >3× ULN and any AST) hepatic impairment. Reduce the starting dose in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.8), Clinical Pharmacology (12.3)] . During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving Bortezomib for Injection treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication.

Přehled produktů:

Bortezomib for Injection is supplied as individually cartoned 10 mL vials containing 3.5 mg of bortezomib as a white to off-white cake or powder. Unopened vials may be stored at controlled room temperature 25°C (77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Retain in original package to protect from light. Follow guidelines for handling and disposal for hazardous drugs, including the use of gloves and other protective clothing to prevent skin contact 1 .

Stav Autorizace:

Abbreviated New Drug Application

Charakteristika produktu

BORTEZOMIB- BORTEZOMIB INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
BLUEPOINT LABORATORIES
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BORTEZOMIB FOR
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
BORTEZOMIB FOR
INJECTION.
BORTEZOMIB FOR INJECTION, FOR SUBCUTANEOUS OR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2003
INDICATIONS AND USAGE
Bortezomib for Injection is a proteasome inhibitor indicated for:
treatment of adult patients with multiple myeloma ( 1.1)
treatment of adult patients with mantle cell lymphoma ( 1.2)
DOSAGE AND ADMINISTRATION
For subcutaneous or intravenous use only. Each route of administration
has a different reconstituted
concentration. Exercise caution when calculating the volume to be
administered. ( 2.1, 2.10)
The recommended starting dose of Bortezomib for Injection is 1.3 mg/m
administered either as a 3 to
5 second bolus intravenous injection or subcutaneous injection. ( 2.2,
2.4, 2.6)
Retreatment for Multiple Myeloma: May retreat starting at the last
tolerated dose. ( 2.6)
Hepatic Impairment: Use a lower starting dose for patients with
moderate or severe hepatic
impairment. ( 2.8)
Dose must be individualized to prevent overdose. ( 2.10)
DOSAGE FORMS AND STRENGTHS
For injection: Single-dose vial contains 3.5 mg of bortezomib as
lyophilized powder for reconstitution and
withdrawal of the appropriate individual patient dose. ( 3)
CONTRAINDICATIONS
Patients with hypersensitivity (not including local reactions) to
bortezomib, boron, or mannitol, including
anaphylactic reactions. ( 4)
Contraindicated for intrathecal administration. ( 4)
WARNINGS AND PRECAUTIONS
Peripheral Neuropathy: Manage with dose modification or
discontinuation. ( 2.7) Patients with pre-
existing severe neuropathy should be treated with Bortezomib for
Injection only after careful risk-benefit
assessment. ( 2.7, 5.1)
Hypotension: Use caution when treating patients taking
antihypertensives, with a history of syncope, or
with dehydratio