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OPDIVO (nivolumab) injection, for intravenous use
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use OPDIVO safely and effectively. See full prescribing information for OPDIVO.
OPDIVO (nivolumab) injection, for intravenous use
Initial U.S. Approval: 2014
INDICATIONS AND USAGE
OPDIVO is a human programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. (1, 14)
DOSAGE AND ADMINISTRATION
Administer 3 mg/kg as an intravenous infusion over 60 minutes every 2 weeks. (2.1)
DOSAGE FORMS AND STRENGTHS
Injection: 40 mg/4 mL and 100 mg/10 mL solution in a single-use vial (3)
WARNINGS AND PRECAUTIONS
Immune-mediated adverse reactions: Administer corticosteroids based on the severity of the reaction. (5.1, 5.2, 5.3, 5.4, 5.6)
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Immune-mediated pneumonitis: Withhold for moderate and permanently discontinue for severe or life-threatening pneumonitis. (5.1)
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Immune-mediated colitis: Withhold for moderate or severe and permanently discontinue for life-threatening colitis. (5.2)
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Immune-mediated hepatitis: Monitor for changes in liver function. Withhold for moderate and permanently discontinue for severe or life-threatening transaminase or total bilirubin elevation. (5.3)
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Immune-mediated nephritis and renal dysfunction: Monitor for changes in renal function. Withhold for moderate and permanently discontinue for severe or life-threatening serum creatinine elevation. (5.4)
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Immune-mediated hypothyroidism and hyperthyroidism: Monitor for changes in thyroid function. Initiate thyroid hormone replacement as needed. (5.5)
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Embryofetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. (5.7, 8.1, 8.3)
ADVERSE REACTIONS
Most common adverse reaction (≥20%) was rash. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
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Lactation: Discontinue breastfeeding. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 12/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
OPDIVO® (nivolumab) is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor [see Clinical Studies (14)].
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
The recommended dose of OPDIVO is 3 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.
2.2 Dose Modifications
There are no recommended dose modifications for hypothyroidism or hyperthyroidism.
Withhold OPDIVO for any of the following:
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Grade 2 pneumonitis [see Warnings and Precautions (5.1)]
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Grade 2 or 3 colitis [see Warnings and Precautions (5.2)]
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 and up to 5 times upper limit of normal (ULN) or total bilirubin greater than 1.5 and up to 3 times ULN [see Warnings and Precautions (5.3)]
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Creatinine greater than 1.5 and up to 6 times ULN or greater than 1.5 times baseline [see Warnings and Precautions (5.4)]
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Any other severe or Grade 3 treatment-related adverse reactions [see Warnings and Precautions (5.6)]
Resume OPDIVO in patients whose adverse reactions recover to Grade 0-1.
Permanently discontinue OPDIVO for any of the following:
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Any life-threatening or Grade 4 adverse reaction
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Grade 3 or 4 pneumonitis [see Warnings and Precautions (5.1)]
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Grade 4 colitis [see Warnings and Precautions (5.2)]
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AST or ALT greater than 5 times ULN or total bilirubin greater than 3 times ULN [see Warnings and Precautions (5.3)]
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Creatinine greater than 6 times ULN [see Warnings and Precautions (5.4)]
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Any severe or Grade 3 treatment-related adverse reaction that recurs
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Inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks
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Persistent Grade 2 or 3 treatment-related adverse reactions that do not recover to Grade 0-1 within 12 weeks after last dose of OPDIVO
2.3 Preparation and Administration
Visually inspect drug product solution for particulate matter and discoloration prior to administration. OPDIVO is a clear to opalescent, colorless to pale-yellow solution. Discard the vial if the solution is cloudy, is discolored, or contains extraneous particulate matter other than a few translucent-to-white, proteinaceous particles. Do not shake the vial.
Preparation
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Withdraw the required volume of OPDIVO and transfer into an intravenous container.
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Dilute OPDIVO with either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP, to prepare an infusion with a final concentration ranging from 1 mg/mL to 10 mg/mL.
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Mix diluted solution by gentle inversion. Do not shake.
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Discard partially used vials or empty vials of OPDIVO.
Storage of Infusion
The product does not contain a preservative.
After preparation, store the OPDIVO infusion either:
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at room temperature for no more than 4 hours from the time of preparation. This includes room temperature storage of the infusion in the IV container and time for administration of the infusion or
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under refrigeration at 2°C to 8°C (36°F-46°F) for no more than 24 hours from the time of infusion preparation.
Do not freeze.
Administration
Administer the infusion over 60 minutes through an intravenous line containing a sterile, non-pyrogenic, low protein binding in-line filter (pore size of 0.2 micrometer to 1.2 micrometer).
Do not coadminister other drugs through the same intravenous line.
Flush the intravenous line at end of infusion.
3 DOSAGE FORMS AND STRENGTHS
Injection: 40 mg/4 mL (10 mg/mL) and 100 mg/10 mL (10 mg/mL) solution in a single-use vial.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Immune-Mediated Pneumonitis
Severe pneumonitis or interstitial lung disease, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience in 574 patients with solid tumors, fatal immune-mediated pneumonitis occurred in 0.9% (5/574) of patients receiving OPDIVO. No cases of fatal pneumonitis occurred in Trial 1; all five fatal cases occurred in a dose-finding study with OPDIVO doses of 1 mg/kg (two patients), 3 mg/kg (two patients), and 10 mg/kg (one patient).
In Trial 1, pneumonitis, including interstitial lung disease, occurred in 3.4% (9/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Immune-mediated pneumonitis, defined as requiring use of corticosteroids and no clear alternate etiology, occurred in 2.2% (6/268) of patients receiving OPDIVO: one with Grade 3 and five with Grade 2 pneumonitis. The median time to onset for the six cases was 2.2 months (range: 25 days-3.5 months). In two patients, pneumonitis was diagnosed after discontinuation of OPDIVO for other reasons, and Grade 2 pneumonitis led to interruption or permanent discontinuation of OPDIVO in the remaining four patients. All six patients received high-dose corticosteroids (at least 40 mg prednisone equivalents per day); immune-mediated pneumonitis improved to Grade 0 or 1 with corticosteroids in all six patients. There were two patients with Grade 2 pneumonitis that completely resolved (defined as improved to Grade 0 with completion of corticosteroids) and OPDIVO was restarted without recurrence of pneumonitis.
Monitor patients for signs and symptoms of pneumonitis. Administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents for Grade 2 or greater pneumonitis, followed by corticosteroid taper. Permanently discontinue OPDIVO for severe (Grade 3) or life-threatening (Grade 4 |
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