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Nivolumab And Hyaluronidase-Nvhy

FDA Drug Information • Also known as: Opdivo Qvantig

Brand Names
Opdivo Qvantig
Drug Class
Programmed Death Receptor-1 Blocking Antibody [EPC], Endoglycosidase [EPC]
Route
SUBCUTANEOUS
Dosage Form
INJECTION, SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION OPDIVO QVANTIG is a fixed-combination drug product containing nivolumab and hyaluronidase (human recombinant). Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody. Nivolumab is an IgG4 kappa immunoglobulin that has a calculated molecular mass of 146 kDa. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Hyaluronidase (human recombinant) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. Hyaluronidase (human recombinant) is a glycosylated single-chain protein produced by CHO cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (human recombinant) has a molecular weight of approximately 61 kDa. OPDIVO QVANTIG (nivolumab and hyaluronidase-nvhy) injection is a sterile, preservative-free, clear to opalescent, colorless to yellow solution that may contain a few translucent-to-white particles, supplied in a single-dose vial for subcutaneous use. Each 2.5 mL single-dose vial contains 300 mg of nivolumab and 5,000 units of hyaluronidase (human recombinant), and the inactive ingredients: histidine (3.88 mg), histidine hydrochloride monohydrate (5.25 mg), methionine (1.87 mg), pentetic acid (0.049 mg), polysorbate 80 (1.25 mg), sucrose (214 mg), and Water for Injection, USP. The pH is 5.5 to 6.5. Each 5 mL single-dose vial contains 600 mg of nivolumab and 10,000 units of hyaluronidase (human recombinant), and the inactive ingredients: histidine (7.75 mg), histidine hydrochloride monohydrate (10.5 mg), methionine (3.73 mg), pentetic acid (0.0985 mg), polysorbate 80 (2.5 mg), sucrose (428 mg), and Water for Injection, USP. The pH is 5.5 to 6.5.

What Is Nivolumab And Hyaluronidase-Nvhy Used For?

1 INDICATIONS AND USAGE OPDIVO QVANTIG is a combination of nivolumab, a programmed death receptor-1 (PD-1)-blocking antibody, and hyaluronidase, an endoglycosidase, indicated for the treatment of: Renal Cell Carcinoma (RCC)

  • adult patients with intermediate or poor risk advanced RCC, as a first-line treatment following combination treatment with intravenous nivolumab and ipilimumab. (1.1)
  • Limitations of Use: OPDIVO QVANTIG is not indicated in combination with ipilimumab for the treatment of renal cell carcinoma.
  • adult patients with advanced RCC, as a first-line treatment in combination with cabozantinib. (1.1)
  • adult patients with advanced RCC who have received prior anti-angiogenic therapy. ( 1.1 ) Melanoma
  • adult and pediatric (12 years and older who weigh 30 kg or greater) patients with unresectable or metastatic melanoma. (1.2)
  • adult and pediatric (12 years and older who weigh 30 kg or greater) patients with unresectable or metastatic melanoma following combination treatment with intravenous nivolumab and ipilimumab. (1.2)
  • Limitations of Use: OPDIVO QVANTIG is not indicated in combination with ipilimumab for the treatment of unresectable or metastatic melanoma.
  • for the adjuvant treatment of adult and pediatric (12 years and older who weigh 30 kg or greater) patients with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. (1.3) Non-Small Cell Lung Cancer (NSCLC)
  • adult patients with resectable (tumors ≥4 cm or node positive) NSCLC in the neoadjuvant setting, in combination with platinum-doublet chemotherapy. (1.4)
  • adult patients with resectable (tumors ≥4 cm or node positive) NSCLC and no known EGFR mutations or ALK rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy, followed by OPDIVO QVANTIG monotherapy as adjuvant treatment after surgery. (1.5)
  • adult patients with metastatic NSCLC and progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO QVANTIG. (1.6)
  • Limitations of Use: OPDIVO QVANTIG is not indicated in combination with ipilimumab for the treatment of metastatic NSCLC. Squamous Cell Carcinoma of the Head and Neck (SCCHN)
  • adult patients with recurrent or metastatic SCCHN with disease progression on or after a platinum-based therapy. (1.7) Urothelial Carcinoma (UC)
  • adjuvant treatment of adult patients with UC who are at high risk of recurrence after undergoing radical resection of UC. (1.8)
  • adult patients with unresectable or metastatic urothelial carcinoma, as first-line treatment in combination with cisplatin and gemcitabine. (1.8)
  • adult patients with locally advanced or metastatic UC who:
  • have disease progression during or following platinum-containing chemotherapy.
  • have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (1.8)...

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION

  • OPDIVO QVANTIG has different dosage and administration instructions than intravenous nivolumab products.
  • OPDIVO QVANTIG is for subcutaneous use only in the abdomen or thigh.
  • OPDIVO QVANTIG is to be administered by a healthcare professional only. (2.1) OPDIVO QVANTIG is for subcutaneous use only.
  • Administer by subcutaneous injection over 3 to 5 minutes. (2.3)
  • Renal cell carcinoma
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks administered in combination with cabozantinib 40 mg once daily without food. (2.3)
  • Melanoma
  • Adult and pediatric patients (12 years and older) who weigh 40 kg or greater: 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • Pediatric patients (12 years and older) who weigh 30 kg or greater but less than 40 kg: 300 mg/5,000 units every 2 weeks or 600 mg/10,000 units every 4 weeks. (2.3)
  • Neoadjuvant treatment of resectable (tumors ≥4 cm or node positive) non-small cell lung cancer
  • 900 mg/15,000 units with platinum-doublet chemotherapy on the same day every 3 weeks for 3 cycles. (2.3)
  • Neoadjuvant and adjuvant treatment of resectable non-small cell lung cancer
  • 900 mg/15,000 units with platinum-doublet chemotherapy on the same day every 3 weeks for up to 4 cycles, then continued as single-agent OPDIVO QVANTIG 1,200 mg/20,000 units every 4 weeks after surgery for up to 13 cycles (~1 year). (2.3)
  • Metastatic non-small cell lung cancer
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • Squamous cell carcinoma of the head and neck
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • Urothelial carcinoma
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • First-line unresectable or metastatic urothelial carcinoma
  • 900 mg/15,000 units every 3 weeks with cisplatin and gemcitabine on the same day for up to 6 cycles, then 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • MSI-H or dMMR metastatic Colorectal cancer
  • Adult and pediatric patients weighing 40 kg or greater: 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • Pediatric patients weighing 30 kg or greater but less than 40 kg: 300 mg/5,000 units every 2 weeks or 600 mg/10,000 units every 4 weeks. (2.3)
  • Hepatocellular carcinoma
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • Esophageal cancer
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks. (2.3)
  • 600 mg/10,000 units every 2 weeks or 1,200 mg/20,000 units every 4 weeks administered in combination with fluoropyrimidine- and platinum-containing chemotherapy. (2.3)
  • Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma
  • 600 mg/10,000 units every 2 weeks in combination with fluoropyrimidine- and...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling.

  • Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ]
  • Complications of Allogeneic HSCT [see Warnings and Precautions (5.2) ]
  • Most common adverse reactions (≥10%) with OPDIVO QVANTIG as monotherapy in patients with Renal Cell Carcinoma were: musculoskeletal pain, fatigue, pruritus, rash, hypothyroidism, diarrhea, cough, and abdominal pain. (6.1)
  • Safety of OPDIVO QVANTIG for the following indications is based on safety of intravenous nivolumab in these populations. The most common adverse reactions with intravenous nivolumab for these indications are presented below.
  • As monotherapy for the treatment of advanced renal cell carcinoma; adjuvant treatment of completely resected Stage IIB, IIC, III, or IV melanoma; unresectable or metastatic melanoma; adjuvant treatment of NSCLC, metastatic NSCLC; squamous cell carcinoma of the head and neck; urothelial carcinoma; MSI-H or dMMR mCRC; hepatocellular carcinoma; esophageal cancer: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, vomiting, and urinary tract infection. (6.1)
  • In combination with cabozantinib for the first-line treatment of advanced renal cell carcinoma: diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection. (6.1)
  • In combination with platinum-doublet chemotherapy for the neoadjuvant treatment of NSCLC: nausea, constipation, fatigue, decreased appetite, and rash. (6.1)
  • In combination with cisplatin and gemcitabine for the treatment of urothelial cancer: nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy. (6.1)
  • In combination with fluoropyrimidine- and platinum- containing chemotherapy for the treatment of esophageal cancer and gastric cancer: nausea, peripheral neuropathy, decreased appetite, fatigue, constipation, stomatitis, diarrhea, vomiting, abdominal pain, and musculoskeletal pain. (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. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in WARNINGS AND PRECAUTIONS reflect exposure to OPDIVO QVANTIG as a single agent in 247 patients enrolled in CHECKMATE-67T, with additional data from intravenous nivolumab single-agent (1994 patients), and from intravenous nivolumab in combination with cabozantinib (320 patients) for select adverse reactions. Advanced Renal Cell Carcinoma CHECKMATE-67T was a multicenter, randomized, open-label study in adult patients with advanced or metastatic RCC. Patients received OPDIVO QVANTIG dose of 1,200 mg of nivolumab and 20,000 units of hyaluronidase subcutaneously every 4 weeks (n=247) or 3 mg/kg of nivolumab intravenously every 2 weeks (n=245). Among patients who received OPDIVO QVANTIG, 52% were exposed for 6 months or longer and 20% were exposed for greater than 1 year. Serious adverse reactions occurred in 28% of patients who received OPDIVO QVANTIG. Serious adverse reactions in >1% of patients included pleural effusion (1.6%), pneumonitis (1.6%), hyperglycemia (1.2%), hyperkalemia (1.2%), hemorrhage (1.2%) and diarrhea (1.2%). Fatal adverse reactions occurred in 3 patients (1.2%) who received OPDIVO QVANTIG and included myocarditis, myositis, and colitis...

    • Contraindications

    4 CONTRAINDICATIONS None.

  • None. (4)

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Based on data from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , OPDIVO QVANTIG can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death (see Data) . Human IgG4 is known to cross the placental barrier and nivolumab is an immunoglobulin G4 (IgG4); therefore, nivolumab has the potential to be transmitted from the mother to the developing fetus. The effects of OPDIVO QVANTIG are likely to be greater during the second and third trimesters of pregnancy. There are no available data on OPDIVO QVANTIG use in pregnant women to evaluate a drug-associated risk. Advise pregnant women of the potential risk to a fetus. The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data OPDIVO QVANTIG for subcutaneous injection contains nivolumab and hyaluronidase [see Description (11) ] . Nivolumab A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to increase fetal loss. The effects of nivolumab on prenatal and postnatal development were evaluated in monkeys that received nivolumab intravenously twice weekly from the onset of organogenesis through delivery, at exposure levels of between 4 and 15 times higher than those observed at the clinical dose of 600 mg once every 2 weeks, 900 mg once every 3 weeks, or 1,200 mg once every 4 weeks (based on AUC). Nivolumab administration resulted in a non-dose-related increase in spontaneous abortion and increased neonatal death. Based on its mechanism of action, fetal exposure to nivolumab may increase...

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING OPDIVO QVANTIG™ (nivolumab and hyaluronidase-nvhy) injection is a sterile, preservative-free, clear to opalescent and colorless to yellow solution for subcutaneous use. It is supplied as an individually packaged single-dose vial as follows: Carton Contents NDC 300 mg nivolumab and 5,000 units hyaluronidase per 2.5 mL (120 mg/2,000 units per mL) single-dose vial 0003-3120-01 600 mg nivolumab and 10,000 units hyaluronidase per 5 mL (120 mg/2,000 units per mL) single-dose vial 0003-6120-01 Store OPDIVO QVANTIG vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.