Nivamo 100 mg/10 ml

INDICATIONS

Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of:

Patients with BRAF V600 wild-type unresectable or metastatic melanoma, as a single agent.
Patients with BRAF V600 mutation-positive unresectable or metastatic melanoma, as a single agent. ... Read moreNivolumab is a programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of:

Patients with BRAF V600 wild-type unresectable or metastatic melanoma, as a single agent.
Patients with BRAF V600 mutation-positive unresectable or metastatic melanoma, as a single agent.
Patients with unresectable or metastatic melanoma, in combination with ipilimumab.
Patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting.
Patients with metastatic non-small cell lung cancer 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 Nivolumab.
Patients with advanced renal cell carcinoma who have received prior antiangiogenic therapy.
Patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma, in combination with ipilimumab.
Adult patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or more lines of systemic therapy that includes autologous HSCT.
Patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy.
Patients with locally advanced or metastatic urothelial carcinoma 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.
Adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Patients with hepatocellular carcinoma who have been previously treated with sorafenib.

PHARMACOLOGY

Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) mediated inhibition results in enhanced T-cell function that is greater than the effects of either antibody alone, and results in improved anti-tumor responses in metastatic melanoma and advanced RCC. In murine syngeneic tumor models, dual blockade of PD-1 and CTLA-4 resulted in increased anti-tumor activity.

DOSAGE

Recommended Dosage for Unresectable or Metastatic Melanoma: Single Agent: The recommended dose of Nivolumab as a single agent is either: 240 mg every 2 weeks or 480 mg every 4 weeks. Administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity. With Ipilimumab : The recommended dose of Nivolumab is 1 mg/kg administered as an intravenous infusion over 30 minutes, followed by ipilimumab 3 mg/kg administered as an intravenous infusion over 90 minutes on the same day, every 3 weeks for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier. After completing 4 doses of the combination, administer Nivolumab as a single agent, either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.Recommended Dosage for Adjuvant Treatment of Melanoma: The recommended dose of Nivolumab is either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease recurrence or unacceptable toxicity for up to 1 year.Recommended Dosage for NSCLC: The recommended dose of Nivolumab is either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.Recommended Dosage for RCC: The recommended dose of Nivolumab as a single agent is either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.Recommended Dosage for cHL: The recommended dose of Nivolumab is either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.Recommended Dosage for SCCHN: The recommended dose of Nivolumab is either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.Recommended Dosage for Urothelial Carcinoma: The recommended dose of Nivolumab is either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progressionor unacceptable toxicity.Recommended Dosage for CRC: The recommended dose of Nivolumab is 240 mg every 2 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.Recommended Dosage for HCC: The recommended dose of Nivolumab is either: 240 mg every 2 weeks or 480 mg every 4 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity.

SIDE EFFECTS

Most common adverse reactions (≥20%) in patients were:

Nivolumabas a single agent: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, and abdominal pain.
Nivolumab with ipilimumab for melanoma: fatigue, rash, diarrhea, nausea, pyrexia, vomiting, and dyspnea.
Nivolumab with ipilimumab for renal cell carcinoma: fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite.

PREGNANCY & LACTATION

Pregnancy: Based on its mechanism of action and data from animal studies, Nivolumab can cause fetal harm when administered to a pregnant woman. The effects of Nivolumab are likely to be greater during the second and third trimesters of pregnancy. There are no available human data informing the drug-associated risk. Advise pregnant women of the potential risk to a fetus.Lactation: It is not known whether Nivolumab is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Nivolumab, advise women to discontinue breastfeeding during treatment with Nivolumab.Contraception: Based on its mechanism of action, Nivolumab can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with Nivolumab and for at least 5 months following the last dose of Nivolumab.

PRECAUTIONS & WARNINGS

Immune-mediated pneumonitis: Withhold for moderate and permanently discontinue for severe or life-threatening pneumonitis.Immune-mediated colitis: Withhold Nivolumab when given as a single agent for moderate or severe and permanently discontinue for life-threatening colitis. Withhold Nivolumab when given with ipilimumab for moderate and permanently discontinue for severe or life-threatening colitis.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.Immune-mediated endocrinopathies: Withhold for moderate or severe and permanently discontinue for life-threatening hypophysitis. Withhold for moderate and permanently discontinue for severe or life-threatening adrenal insufficiency. Monitor for changes in thyroid function. Initiate thyroid hormone replacement as needed. Monitor for hyperglycemia. Withhold for severe and permanently discontinue for life-threatening hyperglycemia.Immune-mediated nephritis and renal dysfunction: Monitor for changes in renal function. Withhold for moderate or severe and permanently discontinue for life-threatening serum creatinine elevation.Immune-mediated skin adverse reactions: Withhold for severe and permanently discontinue for life-threatening rash.Immune-mediated encephalitis: Monitor for changes in neurologic function. Withhold forb new-onset moderate to severe neurological signs or symptoms and permanently discontinue for immune-mediated encephalitis.Infusion reactions: Discontinue Nivolumab for severe and life-threatening infusion reactions. Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions.Complications of allogeneic HSCT after Nivolumab: Monitor for hyperacute graft-versus-host-disease (GVHD), grade 3-4 acute GVHD, steroid requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions. Transplant-related mortality has occurred.Embryo-fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception.

THERAPEUTIC CLASS

Immunological Chemotherapy, Immunosuppressant

STORAGE CONDITIONS

Store vials under refrigeration at 2°C-8°C in original carton to protect from light. Do not freeze or shake. Keep out of the reach of children.