Drug information of nivolumab

nivolumab

Drug group: Antineoplastic Agents

It is used to treat cancer.

nivolumab

Mechanism of effect

The ligands PD-L1 and PD-L2 bind to the PD-1 receptor on T-cells, inhibiting the action of these cells. Tumor cells express PD-L1 and PD-L2. Nivolumab binds to PD-1, preventing PD-L1 and PD-L2 from inhibiting the action of T-cells, restoring a patient's tumor-specific T-cell response.

Pharmacodynamic

Nivolumab blocks PD-1 inhibitory signalling to T-cells. It has a long duration of action as it is administered every 2-4 weeks. Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion-related adverse effects, complications of allogenic hematopoietic stem cell transplants, embryo-fetal toxicity.

Pharmacokinetics

Absorption

Pharmacokinetic studies have suggested that nivolumab presents linear pharmacokinetics with a dose-proportional increase in peak concentration and AUC. The time to peak plasma concentration ranges between 1-4 hours. The absorption pharmacokinetic properties respective to the administration of a dose of 10 mg/kg are reported to be Cmax, Tmax and AUC of 242 µg/kg, 2.99 hours and 68100 µg*h/mL respectively.

Volume of distribution

The volume of distribution at steady state when a dose of 10 mg/kg of nivolumab is administered is reported to be 91.1 mL/kg. At doses ranging from 0.1 to 20 mg/kg the volume of distribution is reported to be 8L.
 
Protein binding

There is no information regarding the plasma protein binding of nivolumab

Metabolism
There have not been formal studies regarding the specific metabolism of nivolumab but as a human monoclonal antibody, it has been suggested to be degraded to small peptides and individual amino acids
 
Route of elimination

There have not been studies regarding the specific route of elimination of nivolumab.

 
Half-life

The serum half life of nivolumab is approximately 20 days1 with an elimination half life of 26.7 days


 


 

Drug indications

lung cancer , Hodgkin's Disease , liver cancer

Adjuvant Treatment of Melanoma

Unresectable or Metastatic Melanoma

Non-Small Cell Lung Cancer (NSCLC)

Metastatic Small Cell Lung Cancer (SCLC)

Advanced Renal Cell Carcinoma

Hodgkin Lymphoma

Recurrent of Metastatic Squamous Head & Neck Carcinoma (SCCHN)

Advanced or Metastatic Urothelial Carcinoma

Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer

Hepatocellular Carcinoma

Esophageal Squamous Cell Carcinoma

Dosage

Adjuvant Treatment of Melanoma
Patients with involvement of lymph nodes or metastatic disease who have undergone complete resection
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity for up to 1 year
Unresectable or Metastatic Melanoma
Indicated as a single agent or in combination with ipilimumab
Single agent
  • 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Combination with ipilimumab
  • Nivolumab 1 mg/kg IV q3Weeks PLUS  
  • Ipilimumab 3 mg/kg IV on the same day for maximum of 4 doses
  • After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Non-Small Cell Lung Cancer (NSCLC)
Monotherapy
  • Indicated for metastatic NSCLC with progression in patients on or after platinum-based chemotherapy
  • Patients with EGFR or ALK genomic tumor aberrations should have disease progression prior to initiation
  • 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Combination therapy with ipilimumab
  • Indicated in combination with ipilimumab for first-line treatment of metastatic NSCLC in adults whose tumors express PD-L1 (≥1%) with no EGFR or ALK genomic tumor aberrations
  • Nivolumab 3 mg/kg IV q2Weeks, PLUS  
  • Ipilimumab 1 mg/kg IV q6Weeks
  • Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
Combination with ipilimumab and platinum chemotherapy
  • Indicated in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy for first-line treatment of metastatic or recurrent NSCLC in adults with no EGFR or ALK genomic tumor aberrations
  • Nivolumab 360 mg/kg IV q3Weeks, PLUS  
  • Ipilimumab 1 mg/kg IV q6Weeks, PLUS
  • Histology-based platinum doublet chemotherapy q3Weeks for 2 cycles
  • Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
Metastatic Small Cell Lung Cancer (SCLC)
Patients with progression after platinum-based chemotherapy and at least 1 other line of therapy
240 mg IV q2Weeks
Continue until disease progression or unacceptable toxicity
Advanced Renal Cell Carcinoma
Single agent
  • Patients who have received prior anti-angiogenic therapy
  • 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Combination with ipilimumab
  • Indicated for patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma
  • Nivolumab 3 mg/kg IV q3Weeks PLUS  
  • Ipilimumab 1 mg/kg IV on the same day for 4 doses
  • After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
  • Also see ipilimumab drug monograph for dose
Hodgkin Lymphoma
Indicated for classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin, or ≥3 lines of systemic therapy (eg, autologous HSCT)
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity
Recurrent of Metastatic Squamous Head & Neck Carcinoma (SCCHN)
Patients with disease progression on or after a platinum-based therapy
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity
Advanced or Metastatic Urothelial Carcinoma
Patients who have disease progression during or following platinum-containing chemotherapy
Patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity
Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer
Indicated as a single agent or in combination with ipilimumab, is indicated for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) which progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
Single agent
  • 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Combination with ipilimumab
  • Nivolumab 3 mg/kg IV q3Weeks PLUS  
  • Ipilimumab 1 mg/kg IV on the same day for 4 doses
  • After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Hepatocellular Carcinoma
Indicated as a single agent or in combination with ipilimumab for hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib
Single agent
  • 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Combination with ipilimumab
  • Nivolumab 1 mg/kg IV q3Weeks PLUS  
  • Ipilimumab 3 mg/kg IV on the same day for 4 doses
  • After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
Esophageal Squamous Cell Carcinoma
Indicated for unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) in patients previously treated with fluoropyrimidine- and platinum-based chemotherapy
240 mg IV q2Weeks or 480 mg IV q4Weeks
Continue until disease progression or unacceptable toxicity

Drug contraindications

none

Side effects

Pain , edema , pneumonia

>10% (All grades)

Melanoma

  • Increased AST (28%)
  • Hyponatremia (25%)
  • Increased alkaline phosphatase (22%)
  • Rash (21%)
  • Pruritus (19%)
  • Cough (17%)
  • Increased ALT (16%)
  • Hyperkalemia (15%)
  • URTI (11%)

NSCLC

  • Fatigue (50%)
  • Lymphopenia (47%)
  • Dyspnea, hyponatremia (38%)
  • Musculoskeletal pain (36%)
  • Cough (32%)
  • Nausea (29%)
  • Increases creatinine (22%)
  • Hypercalcemia, hypokalemia, hypomagnesemia (20%)
  • Vomiting, asthenia (19%)
  • Hypocalcemia, hyperkalemia, diarrhea (18%)
  • Edema, pyrexia (17%)
  • Abdominal pain, rash, increased AST (16%)
  • Increased alkaline phosphatase, thrombocytopenia (14%)
  • Chest pain, arthralgia, decreased appetite and weight (13%)
  • Increased ALT (12%)

1-10% (all grades)

Melanoma

  • Peripheral edema (10%)

NSCLC

  • Pneumonia (10%)
  • Pain (10%)

1-10% (grades 3-4)

Melanoma

  • Hyponatremia (5%)
  • Increased AST (2.4%)
  • Increased alkaline phosphatase (2.4%)
  • Hyperkalemia (2%)
  • Increased ALT (1.6%)

NSCLC

  • Dyspnea (9%)
  • Fatigue (7%)
  • Musculoskeletal pain (6%)
  • Pneumonia (5%)
  • Decreased appetite (2.6%)
  • Pain (2.6%)
  • Nausea (1.7%)
  • Abdominal pain (1.7%)
  • Asthenia (1.7%)
  • Edema (1.7%)
  • Cough (1.7%)

1-10% (other clinically important adverse effects)

Melanoma

  • Cardiac disorders: Ventricular arrhythmia
  • Eye disorders: Iridocyclitis
  • General disorders and administration site conditions: Infusion-related reactions
  • Immune-mediated disorders: Severe pneumonitis or interstitial lung disease, including fatal cases; colitis; hepatitis; nephritis; thyroid disorders; other immune disorders (pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal insufficiency, facial and abducens nerve paresis, hypophysitis, polymyalgia rheumatica, diabetic ketoacidosis, hypopituitarism, Guillain-Barré syndrome, myasthenic syndrome)
  • Investigations: Increased amylase, increased lipase
  • Nervous system disorders: Dizziness, peripheral and sensory neuropathy
  • Skin and subcutaneous tissue disorders: Exfoliative dermatitis, erythema multiforme, vitiligo, psoriasis

NSCLC

  • General disorders and administration site conditions: Stomatitis
  • Nervous system disorders: Peripheral neuropathy
  • Infections and infestations: Bronchitis, upper respiratory tract infection

Interactions

Deferasirox , Lomustine , Floxuridine , Ustekinumab , Carmustine , Temsirolimus , Ifosfamide , Procarbazine , Thalidomide , Dexamethasone , Palifermin , Selinexor , Siltuximab , sirukumab , alirocumab
dexamethasone
ifosfamide
lomustine
mechlorethamine
melphalan
palifermin
procarbazine
selinexor
thalidomide

Alerts

Immune-mediated colitis reported; withhold for moderate or severe and permanently discontinue for life-threatening colitis
Immune-mediated hepatitis observed in clinical trials; monitor for changes in liver function; withhold for moderate and permanently discontinue for severe or life-threatening transaminase or total bilirubin elevation
Immune-mediated nephritis and renal dysfunction may occur; monitor for changes in renal function; withhold for moderate and permanently discontinue for severe or life-threatening serum creatinine elevation; withhold therapy for moderate (Grade 2) or severe (Grade 3) increased serum creatinine; permanently discontinue therapy for life-threatening (Grade 4) increased serum creatinine
Immune-mediated encephalitis can occur; withhold therapy in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out infectious or other causes of moderate to severe neurologic deterioration; evaluation may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture; if other etiologies ruled out, administer corticosteroids at a dose of 1 - 2 mg/kg/day prednisone equivalents for patients with immune-mediated encephalitis, followed by corticosteroid taper; permanently discontinue therapy for immune-mediated encephalitis
Other clinically significant and potentially fatal immune-mediated adverse reactions (eg, myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis) can occur after therapy discontinuation
Severe infusion reactions reported (rare, <1%); discontinue if severe or life-threatening; interrupt or slow rate of infusion in patients with mild or moderate infusion reactions

Pregnancy level

Based on its mechanism of action and data from animal studies, fetal harm may occur when administered to a pregnant woman
There are no available human data informing the drug-associated risk

Breast feeding warning

Unknown if distributed in human breast milk; advise women to discontinue breastfeeding during treatment

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