NAV

Nivolumab

Identification

Summary

Nivolumabis a PD-1 blocking antibody used to treat melanoma, non small-cell lung cancer, renal cell cancer, head and neck cancer, and Hodgkin lymphoma.

Brand Names
Opdivo, Opdualag
Generic Name
Nivolumab
DrugBank Accession Number
DB09035
Background

Nivolumab is a fully human IgG4 antibody targeting the immune checkpoint programmed death receptor-1 (PD-1).6这个抗体是完全在老鼠身上and grafted onto human kappa and IgG4 Fc region with the mutationS228Pfor additional stability and reduced variability.5It was developed by Bristol Myers Squibb.6

Nivolumab was granted FDA approval on 22 December 2014.6

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
C6362H9862N1712O1995S42
Protein Average Weight
143597.3811 Da
Sequences
> QVQLVESGGGVVQPGRSLRLDCKASGIT重链序列FSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY ADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPS VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKP KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV MHEALHNHYTQKSLSLSLGK
>Light Chain Sequence EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA RFSGSGSGTDFTLTISSLEPEDFAVYYCQQSSNWPRTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Nivolumab
External IDs
  • BMS 936558
  • BMS-936558
  • GTPL7335
  • MDX 1106
  • MDX-1106
  • ONO 4538
  • ONO-4538

Pharmacology

Indication

Nivolumab is indicated to treat unresectable or metastatic melanoma, melanoma as adjuvant treatment, resectable or metastatic non-small cell lung cancer, small cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer, hepatocellular carcinoma, and esophageal cancer.6,9

Nivolumab is also approved for the treatment of HER2-negative advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma when used in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen.8

In combination withrelatlimab, nivolumab is indicated for the treatment of patients ≥12 years old with unresectable or metastatic melanoma.[L41265]

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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Nivolumab blocks PD-1 inhibitory signalling to T-cells.6It has a long duration of action as it is administered every 2-4 weeks.6Patients 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.6

Mechanism of action

The ligands PD-L1 and PD-L2 bind to the PD-1 receptor on T-cells, inhibiting the action of these cells.6Tumor cells express PD-L1 and PD-L2.6Nivolumab 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.1

Target Actions Organism
AProgrammed cell death protein 1
inhibitor
antibody
 Humans
UProgrammed cell death 1 ligand 1
inhibitor
antibody
 Humans
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.1The 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.3

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.3At doses ranging from 0.1 to 20 mg/kg the volume of distribution is reported to be 8L.4

Protein binding

There is no information regarding the plasma protein binding of nivolumab.7

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.7

Route of elimination

There have not been studies regarding the specific route of elimination of nivolumab.7

Half-life

serum half life of nivolumab is approximately 20 days1with an elimination half life of 26.7 days.4

Clearance

The estimated clearance rate of nivolumab is 9.4 mL/h.2The clearance rate seems to be increased according to body weight.4

Adverse Effects
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Toxicity

Data regarding overdoses of nivolumab are not readily available.6Common adverse effects include Rash, pruritus, cough, upper respiratory tract infection, and peripheral edema.6

Pathways
Not Available
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction
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interactions in your software
Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Nivolumab.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Nivolumab.
Aducanumab The risk or severity of adverse effects can be increased when Nivolumab is combined with Aducanumab.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Nivolumab.
Alirocumab The risk or severity of adverse effects can be increased when Nivolumab is combined with Alirocumab.
Ambroxol The risk or severity of methemoglobinemia can be increased when Nivolumab is combined with Ambroxol.
Amivantamab The risk or severity of adverse effects can be increased when Nivolumab is combined with Amivantamab.
Anifrolumab The risk or severity of adverse effects can be increased when Nivolumab is combined with Anifrolumab.
Ansuvimab The risk or severity of adverse effects can be increased when Nivolumab is combined with Ansuvimab.
Anthrax immune globulin human The risk or severity of adverse effects can be increased when Nivolumab is combined with Anthrax immune globulin human.
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Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
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dosage, form, labeller, route of administration, and marketing period.
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Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Nivolumab Bms Injection, solution, concentrate 10 mg/ml Intravenous Bristol Myers Squibb Pharma Eeig 2021-01-12 2016-01-14 EU flag
Nivolumab Bms Injection, solution, concentrate 10 mg/ml Intravenous Bristol Myers Squibb Pharma Eeig 2021-01-12 2016-01-14 EU flag
Opdivo Injection 10 mg/1mL Intravenous E.R. Squibb & Sons, L.L.C. 2014-12-22 Not applicable US flag
Opdivo Injection 10 mg/ml Intravenous Bristol Myers Squibb Pharma Eeig 2020-12-15 Not applicable EU flag
Opdivo Solution 10 mg / mL Intravenous Bristol Myers Squibb 2015-10-23 Not applicable Canada flag
Opdivo Injection 10 mg/1mL Intravenous E.R. Squibb & Sons, L.L.C. 2017-12-08 Not applicable US flag
Opdivo Injection 10 mg/ml Intravenous Bristol Myers Squibb Pharma Eeig 2020-12-15 Not applicable EU flag
Opdivo Solution 10 mg / mL Intravenous Bristol Myers Squibb 2015-10-23 Not applicable Canada flag
Opdivo Injection 10 mg/1mL Intravenous E.R. Squibb & Sons, L.L.C. 2014-12-22 Not applicable US flag
Opdivo Injection, solution, concentrate 10 mg/ml Intravenous Bristol Myers Squibb Pharma Eeig 2022-05-04 Not applicable EU flag
Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image
Opdualag Nivolumab(12 mg/1mL)+Relatlimab(4 mg/1mL) Injection Intravenous E.R. Squibb & Sons, L.L.C. 2022-03-18 Not applicable US flag
Opdualag Nivolumab(12 mg/ml)+Relatlimab(4 mg/ml) Injection, solution, concentrate Intravenous Bristol Myers Squibb Pharma Eeig 2022-12-02 Not applicable EU flag

Categories

ATC Codes
L01FF01 — Nivolumab L01XY03 — Nivolumab and relatlimab
Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
羧酸和衍生品
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
31YO63LBSN
CAS number
946414-94-4

References

General References
  1. Brahmer JR, Hammers H, Lipson EJ: Nivolumab: targeting PD-1 to bolster antitumor immunity. Future Oncol. 2015;11(9):1307-26. doi: 10.2217/fon.15.52. Epub 2015 Mar 23. [Article]
  2. Bajaj G, Wang X, Agrawal S, Gupta M, Roy A, Feng Y: Model-Based Population Pharmacokinetic Analysis of Nivolumab in Patients With Solid Tumors. CPT Pharmacometrics Syst Pharmacol. 2017 Jan;6(1):58-66. doi: 10.1002/psp4.12143. Epub 2016 Dec 26. [Article]
  3. Lee KW, Lee DH, Kang JH, Park JO, Kim SH, Hong YS, Kim ST, Oh DY, Bang YJ: Phase I Pharmacokinetic Study of Nivolumab in Korean Patients with Advanced Solid Tumors. Oncologist. 2018 Feb;23(2):155-e17. doi: 10.1634/theoncologist.2017-0528. Epub 2017 Nov 20. [Article]
  4. Solimando DA Jr, Waddell JA: Nivolumab and Olaparib. Hosp Pharm. 2015 May;50(5):356-66. doi: 10.1310/hpj5005-356. [Article]
  5. Mashima E, Inoue A, Sakuragi Y, Yamaguchi T, Sasaki N, Hara Y, Omoto D, Ohmori S, Haruyama S, Sawada Y, Yoshioka M, Nishio D, Nakamura M: Nivolumab in the treatment of malignant melanoma: review of the literature. Onco Targets Ther. 2015 Aug 6;8:2045-51. doi: 10.2147/OTT.S62102. eCollection 2015. [Article]
  6. FDA Approved Drug Products: Opdivo (nivolumab) for intravenous injection [Link]
  7. BC Cancer Agency: Opdivo Monograph [Link]
  8. Health Canada Product Monograph: Opdivo (nivolumab) for intravenous injection [Link]
  9. Health Canada Approved Drug Products: OPDIVO (nivolumab) injection for Intravenous Infusion (August 2022) [Link]
KEGG Drug
D10316
PubChem Substance
347910393
RxNav
1597876
ChEMBL
CHEMBL2108738
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nivolumab
FDA label
Download (2.51 MB)
MSDS
Download (1.26 MB)

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
4 Completed Other Renal Cell Carcinoma (RCC) 1
4 Completed Treatment Liver Cancer 1
4 Completed Treatment Lung Cancer 1
4 Completed Treatment Non-Small Cell Lung Cancer (NSCLC)/Non-Small Cell Lung Carcinoma/Renal Cancer/Renal Neoplasms 1
4 Completed Treatment Renal Cell Carcinoma (RCC) 1
4 Not Yet Recruiting Treatment Metastatic Non-Small Cell Lung Cancer 1
4 Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1
4 Recruiting Treatment Renal Neoplasms 1
4 Unknown Status Diagnostic Lung Cancer/Melanoma/Non Small Cell 1
4 Unknown Status Other Metastatic Melanoma 1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Form Route Strength
Injection, solution, concentrate Intravenous 10 MG/ML
Injection Intravenous 10 mg/1mL
Injection Intravenous 10 mg/ml
Injection, solution, concentrate Intravenous; Parenteral 10 MG/ML
Solution Intravenous 10 mg / mL
Solution Intravenous 100 mg/10ml
Injection, solution Intravenous
Solution Intravenous 40 mg/4ml
Solution Intravenous drip 10 mg/mL
Solution Intravenous 40 mg
Solution Intravenous 100 mg
Injection Intravenous
Injection, solution, concentrate Intravenous
Injection, solution, concentrate Intravenous 10 mg/1ml
Prices
Not Available
Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region
US2013173223 No 2013-05-13 2033-05-13 US flag

Properties

State
Liquid
Experimental Properties
Property Value Source
melting point (°C) 80-90 ºC (based on IgG properties) McConnell A., et al. (2014). MAbs. Sep-Oct; 6 (5); 1274-1282
boiling point (°C) Fab and Fc domains denaturates at 60 and 70 ºC respectively Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404
water solubility 50 mg/ml Human IgG purified. Product Information
isoelectric point 6.1-8.5 Agrisera Information about IgG antibodies.

Targets

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Details 1.Programmed cell death protein 1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Antibody
General Function
Signal transducer activity
Specific Function
Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. ...
Gene Name
PDCD1
Uniprot ID
Q15116
Uniprot Name
Programmed cell death protein 1
分子量
31646.635 Da
References
  1. Taneja SS: Re: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. J Urol. 2012 Dec;188(6):2149. [Article]
  2. Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]
Details 2.Programmed cell death 1 ligand 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Antibody
General Function
Not Available
Specific Function
Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell ...
Gene Name
CD274
Uniprot ID
Q9NZQ7
Uniprot Name
Programmed cell death 1 ligand 1
分子量
33275.095 Da
References
  1. Kyriakidis I, Vasileiou E, Rossig C, Roilides E, Groll AH, Tragiannidis A: Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies. J Fungi (Basel). 2021 Mar 5;7(3). pii: jof7030186. doi: 10.3390/jof7030186. [Article]

Drug created at February 24, 2015 23:02 / Updated at December 01, 2022 11:26