Identification

Summary

Nivolumab is 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
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 This antibody was produced entirely in mice and grafted onto human kappa and IgG4 Fc region with the mutation S228P for additional stability and reduced variability.5 It 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
Db09035
Protein Chemical Formula
C6362H9862N1712O1995S42
Protein Average Weight
143597.3811 Da
Sequences
>Heavy Chain Sequence
QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY
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, adjuvant treatment of melanoma, 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, and hepatocellular carcinoma.6

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

Pharmacology
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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Nivolumab blocks PD-1 inhibitory signalling to T-cells.6 It has a long duration of action as it is administered every 2-4 weeks.6 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.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.6 Tumor cells express PD-L1 and PD-L2.6 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.1

TargetActionsOrganism
AProgrammed cell death protein 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.1 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.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.3 At 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

The serum half life of nivolumab is approximately 20 days1 with an elimination half life of 26.7 days.4

Clearance

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

Adverse Effects
Adverseeffects
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Toxicity

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

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Nivolumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Nivolumab.
AducanumabThe risk or severity of adverse effects can be increased when Nivolumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Nivolumab.
AlirocumabThe risk or severity of adverse effects can be increased when Nivolumab is combined with Alirocumab.
AmivantamabThe risk or severity of adverse effects can be increased when Nivolumab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Nivolumab is combined with Anifrolumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Nivolumab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Nivolumab is combined with Anthrax immune globulin human.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Nivolumab is combined with Antilymphocyte immunoglobulin (horse).
Interactions
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Food Interactions
No interactions found.

Products

Products2
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dosage, form, labeller, route of administration, and marketing period.
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Nivolumab BmsInjection, solution, concentrate10 mg/mlIntravenousBristol Myers Squibb Pharma Eeig2021-01-122016-01-14EU flag
Nivolumab BmsInjection, solution, concentrate10 mg/mlIntravenousBristol Myers Squibb Pharma Eeig2021-01-122016-01-14EU flag
OpdivoInjection10 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2014-12-22Not applicableUS flag
OpdivoInjection10 mg/mlIntravenousBristol Myers Squibb Pharma Eeig2020-12-15Not applicableEU flag
OpdivoInjection10 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2021-08-30Not applicableUS flag
OpdivoInjection10 mg/mlIntravenousBristol Myers Squibb Pharma Eeig2020-12-15Not applicableEU flag
OpdivoInjection10 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2014-12-22Not applicableUS flag
OpdivoSolution10 mg / mLIntravenousBristol Myers Squibb2015-10-23Not applicableCanada flag
OpdivoInjection10 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2017-12-08Not applicableUS flag
OpdivoInjection10 mg/mlIntravenousBristol Myers Squibb Pharma Eeig2020-12-15Not applicableEU flag

Categories

ATC Codes
L01XC17 — Nivolumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
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]
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 Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingOtherRenal Cell Adenocarcinoma1
4Active Not RecruitingTreatmentLung Cancers1
4Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
4CompletedTreatmentLiver Cancer1
4CompletedTreatmentNeoplasms, Kidney / Non-Small Cell Lung Carcinoma (NSCLC) / Renal Cancers / Renal Neoplasms1
4Not Yet RecruitingDiagnosticLung Cancers / Malignant Melanoma of Skin / Non Small Cell1
4Not Yet RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
4Not Yet RecruitingTreatmentRenal Cancers1
4Unknown StatusOtherMetastatic Melanoma1
3Active Not RecruitingTreatmentAdvanced Non Small Cell Lung Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous10 MG/ML
SolutionIntravenous drip10 mg/mL
InjectionIntravenous10 mg/ml
InjectionIntravenous10 mg/1mL
Injection, solution, concentrateIntravenous; Parenteral10 MG/ML
SolutionIntravenous10 mg / mL
SolutionIntravenous
Injection, solutionIntravenous
SolutionIntravenous40 mg
SolutionIntravenous100 mg
Injection, solution, concentrateIntravenous10 mg/1ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US2013173223No2013-05-132033-05-13US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
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 respectivelyArnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404
water solubility50 mg/mlHuman IgG purified. Product Information
isoelectric point6.1-8.5 Agrisera Information about IgG antibodies.

Targets

Drugtargets2
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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
Molecular Weight
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]

Drug created at February 24, 2015 23:02 / Updated at November 28, 2021 11:56