Obinutuzumab

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Obinutuzumab
Accession Number
DB08935
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Obinutuzumab is a humanized monoclonal antibody used as a combination treatment with chlorambucil to treat patients with untreated chronic lymphocytic leukemia. It was approved by the FDA in November 2013 and is marketed under the brand name Gazyva. There is a black box warning of fatal Hepatitis B Virus (HBV) reactivation and fatal Progressive Multifocal Leukoencephalopathy (PML).

Protein structure
Db08935
Protein chemical formula
C6512H10060N1712O2020S44
Protein average weight
146100.0 Da
Sequences
Not Available
Synonyms
  • Afutuzumab
External IDs
GA-101
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GazyvaSolution25 mgIntravenousHoffmann La Roche2014-11-28Not applicableCanada
GazyvaInjection, solution, concentrate1000 mg/40mLIntravenousGenentech, Inc.2013-11-01Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Categories
UNII
O43472U9X8
CAS number
949142-50-1

Pharmacology

Indication

Obinutuzumab is used as a combination treatment with chlorambucil to treat patients with untreated chronic lymphocytic leukemia.

Associated Conditions
Pharmacodynamics

Obinutuzumab is more potent than rituximab in depleting B-cells, antitumor activity, and tumor regression.

Mechanism of action

In contrast to rituximab, which is a classic type I CD20 antibody, obinutuzumab binds to type II CD20 antibodies. This allows obinutuzumab to have a much higher induction of antibody-dependant cytotoxicity and a higher direct cytotoxic effect than the classic CD20 antibodies.

TargetActionsOrganism
AB-lymphocyte antigen CD20
antibody
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
Absorption

Obinutuzumab is administered intravenously, so its absorption is 100%.

Volume of distribution

Obinutuzumab has a volume of distribution of about 3.8 L.

Protein binding

Obinutuzumab does not bind to plasma proteins.

Metabolism

Obinutuzumab is not metabolized by the liver.

Route of elimination

The route of elimination of obinutuzumab was not indicated (FDA label).

Half life

The half life of obinutuzumab is 28.4 days.

Clearance

The clearance of obinutuzumab is 0.09L/day.

Toxicity

The most serious toxicities observed with obinutuzumab are Hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy (PML). HBV reactivation can occur with all anti-CD20 antibodies and can result in hepatic failure, fulminant hepatitis, and death. PML occurs as a result of JC virus infection and can be fatal as well. Other common but less serious adverse reactions include infusion reactions (pre-treat with glucocorticoids, acetaminophen, and anti-histamine to prevent this), neutropenia, thrombocytopenia, and Tumor Lysis Syndrome (TLS) (pre-treat patients, especially with a high lymphocyte count and/or a high tumor burden, with anti-hyperuricemics and hydration). It is also recommended to NOT administer live virus vaccinations prior to or during obinutuzumab treatment.

Affected organisms
  • Humans and other mammals
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
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when (R)-warfarin is combined with Obinutuzumab.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when (S)-Warfarin is combined with Obinutuzumab.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Obinutuzumab.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when 4-hydroxycoumarin is combined with Obinutuzumab.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the orthostatic hypotensive activities of Obinutuzumab.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Obinutuzumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Obinutuzumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Obinutuzumab.
AbetimusThe risk or severity of adverse effects can be increased when Abetimus is combined with Obinutuzumab.
AbituzumabThe risk or severity of adverse effects can be increased when Obinutuzumab is combined with Abituzumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Echinacea: diminished therapeutic effect of immunosuppressants

References

Synthesis Reference

Robak T: GA-101, a third-generation, humanized and glyco-engineered anti-CD20 mAb for the treatment of B-cell lymphoid malignancies. Curr Opin Investig Drugs. 2009 Jun;10(6):588-96.

General References
Not Available
External Links
KEGG Drug
D09321
PubChem Substance
347910388
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Obinutuzumab
ATC Codes
L01XC15 — Obinutuzumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (484 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentB-Cell Malignancies1
1Active Not RecruitingTreatmentB-cell Lymphoid Malignancies1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Prolymphocytic / Small Lymphocytic Lymphoma (SLL)1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Peripheral T-Cell Lymphoma (PTCL)1
1Active Not RecruitingTreatmentFollicular Lymphoma (FL)1
1Active Not RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Non-Hodgkin's Lymphoma (NHL)1
1Active Not RecruitingTreatmentMalignant Lymphomas1
1Active Not RecruitingTreatmentMalignant Lymphomas / NHL - Non-Hodgkin's Lymphoma / Relapsed or Refractory Follicular Lymphoma1
1Active Not RecruitingTreatmentSolid Cancers1
1Active Not RecruitingTreatmentSolid Cancers / Tumors, Solid1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)2
1CompletedTreatmentChronic Renal Failure (CRF)1
1CompletedTreatmentLymphocytic Leukemia, Chronic, Diffuse Large B-cell Lymphoma, Follicular Lymphoma / Lymphocytic Leukemia, Chronic, Diffuse Large B-Cell Lymphoma, Non-Hodgkin's Lymphoma1
1CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)2
1CompletedTreatmentTumors, Solid1
1Not Yet RecruitingTreatmentPrimary Central Nervous System Lymphoma (PCNSL)1
1RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Lymphoma, B-Cell1
1RecruitingTreatmentAdvanced B-cell Malignancies / Part1: Advanced B-cell Malignancies / Part2: r/rCLL and r/rMCL / Part3: Untreated CLL1
1RecruitingTreatmentB-Cell / Chronic / Leukemias / Lymphocytic1
1RecruitingTreatmentBurkitt's Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Richter's Syndrome1
1RecruitingTreatmentColorectal Cancers1
1RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, B-Cell / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)5
1RecruitingTreatmentRelapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma1
1SuspendedTreatmentB-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma / Grade 1 Follicular Lymphoma / Grade 2 Follicular Lymphoma / Grade 3a Follicular Lymphoma / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Transformed Recurrent Non-Hodgkin Lymphoma1
1SuspendedTreatmentBreast Adenocarcinoma / Recurrent Breast Carcinoma / Recurrent Hodgkin Lymphoma / Recurrent Mycosis Fungoides / Recurrent Non-Hodgkin Lymphoma / Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Refractory Hodgkin Lymphoma / Refractory Nodal Marginal Zone Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory, advanced Mycosis fungoides / Refractory, primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Breast Cancer AJCC v6 and v71
1TerminatedTreatmentB-Cell Chronic Lymphocytic Leukemia / Chronic Lymphocytic Leukaemia (CLL)1
1TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
1WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)1
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leukemia (CLL) - Refractory1
1, 2Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma, Lymphoma Follicular / Diffuse Large B-Cell Lymphoma, Lymphoma, Follicular1
1, 2Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma, Lymphoma, Non Hodgkin, Lymphoma, Follicular / Malignant Lymphomas1
1, 2Active Not RecruitingTreatmentFollicular Lymphoma (FL)1
1, 2Active Not RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2Active Not RecruitingTreatmentFollicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II) / Follicular Lymphoma Patients (Phase IB)1
1, 2Active Not RecruitingTreatmentGrade 3a Follicular Lymphoma / Malignant Lymphomas / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Follicular Lymphoma / Refractory Small Lymphocytic Lymphoma1
1, 2Active Not RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
1, 2Active Not RecruitingTreatmentMalignant Lymphomas2
1, 2CompletedTreatmentDiffuse Large B-Cell Lymphoma, Lymphoma, Follicular / Follicular Lymphoma (FL) / Follicular Lymphoma, Diffuse Large B-Cell Lymphoma / Lymphoma, Follicular, Diffuse Large B-Cell Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2CompletedTreatmentLymphoma, B-Cell, Non-Hodgkin's Lymphoma / Non Hodgkin Lymphoma (NHL)1
1, 2CompletedTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
1, 2RecruitingTreatmentAnemias / B-Cell Prolymphocytic Leukemia / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Fevers / Grade 1 Follicular Lymphoma / Grade 2 Follicular Lymphoma / Grade 3a Follicular Lymphoma / Hairy Cell Leukemia (HCL) / Lymphadenopathy / Lymphocytosis / Lymphoplasmacytic Lymphoma / Mantle Cell Lymphoma (MCL) / Marginal Zone Lymphoma / Night Sweats / Obese experiencing rapid weight loss / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma / Richter's Syndrome / Splenomegaly / Thrombocytopenia / Tiredness1
1, 2RecruitingTreatmentFollicular Lymphoma (FL)1
1, 2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1, 2TerminatedTreatmentCD20+ Follicular Lymphoma1
1, 2TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentAnn Arbor Stage II Grade 1 Follicular Lymphoma / Ann Arbor Stage II Grade 2 Follicular Lymphoma / Ann Arbor Stage III Grade 1 Follicular Lymphoma / Ann Arbor Stage III Grade 2 Follicular Lymphoma / Ann Arbor Stage IV Grade 1 Follicular Lymphoma / Ann Arbor Stage IV Grade 2 Follicular Lymphoma / Bulky Disease / Fevers / Follicular Lymphoma (FL) / Grade 3a Follicular Lymphoma / Night Sweats / Obese experiencing rapid weight loss / Splenomegaly / Tiredness1
2Active Not RecruitingTreatmentChronic Lymphocytic Leucemia3
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
2Active Not RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Leukemias / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma1
2Active Not RecruitingTreatmentIndolent Non-Hodgkin's Lymphomas1
2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2Active Not RecruitingTreatmentNephritis, Lupus1
2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
2CompletedTreatmentChronic Lymphocytic Leucemia1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)4
2CompletedTreatmentIndolent Non-Hodgkin's Lymphomas1
2CompletedTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
2CompletedTreatmentLymphoma, B-Cell1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Not Yet RecruitingTreatmentCCND1 Positive / Mantle Cell Lymphoma (MCL) / T(11;14) Positive1
2Not Yet RecruitingTreatmentCLL Transformation1
2Not Yet RecruitingTreatmentFollicular Lymphoma (FL)1
2RecruitingTreatmentB-Cell Chronic Lymphocytic Leukemia / B-Cell Chronic Lymphocytic Leukemia in Relapse (Diagnosis)1
2RecruitingTreatmentBurkitt's Lymphoma / CD20+ Lymphoblastic Lymphoma / Follicular Lymphoma, Grade III / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Non-Hodgkin's Lymphoma (NHL) / Primary Mediastinal B-Cell Lymphoma1
2RecruitingTreatmentCCND1 Negative / Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL) / T(11;14) Negative1
2RecruitingTreatmentCD20 Positive / Central Nervous System B-Cell Non-Hodgkin Lymphoma / Central Nervous System Lymphoma1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Loss of Chromosome 11q / Loss of Chromosome 17p / Recurrent Small Lymphocytic Lymphoma / Recurrent Transformed Chronic Lymphocytic Leukemia / Refractory Small Lymphocytic Lymphoma / Refractory Transformed Chronic Lymphocytic Leukemia / Richter's Syndrome / Small Lymphocytic Lymphoma (SLL) / TP53 Gene Mutation / Untreated Chronic Lymphocytic Leukemia / Untreated Small Lymphocytic Lymphoma1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Immunoglobulin Heavy Chain Locus Variable Region Mutation / Leukemias / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Leukemia (SLL)1
2RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Marginal Zone Lymphoma / Mucosa Associated Lymphoid Tissue1
2RecruitingTreatmentGraft Versus Host Disease (GVHD)1
2RecruitingTreatmentHairy Cell Leukemia (HCL) / Leukemias1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2RecruitingTreatmentMantle Cell Lymphoma (MCL) / Non Hodgkin Lymphoma (NHL) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentMarginal Zone Lymphoma1
2RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)2
2RecruitingTreatmentRecurrent Mantle Cell Lymphoma / Refractory Mantle Cell Lymphoma1
2RecruitingTreatmentRelapsed/Refractory Follicular Non-Hodgkin Lymphoma1
2RecruitingTreatmentStage I Follicular Lymphoma Grade 1 / Stage II Follicular Lymphoma Grade 2 / Stage II Grade 1 Follicular Lymphoma / Stage II Grade 2 Follicular Lymphoma1
2RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
2SuspendedTreatmentCD20 Positive Diffuse Large B-cell Lymphoma / Elderly Unfit Patients1
2SuspendedTreatmentGrade 1 Follicular Lymphoma / Grade 2 Follicular Lymphoma / Grade 3a Follicular Lymphoma / Recurrent Follicular Lymphoma / Refractory Follicular Lymphoma1
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Richter's Transformation1
2TerminatedTreatmentLymphatic Diseases / Lymphoma, B-Cell1
2TerminatedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2TerminatedTreatmentRichter's Syndrome1
2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)1
2WithdrawnTreatmentPost Transplant Lymphoproliferative Disorder / PTLD1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)4
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Lymphoma, Small-Cell1
3Active Not RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
3Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)4
3CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3RecruitingTreatmentCCND1 Negative / CCND1/IGHG1 Fusion Negative / Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL) / T(11;14) Negative1
3RecruitingTreatmentCancer - Chronic Lymphocytic Leukemia / Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
3RecruitingTreatmentIndolent Non-Hodgkin's Lymphomas1
3TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL)1
3TerminatedTreatmentDiffuse Large B Cell Lymphoma CD20 Positive / Diffuse Large B Cell Lymphoma CD20+1
3TerminatedTreatmentLymphoma, B-Cell / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
4RecruitingTreatmentAdvanced Follicular Lymphoma1
Not AvailableActive Not RecruitingNot AvailableChronic Lymphocytic Leukaemia (CLL)1
Not AvailableCompletedNot AvailableChronic Lymphocytic Leukaemia (CLL)1
Not AvailableRecruitingNot AvailableChronic Lymphocytic Leukaemia (CLL) / Follicular Lymphoma (FL)1
Not AvailableRecruitingNot AvailableFollicular Lymphoma (FL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous1000 mg/40mL
SolutionIntravenous25 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
water solubilityWater solubleNot Available

Taxonomy

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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Mhc class ii protein complex binding
Specific Function
This protein may be involved in the regulation of B-cell activation and proliferation.
Gene Name
MS4A1
Uniprot ID
P11836
Uniprot Name
B-lymphocyte antigen CD20
Molecular Weight
33076.99 Da
References
  1. Robak T: GA-101, a third-generation, humanized and glyco-engineered anti-CD20 mAb for the treatment of B-cell lymphoid malignancies. Curr Opin Investig Drugs. 2009 Jun;10(6):588-96. [PubMed:19513948]

Drug created on January 05, 2014 13:42 / Updated on November 11, 2019 07:01