cladribine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
ribofuranyl-derivatives of the "pyrazofurin" type 667 4291-63-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • mavenclad
  • litak
  • cladribine
  • cladarabine
  • leustatin
An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia.
  • Molecular weight: 285.69
  • Formula: C10H12ClN5O3
  • CLOGP: -0.91
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 3
  • TPSA: 119.31
  • ALOGS: -1.65
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.34 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 18 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.32 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 45 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 7.70 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 14 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.79 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 16 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Feb. 26, 1993 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Lymphopenia 263.11 27.38 76 2772 16767 53329451
Lymphocyte count decreased 213.13 27.38 73 2775 27979 53318239
Multiple sclerosis relapse 169.48 27.38 70 2778 44783 53301435
Leukopenia 99.98 27.38 57 2791 73406 53272812
Neutropenia 78.37 27.38 66 2782 159119 53187099
Drug reaction with eosinophilia and systemic symptoms 57.12 27.38 30 2818 32770 53313448
Febrile neutropenia 56.75 27.38 46 2802 104890 53241328
Thrombocytopenia 53.22 27.38 50 2798 138677 53207541
Rash maculo-papular 48.38 27.38 26 2822 29723 53316495
Acute myeloid leukaemia recurrent 48.12 27.38 12 2836 1501 53344717
Multiple sclerosis 47.74 27.38 25 2823 27128 53319090
Pancytopenia 47.33 27.38 39 2809 90889 53255329
Abdominal wall wound 46.07 27.38 7 2841 60 53346158
Myeloblast percentage decreased 40.69 27.38 6 2842 41 53346177
COVID-19 40.59 27.38 25 2823 36863 53309355
White blood cell count decreased 40.46 27.38 41 2807 124434 53221784
Intercepted product prescribing error 38.78 27.38 7 2841 183 53346035
Alanine aminotransferase increased 35.88 27.38 34 2814 95061 53251157
Refractory cytopenia with multilineage dysplasia 33.73 27.38 6 2842 144 53346074
Gamma-glutamyltransferase increased 32.55 27.38 21 2827 33534 53312684
Optic neuritis 29.49 27.38 12 2836 7323 53338895

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myelodysplastic syndrome 100.54 29.48 46 3199 19992 32490289
Pancytopenia 92.93 29.48 75 3170 91160 32419121
Multiple sclerosis relapse 71.75 29.48 31 3214 11750 32498531
Febrile neutropenia 66.30 29.48 70 3175 119496 32390785
Rash maculo-papular 64.14 29.48 38 3207 27984 32482297
Lymphopenia 62.61 29.48 30 3215 14426 32495855
Neutropenia 56.39 29.48 70 3175 142105 32368176
Acute generalised exanthematous pustulosis 48.94 29.48 20 3225 6593 32503688
Hairy cell leukaemia 46.53 29.48 8 3237 80 32510201
Lymphocyte count decreased 44.06 29.48 27 3218 21092 32489189
Toxic skin eruption 41.05 29.48 21 3224 11593 32498688
Face oedema 40.78 29.48 21 3224 11754 32498527
Leukaemia recurrent 39.73 29.48 12 3233 1627 32508654
Clostridium bacteraemia 38.48 29.48 7 3238 99 32510182
Febrile bone marrow aplasia 38.05 29.48 18 3227 8397 32501884
Thrombocytopenia 34.93 29.48 57 3188 148242 32362039
Acute erythroid leukaemia 34.90 29.48 7 3238 170 32510111
Herpes zoster 31.55 29.48 26 3219 32315 32477966
Generalised oedema 31.36 29.48 18 3227 12465 32497816
Systemic mastocytosis 30.44 29.48 6 3239 133 32510148

Pharmacologic Action:

SourceCodeDescription
ATC L01BB04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Purine analogues
ATC L04AA40 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Selective immunosuppressants
FDA EPC N0000175712 Purine Antimetabolite
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:35705 immunosuppressant
MeSH PA D000970 Antineoplastic Agents
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hairy cell leukemia indication 118613001
Relapsing remitting multiple sclerosis indication 426373005 DOID:2378
Langerhans cell histiocytosis off-label use 65399007 DOID:2571
Waldenström macroglobulinemia off-label use 190818004 DOID:0050747
Hyperuricemia contraindication 35885006 DOID:1920
Kidney disease contraindication 90708001 DOID:557
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Peripheral nerve disease contraindication 302226006
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001
Uric Acid Nephropathy Gout contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.14 acidic
pKa2 13.72 acidic
pKa3 3.11 Basic
pKa4 2.3 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL 7888328 April 11, 2024 TREATMENT OF MS WITH A TABLET WITH AN ADMIXTURE OF (A) AN AMORPHOUS INCLUSION COMPLEX OF CLADRIBINE AND HYDROXYPROPYL-B-CYCLODEXTRIN AND (B) AMORPHOUS FREE CLADRIBINE AND CYCLODEXTRIN AS A NON-INCLUSION COMPLEX, CLADRIBINE/CYCLODEXTRIN 1:10-1:16 W/W
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL 8785415 April 11, 2024 TREATMENT OF MS WITH AN ADMIXTURE OF (A) AN AMORPHOUS INCLUSION COMPLEX OF CLADRIBINE (2CDA) AND CYCLODEXTRIN AND (B) AMORPHOUS FREE 2CDA AND CYCLODEXTRIN AS A NON-INCLUSION COMPLEX, FORMULATED AS A SOLID ORAL FORM, W/O SIGN. AMOUNTS OF CRYST. 2CDA
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL 8377903 May 31, 2026 TREATING RRMS OR SPMS WITH ORAL CLADRIBINE: (I) 2-4 MONTHS INDUCTION WITH 1.7 MG/KG - 3.5 MG/KG CLADRIBINE; (II) CLADRIBINE-FREE PERIOD OF ABOUT 8-10 MONTHS; (III) 2-4 MONTHS MAINTENANCE WITH ABOUT 1.7 MG/KG CLADRIBINE; (IV) CLADRIBINE-FREE PERIOD
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL 7713947 Oct. 16, 2026 TREATING MS WITH ORAL CLADRIBINE ACC. TO THE STEPS (I) INDUCTION PERIOD WITH ABOUT 1.7 MG/KG-3.5 MG/KG CLADRIBINE; (II) CLADRIBINE-FREE PERIOD OF ABOUT 8-10 MONTHS; (III) MAINTENANCE PERIOD WITH ABOUT 1.7 MG/KG CLADRIBINE; (IV) CLADRIBINE-FREE PERIOD

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL March 29, 2022 NEW PRODUCT

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Deoxycytidine kinase Kinase WOMBAT-PK
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme IC50 5.44 DRUG MATRIX
Adenosine receptor A1 GPCR Ki 5.14 CHEMBL
Adenosine receptor A2a GPCR Ki 4.69 CHEMBL

External reference:

IDSource
4020629 VUID
N0000148293 NUI
D01370 KEGG_DRUG
C0092801 UMLSCUI
CHEBI:567361 CHEBI
CL9 PDB_CHEM_ID
CHEMBL1619 ChEMBL_ID
DB00242 DRUGBANK_ID
D017338 MESH_DESCRIPTOR_UI
20279 PUBCHEM_CID
4799 IUPHAR_LIGAND_ID
6997 INN_ID
47M74X9YT5 UNII
2122636 RXNORM
1760 MMSL
262155 MMSL
31821 MMSL
4461 MMSL
d03001 MMSL
004145 NDDF
108800000 SNOMEDCT_US
386916009 SNOMEDCT_US
4020629 VANDF

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 0143-9871 INJECTION 1 mg INTRAVENOUS ANDA 23 sections
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 42658-010 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 26 sections
Mavenclad HUMAN PRESCRIPTION DRUG LABEL 1 44087-4000 TABLET 10 mg ORAL NDA 32 sections
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 63323-140 INJECTION 1 mg INTRAVENOUS ANDA 15 sections
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 67457-450 INJECTION 1 mg INTRAVENOUS ANDA 23 sections