cladribine 🐶 Veterinary Use | 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: -0.10
  • 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 329.43 25.10 91 2993 16683 56272300
Lymphocyte count decreased 255.07 25.10 84 3000 27855 56261128
Multiple sclerosis relapse 226.85 25.10 87 2997 44816 56244167
Leukopenia 89.76 25.10 53 3031 70887 56218096
Multiple sclerosis 79.58 25.10 36 3048 27766 56261217
Neutropenia 67.16 25.10 61 3023 158106 56130877
COVID-19 59.94 25.10 42 3042 75016 56213967
Febrile neutropenia 59.66 25.10 48 3036 105497 56183486
Drug reaction with eosinophilia and systemic symptoms 55.73 25.10 29 3055 30275 56258708
Acute myeloid leukaemia recurrent 47.69 25.10 12 3072 1516 56287467
Alanine aminotransferase increased 47.47 25.10 40 3044 93622 56195361
Rash maculo-papular 45.65 25.10 25 3059 28882 56260101
Abdominal wall wound 44.73 25.10 7 3077 72 56288911
Thrombocytopenia 41.75 25.10 44 3040 136180 56152803
Pancytopenia 41.11 25.10 36 3048 88679 56200304
Myeloblast percentage decreased 40.53 25.10 6 3078 41 56288942
Gamma-glutamyltransferase increased 38.70 25.10 23 3061 30982 56258001
Intercepted product prescribing error 38.67 25.10 7 3077 181 56288802
White blood cell count decreased 37.36 25.10 40 3044 125950 56163033
Refractory cytopenia with multilineage dysplasia 33.65 25.10 6 3078 142 56288841
Aspartate aminotransferase increased 31.38 25.10 30 3054 82572 56206411
Optic neuritis 28.46 25.10 12 3072 7792 56281191

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 95.07 29.47 43 2955 19208 31675138
Multiple sclerosis relapse 86.20 29.47 35 2963 12012 31682334
Pancytopenia 84.22 29.47 68 2930 87248 31607098
Febrile neutropenia 75.79 29.47 74 2924 121775 31572571
Rash maculo-papular 66.35 29.47 37 2961 25682 31668664
Lymphopenia 52.26 29.47 26 2972 14303 31680043
Acute generalised exanthematous pustulosis 51.75 29.47 20 2978 6020 31688326
Neutropenia 50.38 29.47 64 2934 140300 31554046
Face oedema 43.92 29.47 21 2977 10595 31683751
Leukaemia recurrent 40.64 29.47 12 2986 1590 31692756
Febrile bone marrow aplasia 40.19 29.47 18 2980 7828 31686518
Clostridium bacteraemia 39.13 29.47 7 2991 95 31694251
Lymphocyte count decreased 35.75 29.47 23 2975 20626 31673720
Toxic skin eruption 35.72 29.47 18 2980 10162 31684184
Acute erythroid leukaemia 35.24 29.47 7 2991 171 31694175
Generalised oedema 33.65 29.47 18 2980 11483 31682863
Systemic mastocytosis 30.51 29.47 6 2992 139 31694207

FDA Adverse Event Reporting System (Geriatric)

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 249.18 22.82 89 5237 27270 70895848
Multiple sclerosis relapse 203.42 22.82 87 5239 42930 70880188
Lymphocyte count decreased 151.25 22.82 71 5255 43468 70879650
Febrile neutropenia 137.02 22.82 117 5209 204201 70718917
Neutropenia 108.58 22.82 114 5212 257042 70666076
Rash maculo-papular 106.96 22.82 59 5267 50486 70872632
Pancytopenia 98.03 22.82 85 5241 151022 70772096
Myelodysplastic syndrome 86.51 22.82 43 5283 29742 70893376
Leukopenia 85.85 22.82 68 5258 106492 70816626
Thrombocytopenia 71.90 22.82 89 5237 239021 70684097
Clostridium bacteraemia 56.81 22.82 11 5315 298 70922820
Acute myeloid leukaemia recurrent 52.18 22.82 16 5310 3038 70920080
Multiple sclerosis 46.64 22.82 27 5299 25258 70897860
Systemic mastocytosis 43.82 22.82 9 5317 331 70922787
Abdominal wall wound 41.61 22.82 7 5319 83 70923035
Leukaemia recurrent 40.96 22.82 13 5313 2762 70920356
Drug reaction with eosinophilia and systemic symptoms 40.30 22.82 34 5292 57979 70865139
Myeloblast percentage decreased 38.64 22.82 6 5320 41 70923077
Acute generalised exanthematous pustulosis 38.20 22.82 20 5306 15377 70907741
Acute erythroid leukaemia 33.68 22.82 7 5319 273 70922845
Product use in unapproved indication 31.38 22.82 56 5270 207422 70715696
Toxic skin eruption 30.61 22.82 19 5307 20143 70902975
Dermatitis allergic 28.85 22.82 17 5309 16414 70906704
COVID-19 27.96 22.82 37 5289 105720 70817398
Stomatococcal infection 27.72 22.82 6 5320 285 70922833
Alanine aminotransferase increased 26.50 22.82 43 5283 147437 70775681
Peptic ulcer haemorrhage 25.71 22.82 7 5319 873 70922245
Leukaemia cutis 24.39 22.82 5 5321 182 70922936
Herpes zoster 24.36 22.82 31 5295 85204 70837914
Acute myeloid leukaemia 23.28 22.82 19 5307 30921 70892197

FDA Adverse Event Reporting System (Pediatric)

None

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 antineoplastic agents
CHEBI has role CHEBI:35705 immunosuppressive agents
MeSH PA D000970 Antineoplastic Agents
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL 10849919 Nov. 23, 2038 TREATING NON-EARLY SPMS BY ADMINISTERING ORAL CLADRIBINE AT A FIXED DOSE PER PATIENT, PER BODY WEIGHT AND PER TREATMENT YEAR, WHICH FIXED DOSE IS 1.75 +/- 0.2 MG/KG, TO BE ADMINISTERED WITHIN MONTHS 1 AND 2 IN EACH OF 2 ADJACENT TREATMENT YEARS

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
2122636 RXNORM
4020629 VANDF
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
1760 MMSL
262155 MMSL
31821 MMSL
4461 MMSL
d03001 MMSL
004145 NDDF
108800000 SNOMEDCT_US
386916009 SNOMEDCT_US

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 34 sections
Mavenclad HUMAN PRESCRIPTION DRUG LABEL 1 44087-4000 TABLET 10 mg ORAL NDA 34 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
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 67457-450 INJECTION 1 mg INTRAVENOUS ANDA 23 sections