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) 1 Bocci G, Oprea TI, Benet LZ
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
S (Water solubility) 0.10 mg/mL Bocci G, Oprea TI, Benet LZ

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 368.30 26.02 102 3498 18225 63467197
Lymphocyte count decreased 305.52 26.02 99 3501 30158 63455264
Multiple sclerosis relapse 270.74 26.02 102 3498 48376 63437046
Leukopenia 88.87 26.02 55 3545 77235 63408187
Neutropenia 63.76 26.02 63 3537 174942 63310480
Febrile neutropenia 61.43 26.02 52 3548 118397 63367025
Alanine aminotransferase increased 56.78 26.02 47 3553 103723 63381699
Drug reaction with eosinophilia and systemic symptoms 51.78 26.02 29 3571 33807 63451615
COVID-19 49.30 26.02 45 3555 113058 63372364
Dysmenorrhoea 48.23 26.02 15 3585 3958 63481464
Abdominal wall wound 43.43 26.02 7 3593 85 63485337
Rash maculo-papular 42.54 26.02 25 3575 31871 63453551
Maternal exposure before pregnancy 42.29 26.02 16 3584 7587 63477835
White blood cell count decreased 41.44 26.02 45 3555 139059 63346363
Gamma-glutamyltransferase increased 41.04 26.02 25 3575 34006 63451416
Myeloblast percentage decreased 40.32 26.02 6 3594 41 63485381
Thrombocytopenia 40.06 26.02 46 3554 151111 63334311
Aspartate aminotransferase increased 39.47 26.02 36 3564 90241 63395181
Intercepted product prescribing error 37.65 26.02 7 3593 203 63485219
Pancytopenia 37.29 26.02 36 3564 96897 63388525
Acute myeloid leukaemia recurrent 36.99 26.02 10 3590 1613 63483809
Refractory cytopenia with multilineage dysplasia 33.45 26.02 6 3594 142 63485280
Haematotoxicity 32.35 26.02 14 3586 9362 63476060
Optic neuritis 30.43 26.02 13 3587 8422 63477000
Drug-induced liver injury 27.95 26.02 21 3579 40201 63445221
Gastrointestinal protozoal infection 27.63 26.02 4 3596 22 63485400

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 101.51 30.40 45 3263 19163 34934460
Multiple sclerosis relapse 93.42 30.40 38 3270 13095 34940528
Pancytopenia 87.29 30.40 72 3236 95085 34858538
Febrile neutropenia 84.89 30.40 83 3225 136766 34816857
Rash maculo-papular 65.47 30.40 38 3270 28413 34925210
Lymphopenia 54.76 30.40 28 3280 16307 34937316
Acute generalised exanthematous pustulosis 49.50 30.40 20 3288 6756 34946867
Neutropenia 47.75 30.40 66 3242 156712 34796911
Face oedema 42.28 30.40 21 3287 11495 34942128
Leukaemia recurrent 40.53 30.40 12 3296 1603 34952020
Febrile bone marrow aplasia 39.39 30.40 18 3290 8191 34945432
Lymphocyte count decreased 36.22 30.40 24 3284 22598 34931025
Acute erythroid leukaemia 35.23 30.40 7 3301 171 34953452
Clostridium bacteraemia 34.89 30.40 7 3301 180 34953443
Toxic skin eruption 33.81 30.40 18 3290 11367 34942256
Generalised oedema 32.35 30.40 18 3290 12390 34941233
Off label use 31.71 30.40 99 3209 419425 34534198
Gastrointestinal toxicity 30.58 30.40 11 3297 2708 34950915

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 268.96 21.58 97 5908 30460 79707923
Multiple sclerosis relapse 246.16 21.58 102 5903 46431 79691952
Lymphocyte count decreased 176.14 21.58 81 5924 47208 79691175
Febrile neutropenia 151.97 21.58 131 5874 230868 79507515
Myelodysplastic syndrome 106.83 21.58 50 5955 30251 79708132
Rash maculo-papular 103.71 21.58 60 5945 56018 79682365
Neutropenia 102.74 21.58 117 5888 287593 79450790
Pancytopenia 96.83 21.58 88 5917 165657 79572726
Leukopenia 90.78 21.58 73 5932 116440 79621943
Thrombocytopenia 70.47 21.58 93 5912 265166 79473217
Haematotoxicity 59.00 21.58 27 5978 15492 79722891
Clostridium bacteraemia 54 21.58 11 5994 387 79737996
Gastrointestinal protozoal infection 48.00 21.58 8 5997 89 79738294
Dysmenorrhoea 47.96 21.58 15 5990 3030 79735353
Acute myeloid leukaemia recurrent 42.36 21.58 14 5991 3369 79735014
Leukaemia recurrent 40.92 21.58 13 5992 2761 79735622
Abdominal wall wound 40.65 21.58 7 5998 96 79738287
Drug reaction with eosinophilia and systemic symptoms 39.18 21.58 35 5970 64209 79674174
Myeloblast percentage decreased 38.62 21.58 6 5999 41 79738342
Acute generalised exanthematous pustulosis 36.01 21.58 20 5985 17234 79721149
Alanine aminotransferase increased 34.14 21.58 51 5954 162519 79575864
Gastrointestinal toxicity 33.65 21.58 15 5990 8094 79730289
Acute erythroid leukaemia 33.64 21.58 7 5998 274 79738109
Toxic skin eruption 31.26 21.58 20 5985 22273 79716110
Myelosuppression 28.70 21.58 24 5981 40272 79698111
Product use in unapproved indication 28.46 21.58 60 5945 250299 79488084
Herpes zoster 28.36 21.58 35 5970 93048 79645335
Disease progression 28.06 21.58 50 5955 184312 79554071
Stomatococcal infection 27.42 21.58 6 5999 299 79738084
Dermatitis allergic 27.26 21.58 17 5988 18113 79720270
Peptic ulcer haemorrhage 24.94 21.58 7 5998 974 79737409
Pyrexia 24.18 21.58 108 5897 678601 79059782
Leukaemia cutis 23.94 21.58 5 6000 199 79738184
Hairy cell leukaemia recurrent 23.40 21.58 3 6002 3 79738380
COVID-19 23.01 21.58 42 5963 157632 79580751
BRAF gene mutation 22.71 21.58 4 6001 63 79738320
Refractory cytopenia with multilineage dysplasia 22.53 21.58 5 6000 266 79738117
Gamma-glutamyltransferase increased 22.46 21.58 24 5981 54656 79683727
Off label use 22.28 21.58 130 5875 907085 78831298
Gastroenteritis staphylococcal 21.89 21.58 5 6000 303 79738080
Aspartate aminotransferase increased 21.60 21.58 38 5967 138603 79599780

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)

None

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 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
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