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 278.07 27.17 78 2619 15543 50586884
Lymphocyte count decreased 225.88 27.17 75 2622 26232 50576195
Multiple sclerosis relapse 189.96 27.17 75 2622 42889 50559538
Leukopenia 90.91 27.17 52 2645 67476 50534951
Neutropenia 70.15 27.17 60 2637 147905 50454522
Drug reaction with eosinophilia and systemic symptoms 58.26 27.17 29 2668 28395 50574032
Febrile neutropenia 55.41 27.17 44 2653 97623 50504804
Rash maculo-papular 48.23 27.17 25 2672 26616 50575811
Thrombocytopenia 45.19 27.17 44 2653 127629 50474798
Abdominal wall wound 44.93 27.17 7 2690 72 50602355
COVID-19 44.85 27.17 29 2668 46633 50555794
Pancytopenia 43.70 27.17 36 2661 83994 50518433
Myeloblast percentage decreased 40.70 27.17 6 2691 41 50602386
Intercepted product prescribing error 39.65 27.17 7 2690 161 50602266
Alanine aminotransferase increased 36.11 27.17 33 2664 88326 50514101
Gamma-glutamyltransferase increased 34.99 27.17 21 2676 29602 50572825
Acute myeloid leukaemia recurrent 34.29 27.17 9 2688 1381 50601046
Refractory cytopenia with multilineage dysplasia 33.82 27.17 6 2691 142 50602285
Optic neuritis 30.23 27.17 12 2685 6878 50595549

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 95.42 28.61 42 2733 17752 29554000
Pancytopenia 85.50 28.61 67 2708 83101 29488651
Multiple sclerosis relapse 77.94 28.61 32 2743 11387 29560365
Rash maculo-papular 68.62 28.61 37 2738 24252 29547500
Febrile neutropenia 66.22 28.61 66 2709 112174 29459578
Acute generalised exanthematous pustulosis 53.44 28.61 20 2755 5563 29566189
Lymphopenia 47.90 28.61 24 2751 13509 29558243
Neutropenia 47.57 28.61 60 2715 131651 29440101
Face oedema 44.72 28.61 21 2754 10262 29561490
Leukaemia recurrent 41.70 28.61 12 2763 1465 29570287
Febrile bone marrow aplasia 41.46 28.61 18 2757 7333 29564419
Clostridium bacteraemia 40.06 28.61 7 2768 83 29571669
Toxic skin eruption 36.58 28.61 18 2757 9739 29562013
Acute erythroid leukaemia 35.49 28.61 7 2768 166 29571586
Generalised oedema 34.29 28.61 18 2757 11147 29560605
Herpes zoster 30.29 28.61 24 2751 30028 29541724
Lymphocyte count decreased 29.94 28.61 20 2755 19251 29552501

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 209.57 23.41 77 4761 25580 64468314
Multiple sclerosis relapse 167.93 23.41 75 4763 41060 64452834
Lymphocyte count decreased 131.13 23.41 63 4775 40636 64453258
Febrile neutropenia 120.94 23.41 105 4733 187552 64306342
Rash maculo-papular 111.05 23.41 59 4779 46967 64446927
Neutropenia 109.97 23.41 111 4727 239513 64254381
Pancytopenia 100.01 23.41 84 4754 143225 64350669
Myelodysplastic syndrome 86.69 23.41 42 4796 27537 64466357
Leukopenia 82.49 23.41 65 4773 101177 64392717
Thrombocytopenia 71.79 23.41 86 4752 223715 64270179
Clostridium bacteraemia 57.52 23.41 11 4827 279 64493615
Drug reaction with eosinophilia and systemic symptoms 42.36 23.41 34 4804 54183 64439711
Leukaemia recurrent 41.84 23.41 13 4825 2581 64491313
Abdominal wall wound 41.62 23.41 7 4831 83 64493811
Acute generalised exanthematous pustulosis 39.95 23.41 20 4818 14038 64479856
Myeloblast percentage decreased 38.64 23.41 6 4832 41 64493853
Acute myeloid leukaemia recurrent 36.84 23.41 12 4826 2772 64491122
Acute erythroid leukaemia 34.51 23.41 7 4831 242 64493652
Toxic skin eruption 31.41 23.41 19 4819 19265 64474629
Product use in unapproved indication 31.14 23.41 51 4787 176567 64317327
Dermatitis allergic 30.20 23.41 17 4821 15092 64478802
Stomatococcal infection 28.61 23.41 6 4832 245 64493649
Peptic ulcer haemorrhage 25.87 23.41 7 4831 854 64493040
Multiple organ dysfunction syndrome 24.59 23.41 34 4804 101379 64392515
Herpes zoster 24.59 23.41 30 4808 79157 64414737

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

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 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
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 67457-450 INJECTION 1 mg INTRAVENOUS ANDA 23 sections