cladribine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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
6.30 mg P
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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.254 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 37.154 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 5.297 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 1.493 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 84.540 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 92.290 % High 1
herg hERG pIC50 3.888 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.135 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 2.999 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 82.950 % High 1
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 6.368 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 15.066 High 1
mh-clint Mouse hepatocyte intrinsic clearance 3.119 High 1
mppb Mouse plasma protein binding (% unbound) 88.520 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 6.792 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 90.340 % High 1
rat-kpuu-brain Rat brain Kpuu 0.026 % High 1
rh-clint Rat hepatocyte intrinsic clearance 1.758 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 95.630 % High 1
rppb Rat plasma protein binding (% unbound) 78.480 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 939.723 uM High 1

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
Lymphocyte count decreased 514.77 22.77 156 5471 34894 90587926
Multiple sclerosis relapse 484.77 22.77 164 5463 52141 90570679
Lymphopenia 464.58 22.77 131 5496 22750 90600070
Maternal exposure before pregnancy 118.83 22.77 39 5588 11174 90611646
Leukopenia 108.13 22.77 71 5556 100639 90522181
Alanine aminotransferase increased 86.54 22.77 66 5561 118272 90504548
White blood cell count decreased 74.33 22.77 70 5557 167039 90455781
Aspartate aminotransferase increased 69.98 22.77 55 5572 102882 90519938
Febrile neutropenia 67.87 22.77 65 5562 158284 90464536
Expanded disability status scale score increased 64.65 22.77 14 5613 809 90622011
Neutropenia 63.69 22.77 74 5553 224830 90397990
Abortion spontaneous 62.60 22.77 40 5587 54016 90568804
Gamma-glutamyltransferase increased 56.54 22.77 33 5594 37919 90584901
Pancytopenia 54.62 22.77 51 5576 120212 90502608
Rash maculo-papular 54.23 22.77 33 5594 40900 90581920
Dysmenorrhoea 48.48 22.77 16 5611 4656 90618164
COVID-19 46.83 22.77 55 5572 168788 90454032
Maternal exposure timing unspecified 45.71 22.77 24 5603 22459 90600361
Drug reaction with eosinophilia and systemic symptoms 45.47 22.77 30 5597 42728 90580092
Thrombocytopenia 45.11 22.77 60 5567 208665 90414155
Optic neuritis 43.82 22.77 18 5609 9660 90613160
Multiple sclerosis 43.57 22.77 25 5602 27815 90595005
Acute myeloid leukaemia recurrent 42.65 22.77 12 5615 2045 90620775
Abdominal wall wound 41.93 22.77 7 5620 97 90622723
Myeloblast percentage decreased 39.78 22.77 6 5621 41 90622779
Headache 36.69 22.77 127 5500 862619 89760201
Breast cancer 34.94 22.77 28 5599 53733 90569087
Intercepted product prescribing error 34.34 22.77 7 5620 301 90622519
Refractory cytopenia with multilineage dysplasia 33.23 22.77 6 5621 134 90622686
Hypersplenism 33.01 22.77 7 5620 366 90622454
Drug-induced liver injury 31.16 22.77 33 5594 90285 90532535
Herpes zoster 29.89 22.77 33 5594 94611 90528209
Gastrointestinal protozoal infection 27.26 22.77 4 5623 22 90622798
Haematotoxicity 27.25 22.77 14 5613 12521 90610299
Graft versus host disease in gastrointestinal tract 26.31 22.77 10 5617 4378 90618442
Myelosuppression 24.83 22.77 23 5604 53568 90569252
Invasive ductal breast carcinoma 23.82 22.77 11 5616 7807 90615013
Abortion 22.83 22.77 8 5619 2787 90620033

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
Multiple sclerosis relapse 178.61 25.79 65 4656 14199 42602415
Myelodysplastic syndrome 99.17 25.79 49 4672 22696 42593918
Febrile neutropenia 90.81 25.79 107 4614 185596 42431018
Rash maculo-papular 78.77 25.79 50 4671 37453 42579161
Lymphopenia 78.11 25.79 41 4680 21522 42595092
Pancytopenia 76.81 25.79 79 4642 117664 42498950
Face oedema 76.56 25.79 35 4686 13631 42602983
Toxic skin eruption 55.16 25.79 28 4693 13702 42602912
Metastatic lymphoma 54.90 25.79 12 4709 401 42616213
Lymphocyte count decreased 53.25 25.79 35 4686 27774 42588840
Bradyarrhythmia 48.15 25.79 16 4705 2659 42613955
Hairy cell leukaemia recurrent 47.58 25.79 7 4714 19 42616595
Febrile bone marrow aplasia 47.53 25.79 23 4698 10158 42606456
Acute generalised exanthematous pustulosis 41.89 25.79 20 4701 8575 42608039
Leukaemia recurrent 41.00 25.79 13 4708 1863 42614751
Disease progression 39.84 25.79 63 4658 143593 42473021
Pyrexia 37.69 25.79 112 4609 393930 42222684
Neutropenia 35.43 25.79 72 4649 199359 42417255
Disseminated intravascular coagulation 35.25 25.79 26 4695 24768 42591846
Cutaneous vasculitis 33.54 25.79 16 4705 6844 42609770
Off label use 33.44 25.79 149 4572 638186 41978428
Septic shock 32.28 25.79 45 4676 91627 42524987
Clostridium bacteraemia 32.22 25.79 7 4714 227 42616387
Acute erythroid leukaemia 31.38 25.79 7 4714 257 42616357
Product use in unapproved indication 30.87 25.79 65 4656 184391 42432223
Thrombocytopenia 30.63 25.79 66 4655 190213 42426401
Generalised oedema 28.61 25.79 19 4702 15317 42601297
Hyperbilirubinaemia 27.90 25.79 21 4700 20614 42596000
Herpes zoster 26.93 25.79 27 4694 38850 42577764
Haematotoxicity 26.46 25.79 16 4705 10969 42605645
Therapy non-responder 26.35 25.79 31 4690 53328 42563286
Gastrointestinal protozoal infection 26.21 25.79 5 4716 83 42616531

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
Multiple sclerosis relapse 427.44 20.59 159 8901 50081 110530158
Lymphopenia 333.76 20.59 125 8935 40045 110540194
Lymphocyte count decreased 314.13 20.59 132 8928 57111 110523128
Febrile neutropenia 176.64 20.59 170 8890 316597 110263642
Rash maculo-papular 132.54 20.59 80 8980 74142 110506097
Myelodysplastic syndrome 124.58 20.59 61 8999 37423 110542816
Pancytopenia 110.08 20.59 109 8951 209504 110370735
Leukopenia 106.49 20.59 92 8968 148699 110431540
Neutropenia 88.90 20.59 130 8930 374490 110205749
Thrombocytopenia 78.34 20.59 118 8942 348767 110231472
Maternal exposure before pregnancy 69.07 20.59 25 9035 7240 110572999
Face oedema 59.50 20.59 36 9024 33433 110546806
Haematotoxicity 54.57 20.59 29 9031 21053 110559186
Alanine aminotransferase increased 54.35 20.59 71 8989 183702 110396537
Expanded disability status scale score increased 54.07 20.59 13 9047 905 110579334
Metastatic lymphoma 53.22 20.59 12 9048 630 110579609
Gastrointestinal protozoal infection 52.85 20.59 9 9051 105 110580134
Toxic skin eruption 52.56 20.59 31 9029 27484 110552755
Clostridium bacteraemia 50.61 20.59 11 9049 487 110579752
Dysmenorrhoea 48.16 20.59 16 9044 3594 110576645
Disease progression 45.66 20.59 76 8984 243958 110336281
Multiple sclerosis 44.03 20.59 27 9033 25671 110554568
Myelosuppression 43.86 20.59 46 9014 94294 110485945
Bradyarrhythmia 43.27 20.59 16 9044 4918 110575321
Acute myeloid leukaemia recurrent 42.64 20.59 16 9044 5123 110575116
Leukaemia recurrent 42.26 20.59 14 9046 3117 110577122
Aspartate aminotransferase increased 41.50 20.59 58 9002 159878 110420361
Abdominal wall wound 40.41 20.59 7 9053 91 110580148
Myeloblast percentage decreased 38.11 20.59 6 9054 41 110580198
Drug reaction with eosinophilia and systemic symptoms 38.11 20.59 40 9020 82055 110498184
Pyrexia 35.94 20.59 157 8903 898108 109682131
Product use in unapproved indication 35.25 20.59 98 8962 447279 110132960
Hyperbilirubinaemia 34.98 20.59 25 9035 30646 110549593
Cutaneous vasculitis 34.33 20.59 18 9042 12711 110567528
Herpes zoster 33.78 20.59 43 9017 108336 110471903
Disseminated intravascular coagulation 32.50 20.59 27 9033 41259 110538980
White blood cell count decreased 32.11 20.59 63 8997 229327 110350912
Septic shock 32.07 20.59 51 9009 157477 110422762
Acute erythroid leukaemia 30.82 20.59 7 9053 380 110579859
Gamma-glutamyltransferase increased 30.48 20.59 31 9029 61278 110518961
Acute generalised exanthematous pustulosis 30.23 20.59 20 9040 21644 110558595
Hairy cell leukaemia recurrent 29.59 20.59 4 9056 7 110580232
Agranulocytosis 28.49 20.59 30 9030 61730 110518509
Central nervous system lesion 28.33 20.59 17 9043 15536 110564703
Leukaemia cutis 28.22 20.59 6 9054 239 110580000
Gastrointestinal toxicity 27.91 20.59 15 9045 11133 110569106
Bacteraemia 27.85 20.59 25 9035 42365 110537874
Febrile bone marrow aplasia 26.52 20.59 17 9043 17448 110562791
Toxicity to various agents 26.29 20.59 4 9056 480551 110099688
Hypersplenism 26.07 20.59 7 9053 759 110579480
Joint swelling 25.86 20.59 3 9057 442842 110137397
COVID-19 25.85 20.59 60 9000 245000 110335239
Haemophagocytic lymphohistiocytosis 25.59 20.59 21 9039 31538 110548701
Stomatococcal infection 25.48 20.59 6 9054 382 110579857
Optic neuritis 25.14 20.59 14 9046 11133 110569106
Off label use 24.21 20.59 207 8853 1499978 109080261
Pneumonia fungal 24.00 20.59 15 9045 14739 110565500
Dermatitis allergic 23.16 20.59 17 9043 21707 110558532
Peptic ulcer haemorrhage 23.12 20.59 7 9053 1166 110579073
Gastrointestinal lymphoma 22.53 20.59 5 9055 244 110579995
Graft versus host disease in gastrointestinal tract 22.26 20.59 12 9048 8956 110571283
Refractory cytopenia with multilineage dysplasia 22.26 20.59 5 9055 258 110579981
Overgrowth bacterial 22.11 20.59 5 9055 266 110579973
JC polyomavirus test positive 22.02 20.59 8 9052 2339 110577900
Breast cancer 21.96 20.59 21 9039 38521 110541718
Drug-induced liver injury 21.90 20.59 37 9023 120030 110460209
Gastrointestinal mucormycosis 21.62 20.59 6 9054 735 110579504
Confusional state 21.32 20.59 6 9054 468674 110111565
Gastroenteritis staphylococcal 21.30 20.59 5 9055 314 110579925
Liver palpable 20.82 20.59 5 9055 346 110579893
Abortion 20.75 20.59 7 9053 1647 110578592

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
MeSH PA D000970 Antineoplastic Agents
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
FDA EPC N0000175712 Purine Antimetabolite
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35705 immunosuppressive agent
CHEBI has role CHEBI:75835 anti-anaemic agent

Related Drugs by ATC class:

L01BB Purine analogues 5 drugs
clofarabinefludarabine phosphatemercaptopurinenelarabinethioguanine
L04AA Selective immunosuppressants 10 drugs
abataceptalefaceptapremilastbelataceptbelumosudilgusperimusimlifidasemycophenolic acidnerandomilastremibrutinib

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 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
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL 12533408 Sept. 10, 2041 TREATMENT OF RELAPSING FORMS OF MULTIPLE SCLEROSIS IN ADULTS BY ADMINISTERING 2 YEARLY TREATMENT COURSES WHEREIN PATIENTS WHO ARE SEROPOSITIVE TO VZV ARE VACCINATED WITH ZOSTER VACCINE RECOMBINANT, ADJUVANTED BETWEEN THE 1ST AND 2ND TREATMENT COURSE
10MG MAVENCLAD EMD SERONO INC N022561 March 29, 2019 RX TABLET ORAL 12539329 Sept. 10, 2041 TREATMENT OF RELAPSING FORMS OF MS IN ADULTS BY ADMINISTERING 2 YEARLY TREATMENT COURSES WHEREIN PATIENTS WHO ARE SEROPOSITIVE TO VZV ARE VACCINATED WITH ZOSTER VACCINE RECOMBINANT, ADJUVANTED WITHIN ABOUT 4 WEEKS PRIOR TO THE 1ST TREATMENT COURSE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Deoxycytidine kinase Kinase WOMBAT-PK
Purine nucleoside phosphorylase Enzyme Ki 8.64 CHEMBL
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
C0092801 UMLSCUI
CHEBI:567361 CHEBI
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
CL9 PDB_CHEM_ID
4020629 VANDF
47M74X9YT5 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 0143-9871 INJECTION 1 mg INTRAVENOUS ANDA 23 sections
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 0781-8201 TABLET 10 mg ORAL ANDA 33 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 35 sections
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 60505-4791 TABLET 10 mg ORAL ANDA 30 sections
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 62049-286 TABLET 10 mg ORAL ANDA 30 sections
Cladribine HUMAN PRESCRIPTION DRUG LABEL 1 63323-140 INJECTION 1 mg INTRAVENOUS ANDA 15 sections