Stem definition | Drug id | CAS RN |
---|---|---|
ribofuranyl-derivatives of the "pyrazofurin" type | 667 | 4291-63-8 |
Dose | Unit | Route |
---|---|---|
0.34 | mg | O |
Property | Value | Reference |
---|---|---|
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 |
Date | Agency | Company | Orphan |
---|---|---|---|
Feb. 26, 1993 | FDA |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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 |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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 |
MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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 |
None
Source | Code | Description |
---|---|---|
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 |
Disease | Relation | SNOMED_ID | DOID |
---|---|---|---|
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 |
None
None
Dissociation level | Dissociation constant | Type (acidic/basic) |
---|---|---|
pKa1 | 12.14 | acidic |
pKa2 | 13.72 | acidic |
pKa3 | 3.11 | Basic |
pKa4 | 2.3 | Basic |
Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent 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 |
Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
---|---|---|---|---|---|---|---|---|---|
10MG | MAVENCLAD | EMD SERONO INC | N022561 | March 29, 2019 | RX | TABLET | ORAL | March 29, 2022 | NEW PRODUCT |
Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA 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 |
ID | Source |
---|---|
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 |
Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
---|---|---|---|---|---|---|---|---|
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 |