rifabutin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antibiotics, rifamycin derivatives 2376 72559-06-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • rifabutin
  • ansamycin
  • mycobutin
  • rifabutine
A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients.
  • Molecular weight: 847.02
  • Formula: C46H62N4O11
  • CLOGP: 4.62
  • LIPINSKI: 2
  • HAC: 15
  • HDO: 5
  • TPSA: 205.55
  • ALOGS: -4.70
  • ROTB: 5
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.19 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 10 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.06 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 20 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 9.30 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.40 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.29 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 37 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.330 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 3.396 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 16.634 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 11.324 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 7.580 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 27.550 % High 1
herg hERG pIC50 4.758 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 4.932 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 27.542 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 14.230 % High 1
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK2,CDK4,CDK5,CDK9,CLK4,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,INSR,ITK,JAK1,JAK2,JAK3,KDR,KIT,MAP2K6,MAP3K1,MAP3K14,MAP3K21,MAP3K7,MAP4K1,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PLK1,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ULK1,ULK2,ZAP70 69
kinase-selectivity-class AXL,BRAF,CAMK2D,CDK4,CDK9,EIF2AK3,GRK2,MAP2K6,MAP3K14,PDK1,STK33,TEK 12
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 10.471 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 8.630 High 1
mh-clint Mouse hepatocyte intrinsic clearance 8.035 High 1
mppb Mouse plasma protein binding (% unbound) 7.960 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 50.234 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 11.370 % High 1
rat-kpuu-brain Rat brain Kpuu 0.010 % High 1
rh-clint Rat hepatocyte intrinsic clearance 5.012 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 37.920 % High 1
rppb Rat plasma protein binding (% unbound) 12.100 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 254.097 uM High 1

Approvals:

DateAgencyCompanyOrphan
Dec. 23, 1992 FDA PHARMACIA AND UPJOHN

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
Mycobacterium avium complex infection 239.57 33.93 49 2985 4049 90621364
Drug resistance 223.62 33.93 69 2965 30380 90595033
Drug reaction with eosinophilia and systemic symptoms 158.67 33.93 58 2976 42700 90582713
Immune reconstitution inflammatory syndrome 150.65 33.93 37 2997 6982 90618431
Disseminated mycobacterium avium complex infection 133.97 33.93 20 3014 252 90625161
Drug interaction 120.48 33.93 88 2946 276365 90349048
Uveitis 108.05 33.93 34 3000 15869 90609544
Immune reconstitution inflammatory syndrome associated tuberculosis 73.48 33.93 13 3021 490 90624923
Hepatotoxicity 66.89 33.93 32 3002 45810 90579603
Iridocyclitis 62.11 33.93 16 3018 3645 90621768
Pathogen resistance 62.03 33.93 19 3015 8096 90617317
Neutropenia 58.30 33.93 53 2981 224851 90400562
Hypopyon 53.78 33.93 11 3023 903 90624510
Drug intolerance 51.84 33.93 69 2965 447522 90177891
Hepatitis cholestatic 48.68 33.93 16 3018 8545 90616868
Mycobacterium abscessus infection 46.32 33.93 10 3024 1065 90624348
Lymphadenitis 46.21 33.93 13 3021 4124 90621289
Hypertransaminasaemia 46.04 33.93 18 3016 15807 90609606
Mycobacterial infection 44.11 33.93 11 3023 2199 90623214
Cholestasis 43.00 33.93 22 3012 36277 90589136
Abscess limb 37.38 33.93 12 3022 5950 90619463
Atypical mycobacterial infection 37.04 33.93 9 3025 1617 90623796
Deafness 36.77 33.93 17 3017 22497 90602916

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
Immune reconstitution inflammatory syndrome 279.92 28.37 79 3530 10064 42607662
Drug resistance 172.58 28.37 75 3534 34173 42583553
Drug interaction 145.42 28.37 143 3466 266856 42350870
Uveitis 80.24 28.37 30 3579 9228 42608498
Atypical mycobacterial infection 73.01 28.37 18 3591 1348 42616378
Mycobacterium avium complex infection 67.45 28.37 20 3589 3007 42614719
Drug level decreased 64.03 28.37 26 3583 9951 42607775
Treatment failure 61.10 28.37 47 3562 62577 42555149
Cytomegalovirus chorioretinitis 59.17 28.37 20 3589 4591 42613135
Mycobacterial infection 52.42 28.37 16 3593 2652 42615074
Immune reconstitution inflammatory syndrome associated tuberculosis 43.21 28.37 10 3599 571 42617155
Pancytopenia 39.20 28.37 49 3560 117694 42500032
Ototoxicity 37.54 28.37 12 3597 2313 42615413
Neutropenia 37.13 28.37 63 3546 199368 42418358
Intra-abdominal haemorrhage 34.82 28.37 12 3597 2916 42614810
Repetitive speech 34.23 28.37 6 3603 81 42617645
Electrocardiogram QT prolonged 34.16 28.37 30 3579 47915 42569811
Lymphopenia 32.17 28.37 21 3588 21542 42596184
Drug ineffective 32.07 28.37 121 3488 630076 41987650
Immunosuppressant drug level decreased 31.87 28.37 10 3599 1814 42615912
Leukopenia 29.60 28.37 34 3575 74712 42543014
Nephropathy toxic 29.11 28.37 18 3591 16820 42600906
Thrombocytopenia 28.85 28.37 55 3554 190224 42427502

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
Immune reconstitution inflammatory syndrome 413.71 24.44 108 5868 16118 110567205
Drug resistance 292.14 24.44 111 5865 56263 110527060
Drug interaction 271.47 24.44 220 5756 499963 110083360
Mycobacterium avium complex infection 260.36 24.44 61 5915 5816 110577507
Uveitis 165.79 24.44 57 5919 21653 110561670
Drug reaction with eosinophilia and systemic symptoms 156.29 24.44 80 5896 82015 110501308
Disseminated mycobacterium avium complex infection 104.94 24.44 19 5957 499 110582824
Atypical mycobacterial infection 98.50 24.44 24 5952 2694 110580629
Immune reconstitution inflammatory syndrome associated tuberculosis 97.32 24.44 20 5956 1034 110582289
Hepatotoxicity 82.30 24.44 48 5928 63352 110519971
Neutropenia 82.13 24.44 101 5875 374519 110208804
Hypopyon 74.68 24.44 17 5959 1423 110581900
Iridocyclitis 73.40 24.44 22 5954 5386 110577937
Pancytopenia 69.11 24.44 70 5906 209543 110373780
Drug ineffective 68.71 24.44 208 5768 1520332 109062991
Leukopenia 60.92 24.44 56 5920 148735 110434588
Mycobacterial infection 60.08 24.44 18 5958 4399 110578924
Cytomegalovirus chorioretinitis 59.41 24.44 20 5956 7108 110576215
Drug level decreased 56.47 24.44 25 5951 18523 110564800
Pathogen resistance 54.38 24.44 24 5952 17648 110565675
Deafness 53.58 24.44 27 5949 26682 110556641
Deafness neurosensory 53.55 24.44 20 5956 9599 110573724
Neuropathy peripheral 45.22 24.44 52 5924 179225 110404098
Thrombocytopenia 43.57 24.44 72 5904 348813 110234510
Acute hepatic failure 43.09 24.44 26 5950 36442 110546881
Drug intolerance 41.80 24.44 77 5899 406435 110176888
Cholestasis 40.29 24.44 31 5945 64487 110518836
Hepatitis cholestatic 38.91 24.44 19 5957 17547 110565776
Transplant rejection 38.35 24.44 21 5955 24546 110558777
Electrocardiogram QT prolonged 36.98 24.44 37 5939 108923 110474400
Corneal deposits 36.16 24.44 8 5968 588 110582735
Ototoxicity 36.05 24.44 12 5964 4119 110579204
Hypertransaminasaemia 35.84 24.44 20 5956 24235 110559088
Pyrexia 34.87 24.44 117 5859 898148 109685175
Nephropathy toxic 33.52 24.44 20 5956 27458 110555865
Treatment failure 32.96 24.44 56 5920 277178 110306145
Paradoxical drug reaction 32.37 24.44 14 5962 9803 110573520
Immunosuppressant drug level decreased 32.17 24.44 10 5966 2761 110580562
Multiple-drug resistance 31.38 24.44 15 5961 13220 110570103
Acid fast bacilli infection 31.25 24.44 6 5970 218 110583105
Intra-abdominal haemorrhage 29.34 24.44 11 5965 5331 110577992
Off label use 27.66 24.44 156 5820 1500029 109083294
Chromaturia 27.33 24.44 18 5958 29342 110553981
Hyperuricaemia 27.13 24.44 14 5962 14517 110568806
Rash maculo-papular 26.65 24.44 26 5950 74196 110509127
Drug ineffective for unapproved indication 24.52 24.44 29 5947 102809 110480514
Tuberculosis 24.49 24.44 14 5962 17760 110565563

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A02BD16 ALIMENTARY TRACT AND METABOLISM
DRUGS FOR ACID RELATED DISORDERS
DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
Combinations for eradication of Helicobacter pylori
ATC J04AB04 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOBACTERIALS
DRUGS FOR TREATMENT OF TUBERCULOSIS
Antibiotics
ATC J04AM11 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOBACTERIALS
DRUGS FOR TREATMENT OF TUBERCULOSIS
Combinations of drugs for treatment of tuberculosis
FDA CS M0019113 Rifamycins
FDA EPC N0000175501 Rifamycin Antimycobacterial
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D000904 Antibiotics, Antitubercular
MeSH PA D000995 Antitubercular Agents
CHEBI has role CHEBI:33231 antitubercular agent
CHEBI has role CHEBI:33282 antibacterial agent
CHEBI has role CHEBI:35441 antiinfective agent
CHEBI has role CHEBI:35718 antifungal agent
CHEBI has role CHEBI:64946 anti-HIV agent

Related Drugs by ATC class:

A02BD Combinations for eradication of Helicobacter pylori 13 drugs
amoxicillinbismuth subcitrateclarithromycinesomeprazolelansoprazolelevofloxacinmetronidazoleomeprazolepantoprazolerabeprazoletetracyclinetinidazole show all 13 →
J04AB Antibiotics 6 drugs
capreomycincycloserineenviomycinrifampicinrifamycinrifapentine
J04AM Combinations of drugs for treatment of tuberculosis 11 drugs
ethambutolisoniazidlevofloxacinlomefloxacinprotionamidepyrazinamiderifampicinstreptomycinsulfamethoxazolethioacetazonetrimethoprim

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Pulmonary Mycobacterium avium complex infection indication 186342000
Inactive tuberculosis off-label use 11999007
Acute tuberculosis off-label use 25629007
Tuberculosis of meninges off-label use 58437007
Pulmonary tuberculosis off-label use 154283005 DOID:2957
Acute nephropathy contraindication 58574008
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Pseudomembranous enterocolitis contraindication 397683000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.13 acidic
pKa2 8.78 acidic
pKa3 12.55 acidic
pKa4 8.26 Basic
pKa5 2.95 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL 11135172 Feb. 12, 2034 TREATMENT OF H. PYLORI INFECTION IN ADULTS
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL 11931463 Feb. 12, 2034 TREATMENT OF HELICOBACTER PYLORI INFECTION IN ADULTS USING SPECIFIED DOSAGE FORM
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL 9050263 Feb. 12, 2034 TREATMENT OF H. PYLORI INFECTION IN ADULTS
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL 9498445 Feb. 12, 2034 TREATMENT OF H. PYLORI INFECTION IN ADULTS
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL 9603806 Feb. 12, 2034 TREATMENT OF H. PYLORI INFECTION IN ADULTS
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL 11878011 May 27, 2042 TREATMENT OF HELICOBACTER PYLORI INFECTION USING THE ADMINISTERED DOSAGE FORMS IN ADULTS WITH DIFFERENT BODY MASS INDEX DETERMINATIONS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL Nov. 1, 2022 NEW PRODUCT
250MG;EQ 10MG BASE;12.5MG TALICIA TALICIA HOLDINGS N213004 Nov. 1, 2019 RX CAPSULE, DELAYED RELEASE ORAL Nov. 1, 2027 GENERATING ANTIBIOTIC INCENTIVES NOW

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Bacterial DNA-directed RNA polymerase Enzyme INHIBITOR CHEMBL CHEMBL
DNA-directed RNA polymerase subunit beta Enzyme Ki 8 WOMBAT-PK

External reference:

IDSource
4020770 VUID
N0000148321 NUI
D00424 KEGG_DRUG
4020770 VANDF
C0140575 UMLSCUI
CHEBI:45367 CHEBI
RBT PDB_CHEM_ID
CHEMBL444633 ChEMBL_ID
D017828 MESH_DESCRIPTOR_UI
DB00615 DRUGBANK_ID
12015 IUPHAR_LIGAND_ID
5668 INN_ID
1W306TDA6S UNII
227450 RXNORM
132500 MMSL
1985 MMSL
5423 MMSL
d01097 MMSL
004117 NDDF
108684009 SNOMEDCT_US
386893001 SNOMEDCT_US
135950975 PUBCHEM_CID
1W306TDA6S INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Mycobutin HUMAN PRESCRIPTION DRUG LABEL 1 0013-5301 CAPSULE 150 mg ORAL NDA 26 sections
Rifabutin HUMAN PRESCRIPTION DRUG LABEL 1 10135-738 CAPSULE 150 mg ORAL ANDA 21 sections
Mycobutin HUMAN PRESCRIPTION DRUG LABEL 1 54868-2841 CAPSULE 150 mg ORAL NDA 23 sections
Mycobutin HUMAN PRESCRIPTION DRUG LABEL 1 55695-010 CAPSULE 150 mg ORAL NDA 27 sections
Talicia HUMAN PRESCRIPTION DRUG LABEL 3 57841-1150 CAPSULE, DELAYED RELEASE 12.50 mg ORAL NDA 32 sections
Rifabutin HUMAN PRESCRIPTION DRUG LABEL 1 59762-1350 CAPSULE 150 mg ORAL NDA authorized generic 26 sections
Rifabutin HUMAN PRESCRIPTION DRUG LABEL 1 70518-4254 CAPSULE 150 mg ORAL NDA authorized generic 25 sections
Rifabutin HUMAN PRESCRIPTION DRUG LABEL 1 70518-4594 CAPSULE 150 mg ORAL ANDA 21 sections
Rifabutin Human Prescription Drug Label 1 70954-041 CAPSULE 150 mg ORAL ANDA 21 sections
Rifabutin HUMAN PRESCRIPTION DRUG LABEL 1 72319-010 CAPSULE 150 mg ORAL ANDA 25 sections
Rifabutin HUMAN PRESCRIPTION DRUG LABEL 1 73141-020 CAPSULE 150 mg ORAL ANDA 25 sections