Details of the Drug Combination

General Information of Drug Combination (ID: DC8N0YC)

Drug Combination Name
Clarithromycin Amoxicillin
Indication
Disease Entry Status REF
H. Pylori Infection Phase 3 [1]
Component Drugs Clarithromycin   DM4M1SG Amoxicillin   DMUYNEI
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Clarithromycin
Disease Entry ICD 11 Status REF
Acute maxillary sinusitis N.A. Approved [2]
Acute otitis media AB00 Approved [2]
Bacterial infection 1A00-1C4Z Approved [3]
Mycoplasma pneumoniae pneumonia N.A. Approved [2]
Staphylococcus aureus infection N.A. Approved [2]
Streptococcal pneumonia N.A. Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [4]
Pneumonia caused by chlamydia N.A. Investigative [2]
Clarithromycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial 50S ribosomal RNA (Bact 50S rRNA) TTUWYEA NOUNIPROTAC Binder [7]
------------------------------------------------------------------------------------
Clarithromycin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
------------------------------------------------------------------------------------
Clarithromycin Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
------------------------------------------------------------------------------------
Clarithromycin Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [13]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH) OTUG4BWA PAHX_HUMAN Decreases Expression [14]
Lanosterol synthase (LSS) OT9W2SFH LSS_HUMAN Decreases Expression [14]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [14]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [14]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [15]
Cytochrome c oxidase subunit 2 (COX2) OTTMVBJJ COX2_HUMAN Decreases Expression [16]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [17]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [18]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [19]
Integrin beta-4 (ITGB4) OT28UK84 ITB4_HUMAN Decreases Expression [20]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Increases ADR [21]
Translation initiation factor IF-2, mitochondrial (MTIF2) OTAIOZ0J IF2M_HUMAN Decreases Response To Substance [16]
Misshapen-like kinase 1 (MINK1) OTKB0RA8 MINK1_HUMAN Increases ADR [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 15 DOT(s)
Indication(s) of Amoxicillin
Disease Entry ICD 11 Status REF
Acute otitis media AB00 Approved [5]
Bacterial infection 1A00-1C4Z Approved [6]
Staphylococcus aureus infection N.A. Approved [5]
Streptococcal pneumonia N.A. Approved [5]
Urinary tract infection GC08 Approved [5]
Pneumonia due to Klebsiella pneumoniae CA40.03 Investigative [5]
Sinusitis CA0A.Z Investigative [5]
Amoxicillin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Cell membrane (Bact CM) TTXT4D5 NOUNIPROTAC Modulator [22]
------------------------------------------------------------------------------------
Amoxicillin Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [23]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [24]
Peptide transporter 2 (SLC15A2) DT8QKNP S15A2_HUMAN Substrate [24]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [25]
------------------------------------------------------------------------------------
Amoxicillin Interacts with 46 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [26]
Beta-lactamase (blaB) DED0TBR A0A414M273_9BACE Metabolism [27]
Beta-lactamase (blaB) DEX8KJO A6NX15_9FIRM Metabolism [28]
Beta-lactamase (blaB) DEAYSTX C0W968_9FIRM Metabolism [29]
Beta-lactamase (blaB) DERGEVU C3WC84_FUSMR Metabolism [30]
Beta-lactamase (blaB) DEV0KWQ Q8KT52_9BACT Metabolism [31]
Beta-lactamase (blaB) DEQMISO F9Z530_ODOSD Metabolism [30]
Beta-lactamase (blaB) DEHFJ4G Q8KT51_9BACT Metabolism [30]
Beta-lactamase (blaB) DEHPJRC Q8KT60_9BACT Metabolism [30]
Beta-lactamase (blaB) DEITMS0 Q9XBM2_ACIFE Metabolism [32]
N-acylhomoserine lactone acylase (lacA) DEIU0XN A0A0A1VBK6_9BURK Metabolism [33]
Beta-lactamase (blaB) DET9I1W BLAC_BACUN Metabolism [34]
Beta-lactamase (blaB) DE7IH52 AMPC_CITFR Metabolism [31]
Beta-lactamase (blaB) DENJ2SQ BLAB_BACFG Metabolism [34]
Beta-lactamase (blaB) DE5HV8P A0A4Q5I6I2_9BACE Metabolism [34]
Beta-lactamase (blaB) DE47ARF B5WXV2_9BACT Metabolism [35]
Beta-lactamase (blaB) DEG2PK9 B5WXV3_BACOV Metabolism [34]
Beta-lactamase (blaB) DEWHJ7A B5WXV7_BACT4 Metabolism [34]
Beta-lactamase (blaB) DEU1RXB BLAC_BACVU Metabolism [34]
Beta-lactamase (blaB) DETDS7E A0A2S0LB67_9FLAO Metabolism [31]
Beta-lactamase (blaB) DE37FJH C6JIU1_FUSVA Metabolism [30]
Beta-lactamase (blaB) DEC7JEF A0A1S1G219_9NEIS Metabolism [31]
Beta-lactamase (blaB) DEP7MN1 Q9X4S7_PREIN Metabolism [36]
Beta-lactamase (blaB) DEAILCM A0A246EJV2_9BACT Metabolism [36]
Beta-lactamase (blaB) DET4XFN Q8KT59_9BACT Metabolism [31]
Metallo-beta-lactamase (blaM) DEPCQ12 Q68K11_ALCXX Metabolism [37]
Beta-lactamase (blaB) DEACNTL Q2F4C6_SHISO Metabolism [38]
Beta-lactamase (blaB) DEE8742 O32372_CAPOC Metabolism [39]
Beta-lactamase (blaB) DEY09SU C9MN73_9BACT Metabolism [31]
Beta-lactamase (blaB) DEQLVCA C9LD75_9BACT Metabolism [36]
Beta-lactamase (blaB) DE2IL34 C2M7J0_CAPGI Metabolism [39]
Beta-lactamase (blaB) DE1NJIW B6VMJ3_PHOAA Metabolism [40]
Beta-lactamase (blaB) DEDIMN9 A0A413GBG0_9BACE Metabolism [34]
Beta-lactamase (blaB) DEJ8X2W A0A412YFL9_9BACE Metabolism [34]
Beta-lactamase (blaB) DEFEVNH A0A381DV31_9FLAO Metabolism [39]
Beta-lactamase (blaB) DEAPGXV A0A347B2J2_9BACT Metabolism [31]
Beta-lactamase (blaB) DE0PDVC A0A2A3N1K0_CAPSP Metabolism [39]
Beta-lactamase (blaB) DEQL32N A0A250F962_9FLAO Metabolism [39]
Beta-lactamase (blaB) DE9HF0I A0A120A1C6_BACSE Metabolism [34]
Beta-lactamase (blaB) DESHI6O A0A108T9G3_9BACE Metabolism [34]
Beta-lactamase (blaB) DEZS3N4 A0A069QS91_PRELO Metabolism [31]
Beta-lactamase (blaB) DE5NSUX A0A095XPV0_9FIRM Metabolism [31]
New delhi metallo-beta-lactamase NDM-1 (blaNDM) DEBGCYQ A0A345N7K5_SALET Metabolism [41]
Beta-lactamase (blaB) DEW193R BLA1_KLEPN Metabolism [37]
Metallo-beta-lactamase (blaM) DEK9VG2 BLAN1_KLEPN Metabolism [37]
Beta-lactamase (blaB) DEQ1CTE A0A2T4TNV5_9BACT Metabolism [42]
------------------------------------------------------------------------------------
⏷ Show the Full List of 46 DME(s)
Amoxicillin Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1) OTVVI3UI DQB1_HUMAN Affects Expression [43]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Affects Expression [43]
C-C chemokine receptor type 9 (CCR9) OT5FSOD8 CCR9_HUMAN Increases ADR [21]
C-C chemokine receptor type 4 (CCR4) OT68KZ9B CCR4_HUMAN Increases ADR [21]
HLA class I histocompatibility antigen, A alpha chain (HLA-A) OTAH14LU HLAA_HUMAN Increases ADR [44]
C-X-C chemokine receptor type 3 (CXCR3) OTIGS220 CXCR3_HUMAN Increases ADR [21]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Increases Expression [45]
Cytochrome P450 11B2, mitochondrial (CYP11B2) OTIOLWYN C11B2_HUMAN Increases Expression [45]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [46]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Increases Expression [47]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [47]
Sulfiredoxin-1 (SRXN1) OTYDBO4L SRXN1_HUMAN Increases Expression [47]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Decreases Expression [48]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [48]
Organic solute transporter subunit alpha (SLC51A) OTDJRZ0P OSTA_HUMAN Increases Expression [49]
------------------------------------------------------------------------------------
⏷ Show the Full List of 15 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Helicobacter Pylori Infection DCQQMYT N. A. Phase 4 [50]
Peptic Ulcer DCEOFR6 N. A. Phase 4 [51]
Antimicrobial Susceptibility Testing DCWZIOF N. A. Phase 4 [52]
Helicobacter Pylori Infection DC3BGTZ N. A. Phase 3 [53]
Helicobacter Pylori Infection DC1GAFQ N. A. Phase 2 [54]
Acid Dyspepsia DCF1IST N. A. Phase 2 [55]
Drug Interaction DC7PA0V N. A. Phase 1 [56]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 DrugCom(s)

References

1 ClinicalTrials.gov (NCT01505127) Efficacy of TAK-438, Amoxicillin and Clarithromycin in the First Line Eradication of H. Pylori
2 Clarithromycin FDA Label
3 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
4 Anti-inflammatory Clarithromycin for Improving COVID-19 Infection Early (ACHIEVE)
5 Amoxicillin FDA Label
6 Emerging therapies for the treatment and prevention of otitis media. Expert Opin Emerg Drugs. 2006 May;11(2):251-64.
7 Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
8 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
9 Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis. J Cyst Fibros. 2014 Mar;13(2):179-85.
10 Drug Interactions Flockhart Table
11 Influence of CYP2C19 polymorphism and Helicobacter pylori genotype determined from gastric tissue samples on response to triple therapy for H pylori infection. Clin Gastroenterol Hepatol. 2005 Jun;3(6):564-73.
12 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
13 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
14 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
15 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
16 A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.
17 Liver toxicity of macrolide antibiotics in zebrafish. Toxicology. 2020 Aug;441:152501. doi: 10.1016/j.tox.2020.152501. Epub 2020 May 23.
18 Differential effects of three antibiotics on T helper cell cytokine expression. J Antimicrob Chemother. 2005 Sep;56(3):502-6. doi: 10.1093/jac/dki251. Epub 2005 Jul 8.
19 T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest. 2001 Jun;107(11):1433-41. doi: 10.1172/JCI12118.
20 Effects of eight antibacterial agents on cell survival and expression of epithelial-cell- or cell-adhesion-related genes in human gingival epithelial cells. J Periodontal Res. 2004 Feb;39(1):50-8. doi: 10.1111/j.1600-0765.2004.00704.x.
21 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
22 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
23 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
24 Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
25 The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos. 2002 Jan;30(1):13-9.
26 High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
27 Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol Nutr Food Res. 2013 Mar;57(3):523-35.
28 The prevalence of beta-lactamase producing bacteria in subgingival plaque and their sensitivity to Augmentin. Br J Oral Maxillofac Surg. 1990 Jun;28(3):180-4.
29 ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages. Environ Microbiol. 2018 Jun;20(6):2288-2300.
30 Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers. Antimicrob Agents Chemother. 1990 Aug;34(8):1546-50.
31 Detection and characterization of beta-lactamase genes in subgingival bacteria from patients with refractory periodontitis. FEMS Microbiol Lett. 2005 Jan 15;242(2):319-24.
32 ACI-1 from Acidaminococcus fermentans: characterization of the first beta-lactamase in Anaerobic cocci. Antimicrob Agents Chemother. 2000 Nov;44(11):3144-9.
33 A novel quorum-quenching N-acylhomoserine lactone acylase from Acidovorax sp. strain MR-S7 mediates antibiotic resistance. Appl Environ Microbiol. 2017 Jun 16;83(13). pii: e00080-17.
34 Prevalence of antimicrobial resistance genes in Bacteroides spp. and Prevotella spp. Dutch clinical isolates. Clin Microbiol Infect. 2019 Sep;25(9):1156.e9-1156.e13.
35 Presence of the cfxA gene in Bacteroides distasonis. Res Microbiol. 2003 Jun;154(5):369-74.
36 Prevotella strains and lactamic resistance gene distribution in different oral environments of children with pulp necrosis. Int Endod J. 2018 Nov;51(11):1196-1204.
37 Interspecies dissemination of a mobilizable plasmid harboring blaIMP-19 and the possibility of horizontal gene transfer in a single patient. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5412-9.
38 IncU plasmid harbouring bla CTX-M-8 in multidrug-resistant Shigella sonnei in Brazil. J Glob Antimicrob Resist. 2018 Sep;14:99-100.
39 High prevalence of beta-lactam and macrolide resistance genes in human oral Capnocytophaga species. J Antimicrob Chemother. 2014 Feb;69(2):381-4.
40 Yersinia enterocolitica and Photorhabdus asymbiotica beta-lactamases BlaA are exported by the twin-arginine translocation pathway. Int J Med Microbiol. 2013 Jan;303(1):16-24.
41 Genomic characterization of an extensively-drug resistance Salmonella enterica serotype Indiana strain harboring bla NDM-1 gene isolated from a chicken carcass in China. Microbiol Res. 2017 Nov;204:48-54.
42 High prevalence of cfxA beta-lactamase in aminopenicillin-resistant Prevotella strains isolated from periodontal pockets. Oral Microbiol Immunol. 2002 Apr;17(2):85-8.
43 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
44 HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. PLoS One. 2013 Jul 9;8(7):e68111. doi: 10.1371/journal.pone.0068111. Print 2013.
45 Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds. Toxicol Appl Pharmacol. 2007 Dec 1;225(2):142-53.
46 Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450. J Toxicol Sci. 2016 Feb;41(1):143-6.
47 Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
48 Systemic drugs inducing non-immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP-1 cells. J Appl Toxicol. 2015 Apr;35(4):398-406. doi: 10.1002/jat.3033. Epub 2014 Aug 4.
49 Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
50 ClinicalTrials.gov (NCT03124420) Intraluminal Therapy for Helicobacter Pylori Infection
51 ClinicalTrials.gov (NCT02648659) The Pilot Study on Tailored Eradication Therapy According to Clarithromycin Resistance in H.Pylori Patients
52 ClinicalTrials.gov (NCT03139253) Antimicrobial Susceptibility Testing Guided Triple Therapy in Salvage Helicobacter Pylori Treatment
53 ClinicalTrials.gov (NCT04167670) Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Helicobacter Pylori Infection
54 ClinicalTrials.gov (NCT05861687) Recurrence Rate Comparison Between Esomeprazole and Lansoprazole in Eradicating Helicobacter Pylori Infection Among Children
55 ClinicalTrials.gov (NCT03428568) Safety Trial of Herbal Melanin in Gastritis Patients
56 ClinicalTrials.gov (NCT03011996) To Investigate PK and PD of CJ-12420, Clarithromycin, Amoxicillin After Multiple Dose Administration