Details of the Drug Combination

General Information of Drug Combination (ID: DCH4YYZ)

• Drug Combination Name: Simeprevir + Sofosbuvir
• Indication: Hepatitis C Virus; Status: Phase 2 [1]
• Component Drugs:
  Simeprevir (DMLUA9D): Small molecular drug
  Sofosbuvir (DMQI86A): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Simeprevir

Disease Entry	ICD 11	Status	REF
Chronic HCV-1 infection	1E51.1	Approved	[2]
Renal hypoplasia	N.A.	Approved	[3]

Simeprevir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A)	TTHC7JD	POLG_HCV1	Modulator	[5]

Simeprevir Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]

Simeprevir Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Indication(s) of Sofosbuvir

Disease Entry	ICD 11	Status	REF
Hepatitis C	1E51	Approved	[4]

Sofosbuvir Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hepatitis C Virus Infection	DC3E5HG	N. A.	Phase 3	[11]
Hepatitis C, Chronic	DCEALG2	N. A.	Phase 2	[12]
Hepatitis C, Chronic	DCF1ADA	N. A.	Phase 2	[13]

References

• [1] ClinicalTrials.gov (NCT02349048) Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7367).
• [3] Simeprevir FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [7] Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. Clin Pharmacokinet. 2016 Feb;55(2):197-208.
• [8] Hepatitis C virus direct-acting antiviral drug interactions and use in renal and hepatic impairment. Top Antivir Med. 2015 May-Jun;23(2):92-6.
• [9] Cytochrome P450 3A Induction Predicts P-glycoprotein Induction; Part 2: Prediction of Decreased Substrate Exposure After Rifabutin or Carbamazepine. Clin Pharmacol Ther. 2018 Dec;104(6):1191-1198.
• [10] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
• [11] ClinicalTrials.gov (NCT02114151) Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis
• [12] ClinicalTrials.gov (NCT02421211) A Study to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir, and Ledipasvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection
• [13] ClinicalTrials.gov (NCT02262728) An Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease