Details of the Drug Combination

General Information of Drug Combination (ID: DCD6K9J)

• Drug Combination Name: Lumacaftor + Ivacaftor
• Indication: Cystic Fibrosis; Status: Phase 1 [1]
• Component Drugs:
  Lumacaftor (DMCLWDJ): Small molecular drug
  Ivacaftor (DMZC1HS): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lumacaftor

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Phase 2	[2]

Lumacaftor Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
cAMP-dependent chloride channel (CFTR)	TTRLZHP	CFTR_HUMAN	Regulator	[4]

Lumacaftor Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Affects Folding	[5]

Indication(s) of Ivacaftor

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Approved	[3]

Ivacaftor Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
cAMP-dependent chloride channel (CFTR)	TTRLZHP	CFTR_HUMAN	Modulator	[6]

Ivacaftor Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Ivacaftor Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]

Ivacaftor Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Increases Activity	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Cystic fibrosis; Acute lung injury	DCEIVC9	N. A.	Approved	[10]

References

• [1] ClinicalTrials.gov (NCT01768663) A Phase 1 Study to Examine the Drug-Drug Interaction of Ciprofloxacin, Itraconazole, and Rifampin on the Combination of Lumacaftor With Ivacaftor in Healthy Adult Subjects
• [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: 7481).
• [3] 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: 4342).
• [4] A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38.
• [5] Novel Therapy of Bicarbonate, Glutathione, and Ascorbic Acid Improves Cystic Fibrosis Mucus Transport. Am J Respir Cell Mol Biol. 2020 Sep;63(3):362-373. doi: 10.1165/rcmb.2019-0287OC.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Investigation of the effects of the CFTR potentiator ivacaftor on human P-glycoprotein (ABCB1). Sci Rep. 2017 Dec 13;7(1):17481.
• [8] Sensitivity of ivacaftor to drug-drug interactions with rifampin, a cytochrome P450 3A4 inducer. Pediatr Pulmonol. 2018 May;53(5):E6-E8.
• [9] Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825.
• [10] FDA Drug Development and Drug Interactions