Details of the Drug Combination

General Information of Drug Combination (ID: DCW83WS)

• Drug Combination Name: Fluvoxamine + Ketoconazole
• Indication: Pharmacology, Clinical; Status: Phase 1 [1]
• Component Drugs:
  Fluvoxamine (DMQTJSX): Small molecular drug
  Ketoconazole (DMPZI3Q): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fluvoxamine

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[2]
Obsessive compulsive disorder	6B20	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

Fluvoxamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[7]

Fluvoxamine 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]

Fluvoxamine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[10]

Indication(s) of Ketoconazole

Disease Entry	ICD 11	Status	REF
Blastomycosis	1F22	Approved	[5]
Chromomycosis	N.A.	Approved	[5]
Coccidioidomycosis	1F25	Approved	[5]
Cutaneous candidiasis	1F23.14	Approved	[5]
Fungal infection	1F29-1F2F	Approved	[6]
Histoplasmosis	N.A.	Approved	[5]
Invasive candidiasis	1F23	Approved	[5]
Mycoses	1F2Z	Approved	[5]
Oral candidiasis	1F23.0	Approved	[5]
Paracoccidioidomycosis	N.A.	Approved	[5]
Pityriasis simplex	N.A.	Approved	[5]
Prostate adenocarcinoma	N.A.	Approved	[5]
Tinea corporis	1F28.Y	Approved	[5]
Tinea cruris	1F28.3	Approved	[5]
Tinea versicolor	1F2D.0	Approved	[5]
Tinea pedis	1F28.2	Investigative	[5]

Ketoconazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Candida Cytochrome P450 51 (Candi ERG11)	TTTSOUD	CP51_CANAL	Inhibitor	[11]

Ketoconazole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Ketoconazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]

Ketoconazole Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases ADR	[10]

References

• [1] ClinicalTrials.gov (NCT01707407) A Phase 1 Open-Label Study to Evaluate the Effect of CYP450 and P-gp Inhibition and Induction on the Pharmacokinetics of Pomalidomide (CC-4047) in Healthy Male 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: 7189).
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 075893.
• [4] ClinicalTrials.gov (NCT04342663) A Double-blind, Placebo-controlled Clinical Trial of Fluvoxamine for Symptomatic Individuals With COVID-19 Infection. U.S. National Institutes of Health.
• [5] Ketoconazole FDA Label
• [6] 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: 2568).
• [7] Changes of functional MRI findings in a patient whose pathological gambling improved with fluvoxamine. Yonsei Med J. 2009 Jun 30;50(3):441-4.
• [8] Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates. J Pharm Pharmacol. 2004 Aug;56(8):967-75.
• [9] Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015 Aug;98(2):127-34.
• [10] 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.
• [11] Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302.
• [12] 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.
• [13] The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59.