Details of the Drug Combination

General Information of Drug Combination (ID: DCLWWW5)

• Drug Combination Name: Sildenafil + Tadalafil
• Indication: Erectile Dysfunction; Status: Phase 1 [1]
• Component Drugs:
  Sildenafil (DM4YDAJ): Small molecular drug
  Tadalafil (DMJZHT1): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sildenafil

Disease Entry	ICD 11	Status	REF
Alveolar capillary dysplasia with misalignment of pulmonary veins	N.A.	Approved	[2]
Erectile dysfunction	HA01.1	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
Respiratory failure	CB41	Investigative	[2]

Sildenafil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HUMAN phosphodiesterase type 5 (PDE5)	TTRYFSB	PDE5A_HUMAN	Inhibitor	[7]

Sildenafil Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)	OTA6HYBA	GBB3_HUMAN	Increases Response	[8]
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Increases Response	[9]

Indication(s) of Tadalafil

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[5]
Erectile dysfunction	HA01.1	Approved	[6]
Plasma cell myeloma	2A83.1	Approved	[5]
Pulmonary hypertension	BB01	Approved	[5]
Priapism	N.A.	Investigative	[5]

Tadalafil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 5A (PDE5A)	TTJ0IQB	PDE5A_HUMAN	Inhibitor	[10]

Tadalafil Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

Tadalafil Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]

Tadalafil Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A)	OTT8Q1AP	PDE5A_HUMAN	Decreases Activity	[13]

References

• [1] ClinicalTrials.gov (NCT01352507) A Study of Tadalafil and Sildenafil in Men With Erectile Dysfunction in China
• [2] Sildenafil FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 206401.
• [4] ClinicalTrials.gov (NCT04304313) A Pilot Study of Sildenafil in COVID-19. U.S. National Institutes of Health.
• [5] Tadalafil 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: 7299).
• [7] Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol. 2005 Feb;79(3):1966-9. doi: 10.1128/JVI.79.3.1966-1969.2005.
• [8] Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study. J Urol. 2003 Mar;169(3):1048-51. doi: 10.1097/01.ju.0000058369.72348.ba.
• [9] ACE gene I/D and NOS3 G894T polymorphisms and response to sildenafil in men with erectile dysfunction. Urology. 2003 Jul;62(1):152-7. doi: 10.1016/s0090-4295(03)00137-7.
• [10] Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
• [11] In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil. Biol Pharm Bull. 2017;40(8):1314-1319.
• [12] Contribution of CYP3A isoforms to dealkylation of PDE5 inhibitors: a comparison between sildenafil N-demethylation and tadalafil demethylenation. Biol Pharm Bull. 2015;38(1):58-65.
• [13] Pharmacotherapy of erectile dysfunction: focus on cardiovascular safety. Expert Opin Drug Saf. 2005 May;4(3):531-40. doi: 10.1517/14740338.4.3.531.