Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI901TVM6)
Drug Name			Sildenafil		Drug Info		Aliskiren		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Impotence Agents/Agents For Pulmonary Hypertension				Antihypertensive Agents
Structure

Mechanism of Sildenafil-Aliskiren Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Sildenafil				Aliskiren
Mechanism		Hypotensive effects Prostacyclin receptor Agonist				Antihypertensive agent Angiotensinogenase Inhibitor
Key Mechanism Factor 1
		Factor Name		Prostacyclin receptor				× Structure Sequence MADSCRNLTYVRGSVGPATSTLMFVAGVVGNGLALGILSARRPARPSAFAVLVTGLAATDLLGTSFLSPAVFVAYARNSSLLGLARGGPALCDAFAFAMTFFGLASMLILFAMAVERCLALSHPYLYAQLDGPRCARLALPAIYAFCVLFCALPLLGLGQHQQYCPGSWCFLRMRWAQPGGAAFSLAYAGLVALLVAAIFLCNGSVTLSLCRMYRQQKRHQGSLGPRPRTGEDEVDHLILLALMTVVMAVCSLPLTIRCFTQAVAPDSSSEMGDLLAFRFYAFNPILDPWVFILFRKAVFQRLKLWVCCLCLGPAHGDSQTPLSQLASGRRDPRAPSAPVGKEGSCVPLSAWGEGQVEPLPPTQQSSGSAVGTSSKAEASVACSLC
		Gene Name		PTGIR
		Uniprot ID		PI2R_HUMAN
		KEGG Pathway		hsa:5739
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Angiotensinogenase renin				× Structure Sequence MDGWRRMPRWGLLLLLWGSCTFGLPTDTTTFKRIFLKRMPSIRESLKERGVDMARLGPEWSQPMKRLTLGNTTSSVILTNYMDTQYYGEIGIGTPPQTFKVVFDTGSSNVWVPSSKCSRLYTACVYHKLFDASDSSSYKHNGTELTLRYSTGTVSGFLSQDIITVGGITVTQMFGEVTEMPALPFMLAEFDGVVGMGFIEQAIGRVTPIFDNIISQGVLKEDVFSFYYNRDSENSQSLGGQIVLGGSDPQHYEGNFHYINLIKTGVWQIQMKGVSVGSSTLLCEDGCLALVDTGASYISGSTSSIEKLMEALGAKKRLFDYVVKCNEGPTLPDISFHLGGKEYTLTSADYVFQESYSSKKLCTLAIHAMDIPPPTGPTWALGATFIRKFYTEFDRRNNRIGFALAR
		Gene Name		REN
		Uniprot ID		RENI_HUMAN
		KEGG Pathway		hsa:5972
		Protein Family		Peptidase A1 family
		Protein Function		Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney. Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Sildenafil and Aliskiren

Recommended Action
Management		Caution is advised if PDE5 inhibitors are prescribed in combination with antihypertensive agents. Patients receiving the combination should be advised to avoid rising abruptly from a sitting or recumbent position, especially following treatment initiation or a dosage increase, and to contact their doctor if they experience symptoms of hypotension such as dizziness, lightheadedness, fainting, or tachycardia.

References
1	Product Information. Levitra (vardenafil). Bayer, West Haven, CT.
2	Product Information. Stendra (avanafil). Vivus Inc, Mountain View, CA.
3	Product Information. Viagra (sildenafil). Pfizer US Pharmaceuticals, New York, NY.