Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI89LNKDX)
Drug Name			Clevidipine		Drug Info		Avanafil		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensives Agent				Impotence Agents
Structure

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

Drug Name		Clevidipine				Avanafil
Mechanism		Antihypertensive agent Calcium channel unspecific Blocker				Hypotensive effects Phosphodiesterase 5A Inhibitor
Key Mechanism Factor 1
		Factor Name		Voltage-dependent L-type calcium channel				Structure Sequence
		Protein Family		Calcium channel beta subunit family
		Protein Function		Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:8107964, PubMed:15615847). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964). Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Phosphodiesterase 5A				× Structure Sequence MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAERVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
		Gene Name		PDE5A
		Uniprot ID		PDE5A_HUMAN
		KEGG Pathway		hsa:8654
		Protein Family		Cyclic nucleotide phosphodiesterase family
		Protein Function		Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334). Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Clevidipine and Avanafil

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.