Drug General Information (ID: DDIODBW4RE)
Drug Name			Theophylline		Drug Info		Riociguat		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Bronchodilators				Vasodilator Agents
Structure

Mechanism of Theophylline-Riociguat Interaction (Severity Level: Major)
Additive hypotensive effects Click to Show/Hide Mechanism Graph
Drug Name		Theophylline				Riociguat
Mechanism		Hypotensive effects Phosphodiesterase 4  Inhibitor				Hypotensive effects Soluble guanylyl cyclase  Agonist
Key Mechanism Factor 1
		Factor Name		Phosphodiesterase 4				Structure Sequence
		Protein Family		Cyclic nucleotide phosphodiesterase family
		Protein Function		Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes.     Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Guanylate cyclase soluble				Structure Sequence
		Protein Family		Adenylyl cyclase class-4/guanylyl cyclase family
		Protein Function		Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP.     Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Theophylline and Riociguat

Recommended Action
Management		Concomitant use of riociguat with PDE inhibitors, including specific PDE-5 inhibitors (e.g., avanafil, sildenafil, tadalafil, vardenafil) or nonspecific PDE inhibitors (e.g., dipyridamole, theophylline), is considered contraindicated. Riociguat should be discontinued at least 24 hours before administering a PDE-5 inhibitor, and avoidance of riociguat administration within 24 hours after sildenafil or within 48 hours after tadalafil is recommended. Limited data exists for other PDE inhibitors.

References
1	Cerner Multum, Inc. "Australian Product Information.".
2	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3	Product Information. Adempas (riociguat). Bayer Pharmaceutical Inc, West Haven, CT.