Title:Update on Drug Interactions With Phosphodiesterase-5 Inhibitors Prescribed as First-Line Therapy for Patients with Erectile Dysfunction or Pulmonary Hypertension
VOLUME: 14 ISSUE: 2
Author(s):Serap Gur, Philip J. Kadowitz, Ahmet Gokce, Suresh C. Sikka, Utku Lokman and Wayne J.G. Hellstrom
Affiliation:Section of Andrology, Tulane University, Health Sciences Center, Department of Urology, 1430 Tulane Avenue, SL-42, New Orleans, LA 70112, USA.
Keywords:PDE5 inhibitor, tadalafil, sildenafil, bosentan, erectile dysfunction, pulmonary hypertension, Drug Interactions, Phosphodiesterase-5 Inhibitors, First-Line Therapy, PDE5i, Vardenafil, PAH, Microsomes, Avanafil
Abstract:Phosphodiesterase-5 inhibitors (PDE5i, sildenafil, vardenafil, tadalafil and avanafil) are a first-line medical therapy for erectile
dysfunction (ED). In all likelihood, PDE5i usage will increase because sildenafil (Viagra® and Revatio®) and tadalafil (Cialis® and Adcirca
®) have recently been recommended as first-line therapy for patients with pulmonary hypertension (PH). PDE5i exhibit higher
plasma concentrations when co-administered with cytochrome P (CYP) 3A inhibitors, which influences their side-effect profile. The
higher PDE5i plasma concentrations, caused by CYP3A inhibitors, influence the severity and timing of PDE5i drug interactions and require
dose adjustment. PDE5i are safe when used with most antihypertensive agents, but co-administration with nitrates or α-blockers can
cause severe hypotension and syncope. Dose adjustment is also necessary when PDE5i are co-administered with CYP3A inducers. The
combination of oral tadalafil and bosentan (endothelin receptor antagonist) reduces tadalafil levels and requires dose adjustment. Current
literature reports a number of interactions between PDE5i and other agents and further studies are needed to expand our knowledge base
of these interactions. This review discusses relevant PDE5i drug interactions, including those with CYP 450 inhibitors and inducers
which are frequently used during the treatment of ED and PH.
