INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are indicated for the 
treatment of erectile dysfunction (ED); however, they can also inhibit other PDE 
isozymes, affecting their target tissues (e.g., PDE1: heart; PDE6: retina; and 
PDE11: skeletal muscle), which in some cases can cause unwanted side effects and 
therapy discontinuation. Data from in vitro studies showed that avanafil, a PDE5 
inhibitor for the treatment of ED, exhibited strong selectivity toward PDE5 and 
against all other PDE isozymes.
AIM: To review the inhibitory effects of avanafil for PDE isozymes compared with 
those of sildenafil, tadalafil, and vardenafil and to discuss these results 
within the context of clinical trial safety observations.
METHODS: Review of in vitro selectivity data for avanafil (published primary 
data from a peer-reviewed journal and scientific congress abstracts); PubMed 
search for pertinent publications on PDE5 inhibitor safety data; and review of 
published articles and abstracts from avanafil phase 1, 2, and 3 clinical 
trials.
MAIN OUTCOME MEASURES: A low incidence of some PDE-related adverse events may be 
reflected by the high selectivity of avanafil against non-PDE5 isozymes.
RESULTS: Avanafil is highly selective toward PDE5 and against all other PDE 
isozymes tested. Lower selectivity against PDE1, PDE6, and PDE11 is consistent 
with results from randomized, placebo-controlled, phase 3 trials in which 
musculoskeletal and hemodynamic adverse events were reported in <2% of patients 
and no color vision-related abnormalities were reported with avanafil doses up 
to 200 mg once daily.
CONCLUSIONS: Data suggest that avanafil may confer a safety benefit, in terms of 
a lower incidence of specific adverse events, by virtue of its high specificity 
to PDE5 and its overall selectivity against other PDE isozymes.