The present invention relates to derivatives of tadalafil represented by the formula: or a salt thereof, wherein: X1 and X2 are simultaneously fluoro; or X1 is deuterium and X2 is selected from hydrogen or deuterium; each Y is independently selected from deuterium or hydrogen; the hydrogen attached to the indole nitrogen is optionally replaced by deuterium; and each carbon is independently optionally replaced by 13C. These compounds are selective PDE5 inhibitors and possess advantageous biopharmaceutical and pharmacokinetic properties. The invention further provides compositions comprising these compounds and methods of treating diseases and conditions that are responsive to PDE5 inhibition, alone and in combination with additional agents.