Hemodynamic effect of avanafil and glyceryl trinitrate coadministration

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Abstract

A Phase I, double-blind, randomized, crossover study in healthy males (N=106) was conducted between March 21, 2004, and May 17, 2004, to determine the magnitude and duration of the hemodynamic interaction of avanafil (a phosphodiesterase type-5 inhibitor for treating males with erectile dysfunction) when coadministered with glyceryl trinitrate (NTG) compared with sildenafil and placebo. Subjects received avanafil (200 mg), sildenafil (100 mg), and placebo (on separate days) via the oral route followed by NTG (0.4 mg) 12, 8, 4, 1, or 0.5 hours post-dose via the sublingual route. Blood pressure (BP) and heart rate (HR) were assessed at defined intervals.

Throughout the study (after administration of the study drug, and including the period after NTG administration), the effects of avanafil and sildenafil on BP and HR were significantly greatest overall, at the shortest (0.5-hour) time interval compared with placebo. By the 8- and 12-hour time intervals, no significant difference in BP or HR was observed for avanafil (8 and 12 hours) or sildenafil (12 hours) (p>0.05, compared with placebo). Compared with avanafil, sildenafil had a significantly greater effect when dosed 0.5 hours before NTG on standing HR (p=0.05); 1 hour before NTG on standing systolic blood pressure (SBP) (p<0.05), sitting SBP (p=0.01) and standing HR (p<0.01); and 12 hours before NTG on standing SBP (p=0.05). Throughout the study, symptomatic hypotension adverse events occurred in 27%, 29%, and 12%, and clinically significant reductions in standing SBP (≥30 mmHg) occurred in 15%, 29%, and 12% of subjects dosed with avanafil, sildenafil, and placebo, respectively (overall treatment differences: p<0.01 and p<0.05,
respectively).

These data show that avanafil and sildenafil have no significant effect on BP and HR if administered to healthy males ≥8 hours (avanafil) or ≥12 hours (sildenafil) before a sublingual dose of NTG. However, results may differ in populations with known vascular disease, especially those using other concurrent pharmacotherapy. These findings may be of interest to clinicians who treat patients with erectile dysfunction and who also have a cardiovascular condition. Of note, the applicability of these results in such patients may be limited because the enrollment comprised healthy, normal subjects.

Keywords: avanafil, PDE5 inhibitor, erectile dysfunction, hypotension, drug–drug interaction, nitrates

Citation: Swearingen D, Nehra A, Morelos S, Peterson CA. Hemodynamic effect of avanafil and glyceryl trinitrate coadministration. Drugs in Context 2013;212248. doi: 10.7573/dic.212248

Provenance: Submitted; externally peer reviewed

DatesSubmitted: 28 November 2012; Accepted, subject to peer review: 7 December 2012; Published: 26 February 2013

Copyright: © 2013 Swearingen D, Nehra A, Morelos S, Peterson CA. This is an open-access article distributed under the terms of the Creative Commons Attribution License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute and transmit the article provided it is properly attributed in the manner specified below. No other uses without permission.

Correct attribution: Copyright © 2013 Swearingen D, Nehra A, Morelos S, Peterson CA. http://dx.doi.org/10.7573/dic.212248. Published by Drugs in Context under Creative Commons Attribution License Deed CC BY NC ND 3.0.

Correspondence: Dennis Swearingen, MD, CPI, Principal Investigator, Site Medical Director, Celerion, 2420 West Baseline Road, Tempe, AZ 85283, USA

Emaildennis.swearingen@celerion.com

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