This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kloner, R. A. Articles by Jackson, G. Search for Related Content PubMed PubMed Citation Articles by Kloner, R. A. Articles by Jackson, G.

EXPRESS PUBLICATION

Time course of the interaction between tadalafil and nitrates

Robert A. Kloner, MD, PhD^*,*, Adolph M. Hutter, MD, Jeffrey T. Emmick, MD, PhD, Malcolm I. Mitchell, MBBS, MFPM, Jonathan Denne, PhD and Graham Jackson, MD^||

^* The Heart Institute, Good Samaritan Hospital, Cardiovascular Division, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Eli Lilly and Company, Indianapolis, Indiana, USA
Erl Wood Manor, Windlesham, Surrey, United Kingdom;
^|| Guys and St. Thomas Hospital, London, United Kingdom

^* Reprint requests and correspondence: Dr. Robert A. Kloner, Good Samaritan Hospital, Cardiovascular Division, 1225 Wilshire Boulevard, Los Angeles, California 90017, USA.
rkloner{at}goodsam.org

OBJECTIVES: This study was designed to determine the time course of nitrate interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half-life (t_1/2) of 17.5 h.

BACKGROUND: The PDE5 inhibitors augment the blood pressure (BP)-lowering effects of nitrates, yet the time course of this interaction is unclear. Recent guidelines from the American College of Cardiology/American Heart Association recommend that nitrates be withheld for 24 h after taking sildenafil (t_1/2 = 4 h).

METHODS: Male subjects (n = 150) received seven consecutive daily doses of placebo or tadalafil (20 mg). On day 7 and beyond, subjects received repeated doses of sublingual nitroglycerin (0.4 mg) after the last dose of placebo or tadalafil. After a 10- to 21-day washout period, subjects crossed over to either placebo or tadalafil, and nitrate dosing was repeated.

RESULTS: In response to nitroglycerin at 4, 8, and 24 h, standing systolic BP fell below 85 mm Hg in more subjects on tadalafil compared with placebo (p < 0.05), with no difference in the response to nitroglycerin at 48, 72, and 96 h (p > 0.2). Similar observations were made for standing diastolic BP <45 mm Hg, decrease in systolic BP >30 mm Hg, and decrease in diastolic BP >20 mm Hg. Nitroglycerin also evoked greater mean maximal decreases in standing systolic BP at 8 and 24 h after taking tadalafil versus placebo (p < 0.02), with no significant difference at 48, 72, or 96 h (p > 0.49).

CONCLUSIONS: The hemodynamic interaction between tadalafil and sublingual nitroglycerin lasted 24 h, but was not seen at 48 h and beyond. Similar to other PDE5 inhibitors, tadalafil should not be administered in combination with organic nitrates.

Abbreviations and Acronyms   BP = blood pressure   cGMP = cyclic guanosine monophosphate   PDE5 = phosphodiesterase 5   t1/2 = half-life

This article has been cited by other articles:

				J. W. M. Cheng and S. R. Berhane Managing Erectile Dysfunction in Patients With Cardiovascular Diseases: The Efficacy and Safety of Phosphodiesterase-5 Inhibitors American Journal of Lifestyle Medicine, May 1, 2009; 3(3): 201 - 211. [Abstract] [PDF]

				M. J Boyle A dramatic drop in blood pressure following prehospital GTN administration Emerg. Med. J., March 1, 2007; 24(3): 225 - 226. [Abstract] [Full Text] [PDF]

				C. E. Teixeira, F. B. M. Priviero, and R. C. Webb Differential Effects of the Phosphodiesterase Type 5 Inhibitors Sildenafil, Vardenafil, and Tadalafil in Rat Aorta J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 654 - 661. [Abstract] [Full Text] [PDF]

				P. Aguiar-Souto, L. Silva-Melchor, F. J. Ortigosa-Aso, and J. Abrams Chronic Stable Angina N. Engl. J. Med., October 6, 2005; 353(14): 1524 - 1524. [Full Text] [PDF]

				R. A. Kloner Cardiovascular Effects of the 3 Phosphodiesterase-5 Inhibitors Approved for the Treatment of Erectile Dysfunction Circulation, November 9, 2004; 110(19): 3149 - 3155. [Full Text] [PDF]

				D. A. Norwood, N. E. Eraikhuemen, M. Larose-Pierre, E. Branch III, and R. M. Norwood Advances in the Treatment of Erectile Dysfunction: A Focus on Tadalafil Journal of Pharmacy Practice, August 1, 2004; 17(4): 239 - 250. [Abstract] [PDF]

				J. Abrams Time course of the interaction between tadalafil and nitrates J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2150 - 2150. [Full Text] [PDF]

				R. A. Kloner, A. M. Hutter, J. T. Emmick, M. I. Mitchell, J. Denne, and G. Jackson Reply J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2150 - 2151. [Full Text] [PDF]

				Nitroglycerin and the Newest Drug for Erectile Dysfunction Journal Watch Cardiology, February 13, 2004; 2004(213): 2 - 2. [Full Text]