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.
RCT Entities:
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.
Authors: Crystal S Denlinger; Robert W Carlson; Madhuri Are; K Scott Baker; Elizabeth Davis; Stephen B Edge; Debra L Friedman; Mindy Goldman; Lee Jones; Allison King; Elizabeth Kvale; Terry S Langbaum; Jennifer A Ligibel; Mary S McCabe; Kevin T McVary; Michelle Melisko; Jose G Montoya; Kathi Mooney; Mary Ann Morgan; Tracey O'Connor; Electra D Paskett; Muhammad Raza; Karen L Syrjala; Susan G Urba; Mark T Wakabayashi; Phyllis Zee; Nicole McMillian; Deborah Freedman-Cass Journal: J Natl Compr Canc Netw Date: 2014-03-01 Impact factor: 11.908
Authors: Alberto Briganti; Andrea Salonia; Federico Deho'; Giuseppe Zanni; Luigi Barbieri; Patrizio Rigatti; Francesco Montorsi Journal: World J Urol Date: 2005-11-05 Impact factor: 4.226
Authors: Crystal S Denlinger; Tara Sanft; K Scott Baker; Shrujal Baxi; Gregory Broderick; Wendy Demark-Wahnefried; Debra L Friedman; Mindy Goldman; Melissa Hudson; Nazanin Khakpour; Allison King; Divya Koura; Elizabeth Kvale; Robin M Lally; Terry S Langbaum; Michelle Melisko; Jose G Montoya; Kathi Mooney; Javid J Moslehi; Tracey O'Connor; Linda Overholser; Electra D Paskett; Jeffrey Peppercorn; M Alma Rodriguez; Kathryn J Ruddy; Paula Silverman; Sophia Smith; Karen L Syrjala; Amye Tevaarwerk; Susan G Urba; Mark T Wakabayashi; Phyllis Zee; Deborah A Freedman-Cass; Nicole R McMillian Journal: J Natl Compr Canc Netw Date: 2017-09 Impact factor: 11.908