Key result
Tadalafil significantly increases nitroglycerin-induced standing hypotension vs. placebo for up to 24 hours.
Why the study?
The time course of the hemodynamic interaction between tadalafil and nitrates was unclear despite known augmentation of blood pressure-lowering effects by PDE5 inhibitors.
Does tadalafil augment the hypotensive effects of sublingual nitroglycerin over time in male subjects?
RCT (n=150)
Does tadalafil augment the hypotensive effects of sublingual nitroglycerin over time in male subjects?
p-value: p=<0.05
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Viagra has about a four-hour window, but Cialis is a 24-hour medication. If they've taken an ED drug and if they were to pop one or two nitros because of chest pain, they still stand the risk of potentially having some concomitant effect together and can drop their blood pressure.”
“if they've used the erectile dysfunction agent in the past 24 to 48 hours, depending on which agent they used, they absolutely cannot pop one of the sublingual nitros”
“Spacing out doses of erectile dysfunction and nitrate medications will decrease the chances that there will be a drug interaction.”
The clinically significant hypotensive interaction between tadalafil and sublingual nitroglycerin lasts up to 24 hours, but dissipates by 48 hours.
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.
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Kloner et al. (2003) reported an RCT. Tadalafil vs. Placebo was evaluated on Standing systolic blood pressure falling below 85 mm Hg after sublingual nitroglycerin administration (p=<0.05). Tadalafil increased the occurrence of standing systolic blood pressure <85 mm Hg in response to sublingual nitroglycerin at 4, 8, and 24 hours compared with placebo (p<0.05).
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