Tadalafil (Generic) Pre-Surgery Hold Window: What Patients and Clinicians Need to Know

What the Cialis label says about timing

Generic tadalafil 2.5, 5, 10 and 20 mg tablets are approved under ANDAs and follow the Cialis indications [2]. In the Cialis label the time-based rule concerns nitrates, not surgery. The label contraindicates any form of organic nitrate, taken regularly or intermittently, and says tadalafil was shown to potentiate the hypotensive effect of nitrates [1]. The same section contraindicates guanylate cyclase stimulators such as riociguat [1].

The 48-hour figure is the emergency exception for a life-threatening situation. The label does not offer it as a routine spacing rule or as permission to combine the drugs [1].

Half-life and duration of effect

Tadalafil's mean terminal half-life is 17.5 hours in healthy subjects. Peak concentrations arrive between 30 minutes and 6 hours (median 2 hours) after a dose [1]. The label says one as-needed dose improves erectile function versus placebo for up to 36 hours [1]. Once-daily dosing reaches steady state within 5 days at about 1.6 times single-dose exposure. The label says once-daily use gives continuous plasma levels and that this should be considered when evaluating interactions with nitrates, alpha-blockers, antihypertensives and potent CYP3A4 inhibitors [1].

What a nitroglycerin challenge showed

Kloner et al. reported the time course in the Journal of the American College of Cardiology in 2003. In 150 men, tadalafil 20 mg or placebo was given daily for 7 days, followed by sublingual nitroglycerin 0.4 mg. The groups crossed over after a 10- to 21-day washout [3].

At 4, 8 and 24 hours after the last dose, standing systolic pressure fell below 85 mm Hg in more men on tadalafil than on placebo (P<0.05). At 48, 72 and 96 hours there was no significant difference [3]. The authors concluded the interaction lasted 24 hours and was not seen at 48 hours [3]. The study tested tadalafil with sublingual nitroglycerin. It did not test surgery, anesthesia, surgical outcomes, or different preoperative hold periods [3].

Alpha-blockers add to the blood pressure effect

Alpha-blockers and tadalafil both lower blood pressure, and the label says the effect is additive [1]. With doxazosin 8 mg daily, tadalafil 20 mg gave a placebo-subtracted maximal standing systolic fall of 9.8 mm Hg [1]. For ED, the label says to be stable on the alpha-blocker first and start tadalafil at the lowest dose. For BPH, it does not recommend the combination [1].