Safety and drug interactions
As with every PDE5 inhibitor, tadalafil is absolutely contraindicated with nitrate medications for angina pectoris secondary to the potentiated hypotensive effect the drugs can have together. Because of the longer half-life, treatment with nitrate medications must be deferred for at least 48 hours after ingestion of tadalafil, compared with 24 hours for sildenafil (Viagra) and vardenafil (Levitra).
The cardiac effects of PDE5 inhibitors have received considerable attention because the drugs were originally studied as a treatment for angina pectoris secondary to their action of smooth muscle relaxation. All of the PDE5 inhibitor trials have tediously monitored study participants’ vital signs, particularly heart rate and blood pressure, monitored drug effects on cardiac electrophysiology, and tabulated the numbers of cardiovascular adverse events.
In a review of more than 4000 patients from over 60 studies, data reported by Kloner and co-workers contended that tadalafil does cause small changes in blood pressure secondary to its vasodilatory properties, but that the changes were not clinically meaningful. In a separate, more recent study, the same author retrospectively reviewed serious cardiovascular treatment-emergent adverse events reported in 36 tadalafil trials and found that the incidence of these events were comparable among patients taking canadian tadalafil as needed, 3 times per week, once-daily, and placebo.
The Second Princeton Consensus Conference, an expert conference on sexual dysfunction and cardiac risk, convened in 2004 to develop practice guidelines for the management of ED in patients with significant cardiac risk. After reviewing all available literature, the Second Princeton Consensus Conference not only determined that patients with significant cardiac risk factors did not exhibit worsening ischemia or unstable hemodynamics while taking PDE5 inhibitors, but also that cardiovascular function was actually improved by PDE5 inhibitors in some studies. Although reported with vardenafil, prolongation of the QTc interval is not observed with tadalafil professional.
Tadalafil does not cause increased hypotension or orthostatic hypotension in men that are also taking multiple antihypertensive medications, and it is safe and well tolerated in this population. The primary exception is with α-blockers. Frequently prescribed for men with benign prostatic hyperplasia (BPH) as well as for men with hypertension, α-blockers share a similar mechanism of action with PDE5 inhibitors through peripheral vasodilation and may have more of an additive effect than other antihypertensives. Recently, the FDA changed its previous recommendation from contraindicated co-administration to precautionary co-administration. In a study of the blood pressure effects of tadalafil coupled with either of two α-blockers, doxazosin (Cardura; Pfizer, New York, NY, USA) and tamsulosin (Flomax; Boehringer Ingelheim, Ridgefield, CT, USA), the hypotensive effect of doxazosin was exaggerated by almost 10 mmHg with tadalafil while there was no change in blood pressure with cheap tamsulosin and cheap tadalafil. The authors concluded canadian tamsulosin to be a safe α-blocker to administer concurrently with tadalafil. Until more studies are available, precaution is recommended with the co-administration of tadalafil with any α-blocker, including mixed α-blockers such as labetalol and carvedilol.
Because of its metabolism through the cytochrome P450 pathway, tadalafil (Cialis Professional) is susceptible to changes in serum concentration by other drugs that inhibit or promote its metabolism. Inhibitors of the CYP34A enzyme include ketoconazole, erythromycin, grapefruit juice, and protease inhibitors, and co-administration of these drugs with tadalafil may increase serum concentrations of tadalafil. On the contrary, co-administration with inducers of CYP34A including rifampin, carbamazepine, phenytoin, and phenobarbital, would require a larger dose of tadalafil for a similar clinical effect.