How has the safety of tadalafil been assessed?

Regulatory agencies around the world have  approved up to once-daily dosing of tadalafil  at doses of up to 20 mg. The safety of a drug is  determined by the monitoring of adverse  events reported in humans that take a drug  during clinical trials or in a real-world setting.  The evidence of the safety of tadalafil is based  on data from over 12,000 patients in over 100  studies, including men who have taken tadalafil  10 mg or 20 mg daily for up to 6 months,  and global safety monitoring from use in  nearly 3 million men.

The safety of tadalafil  is continually monitored worldwide to add to  this core safety database.  In a long-term (18 to 24 months) study of  tadalafil taken as needed, 493 men completed  24 months of treatment, and a further 234  completed 18 months of treatment. The total  tadalafil exposure was 1676.0 patient-years.  The rate of discontinuations due to adverse  events for this 18 to 24 month duration study  was 6.3% and the rate of discontinuation for  any individual adverse event was <1%.  No consistent pattern of serious adverse  events assessed as causally associated with  tadalafil administration was observed in this  study. None of the four deaths that occurred  during the study was assessed as tadalafil  related. There were no clinically significant  laboratory abnormalities, electrocardiographic  findings, or changes in vital signs in  mean baseline-to-endpoint analysis attributable  to tadalafil. Tadalafil administration was  not causally associated with hepatotoxicity,  neutropenia, thrombocytopenia, or renal  dysfunction. As a result, tadalafil at doses of  5, 10, or 20 mg taken as needed up to once  daily for 18 to 24 months was considered to  be safe and well tolerated. [Cardiac safety will  be discussed below].  The safety profile of any medication, including  tadalafil, is established by a combination  of clinical pharmacology trials exploring  drug interactions, placebo controlled efficacy  and safety trials, long-term, open-label safety  studies, and finally post-marketing surveillance.  To date, studies have shown that even  with long-term use, inhibition of PDE5 can be  used to treat ED safely and effectively  [49,50,55–57].