PURPOSE: Although only the 40-mg daily dose of tadalafil is approved, clinicians sometimes initiate treatment at the lower off-label 20-mg dose and then titrate up to 40-mg, in an attempt to diminish adverse events (AE), with potential compromise of efficacy. To evaluate AEs over time in cohorts receiving the 20-mg and 40-mg daily doses at week 16 (PHIRST-1 trial) and up to 68 weeks of open label (PHIRST-2 trial) we examined the dose relationship of common AEs.
METHODS: Treatment arms across both studies included placebo (n=82), 20-mg tadalafil (n=82) and 40-mg tadalafil (n=154; included patients on placebo and 40-mg tadalafil in PHIRST-1 trial who received 40 mg tadalafil in PHIRST-2 study). Incidence of common AEs (defined as an event occurring any time during the interval measured) was analyzed at week 1 and at quartiles (week 2-68).
RESULTS: In the PHIRST-1 trial, headache was the most common AE at week 16 in the tadalafil 40-mg (9%) and 20-mg (9%) groups compared with placebo (7%). By 68 weeks, headache was slightly less prominent in the tadalafil 40-mg group (8%) compared with the 20-mg group (13%). In those subjects who continued the same dose through both studies, the incidence of headache was about 15% in PHIRST-2 which is comparable to that observed in placebo arm (15%) of PHIRST-1. The incidence of headache for both groups appears to decrease after one week. Similarly, other AEs also decreased over time (1-68 weeks).
CONCLUSION: Overall, these treatment-emergent AEs were mild to moderate in quality and diminished shortly after treatment initiation. In general, patients on 40-mg tadalafil over the full 68-week treatment period across both studies did not experience a higher incidence of these AEs than patients receiving 20-mg tadalafil.
CLINICAL IMPLICATIONS: These data suggest that the incidence of these commonly reported AEs does not appear to be dose related over 68 weeks of treatment. These data are useful for clinicians and patients as they suggest that TEAEs frequently diminish rapidly and may not be dose related.
DISCLOSURE: Erika Berman Rosenzweig, Grant monies (from industry related sources) Dr. Erika Rosenzweig has received research grant support from United Therapeutics, Eli Lilly and Pfizer.; Employee Dr. Carl Arneson and Dr. Gil Golden are paid employees of United Therapeutics.; Consultant fee, speaker bureau, advisory committee, etc. Dr. Erika Rosenzweig has received honoraria for scientific advisory board and lectures from United Therapeutics.; No Product/Research Disclosure Information