Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data

Abstract

Objective: To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice.

Methods: This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography.

Results: Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement.

Conclusion: This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

Keywords:

• Phosphodiesterase type 5 inhibitors
• postmarketing surveillance
• pulmonary arterial hypertension
• tadalafil

Note

Transparency

Declaration of funding

The surveillance was sponsored by Eli Lilly Japan KK.

Declaration of financial/other relationships

H.Y., N.K., and M.T. have disclosed that they are employees of Eli Lilly Japan KK. M.M. has disclosed that he is an employee of Eli Lilly and Company. K.T. has disclosed that she is an employee of Nippon Shinyaku Co. Ltd. Nippon Shinyaku Co. was involved in the contract, data collection, and data analysis with funding from Eli Lilly Japan KK.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors acknowledge the efforts of the investigators who participated in the surveillance. This study was sponsored by Eli Lilly Japan, manufacturer/licensee of tadalafil (Adcirca¹). Medical writing assistance was provided by Nahoko Suzuki from Eli Lilly Japan KK and Deborah D’Souza PhD MBA of inVentiv Clinical LCC, and was funded by Eli Lilly Japan. inVentiv’s services complied with international guidelines for Good Publication Practice (GPP3).

Notes

1 Adcirca is a registered traded name of Eli Lilly Japan