title: 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.
  
  
  CONCLUSIONS
  This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.
authors.affiliation: a Global Patient Safety Japan, Quality & Patient Safety, Eli Lilly Japan KK.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: b Post Marketing Study Management, Medicines Development Unit Japan, Eli Lilly Japan KK.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: c Statistical Sciences, Medicines Development Unit Japan, Eli Lilly Japan KK.
authors.forename: Masanori
authors.initials: M
authors.lastname: Taketsuna
authors.affiliation: d Post Marketing Surveillance Clinical Research Department , Nippon Shinyaku Co. Ltd.
authors.forename: Koyuki
authors.initials: K
authors.lastname: Tajima
authors.affiliation: e Medical Science , Medicines Development Unit Japan , Eli Lilly Japan KK.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007564:Japan; D008297:Male; D040541:Marketing; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D000068581:Tadalafil / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil
keywords: Phosphodiesterase type 5 inhibitors; postmarketing surveillance; pulmonary arterial hypertension; tadalafil