A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy

Amyloid. 2019 Dec;26(4):203-209. doi: 10.1080/13506129.2019.1643714. Epub 2019 Jul 27.


Background: Tafamidis is approved in over 40 countries to delay neurologic progression in patients with transthyretin amyloid polyneuropathy (ATTR-PN). A comprehensive, integrated analysis of safety data from interventional, observational and surveillance studies of tafamidis in ATTR-PN patients was conducted. Methods: Safety data from all sponsored, completed, or ongoing, Phase 2/3 studies of tafamidis in ATTR-PN patients as of 3 January 2017 were pooled. Also assessed were safety data from the ongoing Transthyretin Amyloidosis Outcomes Survey (THAOS) as of 3 January 2017 and post-marketing surveillance reports as of 31 March 2017. Results: There were 137 patients in Phase 2/3 studies (mean duration of tafamidis exposure, 44.2 months), with 134 (97.8%) experiencing ≥1 treatment-emergent adverse event (TEAE) and 46 (33.6%) ≥1 treatment-emergent serious adverse event (TESAE). The most common TEAEs were diarrhoea (26.3%), urinary tract infection (UTI; 25.5%) and influenza (21.2%). In THAOS, 661 subjects had tafamidis exposure (mean duration, 27.6 months), with 250 (37.8%) experiencing ≥1 TEAE and 96 (14.5%) ≥1 TESAE. The most common TEAE was UTI (6.1%). Post-marketing surveillance reports generally reflected the known safety profile of tafamidis. Conclusions: This analysis did not reveal any significant new safety findings; tafamidis was generally safe and well tolerated in ATTR-PN patients. ClinicalTrials.gov: NCT00409175, NCT00791492, NCT00630864, NCT01435655, NCT00925002, and NCT00628745.

Keywords: Transthyretin amyloidosis; adverse events; clinical trials; post-marketing surveillance; safety; tafamidis.

MeSH terms

  • Adult
  • Amyloid Neuropathies, Familial / complications
  • Amyloid Neuropathies, Familial / drug therapy*
  • Benzoxazoles / administration & dosage
  • Benzoxazoles / adverse effects*
  • Benzoxazoles / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Observational Studies as Topic
  • Polyneuropathies / complications
  • Polyneuropathies / drug therapy*
  • Product Surveillance, Postmarketing


  • Benzoxazoles
  • tafamidis

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT01435655
  • ClinicalTrials.gov/NCT00409175
  • ClinicalTrials.gov/NCT00628745
  • ClinicalTrials.gov/NCT00791492
  • ClinicalTrials.gov/NCT00925002
  • ClinicalTrials.gov/NCT00630864