Bismuth Concentrations in Patients Treated in Real-Life Practice with a Bismuth Subcitrate-Metronidazole-Tetracycline Preparation: The SAPHARY Study

Drug Saf. 2019 Aug;42(8):993-1003. doi: 10.1007/s40264-019-00821-6.


Introduction: A fixed-dose association of bismuth subcitrate, metronidazole and tetracycline (BMT) (Pylera®, Allergan, NJ, USA) was made available in France in 2013 for the eradication of Helicobacter pylori. Due to a historical issue of bismuth encephalopathy, the French Health Authorities requested a study of blood and plasma bismuth concentrations with BMT in daily practice.

Aims: The aim of the study was to measure eventual bismuth accumulation and neurological toxicity in patients prescribed BMT.

Methods: Patients initiating BMT for H. pylori between March 2014 and December 2015 were included. A blood sample was taken before first BMT intake and 24 h after the last intake, for assay of bismuth. A concentration > 50 μg/L was considered abnormal. Neurological complaints were assessed at inclusion, at the end of the 10-day treatment course, and 28 days later.

Results: 202 patients were included, of whom 190 took at least one dose of BMT, and 167 provided both required blood samples. Mean blood bismuth concentrations after the BMT course were 16.9 μg/L (95% confidence interval 15.6-18.3). Concentrations were > 50 μg/L (56.0 μg/L and 50.9 μg/L) in two elderly patients, one of whom presented mild, transient memory impairment during treatment. Non-serious neurological symptoms occurred in 20% of all patients and treatment failure was documented in 5% of patients.

Conclusions: In this study measuring blood bismuth concentrations in real-life practice, in < 1% of patients the BMT course resulted in blood bismuth concentrations > 50 μg/L. No serious neurological adverse events were observed.

Study registration: EU-PAS register EUPAS3142 at ; ENCePP study seal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bismuth / blood*
  • Cohort Studies
  • Drug Combinations
  • Female
  • Helicobacter Infections / blood*
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / isolation & purification
  • Humans
  • Male
  • Metronidazole / administration & dosage*
  • Metronidazole / pharmacokinetics
  • Middle Aged
  • Neurotoxicity Syndromes / blood
  • Neurotoxicity Syndromes / etiology
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / blood
  • Organometallic Compounds / pharmacokinetics*
  • Tetracycline / administration & dosage*
  • Tetracycline / pharmacokinetics
  • Treatment Failure


  • Drug Combinations
  • Organometallic Compounds
  • Metronidazole
  • Tetracycline
  • bismuth tripotassium dicitrate
  • Bismuth