PMID- 35833202
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1939-4551 (Print)
IS  - 1939-4551 (Electronic)
IS  - 1939-4551 (Linking)
VI  - 15
IP  - 7
DP  - 2022 Jul
TI  - Safety of fexofenadine and other second-generation oral antihistamines before and 
      after the removal of the prescription requirement in Italy and other European 
      countries: A real-world evidence study and systematic review.
PG  - 100658
LID - 10.1016/j.waojou.2022.100658 [doi]
LID - 100658
AB  - BACKGROUND: The change from prescription to over-the-counter (OTC) status of oral 
      antihistamines may raise concerns about drug safety due to the possibility of 
      misuse/abuse. In most European countries, oral antihistamines are available 
      without prescription, whereas in Italy, only <10-tablet packs are available OTC. 
      OBJECTIVES: To evaluate the safety profile of fexofenadine after OTC switch in 
      Italy in a real-world setting, and to compare its safety profile to that of other 
      European countries where larger pack sizes are available. To compare the safety 
      of fexofenadine, cetirizine, and loratadine in Italy. To examine safety/efficacy 
      across Europe with a systematic review. METHODS: This case-by-case analysis used 
      the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) 
      to extract data of the adverse events (AEs) related to fexofenadine, loratadine 
      and cetirizine in Italy January 2010-June 2020. The year 2016 was taken as the 
      index date (removal of prescription requirement) for evaluation of the reporting 
      trend of AEs of fexofenadine in Italy and make a comparison pre/post-OTC switch. 
      A comparison of AEs with other European countries where fexofenadine is sold OTC 
      in large packs >20 tablets (Belgium, Portugal, Switzerland, Finland, Hungary) was 
      made. The rate at which an AE related to oral antihistamines occurred was 
      estimated by calculation of the reporting rate (number of cases/[defined daily 
      dose/1000 inhabitants per day]) on the basis of IQVIA sales data using the 
      Italian Institute of Statistics database. A systematic review of the literature 
      was also performed. RESULTS: There were 3760 reports of AEs with a suspected 
      association with fexofenadine; of these, eight were reported from Italy. There 
      was a slightly increasing trend per year, in line with a general reporting trend 
      of other drugs. In European countries where fexofenadine is available, the impact 
      of OTC switch on AE reporting activity was negligible: from 2016, the reporting 
      rate increased slightly and then normalized at 3.01, an incidence value similar 
      to that recorded before the OTC switch (3.7 in 2015). Of 22 studies included in 
      the systematic review, 18 (82%) positively evaluated the OTC use of oral 
      antihistamines, confirming an acceptable safety/tolerability profile. CONCLUSION: 
      There was no difference in number of AEs reported for fexofenadine pre/post-OTC 
      switch, indicating a similar safety profile. Spontaneous reporting systems are a 
      valuable source of real-world data and support the OTC provision of oral 
      antihistamines in Europe and fexofenadine in Italy, in addition to supporting the 
      use of larger pack sizes in Italy.
CI  - (c) 2022 The Author(s).
FAU - Carnovale, Carla
AU  - Carnovale C
AD  - Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, 
      "Luigi Sacco" University Hospital, Universita degli Studi di Milano, 20157, 
      Italy.
FAU - Battini, Vera
AU  - Battini V
AD  - Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, 
      "Luigi Sacco" University Hospital, Universita degli Studi di Milano, 20157, 
      Italy.
FAU - Gringeri, Michele
AU  - Gringeri M
AD  - Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, 
      "Luigi Sacco" University Hospital, Universita degli Studi di Milano, 20157, 
      Italy.
FAU - Volonte, Marina
AU  - Volonte M
AD  - Scientific Affairs Department, Sanofi, Milan, Italy.
FAU - Uboldi, Maria Chiara
AU  - Uboldi MC
AD  - Scientific Affairs Department, Sanofi, Milan, Italy.
FAU - Chiarenza, Andrea
AU  - Chiarenza A
AD  - Pharmacovigilance and Safety Department, Sanofi Italia & Malta MCO, Italy.
FAU - Passalacqua, Giovanni
AU  - Passalacqua G
AD  - Allergy and Respiratory Diseases, IRCCS Policlinico San Martino, University of 
      Genoa, Genoa, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220702
PL  - United States
TA  - World Allergy Organ J
JT  - The World Allergy Organization journal
JID - 101481283
PMC - PMC9260294
OTO - NOTNLM
OT  - Fexofenadine
OT  - Food and drug administration adverse event reporting system (FAERS)
OT  - Over-the-counter (OTC)
OT  - Pharmacovigilance
OT  - Second-generation oral antihistamines
EDAT- 2022/07/15 06:00
MHDA- 2022/07/15 06:01
PMCR- 2022/07/02
CRDT- 2022/07/14 02:37
PHST- 2021/12/03 00:00 [received]
PHST- 2022/03/10 00:00 [revised]
PHST- 2022/05/23 00:00 [accepted]
PHST- 2022/07/14 02:37 [entrez]
PHST- 2022/07/15 06:00 [pubmed]
PHST- 2022/07/15 06:01 [medline]
PHST- 2022/07/02 00:00 [pmc-release]
AID - S1939-4551(22)00034-5 [pii]
AID - 100658 [pii]
AID - 10.1016/j.waojou.2022.100658 [doi]
PST - epublish
SO  - World Allergy Organ J. 2022 Jul 2;15(7):100658. doi: 
      10.1016/j.waojou.2022.100658. eCollection 2022 Jul.