On the clinical evidence leading to tetrazepam withdrawal.
BACKGROUND
In July 2013, the European Medicines Agency suspended the marketing authorizations of tetrazepam across the European Union. Herein, we examine the various kinds of adverse drug reactions (ADRs) reported to be associated with tetrazepam.


METHODS
We undertook a two-sided systematic approach. First, we conducted a search in Medline for all studies that have published about tetrazepam ADRs in peer-reviewed journals. Second, we collected tetrazepam ADRs from pharmacovigilance system databases. Our study reveals discrepancies in the information provided by these two different sources, both in the number of cases reported as well as in the kind of reported ADRs. Whereas cutaneous alterations are the only ADRs reported in peer-reviewed journals, pharmacovigilance system databases include others (hepatobiliary, neurological and psychiatric).


CONCLUSIONS
We noted the lack of randomized controlled clinical trials evaluating tetrazepam efficiency and safety. We failed to find a turning point in the amount of ADRs reported following tetrazepam withdrawal to underpin the validity of the withdrawal. We stress the importance of a better communication of knowledge in scientific literature, pharmacovigilance agencies, and from doctors to prevent marketed usage of drugs with well-established side effects during long periods.
Servicio de Farmacia, Complejo Hospitalario Universitario de Albacete , Albacete , Spain.
Beatriz
B
Proy-Vega
Carmelo
C
Aguirre
Piet
P
de Groot
Julián
J
Solís-García del Pozo
Joaquín
J
Jordán
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D001569:Benzodiazepines / Q000009:adverse effects*; D016208:Databases, Factual; D005062:European Union; D006801:Humans; D009125:Muscle Relaxants, Central / Q000009:adverse effects*; D060735:Pharmacovigilance; D057051:Product Recalls and Withdrawals
D009125:Muscle Relaxants, Central; D001569:Benzodiazepines; C005245:tetrazepam
European Medicines Agency; French National Agency for Safety of Medicine and Health Products; Spanish Agency of Medicines and Health Products; United States FDA; pharmacovigilance; side effects; withdrawal