title: From antiretroviral originator to generic drugs: bioequivalence and pharmacovigilance.
abstract: Antiretroviral drugs have been available in generic form in developing countries, which has expanded access to treatment; they have also become available in developed countries more recently.
  
  
  OBJECTIVE
  The validation of generic drugs (GD) compared to originator drugs (OD) is mandatory to ensure that using generics will lead to a decreased cost of treatment.
  
  
  RESULTS
  The results were obtained by analyzing published data as well as European Medicines Agency recommendations.
  
  
  METHODS
  The GD should have the same qualitative and quantitative active principle formula, the same pharmaceutical forms, and the same criteria in terms of quality, effectiveness, and safety. This equivalence is based on bioequivalence rules: comparison of the concentration/time curves (AUC); Cmax and Tmax (90%), for which the confidence intervals in the range of 80-125% should be included. Naturally, that does not mean that the concentrations can vary from 80 to 125%: this would indicate unacceptable deviations. Conforming to these criteria allows substituting an OD by a GD. Adverse effects should not be different from those observed for the OD. Adverse effects observed when the GD is used must be notified, as is the case for the OD. Accountability is established according to 4 essential pieces of information: a prescriber, a patient, a drug, and an adverse effect. It is sometimes difficult to identify the provider of the GD that has been delivered.
  
  
  CONCLUSIONS
  The level of safety concerning effectiveness and tolerance required is identical for OD and GD, in Europe. Analyzing confirmed adverse effects and therapeutic failures is the only way to identify differences that could question a GD's effectiveness.
authors.affiliation: Équipe de pharmacoépidémiologie de l'Inserm U1027, service de pharmacologie clinique, centre Midi-Pyrénées de pharmacovigilance, de pharmacoépidémiologie et d'informations sur le médicament (CRPV), faculté de médecine, CHU de Toulouse, 37, allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: H
authors.initials: H
authors.lastname: Bagheri
authors.affiliation: Laboratoire de pharmacologie, université de Nice-Sophia-Antipolis, hôpital Pasteur, CHU de Nice, CS 51069, 06001 Nice cedex 1, France.
authors.forename: R
authors.initials: R
authors.lastname: Garraffo
authors.affiliation: Service d'infectiologie, université Nice-Sophia-Antipolis, hôpital Archet 1, CHU de Nice, CS 23079, 06202 Nice cedex 3, France. Electronic address: dellamonica.p@chu-nice.fr.
authors.forename: P
authors.initials: P
authors.lastname: Dellamonica
mesh_terms: D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics*; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D060735:Pharmacovigilance; D013810:Therapeutic Equivalency
chemical_list: D044966:Anti-Retroviral Agents; D016568:Drugs, Generic
keywords: Antiretroviral drugs; Antirétroviraux; Bioequivalence; Bioéquivalence; Generic drugs; Génériques; Pharmacovigilance; Substitution