title: [How to act when an alpha-blocker is associated with a potent inhibitor of CYP3A4].
abstract: OBJECTIVE
  Combination of alpha-blockers with potent CYP3A4 inhibitors is either contra-indicated or not recommended. We searched data supporting this classification and guiding prescribers when such an interaction occurs.
  
  
  METHODS
  We analyzed reports published by the French agency for drug safety, reference books and performed search in databases of pharmacokinetics studies and case or case series related with these interactions.
  
  
  RESULTS
  The classification of the potential severity of these interactions defined by the French agency for drug safety evolved over time. Our literature search did not identify any cases or case series reporting serious clinical consequences of such interactions and no pharmacoepidemiological studies on the association between alpha-blockers and inhibitors of CYP3A4. The content of the summaries of product characteristics indicate that the combination of ketoconazole with alfuzosin, silodosin and tamsulosin increases the area under the curve of the alpha-blocker 3 fold.
  
  
  CONCLUSIONS
  Data demonstrating the clinical consequences of an association between alpha-blocker and a potent CYP3A4 inhibitor are lacking. The 3 fold increase of the area under the curve for alfuzosin, silodosin and tamsulosin associated with ketoconazole while the association with the two first is contra-indicated and is not recommended with the third raises questions. This lack of data leaves doctors and pharmacists in a situation of uncertainty on how to proceed when such an interaction occurs.
authors.affiliation: Centre de documentation et d'information pharmaceutique, pharmacie centrale, hospices civils de Lyon, 57, rue Francisque-Darcieux, 69561 Saint-Genis-Laval cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Bensalah
authors.affiliation: Centre de documentation et d'information pharmaceutique, pharmacie centrale, hospices civils de Lyon, 57, rue Francisque-Darcieux, 69561 Saint-Genis-Laval cedex, France. Electronic address: stephan.garcia@chu-lyon.fr.
authors.forename: S
authors.initials: S
authors.lastname: Garcia
authors.affiliation: EPSM-Morbihan, service pharmacie, 22, rue de l'Hôpital, 56890 Saint-Avé, France; Groupe de travail « standardisation et valorisation des activités de pharmacie clinique » de la Société française de pharmacie clinique, France.
authors.forename: F X
authors.initials: FX
authors.lastname: Rose
authors.affiliation: Université Grenoble-Alpes, CNRS/TIMC-IMAG UMR5525/ThEMAS, Domaine-de-la-Merci, 38041 Grenoble, France; Groupe de travail « standardisation et valorisation des activités de pharmacie clinique » de la Société française de pharmacie clinique, France.
authors.forename: P
authors.initials: P
authors.lastname: Bedouch
authors.affiliation: Service pharmacie, hôpital Cochin, Assistance publique des Hôpitaux de Paris, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Groupe de travail « standardisation et valorisation des activités de pharmacie clinique » de la Société française de pharmacie clinique, France.
authors.forename: O
authors.initials: O
authors.lastname: Conort
authors.affiliation: Centre hospitalier Auban-Moët, 137, rue de l'Hôpital Auban-Moët, 51200 Épernay, France; Groupe de travail « standardisation et valorisation des activités de pharmacie clinique » de la Société française de pharmacie clinique, France.
authors.forename: M
authors.initials: M
authors.lastname: Juste
authors.affiliation: Service pharmacie, centre hospitalier Lucien-Hussel, montée du Docteur-Chapuis, 38200 Vienne, France; Groupe de travail « standardisation et valorisation des activités de pharmacie clinique » de la Société française de pharmacie clinique, France.
authors.forename: R
authors.initials: R
authors.lastname: Roubille
authors.affiliation: Université Grenoble-Alpes, CNRS/TIMC-IMAG UMR5525/ThEMAS, Domaine-de-la-Merci, 38041 Grenoble, France; Groupe de travail « standardisation et valorisation des activités de pharmacie clinique » de la Société française de pharmacie clinique, France.
authors.forename: B
authors.initials: B
authors.lastname: Allenet
authors.affiliation: Service pharmacie, hôpital de la Croix-Rousse, 103, Grande rue de la Croix-Rousse, 69004 Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Tod
authors.affiliation: Université Grenoble-Alpes, CNRS/TIMC-IMAG UMR5525/ThEMAS, Domaine-de-la-Merci, 38041 Grenoble, France; Groupe de travail « standardisation et valorisation des activités de pharmacie clinique » de la Société française de pharmacie clinique, France.
authors.forename: B
authors.initials: B
authors.lastname: Charpiat
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005602:France; D006077:Government Agencies; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D007654:Ketoconazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077409:Tamsulosin
chemical_list: D000317:Adrenergic alpha-Antagonists; D065692:Cytochrome P-450 CYP3A Inhibitors; D007211:Indoles; D011799:Quinazolines; D013449:Sulfonamides; C047638:alfuzosin; C095285:silodosin; D000077409:Tamsulosin; D007654:Ketoconazole
keywords: Adrenergic alpha-1 receptor antagonists; Alfuzosin; Alfuzosine; Alpha-bloquant; CYP3A inhibitors; Drug-drug interactions; Inhibiteurs du CYP3A4; Interactions médicamenteuses; Tamsulosin; Tamsulosine