title: Crushed and injected buprenorphine tablets: characteristics of princeps and generic solutions.
abstract: Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles <10 µm is systematically higher in the generic solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened.
authors.affiliation: Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France; EA 4275 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, Université de Nantes, Nantes, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bouquié
authors.affiliation: Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Wainstein
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire (LIOAD), Université de Nantes, Nantes, France; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Pilet
authors.affiliation: Laboratoire d'Anatomie Pathologique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Mussini
authors.affiliation: Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deslandes
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 791, Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire (LIOAD), Université de Nantes, Nantes, France; Centre Hospitalier Universitaire Nantes, Pôle Hospitalo-Universitaire (PHU) 7, Pharmacie Centrale, Nantes, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Clouet
authors.affiliation: Clinical Pharmacology, Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France; EA 3826 Thérapeutiques Cliniques et Expérimentales des Infections, Université de Nantes, Nantes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.affiliation: EA 4275 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, Université de Nantes, Nantes, France; Clinical Pharmacology, Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolliet
authors.affiliation: EA 4275 Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, Université de Nantes, Nantes, France; Pharmacology, Service de Pharmacologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Victorri-Vigneau
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000737:chemistry*; D002047:Buprenorphine / Q000009:adverse effects / Q000737:chemistry*; D003872:Dermatitis / Q000209:etiology; D016568:Drugs, Generic / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D007279:Injections, Subcutaneous; D007834:Lasers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012867:Skin / Q000473:pathology; D012996:Solutions / Q000737:chemistry; D019966:Substance-Related Disorders / Q000473:pathology; D013607:Tablets / Q000737:chemistry*
chemical_list: D000701:Analgesics, Opioid; D016568:Drugs, Generic; D012996:Solutions; D013607:Tablets; D002047:Buprenorphine