Once-daily prolonged release tacrolimus in liver transplantation: Experts' literature review and recommendations.
The efficacy and safety of tacrolimus (Tac) twice daily (bid) and once a day (qd) formulations are considered to be similar. However, the available information regarding initiation of Tac qd is sparse, and practical information is lacking. On the basis of a literature review, clinical efficacy, and safety trials, French experts in the liver transplantation field were asked to highlight pharmacokinetic (PK) differences between both formulations to assess efficacy and safety of the qd formulation in the context of de novo initiation or conversion and to provide their recommendations for initiation and day-to-day management of Tac qd. The same efficacy and safety profile is found for both immediate-release and prolonged-release Tac. PK differences carry on absorption because of the difference in formulations but not on metabolism or excretion. Tac qd offers a better reproducibility in exposure than Tac bid but is associated with an increased risk of disturbed absorption in case of a change in intestinal motility. The same therapeutic drug monitoring with Tac qd and bid could be applied, based on minimal concentration (trough level; C(min)), as there is a similar strong correlation between C(min) and the area under the curve (AUC) for both formulations. Different protocols for Tac qd initiation were described through numerous studies, except for early conversion: initiation on day 0, using 0.10 to 0.20 mg/kg/day as monotherapy, or lower dosages in case of concomitant immunosuppressant treatment or poor graft quality; early conversion from day 5 to 6 months, preferably before hospital discharge, using a 1 to 1.3 mg/kg/day schedule and with first C(min) assessment 48 hours after the conversion; and later conversion (>6 months posttransplantation) using a milligram-to-milligram dosage schedule, and with dose adjustment based on weekly C(min) measurement. Experts underline that an increase in treatment adherence was expected using Tac qd in liver recipients. In conclusion, Tac qd has the same efficacy and safety profile as Tac bid. De novo introduction or later conversion are well documented but could differ from day-to-day practice.
Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France.|Unit 1193, INSERM, Villejuif, France.|Unités Mixtes de Recherche en Santé 1193, Universite Paris-Sud, Villejuif, France.
Audrey
A
Coilly
Service d'Hépatologie et de Transplantation Hépatique, AP-HP Hôpital Saint-Antoine, Paris, France.
Yvon
Y
Calmus
Centre d'investigation de la Fibrose Hépatique, Centre Hospitalier Universitaire de Bordeaux Hôpital Haut-Lévêque, Pessac, France.
Faiza
F
Chermak
Unité de Transplantation Hépatique, Hopital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Jerome
J
Dumortier
AP-HP Hôpital Henri Mondor, Créteil, France.
Christophe
C
Duvoux
Unité de Transplantation Hépatique, Hopital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Olivier
O
Guillaud
Service des Maladies du Foie, Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Rennes, France.
Pauline
P
Houssel-Debry
Service de Transplantation Hepatique, Centre Hospitalier Universitaire de Bordeaux Hôpital Pellegrin, Bordeaux, France.
Martine
M
Neau-Cransac
Pharmacie, AP-HP Hôpital Beaujon, Clichy, France.
Jeanick
J
Stocco
D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D018565:Food-Drug Interactions; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D016031:Liver Transplantation / Q000009:adverse effects; D055118:Medication Adherence; D017410:Practice Guidelines as Topic; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus