Dosing of Enteric-Coated Mycophenolate Sodium Under Routine Conditions: An Observational, Multicenter Study in Kidney Transplantation.
BACKGROUND Dosing of enteric-coated mycophenolate sodium (EC-MPS) should be adjusted to reflect concomitant immunosuppression, but it is largely undocumented whether such modifications are carried out during routine clinical practice. MATERIAL AND METHODS MyLIFE was an observational study of adult kidney-only or kidney-pancreas transplant patients starting -EC-MPS at 33 French transplant centers. Data were collected at first EC-MPS dose and 6 months later. The primary objective was to describe initial EC-MPS dosing according to concomitant immunosuppression. RESULTS There were 461 patients analyzed (174 started EC-MPS by month 1 post-transplant ['de novo'] and 287 started EC-MPS >1 month post-transplant ['maintenance']), receiving cyclosporine (CsA) (n=76), tacrolimus (n=363), or a mammalian target of rapamycin (mTOR) inhibitor (n=22). Mean (SD) starting dose was 1130 (511) mg/day, 1006 (441) mg/day, and 769 (300) mg/day in the CsA, tacrolimus, and mTOR inhibitor groups, respectively (p=0.003). In the de novo subpopulation, the starting dose was 1440 mg/day in 66.7% (14/21) of CsA-treated patients and 71.9% (110/153) of tacrolimus-treated patients, with an intensified dose of 2160 mg/day in 28.6% (6/21) and 8.5% (13/153), respectively. There was a non-significant trend to a higher rate of biopsy-proven acute rejection in patients receiving CsA versus tacrolimus or an mTOR inhibitor (p=0.082). Adverse events with a suspected relation to EC-MPS occurred in 21.0%, 23.1%, and 9.1% of the CsA, tacrolimus, and mTOR inhibitor subpopulations, respectively. CONCLUSIONS EC-MPS is usually initiated at the dose recommended for de novo CsA-treated kidney transplant patients, then titrated downwards as required. An early intensified regimen is not used frequently. The EC-MPS dose is modified in <20% of de novo patients to account for concomitant tacrolimus therapy instead of CsA administration.
Department of Nephrology and Renal Transplantation, Hospital Pasteur, Nice, France.
Laetitia
L
Albano
Department of Nephrology and Clinical Immunology, Hospital Bretonneau, Tours, France.
Matthias
M
Buchler
Department of Nephrology and Clinical Immunology, Hospital Hôtel Dieu, Nantes, France.
Diego
D
Cantarovich
Department of Nephrology and Renal Transplantation, Hospital Pasteur, Nice, France.
Elisabeth
E
Cassuto
Department of Nephrology and Organs Transplantation, Hospital de Rangueil, Toulouse, France.
Olivier
O
Cointault
Department of Nephrology, Hospital Sud, Amiens, France.
Hakim
H
Mazouz
Department of Nephrology, Hospital Lapeyronnie, Montpellier, France.
Fernando
F
Vetromile
, Novartis Pharma SAS, Rueil-Malmaison, France.
Aurélie
A
Lecuyer
, Keyrus Biopharma, Levallois Perret, France.
Malka
M
Tindel
Department of Nephrology and Organ Transplantation, Hospital de Rangueil, Paul Sabatier University, INSERM U1043, IFR-BMT, Toulouse, France.
Nassim
N
Kamar
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D016559:Tacrolimus