Bioavailability of a generic of the immunosuppressive agent mycophenolate mofetil in pediatric patients

Abstract

The use of generic immunosuppressive agents is controversial, especially for the treatment of pediatric patients, as information on the bioavailability of generic immunosuppressants in children is particularly scarce. The aim of the study was to compare the bioavailabilities of two products containing mycophenolate mofetil, the innovator and a generic, in children. Pediatric patients with end-stage renal disease on the waiting list for renal transplantation received a single oral dose of mycophenolate mofetil as either the innovator product (CellCept(®) , Roche) or the generic (Tevacept(®) , Teva Pharmaceuticals). A nine point pharmacokinetic profile was obtained. Mycophenolic acid concentration was quantitated in plasma by HPLC, plasma concentration-against-time curves were constructed, and bioavailability parameters were determined. Pharmaceutical quality analysis of both formulations, including drug content and dissolution profile, was also performed. There were no statistically significant differences between formulations in bioavailability parameters. Interindividual variability was very important, but individual values of AUC, an indicator of the extent of drug absorption, were within the same range for both formulations. The two formulations exhibited similar drug content and dissolution profiles, as well as comparable mycophenolic acid plasma levels in an end-stage renal failure population.

Limustin®, a non‐innovator tacrolimus formulation, yields reduced drug exposure in pediatric renal transplant recipients

“…Moreover, generic immunosuppressants are being administrated to pediatric patients, although information on the bioavailability of these products in children is particularly scarce. Our group has reported that a mycophenolate mofetil generic formulation that is bioequivalent in adults also exhibits a comparable bioavailability with regard to that of the innovator in pediatric patients . However, this does not appear to be the case for certain generic tacrolimus formulations.…”

Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

“…In the literature, there are some studies on generic MMF; however, most of them concerned adults. González-Ramírez et al [124] compared the innovator product (CellCept ® , Roche, Basel, Switzerland) and the generic (Tevacept ® , Teva Pharmaceuticals, North Wales, PA, USA) in children with end-stage renal disease who were on the waiting list for renal transplantation. Although an important interindividual variability in bioavailability for both MPA formulations was observed, the authors found individual values of AUC within the same range as well as no statistically significant differences in bioavailability parameters between formulations.…”

Important considerations for drugs, nutritional, and herbal supplements in pediatric solid organ transplant recipients

“…A generic formulation of MMF and mycophenolic acid has been developed and documented to be bioequivalent to the brand name product in healthy adults and kidney transplant recipients 22‐25 . Tevacept has been reported to be bioequivalent to cellcept in a small number of heterogenous group of pediatric transplant recipients 26 …”

“…[22][23][24][25] Tevacept has been reported to be bioequivalent to cellcept in a small number of heterogenous group of pediatric transplant recipients. 26 However, in vitro dissolution studies of MMF formulations available worldwide have documented vast differences in the dissolution of various MMF formulations. 27 Patients should be discouraged from ordering generic immunosuppressive drugs from out of the country.…”