Therapeutic monitoring of pediatric renal transplant patients with conversion to generic cyclosporin

Riva, Natalia; Guido, Paulo Cáceres; Ibañez, Juan; Licciardone, Nieves; Rousseau, M.-A.; Mato, Gabriel; Monteverde, Marta Lidia; Schaiquevich, Paula

doi:10.1007/s11096-014-9959-0

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…This Program supplies, free of charge, to those patients who are in need, with the immunosuppressant drug product depending on the winning bid established by the government. Although we do not have the reliable registry of the brand that patients received, tacrolimus TDM in pediatric transplant patients undergoing immunosuppressant substitution is essential to ensure safety and efficacy of the immunosuppressive treatment, as previously reported for this population 72 . All patients had close clinical and pharmacological monitoring of…”

Section: A C C E P T E Dmentioning

confidence: 99%

Survival Time to Biopsy-Proven Acute Rejection and Tacrolimus Adverse Drug Reactions in Pediatric Liver Transplantation

Riva

Dip

Halac

et al. 2018

Therapeutic Drug Monitoring

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Section: A C C E P T E Dmentioning

confidence: 99%

Survival Time to Biopsy-Proven Acute Rejection and Tacrolimus Adverse Drug Reactions in Pediatric Liver Transplantation

Riva

Dip

Halac

et al. 2018

Therapeutic Drug Monitoring

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“…In contrast, the literature on generic substitution for the treatment of more common conditions is extensive and includes reports of adverse outcomes associated with the switch from branded to generic products in a variety of therapeutic areas, especially when NTI drugs are involved [2,5,4,3,66]. Indeed, problems with generic substitution have been reported more consistently with certain drug classes including levothyroxine, post-transplantation immunosuppressants, anti-epileptic drugs, and antidepressants [67,2,68,69,3]. These reports have prompted additional bioequivalence studies, have often resulted in the withdrawal of the generic product, and have led several authors to recommend caution in the use of generics for certain conditions and patient populations.…”

Section: Problematic Generic Substitutionsmentioning

confidence: 99%

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges

Paolo

Arrigoni

2018

Drugs

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Generic drugs are important components of measures introduced by healthcare regulatory authorities to reduce treatment costs. In most patients and conditions the switch from a branded drug to its generic counterpart is performed with no major complications. However, evidence from complex diseases suggests that generic substitution requires careful evaluation in some settings and that current bioequivalence criteria may not always be adequate for establishing the interchangeability of branded and generic products. Rare diseases, also called orphan diseases, are a group of heterogeneous diseases that share important characteristics: in addition to their scarcity, most are severe, chronic, highly debilitating, and often present in early childhood. Finding a treatment for a rare disease is challenging. Thanks to incentives that encourage research and development programs in rare diseases, several orphan drugs are currently available. The elevated cost of orphan drugs is a highly debated issue and a cause of limited access to treatment for many patients. As patent protection and the exclusivity period of several orphan drugs will expire soon, generic versions of orphan drugs should reach the market shortly, with great expectations about their impact on the economic burden of rare diseases. However, consistent with other complex diseases, generic substitution may require thoughtful considerations and may be even contraindicated in some rare conditions. This article provides an overview of rare disease characteristics, reviews reports of problematic generic substitution, and discusses why generic substitution of orphan drugs may be challenging and should be undertaken carefully in rare disease patients.

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“…35 The optimal blood levels of immunosuppressants for patients with transplants differ according to (і) the type of organ transplanted; (іі) the type of the therapy (i.e., monotherapy or combination therapy with other immunosuppressants); and (ііі) the aim of the treatment (induction or maintenance). Moreover, the transition from innovator to generic medications for cost-saving purposes caused serious side effects, especially in pediatric solid organ transplant recipients due to significant variations in the total integrated area under the plasma drug concentration-time curve (AUC), for example, the AUC 0-12h for the first 12 h after injection, making close TDM essential, 36 Thus, for one of the most widely used immunosuppressants for organ transplantation, cyclosporine, a study reported a 16.7% drop of the AUC and a 13.1% drop of the 2-h concentration after oral administration when switching from innovator drug to generic cyclosporine, 37 indicating a reduced bioavailability of the generic drug, which could be associated with treatment failure (= organ rejection) or the need for more frequent dosing. For tacrolimus, another widely used calcineurin inhibitor (i.e., a drug that inhibits the T-cells of the immune system), it was found that patients with identical C 0 may have very different AUC 0-12h , which explains differences in treatment efficacy.…”

Section: Patients With Organ Transplants: Immunosuppressantsmentioning

confidence: 99%

Utility, promise, and limitations of liquid chromatography‐mass spectrometry‐based therapeutic drug monitoring in precision medicine

et al. 2021

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Therapeutic drug monitoring (TDM) is typically referred to as the measurement of the concentration of drugs in patient blood. Although in the past, TDM was restricted to drugs with a narrow therapeutic range in order to avoid drug toxicity, TDM has recently become a major tool for precision medicine being applied to many more drugs. Through compensating for interindividual differences in a drug's pharmacokinetics, improved dosing of individual patients based on TDM ensures maximum drug effectiveness while minimizing side effects. This is especially relevant for individuals that present a particularly high intervariability in pharmacokinetics, such as newborns, or for critically/severely ill patients. In this article, we will review the applications for and limitations of TDM, discuss for which patients TDM is most beneficial and why, examine which techniques are being used for TDM, and demonstrate how mass spectrometry is increasingly becoming a reliable and convenient alternative for the TDM of different classes of drugs. We will also highlight the advances, challenges, and limitations of the existing repertoire of TDM methods and discuss future opportunities for TDM‐based precision medicine.

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Therapeutic monitoring of pediatric renal transplant patients with conversion to generic cyclosporin

Abstract: Conversion of cyclosporin from innovator brand to generic in pediatric renal transplant patients needs to be closely monitored.

Cited by 8 publications

References 30 publications

Survival Time to Biopsy-Proven Acute Rejection and Tacrolimus Adverse Drug Reactions in Pediatric Liver Transplantation

Survival Time to Biopsy-Proven Acute Rejection and Tacrolimus Adverse Drug Reactions in Pediatric Liver Transplantation

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges

Utility, promise, and limitations of liquid chromatography‐mass spectrometry‐based therapeutic drug monitoring in precision medicine

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