Generic substitution for immunosuppressive drugs

Helderman, J. Harold

doi:10.1002/dat.20526

Cited by 4 publications

(5 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the European Union and Canada, generic products for narrow therapeutic index drugs (NTIDs) should fulfill more restrictive acceptance criteria for bioequivalence (BE) than "common" generics, that is, for the AUC a 90% confidence interval (CI) for a test to reference ratio within 90.00%-111.11% [European Medicines Agency (EMA)] or 90.00%-112.00% (Canada) instead of 80.00%-125.00% (standard BE and for the United States) [129][130][131] A discussion keeps smoldering in the transplant community, whether MPA should be classified as an NTID such as CNIs and mTOR inhibitors. 123,[132][133][134][135] However, the arguments to recognize MPA as an NTID are currently not shared by registration agencies (ie, the EMA maintains classic, wider acceptance criteria for MPA). 123,132,136,137 Irrespective of the classification of MPA as an NTID or not, it is mandatory that the generic products adhere to the criteria for BE.…”

Section: Galenic Formulations and Genericsmentioning

confidence: 99%

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

Bergan¹,

Brunet²,

Hesselink³

et al. 2021

Therapeutic Drug Monitoring

133

237

View full text Add to dashboard Cite

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and

show abstract

Section: Galenic Formulations and Genericsmentioning

confidence: 99%

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

Bergan¹,

Brunet²,

Hesselink³

et al. 2021

Therapeutic Drug Monitoring

133

237

View full text Add to dashboard Cite

show abstract

“…Drugs with a narrow therapeutic index (NTI) should be used with caution. Drugs with NTIs are known to have high intra- and inter-individual pharmacokinetic variability with greater risk of overdosing if not administered with caution for each patient 588 . Their doses must be adjusted for each patient to prevent ADRs 588 .…”

Section: Predicting Potential Adverse Drug Reactions In Nashmentioning

confidence: 99%

“…Drugs with NTIs are known to have high intra- and inter-individual pharmacokinetic variability with greater risk of overdosing if not administered with caution for each patient 588 . Their doses must be adjusted for each patient to prevent ADRs 588 . NTI drugs include several different classes such as immunosuppressive, antiepileptic, or anticoagulant drugs 589 , 590 .…”

Section: Predicting Potential Adverse Drug Reactions In Nashmentioning

confidence: 99%

Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients

Marie

Frost²,

Hau³

et al. 2023

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

“…Safe conversion consumes time and money, thus generating additional costs for less expensive drugs. 5,13,63 C min Bioequivalence studies are not meant to evaluate C min even in a steady state. Steady-state trough concentrations are expected to be similar because of the similar AUC and C max .…”

Section: Generics Of Immunosuppressive Agents-a Challenge For Therape...mentioning

confidence: 99%

“…Safe conversion consumes time and money, thus generating additional costs for less expensive drugs. 5,13,63…”

Section: Generic Medicinal Products Of Immunosuppressive Drugsmentioning

confidence: 99%

Generic Medicinal Products in Immunosuppressive Therapy—Should It be a Challenge for Therapeutic Drug Monitoring?

Kocur

Kunicki

Pawiński

2023

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Immunosuppressants have a narrow therapeutic index (NTIDs). Indisputably cyclosporine, tacrolimus, everolimus, and sirolimus have NTIDs, and only in the case of mycophenolic acid, a scientific discussion has not been yet concluded. Their specificities highlight the implications for generics introduced into the drug market, more precisely, with bioequivalence testing. In the European Union, the European Medicines Agency (EMA) released the "Guideline on the Investigation of Bioequivalence." The bioequivalence (BE) of the generic (tested, T) versus original (reference, R) product should be confirmed by obtaining a 90% confidence interval (CI) for the T:R ratio of each of the 2 decisive pharmacokinetic parameters, namely, the area under the curve (AUC) between 90.00% and 111.11%. A similar approach (90.00%-112.00%) for AUC was adopted by the Canadian Agency for Drugs and Technologies in Health (CADTH) for NTIDs; however, the US Food and Drug Administration is still based on classic acceptance criteria: 90% CI between 80.00% and 125.00% but with special requirements of BE testing. A discussion about long-expected global consensus was performed in this study based on the literature concerning BE testing in the case of NTIDs. The narrow acceptance criteria reduce the potential mean difference in bioavailability between generic and original products by a few percent. To identify this problem, special attention has been paid to switching drugs (generic-generic, original-generic) and therapeutic drug monitoring after conversion (TDM). There is no global consensus on the acceptance criteria for the BE of generic drugs; therefore, consensus and harmonization are strictly necessary. This study presents a review of the generic drug market and its classification by manufacturers, drug agencies, and dates of marketing authorization. Guidelines for TDM optimization (during switching/conversion) have been proposed. Physicians and clinical pharmacists should pay special attention to switching immunosuppressive drugs between original versus generic formulations, and generic versus generic formulations. Patients and their families should be educated on the risks associated with uncontrolled conversion.

show abstract

Generic substitution for immunosuppressive drugs

Cited by 4 publications

References 17 publications

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients

Generic Medicinal Products in Immunosuppressive Therapy—Should It be a Challenge for Therapeutic Drug Monitoring?

Contact Info

Product

Resources

About