Bioequivalence between generic tacrolimus products marketed in Spain by adjusted indirect comparison

• Published in: European journal of clinical pharmacology Vol. 69; no. 5; pp. 1157 - 1162
• Main Authors: Herranz, Marta, Morales-Alcelay, Susana, Corredera-Hernández, Ma Teresa, de la Torre-Alvarado, José María, Blázquez-Pérez, Antonio, Suárez-Gea, Ma Luisa, Álvarez, Covadonga, García-Arieta, Alfredo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2013; Springer; Springer Nature B.V
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Comparative studies; Drug therapy; Drugs, Generic - pharmacokinetics; Generic drugs; Humans; Marketing; Medical sciences; Models, Statistical; Pharmacokinetics and Disposition; Pharmacology. Drug treatments; Pharmacology/Toxicology; Spain; Tacrolimus - pharmacokinetics; Therapeutic Equivalency; Europe; Spain; Therapeutic equivalency; Generic product; Drug substitution; Tacrolimus; Bioequivalence; Indirect comparison; Human; Calcineurin inhibitor; Lactone; Generic drug; Macrolide; Immunomodulator; Treatment; Substitution; Protein synthesis inhibitor; Immunosuppressive agent; Pharmacokinetics; Comparative study
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-012-1456-6

Purpose The objective of the study was to investigate the relative bioavailability between the generic tacrolimus products that are presently authorized in Spain by adjusted indirect comparison. This was based on demonstration of bioequivalence with the reference product (Prograf, Astellas Pharma), which makes these generic tacrolimus products prescribable, switchable and therapeutically equivalent to the reference product; yet, according to Spanish legislation, only prescribers can switch tacrolimus-containing products. Methods Data from independent bioequivalence studies that compare each generic product with the reference product were combined by adjusted indirect comparisons to investigate the relative bioavailability between generic drug products, since there is no direct bioequivalence study comparing generics to each other. Results Eight generic tacrolimus products in the form of capsules are presently authorized in Spain, but only five are marketed. These eight products represent only three different generic product developments. One product is authorized with four different names/companies, while another is authorized under three different names/companies. The adjusted indirect comparisons between generic products show bioequivalence within the conventional 80–125 % confidence interval acceptance criteria for area under the curve (AUC) and maximum concentration (Cmax). Conclusion Not only are the generic products bioequivalent with the reference product, but also with each other.