7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Me‐too pharmaceutical products: History, definitions, examples, and relevance to drug shortages and essential medicines lists

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We define a me‐too drug as a pharmacologically active compound that is structurally related to a first‐in‐class compound, regarded as belonging to the same therapeutic class as the original compound, and used for the same therapeutic purposes, but which may differ in some respects, such as specificity of pharmacological action, adverse reactions profile, or drug–drug interactions. We also offer definitions of related terms, including follow‐on drug and first‐in‐class. The therapeutic advantages of me‐too drugs may include improved target specificity, reduced risks of off‐target adverse reactions and drug–drug interactions, increased chance of benefit in some patients, and improved drug delivery and pharmacokinetics. Me‐too drugs can also demonstrate incremental innovation. Their availability may help in coping with drug shortages. However, they may occasionally cause unexpected adverse reactions that are not class effects. Tricyclic antidepressants, β‐blockers, and statins illustrate the diversity of me‐too drugs. Earlier compounds may be as effective as later ones, or more so. Tricyclic antidepressants have similar chemical structures, and compounds introduced after the first‐in‐class compound (imipramine) mostly offered little in the way of innovative features, but continue to be prescribed. In contrast, me‐too β‐blockers introduced after the first‐in‐class compound, pronethalol, have diverse structures and display several innovative features. Stereoisomers and biosimilars/biobetters provide special examples of me‐too drugs. Although many me‐too drugs offer no significant advantages over their predecessors, over 60% of the drugs listed on the World Health Organization's essential list are me‐toos. Different countries may choose different me‐too drugs when constructing essential medicines lists, partly explaining transnational differences between them.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis

          Summary Background Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. Methods We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. Findings We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72–0·97) and fluoxetine (0·88, 0·80–0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01–1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. Interpretation All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. Funding National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Physiology and pharmacology of erythropoietin.

            Human erythropoietin (Epo) is a 30.4 kDa glycoprotein hormone composed of a single 165 amino acid residues chain to which four glycans are attached. The kidneys are the primary sources of Epo, its synthesis is controlled by hypoxia-inducible transcription factors (HIFs). Epo is an essential factor for the viability and proliferation of erythrocytic progenitors. Whether Epo exerts cytoprotection outside the bone marrow still needs to be clarified. Epo deficiency is the primary cause of the anemia in chronic kidney disease (CKD). Treatment with recombinant human Epo (rhEpo, epoetin) can be beneficial not only in CKD but also for other indications, primarily anemia in cancer patients receiving chemotherapy. Considering unwanted events, the administration of rhEpo or its analogs may increase the incidence of thromboembolism. The expiry of the patents for the original epoetins has initiated the production of similar biological medicinal products ('biosimilars'). Furthermore, analogs (darbepoetin alfa, methoxy PEG-epoetin beta) with prolonged survival in circulation have been developed ('biobetter'). New erythropoiesis-stimulating agents are in clinical trials. These include compounds that augment erythropoiesis directly (e.g. Epo mimetic peptides or activin A binding protein) and chemicals that act indirectly by stimulating endogenous Epo synthesis (HIF stabilizers).
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment.

              Systemic exposure to rosuvastatin had been observed to be approximately 2-fold higher in Japanese subjects living in Japan compared with white subjects in Western Europe or the United States. The organic anion transporting polypeptide 1B1 contributes to the hepatic uptake of rosuvastatin. Polymorphisms in the SLCO1B1 gene can lead to reduced transport function in vitro (T 521>C). This study was conducted to determine whether the pharmacokinetic differences between Japanese and white subjects extended to other Asian ethnic groups and to determine whether polymorphisms in the SLCO1B1 gene contribute to any pharmacokinetic differences observed. Rosuvastatin pharmacokinetics was studied in an open-label, parallel-group, single-oral dose (40 mg) study in 36 white, 36 Chinese, 35 Malay, and 35 Asian-Indian subjects living in Singapore, Singapore. Plasma concentrations of rosuvastatin and metabolites were determined by HPLC-mass spectrophotometry. Two SLCO1B1 polymorphisms (A 388>G and T 521>C) were genotyped. Ratios for rosuvastatin area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration were 2.31, 1.91, and 1.63 and ratios for maximum plasma concentration were 2.36, 2.00, and 1.68 in Chinese, Malay, and Asian-Indian subjects, respectively, compared with white subjects. Similar increases in exposure to N-desmethyl rosuvastatin and rosuvastatin-lactone were observed. SLCO1B1 genotypes did not account for the observed pharmacokinetic differences between Asians and white subjects. Plasma exposure to rosuvastatin and its metabolites was significantly higher in Chinese, Malay, and Asian-Indian subjects compared with white subjects living in the same environment.
                Bookmark

                Author and article information

                Contributors
                jeffrey.aronson@phc.ox.ac.uk
                Journal
                Br J Clin Pharmacol
                Br J Clin Pharmacol
                10.1111/(ISSN)1365-2125
                BCP
                British Journal of Clinical Pharmacology
                John Wiley and Sons Inc. (Hoboken )
                0306-5251
                1365-2125
                13 May 2020
                November 2020
                13 May 2020
                : 86
                : 11 ( doiID: 10.1111/bcp.v86.11 )
                : 2114-2122
                Affiliations
                [ 1 ] Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter Oxford UK
                [ 2 ] School of Life Sciences, Queen's Medical Centre University of Nottingham Nottingham UK
                Author notes
                [*] [* ] Correspondence

                Jeffrey K. Aronson, Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.

                Email: jeffrey.aronson@ 123456phc.ox.ac.uk

                Author information
                https://orcid.org/0000-0003-1139-655X
                https://orcid.org/0000-0002-3075-5098
                Article
                BCP14327 RC-00097-20.R1
                10.1111/bcp.14327
                7576625
                32358800
                bd9c4274-4153-4a16-b7c3-c35c50f33e47
                © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 03 February 2020
                : 20 April 2020
                : 21 April 2020
                Page count
                Figures: 2, Tables: 5, Pages: 9, Words: 6311
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                November 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:21.10.2020

                Pharmacology & Pharmaceutical medicine
                advertising,me‐too drugs,pharmaceutical companies,pharmaceutical products

                Comments

                Comment on this article