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Clinical Therapeutics Nov 2021To best promote drug tolerability and efficacy in the clinic, data from drug-drug interaction (DDI) evaluations and subsequent translation of the results to DDI...
PURPOSE
To best promote drug tolerability and efficacy in the clinic, data from drug-drug interaction (DDI) evaluations and subsequent translation of the results to DDI prevention and/or management strategies must be incorporated into the US Food and Drug Administration (FDA) product labeling in a consistent manner because differences in language might result in varied interpretations. This analysis aimed to assess the consistency in DDI labeling language in New Drug Applications (NDAs).
METHODS
NDAs of recently approved drugs (2012-2020) that increase the exposure of digoxin, midazolam, and S-warfarin, index substrates of P-glycoprotein, cytochrome P450 (CYP) 3A, and CYP2C9 activity, respectively, were fully reviewed. Noninhibitors were also evaluated to appreciate the extent of mechanistic extrapolation in case of negative index studies.
FINDINGS
After a systematic review of the DDI studies available in NDAs, FDA-approved labeling, and commonly used clinical tertiary resources, differences in DDI results presentation and resulting clinical recommendations were found, even for inhibitors that affect similarly the exposure of the same index substrate. Studies with negative results were often reported in the labels without providing mechanistic interpretation, thus limiting the possible extrapolation of this information to other known substrates.
IMPLICATIONS
The variability in language affects how the information was presented to clinicians in tertiary resources. Strategies that aim to improve the translation of mechanistic DDI index studies into consistent labeling recommendations are briefly discussed in this review.
Topics: Digoxin; Drug Interactions; Humans; Language; Midazolam; Pharmaceutical Preparations; Product Labeling; Warfarin
PubMed: 34579970
DOI: 10.1016/j.clinthera.2021.08.016 -
Archives of Surgery (Chicago, Ill. :... Mar 2002St John's wort is one of the most popular herbal medicines, and health care professionals often are unaware that their patients take such supplements. St John's wort... (Review)
Review
HYPOTHESIS
St John's wort is one of the most popular herbal medicines, and health care professionals often are unaware that their patients take such supplements. St John's wort causes a decrease in cyclosporine levels, thus endangering the success of organ transplantations.
DESIGN
Systematic review.
METHODS
Five independent computerized literature searches were conducted to identify all reports of such interactions. Data were extracted and are summarized in narrative form.
RESULTS
Eleven case reports and 2 case series were located. In most instances, causality between St John's wort and the clinical or biochemical result is well established. The mechanism of interaction between St John's wort and cyclosporine has been recently elucidated and involves both P-glycoprotein and cytochrome P 450 3A4 expression. Collectively these data leave little doubt that St John's wort interacts with cyclosporine, causing a decrease of cyclosporine blood levels and leading in several cases to transplant rejection.
CONCLUSIONS
St John's wort can endanger the success of organ transplantations. Adequate information may be the best way to avoid future incidences.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adult; Antidepressive Agents; Cyclosporine; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Female; Graft Rejection; Heart Transplantation; Humans; Hypericum; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mixed Function Oxygenases; Organ Transplantation; Pancreas Transplantation; Plant Extracts
PubMed: 11888457
DOI: 10.1001/archsurg.137.3.316 -
Endocrinology Aug 2019Anaplastic thyroid cancer (ATC) is an aggressive type of thyroid cancer with a high mortality rate. Cytotoxic drugs are among the treatment modalities usually used for...
Anaplastic thyroid cancer (ATC) is an aggressive type of thyroid cancer with a high mortality rate. Cytotoxic drugs are among the treatment modalities usually used for ATC treatment. However, systemic chemotherapies for ATC have not been shown to have remarkable efficacy. ATP-binding cassette (ABC) transporters have been suggested as a possible mechanism in ATC resistance to chemotherapy. This systematic review was aimed to define the possible roles of ABC transporters in ATC resistance to chemotherapy. Numerous databases, including Scopus, Web of Science, PubMed, Cochrane Library, Ovid, ProQuest, and EBSCO, were searched for papers published since 1990, with predefined keywords. The literature searches were updated twice, in 2015 and 2017. All identified articles were reviewed, and 14 papers that met the inclusion criteria were selected. In the eligible studies, the roles of 10 out of 49 ABC transporters were evaluated; among them, three pumps (ABCB1, ABCC1, and ABCG2) were the most studied transporters in ATC samples. ABCC1 and ABCG2 had the highest expression rates in ATC, and ABCB1 ranked second among the inspected transporters. In conclusion, ABC transporters are the major determinants of ATC resistance to chemotherapy. By identifying these transporters, we can tailor the best treatment approach for patients with ATC. Additional studies are needed to define the exact role of each ABC transporter and other mechanisms in ATC drug resistance.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters; Animals; Drug Resistance, Neoplasm; Humans; Neoplastic Stem Cells; Signal Transduction; Thyroid Carcinoma, Anaplastic
PubMed: 31271419
DOI: 10.1210/en.2019-00241