ReviewEuropean journal of clinical pharmacology2015
Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide.
Review in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Utilization of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacoepidemiological Studies: A Systematic Review on Antiarrhythmic and Glucose-Lowering Medicines.Frontiers in pharmacology · 2022Pooled it
- Efficacy and Safety of Dronedarone in Overweight and Obesity: Post Hoc Analysis of the ATHENA Trial.Journal of cardiovascular electrophysiology · 2026Trial
- Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy: The EQUIGEN Randomized Clinical Trial.JAMA neurology · 2017Trial
- Development and evaluation of alginate-based gastroretentive raft-forming systems enabling sustained release of propolis in gastric ulcer treatment.Drug delivery · 2026Article
- Suicide by flecainide: a case report and review of the literature.Forensic science, medicine, and pathology · 2026Review
- Rapid analysis of narrow therapeutic index drugs by sonic spray ionization mass spectrometry.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2026Article
- Investigation and Implementation of Analyte Protectants in the Gas Chromatography-Tandem Mass Spectrometry Analysis of Benzodiazepines and Opioids in Whole Blood Extracts.Journal of separation science · 2026Article
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Design of a cyclic peptide targeting intracellular Staphylococcus aureus.Molecular biomedicine · 2026Article
- Nano-Encapsulated Black Bean-CultivatedNutrients · 2026Article
- Flecainide in Structural Heart Disease: Reconsidering Its Role in Contemporary Arrhythmia Management.Life (Basel, Switzerland) · 2026Review
- Article
- SCOUT: An Exploratory Approach to Scouting Dose-Relevant Covariates.CPT: pharmacometrics & systems pharmacology · 2026Article
- Integrated Assessment of Neurobehavioral and Cardiotoxic Effects of Pyrrolidine-Containing Cathinones in Zebrafish: Structural Determinants of Functional Safety Profiles.International journal of molecular sciences · 2026Article
- N-benzylbenzamide derivative (SBM685) as a novel MDR1 inhibitor for overcoming 5 fluorouracil resistance in gastric cancer through computational and in vitro analysis.Discover oncology · 2026Article
- G9a inhibition reduces stress-potentiated alcohol drinking in both male and female mice: Implications for safe and effective pharmacological therapeutics for alcohol use disorder.Alcohol, clinical & experimental research · 2026Article
- Lifecycle regulation of narrow therapeutic index drugs: Chinese practices, international benchmarks, and optimization pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Adverse drug events from paediatric use of extemporaneously compounded medicines in community pharmacy settings: a scoping review.BMJ paediatrics open · 2026Article
- Cinobufagin as a Potential Intervention Against Liver Cancer-A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Nanotechnology-Driven Therapeutic Potential of Raloxifene in Osteoporosis and Cancer: A Recent Review.Current pharmaceutical design · 2026Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events. Drugs with a narrow TI (NTIDs) have a narrow window between their effective doses and those at which they produce adverse toxic effects. Generic drugs may be substituted for brand-name drugs provided that they meet the recommended bioequivalence (BE) limits. However, an appropriate range of BE for NTIDs is essential to define due to the potential for ineffectiveness or adverse events. Flecainide is an antiarrhythmic agent that has the potential to be considered an NTID. This review aims to evaluate the literature surrounding guidelines on generic substitution for NTIDs and to evaluate the evidence for flecainide to be considered an NTID.
methodsA review of recommendations from various regulatory authorities regarding BE and NTIDs, and publications regarding the NTID characteristics of flecainide, was carried out.
resultsRegulatory authorities generally recommend reduced BE limits for NTIDs. Some, but not all, regulatory authorities specify flecainide as an NTID. The literature review demonstrated that flecainide displays NTID characteristics including a steep drug dose-response relationship for safety and efficacy, a need for therapeutic drug monitoring of pharmacokinetic (PK) or pharmacodynamics measures and intra-subject variability in its PK properties.
conclusionsThere is much evidence for flecainide to be considered an NTID based on both preclinical and clinical data. A clear understanding of the potential of proarrhythmic effects or lack of efficacy, careful patient selection and regular monitoring are essential for the safe and rational administration of flecainide.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.