Study on the interaction between erythrosine B and the cardiac drug amiodarone using fluorescence, scattering, and absorbance spectra and their analytical application.

In an acidic buffered solution, erythrosine B can react with amiodarone to form an association complex, which not only generates great enhancement in resonance Rayleigh scattering (RRS) spectrum of erythrosine B at 346.5 nm but also results in quenching of fluorescence spectra of erythrosine B at λemission = 550.4 nm/λexcitation = 528.5 nm. In addition, the formed erythrosine B-amiodarone complex produces a new absorbance peak at 555 nm. The spectral characteristics of the RRS, absorbance, and fluorescence spectra, as well as the optimum analytical conditions, were studied and investigated. As a result, new spectroscopic methods were developed to determine amiodarone by utilizing erythrosine B as a probe. Moreover, the ICH guidelines were used to validate the developed RRS, photometric, and fluorimetric methods. The enhancements in the absorbance and the RRS intensity and the decrease in the fluorescence intensity of the used probe were proportional to the concentration of amiodarone in ranges of 2.5-20.0, 0.2-2.5, and 0.25-1.75 µg/mL, respectively. Furthermore, limit of detection values were 0.52 ng/mL for the spectrophotometric method, 0.051 µg/mL for the RRS method, and 0.075 µg/mL for the fluorimetric method. Moreover, with good recoveries, the developed spectroscopic procedures were applied to analyze amiodarone in its commercial tablets.

Comparison of the Effects of Lidocaine and Amiodarone on Patients With Cardiac Arrest: A Systematic Review and Meta-Analysis.

The objective of this study was to compare the impact of amiodarone and lidocaine on survival and neurological outcomes following cardiac arrest. A systematic review of randomized controlled trials (RCTs) as well as cohort and cross-sectional trials was undertaken, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Potential relevant studies were searched in databases, including PubMed, Embase, Cochrane Library, and Web of Science, from the beginning of databases to February 15, 2024. Outcomes assessed in this study were survival to hospital discharge, survival to hospital admission or 24 hours, favorable neurological outcomes, and return of spontaneous circulation (ROSC). A total of seven studies (five observational and two RCTs) were included in this meta-analysis encompassing 19,081 patients with cardiac arrest. Pooled analysis showed no difference between amiodarone and lidocaine in terms of survival to hospital discharge (odds ratio (OR): 0.88, 95% confidence interval (CI): 0.75 to 1.04), ROSC (OR: 0.94, 95% CI: 0.84 to 1.05, p-value: 0.25), favorable neurological outcomes (OR: 0.88, 95% CI: 0.66 to 1.17, p-value: 0.38), and survival to 24 hours (OR: 0.82, 95% CI: 0.55 to 1.21, p-value: 0.31). While lidocaine demonstrated a slight survival advantage, the differences were statistically insignificant. Similarly, no significant variations were observed in ROSC incidence, neurological outcomes, or survival at 24 hours. These findings align with current guidelines but underscore the necessity for further rigorous RCTs to provide conclusive recommendations.

The Pharmacologic Management of Cardiac Arrest.

The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of ß-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.

The ion channel basis of pharmacological effects of amiodarone on myocardial electrophysiological properties, a comprehensive review.

Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (IKr). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through IKr blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca2+ current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium.

Effectiveness of antazoline versus amiodarone, flecainide and propafenone in restoring sinus rhythm at the Emergency Department.

PURPOSE: Little is known about the effectiveness of pharmacological cardioversion (PCV) with antazoline in comparison to flecainide. The aim of this study was to compare the effectiveness of antazoline in restoring sinus rhythm (SR) versus amiodarone, flecainide and propafenone in a group of emergency department (ED) patients. MATERIALS/METHODS: This was a single-centre retrospective analysis of patient records from an ED in a large hospital in Poland. We analysed a total of 1878 patient records, divided based on the anti-arrhythmic drug (AAD) administered during PCV: antazoline (n=1080), antazoline + ß-blocker (n=479), amiodarone (n=129), flecainide (n=102), propafenone (n=88). Of the patients, 63.5% were female (median 65 years, [19-100]). RESULTS: The percentage of successful PCV was significantly higher in the antazoline group (84.3%) than in the antazoline + ß-blocker (75.8%, p=0.0001), propafenone (75.6%, p=0.0364) and amiodarone (68.8%, p<0.0001) groups. Post-hoc analysis revealed that patients who received PCV with antazoline, antazoline + ß-blocker, flecainide and propafenone had significantly shorter time to SR than those who received amiodarone (p<0.0001). Univariate regression analysis revealed that patients who underwent PCV with antazoline were almost twice as likely to return to SR compared to the other groups (p<0.0001, OR 1.81, 95% CI 1.44-2.27). CONCLUSIONS: This is the first study comparing the effectiveness of antazoline in PCV versus flecainide in addition to the previously studied amiodarone and propafenone. Our results indicate that antazoline is more effective in restoring SR than amiodarone, flecainide and propafenone. In addition, antazoline restored SR significantly faster than amiodarone or propafenone.

Analysis of a Serious Adverse Reaction of Pulmonary Fibrosis Caused by Dronedarone.

Objective: This study aims to analyze a severe adverse reaction of pulmonary fibrosis induced by dronedarone hydrochloride tablets, and to provide a reference for clinical rational medication through drug precautions. Methods: A case of pulmonary fibrosis induced by dronedarone hydrochloride tablets, along with related literature was retrospectively analyzed. Results: Patients over 65 years old with a history of exposure to amiodarone may increase the incidence of pulmonary toxicity induced by dronedarone, and dronedarone should not be selected as a substitute treatment drug for patients with amiodarone-induced pulmonary toxicity. Conclusions: It is recommended that clinicians monitor the diffusion capacity of carbon monoxide and lung ventilation function of patients before and after using dronedarone for treatment. For patients with a history of amiodarone exposure, intermittent monitoring of chest X-rays and lung function is necessary. If lung function decreases, dronedarone should be immediately discontinued.

Does administration of hydroxychloroquine/amiodarone affect the efficacy of enzyme replacement therapy for Fabry mice?

As a standard therapy for Fabry disease, enzyme replacement therapy (ERT) with recombinant human α-galactosidase A (α-Gal) has been successfully used, and the instructions for this drug state that "it should not be co-administrated with cationic amphiphilic drugs such as hydroxychloroquine (HCQ) and amiodarone (AMI), since these drugs have the potential to inhibit intracellular α-Gal activity". However, there would be cases in which HCQ or AMI is required for patients with Fabry disease, considering their medical efficacy and application. Thus, we examined the impact of HCQ/AMI on recombinant human α-Gal by in vitro, cellular, and animal experiments. The results revealed that HCQ/AMI affected the enzyme activity of α-Gal incorporated into cultured fibroblasts from a Fabry mouse when the cells were cultured in medium containing these drugs and the enzyme, although their direct inhibitory effect on the enzyme is not strong. These lysosomotropic drugs may be trapped and concentrated in lysosomes, followed by inhibition of α-Gal. On the other hand, no reduction of α-Gal activity incorporated into the organs and tissues, or acceleration of glycoshingolipid accumulation was observed in Fabry mice co-administered with HCQ/AMI and the enzyme, compared with in the case of usual ERT. As HCQ/AMI administered are catabolized in the liver, these drugs possibly do not affect ERT for Fabry mice, different from in the case of cultured cells in an environment isolated from the surroundings.

Amiodarone-Associated Optic Neuropathy in a Patient With Associated Arrhythmia.

Amiodarone is a commonly used antiarrhythmic used to treat atrial fibrillation and ventricular tachycardias. While this agent can present with pulmonary, thyroid, and hepatic side effects, it can also, less commonly cause neurologic toxicity, particularly optic neuropathy. Optic neuropathy can manifest as acute vision loss. The management of amiodarone-associated optic neuropathy (AAON) includes early recognition of symptom manifestation so that the medication can be discontinued promptly. Here, we describe a case of a 64-year-old male who developed acute onset complete left-sided vision loss after initiation of amiodarone.

Extracellular acidification reveals the antiarrhythmic properties of amiodarone related to late sodium current-induced atrial arrhythmia.

BACKGROUND: Amiodarone (AMIO) is an antiarrhythmic drug with the pKa in the physiological range. Here, we explored how mild extracellular pH (pHe) changes shape the interaction of AMIO with atrial tissue and impact its pharmacological properties in the classical model of sea anemone sodium channel neurotoxin type 2 (ATX) induced late sodium current (INa-Late) and arrhythmias. METHOD: Isolated atrial cardiomyocytes from male Wistar rats and human embryonic kidney cells expressing SCN5A Na+ channels were used for patch-clamp experiments. Isolated right atria (RA) and left atria (LA) tissue were used for bath organ experiments. RESULTS: A more acidophilic pHe caused negative inotropic effects on isolated RA and LA atrial tissue, without modification of the pharmacological properties of AMIO. A pHe of 7.0 changed the sodium current (INa) related components of the action potential (AP), which was enhanced in the presence of AMIO. ATXinduced arrhythmias in isolated RA and LA. Also, ATX prolonged the AP duration and enhanced repolarization dispersion in isolated cardiomyocytes in both pHe 7.4 and pHe 7.0. Pre-incubation of the isolated RA and LA and isolated atrial cardiomyocytes with AMIO prevented arrhythmias induced by ATX only at a pHe of 7.0. Moreover, AMIO was able to block INa-Late induced by ATX only at a pHe of 7.0. CONCLUSION: The pharmacological properties of AMIO concerning healthy rat atrial tissue are not dependent on pHe. However, the prevention of arrhythmias induced by INa-Late is pHe-dependent. The development of drugs analogous to AMIO with charge stabilization may help to create more effective drugs to treat arrhythmias related to the INa-Late.

Experimental Studies on the Effect of Expired Amiodarone Drug (EAD) as a Corrosion Inhibitor on Mild Steel in 1 M HCl.

In the present investigation, the corrosion tendency of mild steel under acidic pH was studied by employing unused expired amiodarone (EAD) drug as a potential corrosion inhibitor by adopting the weight loss measurement method. The corrosion inhibition efficiency (IE) of the formed protective film (EAD) on the steel surface was analyzed using potentiodynamic polarization and AC-impedance spectroscopy studies. The surface morphology of the mild steel before and after corrosion (in 1.0 M HCl) was analyzed via scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDAX), atomic force microscopy (AFM), and thermodynamic studies. The weight loss measurement under different concentrations of EAD indicated that an excellent inhibition was displayed at a concentration of 0.001 M, and the IE was found to depend on both the concentration and molecular structure of EAD. A potentiodynamic polarization study revealed that EAD predominantly acted as a cathode inhibitor, and electrochemical impedance spectroscopy (EIS) confirmed the adsorption of EAD on the surface of mild steel, which obeyed Temkin's adsorption isotherm model. The calculated thermodynamic parameters revealed that adsorption was spontaneous and exothermic.

Drug-induced interstitial lung disease: a narrative review of a clinical conundrum.

INTRODUCTION: Drug-induced interstitial lung disease (DI-ILD) is increasing in incidence, due to the use of many new drugs across a broad range of cancers and chronic inflammatory diseases. The presentation and onset of DI-ILD are variable even for the same drug across different individuals. Clinical suspicion is essential for identifying these conditions, with timely drug cessation an important determinant of outcomes. AREAS COVERED: This review provides a comprehensive and up-to-date summary of epidemiology, risk factors, pathogenesis, diagnosis, treatment, and prognosis of DI-ILD. Relevant research articles from PubMed and Medline searches up to September 2023 were screened and summarized. Specific drugs including immune checkpoint inhibitors, CAR-T cell therapy, methotrexate, and amiodarone are discussed in detail. The potential role of pharmacogenomic profiling for lung toxicity risk is considered. EXPERT OPINION: DI-ILD is likely to be an increasingly important contributor to respiratory disability in the community. These conditions can negatively impact quality of life and patient longevity, due to associated respiratory compromise as well as cessation of evidence-based therapy for the underlying disease. This clinical conundrum is relevant to all areas of medicine, necessitating increased understanding and greater vigilance for drug-related lung toxicity.

Amiodarone inhibits the Toll-like receptor 3-mediated nuclear factor κB signaling pathway by blocking organelle acidification.

Toll-like receptor (TLR) agonists or pro-inflammatory cytokines converge to activate the nuclear factor κB (NF-κB) signaling pathway, which provokes inflammatory responses. In the present study, we identified amiodarone hydrochloride as a selective inhibitor of the TLR3-mediated NF-κB signaling pathway by screening the RIKEN NPDepo Chemical Library. In human umbilical vein endothelial cells (HUVEC), amiodarone selectively inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) induced by polyinosinic-polycytidylic acid (Poly(I:C)), but not tumor necrosis factor-α, interleukin-1α, or lipopolysaccharide. In response to a Poly(I:C) stimulation, amiodarone at 20 µM reduced the up-regulation of mRNA expression encoding ICAM-1, vascular cell adhesion molecule-1, and E-selectin. The nuclear translocation of the NF-κB subunit RelA was inhibited by amiodarone at 15-20 µM in Poly(I:C)-stimulated HUVEC. Amiodarone diminished the fluorescent dots of LysoTracker® Red DND-99 scattered over the cytoplasm of HUVEC. Therefore, the present study revealed that amiodarone selectively inhibited the TLR3-mediated NF-κB signaling pathway by blocking the acidification of intracellular organelles.

Thyroid Dysfunction in Advanced Heart Failure Patients and Its Correlation with Amiodarone Therapy: A Two-Year Study.

(1) Background: Advanced heart failure often accompanies ventricular arrhythmias, necessitating antiarrhythmic therapies. Amiodarone, commonly used for this purpose, may induce thyroid dysfunction due to its high iodine content. However, the prevalence and correlation of thyroid dysfunction with amiodarone in end-stage heart failure patients remain unclear. Aim: This study aimed to evaluate the prevalence and types of thyroid dysfunction and their association with amiodarone among 200 patients diagnosed with advanced heart failure eligible for transplantation. (2) Methods: Consecutively enrolled patients received treatment following the European Society of Cardiology guidelines and were followed-up for two years. Ventricular arrhythmias affected 58.5% of the cohort, with 24.5% receiving amiodarone therapy. (3) Results: Thyroid metabolism dysfunction was evident in 61 patients, notably overrepresented in women (p = 0.0028). Hyperthyroidism (34 patients) and hypothyroidism (27 patients) were observed, with a significant amiodarone-related correlation. Despite this, thyroid dysfunction was not associated with increased mortality among the studied group. (4) Conclusions: Thyroid dysfunction is prevalent in advanced heart failure patients, with a notable proportion linked to amiodarone. However, its presence does not correspond to higher mortality rates. Understanding these associations is crucial for effective management in this patient population. Further exploration is warranted to refine approaches to thyroid dysfunction in refractory heart failure.

The Villain Who Saved the Day: The Paradoxical Value of Amiodarone in Managing Recurrent Ventricular Tachycardia Secondary to Amiodarone-Induced Thyroiditis.

Thyroiditis is a rare and serious complication for patients taking amiodarone. It can manifest with symptoms of hyperthyroidism and serious life-threatening arrhythmias. We present a case of a patient with amiodarone-induced thyrotoxicosis presenting with an electrical storm in which rhythm control was achieved with the utilization of amiodarone.

Case Report: Ventricular preexcitation-induced dilated cardiomyopathy improved by the pharmacologic suppression of ventricular preexcitation in three infants, and literature review.

The therapy of ventricular preexcitation-induced dilated cardiomyopathy in very small infants or infants with a high risk of ablation is tough and related articles are rare. Effective pharmacotherapy to suppress ventricular preexcitation is valuable. Aims: To evaluate the effectiveness and safety of pharmacotherapy for cardiac resynchronization in infants with ventricular preexcitation-induced dilated cardiomyopathy. Methods and results: Three infants with ventricular preexcitation-induced dilated cardiomyopathy, due to the disappearance of ventricular preexcitation during the placement of catheter, intermittent WPW pattern, and right mid septal accessory pathway respectively, had received pharmacotherapy for cardiac resynchronization. The initial dosage of oral amiodarone was 5 mg/kg.d and it was followed by the maintenance dosage of 2-2.5 mg/kg.d 4 weeks later. Propafenone (15 mg/kg.d) served as a supplement since amiodarone was not adequate in case 3. The three infants achieved successful pharmacologic suppression of ventricular preexcitation 10, 6.5, and 4.5 weeks after the initiation of amiodarone respectively. They all got normalized contraction of interventricular septum and LVEF as well as reduced LVEDD gradually after the disappearance of ventricular preexcitation. No side effects associated with pharmacotherapy happened during the follow-up. Amiodarone had been withdrawn for 2 years and 5 months in Cases 1 and 2. They both remained free from ventricular preexcitation and retained normal LVEF and LVEDD. Conclusions: Pharmacotherapy for cardiac resynchronization with oral amiodarone or in combination with propafenone for infants with ventricular preexcitation-induced dilated cardiomyopathy is effective and safe. Pharmacotherapy for cardiac resynchronization served as another therapeutic choice besides ablation.

Association between amiodarone use and risk of cataract: a population-based active-comparator study.

BACKGROUND: Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. METHODS: This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40 years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. RESULTS: In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. CONCLUSIONS: The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.

Microfluidic production of amiodarone loaded nanoparticles and application in drug repositioning in ovarian cancer.

Amiodarone repositioning in cancer treatment is promising, however toxicity limits seem to arise, constraining its exploitability. Notably, amiodarone has been investigated for the treatment of ovarian cancer, a tumour known for metastasizing within the peritoneal cavity. This is associated with an increase of fatty acid oxidation, which strongly depends on CPT1A, a transport protein which has been found overexpressed in ovarian cancer. Amiodarone is an inhibitor of CPT1A but its role still has to be explored. Therefore, in the present study, amiodarone was tested on ovarian cancer cell lines with a focus on lipid alteration, confirming its activity. Moreover, considering that drug delivery systems could lower drug side effects, microfluidics was employed for the development of drug delivery systems of amiodarone obtaining simultaneously liposomes with a high payload and amiodarone particles. Prior to amiodarone loading, microfluidics production was optimized in term of temperature and flow rate ratio. Moreover, stability over time of particles was evaluated. In vitro tests confirmed the efficacy of the drug delivery systems.

Livogrit prevents Amiodarone-induced toxicity in experimental model of human liver (HepG2) cells and Caenorhabditis elegans by regulating redox homeostasis.

Treatment with cationic amphiphilic drugs like Amiodarone leads to development of phospholipidosis, a type of lysosomal storage disorder characterized by excessive deposition of phospholipids. Such disorder in liver enhances accumulation of drugs and its metabolites, and dysregulates lipid profiles, which subsequently leads to hepatotoxicity. In the present study, we assessed pharmacological effects of herbal medicine, Livogrit, against hepatic phospholipidosis-induced toxicity. Human liver (HepG2) cells and in vivo model of Caenorhabditis elegans (N2 and CF1553 strains) were used to study effect of Livogrit on Amiodarone-induced phospholipidosis. In HepG2 cells, Livogrit treatment displayed enhanced uptake of acidic pH-based stains and reduced phospholipid accumulation, oxidative stress, AST, ALT, cholesterol levels, and gene expression of SCD-1 and LSS. Protein levels of LPLA2 were also normalized. Livogrit treatment restored Pgp functionality which led to decreased cellular accumulation of Amiodarone as observed by UHPLC analysis. In C. elegans, Livogrit prevented ROS generation, fat-6/7 gene overexpression, and lysosomal trapping of Amiodarone in N2 strain. SOD-3::GFP expression in CF1553 strain normalized by Livogrit treatment. Livogrit regulates phospholipidosis by regulation of redox homeostasis, phospholipid anabolism, and Pgp functionality hindered by lysosomal trapping of Amiodarone. Livogrit could be a potential therapeutic intervention for amelioration of drug-induced phospholipidosis and prevent hepatotoxicity.

The priority of mesenchymal stem cells treated with melatonin in ameliorating thyroid impairment induced by amiodarone. Thorough look on the apoptotic pathway.

Amiodarone treatment has been associated with thyroid alterations. This work was planned to consider therapeutic outcome of MSCs versus MSCs treated with melatonin in minimizing amiodarone -induced deviations in thyroid. We handed-down 50 male Wistar rats, then distributed them into 5 groups; I, II, III, IV, V; control, sham control, amiodarone treated, amiodarone and MSCs treated, and amiodarone, MSCs and melatonin treated groups respectively. Light microscopic examination; levels of T3, T4 and TSH, Oxidative/antioxidative tissue markers, immune-histochemical staining (Bcl2, BAX, iNOS) and real time PCR (IL-6 and VEGF and Caspase 3) were done. Results of group III showed degenerated follicles, decreased follicular cell count and diminished colloid. Some of the follicles were dilated with signs of inflammatory response and apoptosis. Increased collagen deposition in group III was marked. The positive immune-reactive cells of Bcl-2 was decreased and that of BAX and iNOS was increased, also T3 and T4 levels were significantly decreased, but TSH was significantly increased in group III comparing it to the group I. There were highly significant diminution in both SOD and GPx and upsurge in MDA intensities in groups III, IV when correlated to the control. In group IV and V the aforementioned values were restored. The PCR results showed significant increase in IL-6 and VEGF and Caspase 3 in group III compared to the control one, whereas, their values in groups IV and V were reestablished. It is concluded that stem cells can to a great extent ameliorate the thyroid damage induced by amiodarone.But, Adding melatonin to the stem cells culture was found to have auxiliary beneficial effect in the improving the thyroid structure and function.

Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations.

OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.