Last update 21 Nov 2024

Amiodarone Hydrochloride

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummaryAmiodarone, also known as CORDARONE, is an antiarrhythmic drug developed in 1961 by chemists Tondeur and Binon. By 1980, it was commonly prescribed throughout Europe for the treatment of arrhythmias. In December 1985, due to the threat of a cut-off from European companies, amiodarone was approved by the FDA for the treatment of arrhythmias, even though it had not undergone rigorous randomized clinical trials. Amiodarone is considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. It blocks sodium and myocardial potassium channels, contributing to slowing of conduction and prolongation of refractoriness. CORDARONE is indicated for the treatment of life-threatening ventricular fibrillation and unstable tachycardia in adults who have not responded to other antiarrhythmics.

Drug Type

Small molecule drug

Synonyms

2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran, 2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone, 2-n-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran

+ [14]

Target

Potassium channel x Sodium channels x VDCCs x β-adrenoceptors

Mechanism

Potassium channel blockers, Sodium channels blockers, VDCCs blockers(Voltage-gated calcium channel blockers)

+ [1]

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Heart ArrestAtrial FibrillationTachycardia, Ventricular+ [2]

Inactive Indication

Heart Failure

Originator Organization

Labaz

Active Organization

Guilin Pharmaceutical Co., Ltd.Baxter Healthcare Corp.Sanofi KK

Inactive Organization

Prism Pharmaceuticals, Inc.Wyeth Pharmaceuticals LLCWyeth AB

Drug Highest PhaseApproved

First Approval Date

CN (01 Jan 1983),

Arrhythmias, Cardiac

RegulationOrphan Drug (JP)

Structure

Molecular FormulaC25H29I2NO3

InChIKeyIYIKLHRQXLHMJQ-UHFFFAOYSA-N

CAS Registry1951-25-3

View All Structures (2)

153

Clinical Trials associated with Amiodarone Hydrochloride

NCT01422148 / Not yet recruitingPhase 2IIT

Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery (MINA)

. New- onset postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and its occurrence increases with age. POAF can result in clinically significant morbidity and mortality. The national trend in the US is that the population older than 65 years is increasing, making healthcare expenditure related to POAF to be a major burden on health care system. Effective treatment of POAF is imperative in ensuring quality of care and reduction of costs.
In 2021 there is a projected total of 377,763 cardiovascular surgeries in the US alone with approximately half of which will have POAF with longer postoperative length of stay (+3.9 days) and higher discharge costs (+$13,993) than no-POAF patients (Reference: Ann Thorac Surg. 2015 Jan;99(1):109-14). Amiodarone, the currently used therapy, is often insufficient to prevent POAF and has multiple side-effects. In this study, we expect to improve the incidence of POAF by using a common acne drug (Minocycline) that is safe and that could be incorporated in clinical care of this disease.

Start Date01 Jul 2025

Sponsor / Collaborator

Baystate Medical Center

NCT06680869 / Not yet recruitingPhase 3IIT

Early Amiodarone in Shockable Cardiac Arrest (Early-Amio) Study

The primary objective of this pilot, pragmatic stepped-wedge cluster randomized trial is to evaluate if a modified cardiac arrest treatment algorithm calling for the administration of the initial amiodarone dose one 2-minute cycle earlier than current guidelines (during the same cycle as the initial dose of epinephrine) improves the time to amiodarone delivery in those with out-of-hospital cardiac arrest due to refractory ventricular fibrillation or ventricular tachycardia compared to usual care.

Start Date01 Jan 2025

Sponsor / Collaborator

Oregon Health & Science University

[+1]

ITMCTR2024000589 / SuspendedIIT

A randomized blind parallel controlled clinical study of acupuncture combined with amiodarone in the treatment of rapid paroxysmal atrial fibrillation

Start Date01 Nov 2024

Sponsor / Collaborator-

100 Clinical Results associated with Amiodarone Hydrochloride

100 Translational Medicine associated with Amiodarone Hydrochloride

100 Patents (Medical) associated with Amiodarone Hydrochloride

10,487

Literatures (Medical) associated with Amiodarone Hydrochloride

01 Jan 2025·Acta Anaesthesiologica Scandinavica

Acute amiodarone‐induced pulmonary toxicity in adult ICU patients with new‐onset atrial fibrillation—A systematic review

Review

Author: Schjørring, Olav L. ; Ling‐Vannerus, Theodor ; Skrubbeltrang, Conni ; Rasmussen, Bodil S. ; Møller, Morten H.

AbstractBackgroundNew‐onset atrial fibrillation or flutter (NOAF) is a common arrhythmia in adult intensive care unit (ICU) patients. Intravenous amiodarone is one of the most used anti‐arrhythmic drugs, despite its risk of inducing acute amiodarone‐induced pulmonary toxicity (APT). We aimed to outline the body of evidence on acute APT in ICU patients with NOAF.MethodsWe performed a systematic search using the population, intervention, comparison, and outcome (PICO) approach. We included studies of adults admitted to the ICU, who developed NOAF during their ICU stay, were treated with amiodarone, and reported on acute APT, irrespective of research design. The CASE guidelines were applied to evaluate the quality of the included studies, and study results are reported in accordance with the preferred reporting items for systematic reviews and meta‐analyses.ResultsNo randomised controlled trials or observational studies were identified. Nine case reports and one retrospective case series of fatal outcomes in ICU patients treated with amiodarone for NOAF constituted the evidence base. The quality of the included studies was high with a mean of 10 (range 8–12) of the 13 CASE guideline criteria fulfilled. The studies included a total of 16 critically ill adults who was diagnosed with acute APT after a mean of 9 days (range 2–20 days) following initiation of amiodarone with a mean total dose of amiodarone of 4553 mg (range 1100–13,500 mg) predominantly administrated intravenously. Three out of nine patients in the case reports died in the ICU during the amiodarone treatment. No long‐term follow‐up was conducted for the survivors.ConclusionAcute APT in adult ICU patients treated with amiodarone for NOAF is poorly described and is based on a total of 16 reported cases. Additional studies assessing the safety of amiodarone in critically ill adults with NOAF in the ICU is warranted.

01 Jan 2025·Current Molecular Medicine

Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related Potassium Channels

Article

Author: Gao, Yang ; Xiong, Xiaobo ; Li, Fangjiang ; Liang, Huiqing ; Li, Huixian

Background:Heart failure (HF) is the ultimate transformation result of various cardiovascular diseases. Mitochondria-mediated cardiomyocyte apoptosis has been uncovered to be associated with this disorder.Objective:This study mainly delves into the mechanism of the anti-arrhythmic drug amiodarone on mitochondrial toxicity of cardiomyocytes.Methods:The viability of H9c2 cells treated with amiodarone at 0.5, 1, 2, 3, and 4 μM was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and Sigmar1 expression was examined by quantitative real-time PCR (qRTPCR). After transfection, the viability, apoptosis, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), and potassium voltage-gated channel subfamily H member 2 (KCNH2) expression in H9c2 cells were assessed by MTT, flow cytometry, ROS assay kit, mitochondria staining kit, and Western blot.Results:Amiodarone at 1-4 μM notably weakened H9c2 cell viability with IC50 value of 2.62 ± 0.43 μM. Amiodarone at 0.5-4 μM also evidently suppressed the Sigmar1 level in H9c2 cells. Amiodarone repressed H9c2 cell viability and KCNH2 level and triggered apoptosis, ROS production and mitochondrial depolarization, while Sigmar1 upregulation reversed its effects. Moreover, KCNH2 silencing neutralized the effect of Sigmar1 up-regulation on H9c2 cell viability, apoptosis, and ROS production.Conclusion:Amiodarone facilitates the apoptosis of H9c2 cells by restraining Sigmar1 expression and blocking KCNH2-related potassium channels.

01 Jan 2025·Radiology Case Reports

One artery to rule them all: A case of single coronary artery arising from the right sinus of Valsalva

Article

Author: Ioakeimidis, Nikolaos S ; Ioakeimidis, Nikolaos S. ; Pepis, Panagiotis ; Mitrousi, Konstantina ; Valasiadis, Dimitrios

A single coronary artery (SCA) is a rare congenital anomaly with an incidence of 0.024 - 0.066% in angiographies and potential implications for adverse events depending on the course of the anomalous artery. We present a unique case of a single coronary artery arising from the right sinus of Valsalva. A 77-year-old female presented to the emergency department with an ongoing 3-hour episode of palpitations and intermittent atypical chest pain over 1 week. Her medical history included hypertension and dyslipidemia. Electrocardiography revealed atrial fibrillation with rapid ventricular response, which was successfully managed with intravenous amiodarone and the diagnostic workup ruled out life threatening thoracic pathology including cardiac ischemia. A CT coronary angiography was performed due to the moderate pretest probability of coronary artery disease. The scan identified a single coronary artery with a common origin of the left main coronary artery (LMCA) and the right coronary artery (RCA), from the right sinus of Valsalva, classified as Lipton Type RII-A which is a benign variant. This case highlights the importance of identifying CAAs, which are often incidental but may have clinical relevance depending on the anatomical course and associated risk factors. Early and accurate diagnosis through advanced imaging techniques is crucial to guide appropriate management and ensure optimal outcomes for the patient.

News (Medical) associated with Amiodarone Hydrochloride

22 Oct 2024

·www.biospace.com

Gilead to Present Latest Research Across Key Liver Disease Indication at the American Association for the Study of Liver Disease (AASLD) Meeting 2024

- Key Insights from Viral Hepatitis, PBC, and MASH/Fibrosis Studies Highlight Gilead’s Ongoing Commitment to Advancing Life-Changing Liver Disease Research - FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced new research to be presented at The Liver Meeting ® 2024, hosted by the American Association for the Study of Liver Diseases (AASLD) from November 15-19 in San Diego, Calif. More than 40 abstracts will be presented with key data, including 11 abstracts reporting new data on primary biliary cholangitis (PBC). The data will include findings from the RESPONSE trial that demonstrate the efficacy and safety pro Livdelzi ® (seladelpar) in people living with PBC and compensated cirrhosis. Additionally, data will be presented on the effects of Livdelzi on pruritus (chronic itching), a symptom that has significant impact on the quality of life of people living with PBC, along with interim long-term efficacy and safety results from the ongoing ASSURE study. Beyond PBC, Gilead will be presenting an interim analysis of the Phase 3 MYR301 study, which is evaluating people living with hepatitis Delta virus (HDV) who received bulevirtide monotherapy (2 mg for 144 weeks; 10 mg for 144 weeks; or 10 mg for 96 weeks) for chronic HDV and have been off treatment for 48 weeks. The study is evaluating whether or not patients treated with bulevirtide monotherapy for 2-3 years maintained virological and biochemical responses one year after stopping treatment. An additional 144-week analysis of patient-reported outcomes for individuals treated with bulevirtide 2 mg will also be presented, adding to the wealth of long-term data for the treatment for chronic HDV. “We’re excited to share our latest research at The Liver Meeting, as we push the boundaries of what’s possible in liver disease treatment. The breadth of this research reflects Gilead’s unwavering dedication to advancing life-changing science and shaping healthier futures for people living with liver disease,” said Anu Osinusi, Vice President of Clinical Development for Hepatitis, Respiratory and Emerging Viruses, Gilead Sciences. “The depth and range of our data, spanning both viral and inflammatory liver diseases, underscores our commitment to making a meaningful impact at every stage of a person’s journey in liver disease. Our goals go far beyond treatment alone—our work spans awareness, education, screening, diagnosis, and long-term care, all intending to address unmet needs and enhance treatment outcomes.” Gilead will also present hepatitis C virus (HCV) data which will include safety and tolerability outcomes for Epclusa ® (velpatasvir/sofosbuvir) in pregnant individuals with chronic HCV (the STORC study). As a special population that is often excluded from clinical research, these results may help clinicians better support pregnant people living with HCV, which in turn may reduce the risk of transmission to infants. Furthermore, real-world findings from the SVR10K study on HCV will be showcased, demonstrating the effects of direct-acting antivirals against all HCV genotypes across diverse regions. Late-breaking data from a Phase 2a open-label study assessing the safety and efficacy of novel combination therapies for chronic hepatitis B virus (HBV) will also be presented by Gilead. Key Abstracts at AASLD 2024: ID Abstract Title PBC 164 Efficacy and Safety of Seladelpar in Patients with PBC and Compensated Cirrhosis in the Phase 3 Placebo-controlled RESPONSE Trial 167 Attenuation, Near Resolution, and Prevention of Pruritis in Patients with PBC Treated with Seladelpar: A Secondary Analysis of Patterns of Pruritis Change in the RESPONSE Trial 4339 Alkaline Phosphatase Changes with Seladelpar Across Subgroups of Primary Biliary Cholangitis Patients in the RESPONSE Trial 4342 Seladelpar and Reductions in Lipids in Patients with Primary Biliary Cholangitis with and without Statin use in the Phase 3 Placebo-controlled RESPONSE Study 4341 Long-term Safety of Seladelpar 10 mg with up to 5 Years of Treatment in Patients with Primary Biliary Cholangitis Primary sclerosing cholangitis (PSC) 151 Associations Between Biomarkers and Magnetic Resonance Imaging-derived ANALI Score in Patients with Primary Sclerosing Cholangitis: Analysis from the Phase 3 PRIMIS Study HDV 1147 Efficacy and Safety of BLV Monotherapy for Chronic Hepatitis Delta: Post Treatment Results through 48 Weeks after the End of Treatment from an Interim Analysis of a Randomized Phase 3 Study MYR301 1193 Patient-reported Outcomes among Patients with Chronic Hepatitis Delta Treated with Bulevirtide 2 mg: A Long-term Analysis of the Phase 3 MYR301 Trial at 144 Weeks 139 Long-term Bulevirtide Monotherapy in Patients with HDV-related Compensated Cirrhosis: Effectiveness, Safety and Clinical Outcomes from the Retrospective Multicenter European Study (SAVE-D) HCV 222 Safety, Tolerability, and Outcomes of Velpatasvir/Sofosbuvir in Treatment of Chronic Hepatitis C Virus during Pregnancy (STORC) 1455 The SVR10K Study: A Real-world Data with Pangenotypic Direct-acting Antivirals across Multiple Diverse Regions 1476 Hepatitis C Treatment Uptake Differs by Gender among a Commercially Insured Population in the United States HBV 1380 Results from a Phase 2a, Open-label Study to Evaluate the Safety and Efficacy of Novel Combination Therapies Containing VIR-2218, Selgantolimod, and Nivolumab for the Treatment of Chronic Hepatitis B 1252 Effectiveness and Safety of Tenofovir Alafenamide in Chronic Hepatitis B Patients with Suboptimal Response to Antiviral Therapy 1337 Characterization of Changes in Noninvasive Fibrosis Markers over 8 Years of Tenofovir-based Treatment in Chronic Hepatitis B Patients Enrolled in Two Phase 3 Trials Nonalcoholic steatohepatitis (NASH)/Fibrosis 1520 Prospective Validation of the Mediterranean Diet Adherence Screener (MEDAS) for Point-of-care Assessment of Diet Quality in Patients with Metabolic Dysfunction-associated Steatotic Liver Disease For more information, including a complete list of abstract titles being presented at the meeting, please visit the AASLD website . In July 2023, the European Commission (EC) granted full Marketing Authorization (MA) for bulevirtide 2 mg for the treatment of adults with chronic HDV and compensated liver disease. Bulevirtide’s conditional MA license in Great Britain was converted to a full MA in August 2023 and a full MA was granted in Switzerland and Australia in 2024. In regions where it is not approved, including the U.S., bulevirtide 2 mg is an investigational product. In these regions, health authorities have not established the safety and efficacy of bulevirtide. Bulevirtide 10 mg is an investigational product and has not been approved anywhere. Cilofexor and selgantolimod are investigational compounds and are not approved by the FDA or any other regulatory authority; their safety and efficacy have not been established. Please see below for the U.S. Indications and Important Safety Information, including BOXED WARNINGS, for Epclusa and Livdelzi. U.S. Important Safety Information And Indication for EPCLUSA BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. Contraindications If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information. Warnings and Precautions Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. Risk of Reduced Therapeutic Effect Due to Use with P-gp Inducers and/or Moderate to Strong Inducers of CYP2B6, CYP2C8 or CYP3A4 : Rifampin, St. John’s wort and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations. Adverse Reactions The most common adverse reactions (≥10%, all grades) with EPCLUSA in adults and pediatric patients 6 years of age and older were headache and fatigue; and when used with RBV in adults with decompensated cirrhosis were fatigue, anemia, nausea, headache, insomnia and diarrhea. The most common adverse reactions (≥10%, grade 1 or 2) in pediatric patients less than 6 years of age were vomiting and spitting up the drug. Drug Interactions Coadministration of EPCLUSA is not recommended with topotecan due to increased concentrations of topotecan. Coadministration of EPCLUSA is not recommended with proton-pump inhibitors, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir. Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments. Indication EPCLUSA is indicated for the treatment of adult and pediatric patients 3 years of age and older with chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis. U.S. Important Safety Information for LIVDELZI Warnings and Precautions Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care. Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels > 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI. Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated. Adverse Reactions The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%). Drug Interactions OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure. Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI. Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (eg, cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure. CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions. Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible. Pregnancy and Lactation Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235. Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI. Indication LIVDELZI is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use: Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy). About HDV HDV is considered the most aggressive or severe form of viral hepatitis, associated with more rapid progression towards liver-related death and liver cancer in people with HBV. On average, HDV progresses to cirrhosis within 5 years and to liver cancer within 10 years. Nearly 5% of people who have a chronic infection with HBV are estimated to have HDV, equating to 12-15 million people worldwide. The prevalence of HDV infection is largely underestimated due to lack of universal testing of HBV-positive individuals for HDV. About PBC PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the U.S.). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of alkaline phosphatase (ALP), alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), enzymes found primarily in the liver, as well as total bilirubin. The most common symptoms of PBC are pruritus and fatigue, which can be debilitating for some people. Progression of PBC is associated with an increased risk of liver-related mortality. About Gilead Sciences in Liver Disease For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with PBC. But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials or studies, including those involving Epclusa, Hepcludex (bulevirtide), Livdelzi (seladelpar), cilofexor and selgantolimod (such as the ASSURE, RESPONSE, MYR301, STORC and SVR10K studies); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA and other regulatory authorities may not approve bulevirtide for the treatment of HDV, and the risk that any such approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of investigational programs for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Epclusa, Hepcludex, Livdelzi, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com

Phase 2Clinical ResultDrug ApprovalPhase 3

16 Oct 2024

·www.prnewswire.com

XYRA Announces FDA Label Guidance for Managing Atrial Fibrillation with Budiodarone and Wearable Monitoring Devices

Key points: Wearable AF monitoring devices are extensively used in routine practice worldwide. The FDA has agreed on the use of AF monitoring devices in clinical trials for budiodarone approval. The FDA has also issued guidance on the steps required to incorporate wearable AF monitoring devices into a drug label. LOS ALTOS, Calif., Oct. 16, 2024 /PRNewswire/ -- XYRA LLC, a private biopharmaceutical company, is committed to developing innovative therapies for cardiac rhythm disorders with high unmet needs. With the widespread use of FDA-approved wearable Atrial Fibrillation (AF) monitoring devices for arrhythmia detection, it is now possible to identify subjects with long episodes of AF (LEAF) and symptoms; these patients are at high risk of complications including stroke, heart failure and progression to permanent AF. Phase 2 clinical data substantiates that XYRA's drug candidate, budiodarone, delivers significant reductions in symptoms, as well as the frequency and duration of AF episodes, among subjects with non-permanent AF which compare favorably to the results obtained with AF-ablation in a recent study. Upon reaching an agreement with the FDA regarding clinical trial endpoints and potential approval pathway for multiple active doses of budiodarone in the management of non-permanent AF, XYRA sought and received guidance from the FDA on a prospective label for budiodarone use post-approval. The FDA's guidance specified indications and directions for use to control AF symptoms and achieve a safe harbor for stroke risk reduction by elimination of LEAF greater than 5 hours. Both endpoints were demonstrated in Phase 2 trials of budiodarone. The FDA indicated that the label likely would include directions for maintaining patients on the appropriate therapeutic dose of budiodarone. In addition, XYRA's unique approach incorporates AF monitoring and enables the identification of patients who do not respond to the maximum therapeutic dose. This early detection allows for the timely discontinuation of budiodarone in non-responsive patients, thereby preventing unnecessary exposure to a non-therapeutic drug. The FDA indicated that a label for budiodarone including an AF monitoring device requirement is possible if upcoming clinical trials demonstrate that AF montoring systems are able to generate data that could be used to successfully adjust the dosage of budiodarone during treatment. "Xyra assured the Agency that if the proposed label includes a requirement for intermittent AF monitoring with approved wearable devices, only eligible subjects will be prescribed Budiodarone. These patients will be established on the lowest, most effective dose to ensure that symptoms and LEAF are controlled and if there is an inadequate response to the highest recommended dose, treatment will be discontinued," said Peter Milner, M.D., FACC, managing member of XYRA. He added, "Budiodarone, with its dose-proportional pharmacology and intermediate half-life offers an ideal opportunity to integrate state-of-the-art digital AF monitoring technology into routine practice, enabling us to identify the patients with AF who benefit most from the drug. We know the odds of having a stroke with AF goes up 5-fold in the 5 days after a LEAF greater than 5.5 hours. So now that it is possible to identify these patients with wearable AF monitoring devices in real time, it makes sense to treat them with budiodarone and monitor the response to therapy to prevent long episodes of AF from happening again." The currently FDA-approved wearable devices available for use in AF and potentially with budiodarone to determine eligibility and response to therapy include patch devices such as Philips' E-patch® or MCOT®, iRhythm's Zio® Patch, and wrist wearables like the Zio® ZEUS and Apple Watch®. This list is expected to rapidly expand thanks to the phenomenal innovation occurring in the digital healthcare sector such that wearable cardiac monitoring is projected by some to be a $4B business globally by 2028. About Budiodarone: Budiodarone, a Phase 3 enabled, potentially best-in-class mixed ion channel blocker, features esterase metabolism and thus a significantly shorter half-life than amiodarone, with no evidence of accumulation in human or animal studies to date. Its superior efficacy is attributed to its enhanced late sodium channel blocking properties. Budiodarone has demonstrated the ability to treat AF by controlling symptoms, eliminating LEAF, reducing AF burden, and maintaining normal sinus rhythm. About Atrial Fibrillation: Atrial Fibrillation (AF) is the most common sustained heart arrhythmia in adults, affecting approximately 44 million individuals worldwide. It is associated with thromboembolic risk, impaired cardiac performance, and other morbidities. Besides patients with symptomatic AF, the condition is often first detected after a stroke, the development of left ventricular dysfunction, or incidentally via patient examination. The management of AF has evolved over time. Due to accumulating evidence of improved outcomes, previous strategies focusing on simple ventricular rate control have shifted to current therapies that seek to restore and maintain sinus rhythm. AF may be treated with anti-arrhythmic drugs (AAD), electrophysiological ablation, or a combination of both. About XYRA LLC: XYRA LLC is a private biopharmaceutical company committed to developing innovative therapies for cardiac rhythm disorders with high unmet needs. The company's goal is to make AF management comparable to that of other common cardiac conditions, such as hypertension and hypercholesterolemia. In these conditions, upward dose titration of effective drugs, guided by simple and widely available monitoring tools to confirm compliance and response to therapy, has consistently improved outcomes. For information: Investor Relations Contact: [email protected] Logo - SOURCE XYRA WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Phase 3

20 Jun 2024

·www.biospace.com

Rutherrin(R) Repurposes Non-Cancer Drugs for Cancer Therapy

TORONTO, ON / ACCESSWIRE / June 20, 2024 / Theralase® Technologies Inc. ("Theralase®" or the "Company") (TSXV:TLT)(OTCQB:TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated small molecules and their formulations, intended for the safe and effective destruction of various cancers, bacteria and viruses, is pleased to announce that in preclinical research, it's lead drug formulation, Rutherrin® was able to repurpose non-cancer drugs for cancer therapy. Drug repurposing is the process of finding new uses for existing clinically approved drugs. Repurposing is a drug development strategy that received heightened attention after the Food and Drug Administration ("FDA") granted emergency use authorization of several repurposed drugs to treat the Covid-19 virus. Drug repurposing, defined as researching new indications for already approved drugs or advancing previously studied, but unapproved drugs, is a core approach in drug development. Some reports state that about 30 to 40% of new drugs and biologics approved by the FDA are repurposed or repositioned products, while only 10% of new drug applications achieve approval. Repurposing drugs has several advantages, such as: Cutting research and development costs Reducing the drug development timeline Reusing drugs that have already demonstrated safety in humans Overcoming some of the challenges and knowledge gaps in testing drugs for rare diseases There is a growing attraction in analyzing off-patent drugs that have established safety, pharmacokinetics (how the human body interacts with a drug) and efficacy and repurposing them for other indications; specifically, cancer, to significantly reduce the cost and time to bring them to market. Theralase® has demonstrated in preclinical research that Rutherrin® is able to accomplish this task with various drugs, by significantly enhancing their efficacy in the destruction of cancer cells and repurposing their use in the treatment of multiple cancer indications. Withaferin A, is a steroid primarily used as an anti-inflammatory drug to combat cancer-associated inflammation is being investigated to improve immune checkpoint blockers for cancer treatments. Amiodarone, an anti-arrhythmic medication used to treat and prevent specific types of cardiac dysrhythmias is being investigated as a cancer treatment. Metformin, which is the most widely prescribed medicine for type 2 diabetes has been investigated for its potential as an anti-cancer treatment. Cells were treated with 3 µM Rutherrin®, before addition of each of the drugs mentioned above, to analyze cell survival. As shown in Figure 1 , Rutherrin® significantly increased the cancer cell kill for all tested non-cancer drugs, without light and/or radiation activation, suggesting that Rutherrin® can be combined with these drugs to repurpose them in the destruction of cancer. Figure 1: Cell Kill (%) After Treatment with Various Drugs (+/- Rutherrin®) Dr. Arkady Mandel, M.D., Ph.D., D.Sc., Chief Scientific Officer of Theralase® stated, "Despite the tremendous resources being invested in cancer prevention and treatment, cancer remains one of the leading causes of mortality worldwide. Progressively increasing failure rates, high cost, poor bioavailability, poor safety, limited efficacy and a lengthy research and development process associated with cancer drug development has necessitated alternative approaches to drug discovery. During the past decade, interest in finding new uses for old drugs has grown among clinicians and researchers. Using a "lock and key" analogy, our latest preclinical research has demonstrated the ability of Rutherrin® as the "key" to "unlock" approved non-cancer drugs to repurpose them for enhanced anti-cancer activity, literally, "Teaching an old dog, a new tricks." The scientific and clinical rational for this repurposing approach lies in the fact that different diseases share common molecular pathways and targets in the cell. We are excited by the results of our latest research, suggesting that there are a large number of existing non-cancer drugs that can be repurposed for cancer treatment, beyond, what we have initially analyzed, but also that Rutherrin® can significantly increase their efficacy in the targeted killing of cancer cells. This latest Theralase® research provides an opportunity for companies and clinicians to rapidly advance therapeutic strategies into clinical studies and commercialization, using pre-existing approved drugs." Roger DuMoulin-White, B.E.Sc., P.Eng., Pro.Dir., President and Chief Executive Officer of Theralase® stated, "Most of the initiatives for repurposing existing drugs has stemmed from the multi-billion-dollar cost and decades of time required in today's regulatory environment to research, develop and gain regulatory approval for the safety and efficacy of a new drug. Drug development is long, resource-intensive and highly uncertain as to clinical success, with significant risks along the way and the path to new treatments rarely straightforward. This is why so few companies are able to undertake this journey; except for the much larger and much better financed international organizations. 8 to 12% of drug candidates are successful in graduating from the preclinical phase to FDA approval. It is estimated that a new medicine will take an average of 10 to 15 years and more than $USD 2 billion before it can reach the pharmacy shelf, with an approximate failure rate of 90%. The drug development process has led to significant clinical advances, but the entire process is tedious, time consuming and extremely expensive; therefore, exploring established non-cancer drugs for anti-cancer activity provides a cost and time efficient, de-risked opportunity to rapidly advance therapeutic strategies into clinical studies and commercialization." About Theralase® Technologies Inc.: Theralase® is a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated small molecule compounds, their associated drug formulations and the light systems that activate them, with a primary objective of efficacy and a secondary objective of safety in the destruction of various cancers, bacteria and viruses. Additional information is available at and Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. Forward Looking Statements: This news release contains "forward-looking statements" within the meaning of applicable Canadian securities laws. Such statements include; but, are not limited to statements regarding the Company's proposed development plans with respect to small molecules and their drug formulations. Forward looking statements may be identified by the use of the words "may,", "should", "will", "anticipates", "believes", "plans", "expects", "estimate", "potential for" and similar expressions; including, statements related to the current expectations of Company's management for future research, development and commercialization of the Company's small molecules and their drug formulations, preclinical research, clinical studies and regulatory approvals. These statements involve significant risks, uncertainties and assumptions; including, the ability of the Company to fund and secure the regulatory approvals to successfully complete various clinical studies in a timely fashion and implement its development plans. Other risks include: the ability of the Company to successfully commercialize its small molecule and drug formulations, the risk that access to sufficient capital to fund the Company's operations may not be available on terms that are commercially favorable to the Company or at all, the risk that the Company's small molecule and drug formulations may not be effective against the diseases tested in its clinical studies, the risk that the Company's fails to comply with the terms of license agreements with third parties and as a result loses the right to use key intellectual property in its business, the Company's ability to protect its intellectual property, the timing and success of submission, acceptance and approval of regulatory filings. Many of these factors that will determine actual results are beyond the Company's ability to control or predict. Readers should not unduly rely on these forward-looking statements, which are not a guarantee of future performance. There can be no assurance that forward-looking statements will prove to be accurate as such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause actual results or future events to differ materially from the forward-looking statements. Although the forward-looking statements contained in the press release are based upon what management currently believes to be reasonable assumptions, the Company cannot assure prospective investors that actual results, performance or achievements will be consistent with these forward-looking statements. All forward-looking statements are made as of the date hereof and are subject to change. Except as required by law, the Company assumes no obligation to update such statements. For investor information on the Company, please feel to reach out Investor Inquiries - Theralase Technologies. For More Information: 1.866.THE.LASE (843-5273) 416.699.LASE (5273) Kristina Hachey, CPA Chief Financial Officer X 224 khachey@theralase.com SOURCE: Theralase Technologies Inc. View the original press release on accesswire.com

100 Deals associated with Amiodarone Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00636	Amiodarone Hydrochloride	C01BD01	DB01118

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Heart Arrest	JP	Sanofi KK	31 May 2013
Atrial Fibrillation	JP	Sanofi KK	03 Jul 1992
Tachycardia, Ventricular	JP	Sanofi KK	03 Jul 1992
Ventricular Fibrillation	JP	Sanofi KK	03 Jul 1992
Arrhythmias, Cardiac	CN	Guilin Pharmaceutical Co., Ltd.	01 Jan 1983

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Preclinical	-	Prism Pharmaceuticals, Inc.	01 Aug 2008
Atrial Fibrillation	Discovery	CA	Wyeth AB	01 Feb 1999

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01722942 (CHAGASICS, Pubmed \| JAMA Cardiol) Manual	Not Applicable	Cardiomyopathies	323	ICD (Implantable Cardioverter-Defibrillator)	(psmhgytrri) = eiynhemmju toctptcqmk (vmcubnmwmw ) View more	Negative	02 Oct 2024
				amiodarone	(psmhgytrri) = kyyaznltrq toctptcqmk (vmcubnmwmw ) View more
ESC2024	Not Applicable	Atrial Fibrillation	-	Amiodarone	fffdexsnzc(tkgmluiltb) = ncpvaiugxv zbqiafnrwr (nexafbyutu )	-	07 Apr 2024
				Dronedarone	fffdexsnzc(tkgmluiltb) = lqudqhieho zbqiafnrwr (nexafbyutu )
NCT03029169 (Pubmed \| Eur Heart J Acute Cardiovasc Care)	Phase 4	Shock, Septic \| Supraventricular arrhythmias left atrial volume (LAVI)	-	Propafenone	jfhgskctwy(itnfbsxkoz): HR = 0.6 (95% CI, 0.4 - 0.9), P-Value = 0.014	Positive	19 Feb 2024
				Amiodarone
NCT05004077 (RADICAL, CTgov)	Phase 4	Atrial Fibrillation	3	Amiodarone (Conventional Amiodarone Dosing Regimen (CDR))	bojggephfy(nsmfqqhkdg) = keqxhpxfto atwldfraqw (anqyjlzfvx, hhandgmojo - athqnyzllg) View more	-	18 Nov 2023
				Amiodarone (Repeated Amiodarone Bolus Dosing Regimen (RBDR))	bojggephfy(nsmfqqhkdg) = ljlqpdpvjs atwldfraqw (anqyjlzfvx, ezbkusltkl - wqmgebxjqq) View more
German DEVICE-registry (ESC2023)	Not Applicable	-	-	Beta-blockers plus amiodarone	gjwyxzkooh(fyptvmiung) = amiodarone was not associated with a significantly reduced risk of ICD discharges prfgruiixh (eyadjfvwtb ) View more	-	28 Aug 2023
ESC2023	Not Applicable	Left ventricular systolic dysfunction	-	Bepridil	azkkqkftvv(xdbncjiyag) = khzgllmutt bpnxvnkepa (pswiwsscjc ) View more	-	26 Aug 2023
				Amiodarone	azkkqkftvv(xdbncjiyag) = gfrnrfxgva bpnxvnkepa (pswiwsscjc ) View more
ESC2023	Not Applicable	Atrial Fibrillation First line	-	Amiodarone	(vlmaddlatm): hazard ratio = 2.52 (95% CI, 2.202 - 2.883)	Negative	25 Aug 2023
				Other-AADs
ATS2023	Not Applicable	Myxedema coma	-	Amiodarone	aonsqndbsh(ammkwzpqly) = She was hypotensive, hypothermic (35.0°C) and bradycardic with a heart rate of 40 beats per minute ozdjrnsmob (xenamygvhn ) View more	-	21 May 2023
				Levothyroxine
ESC2022	Not Applicable	Lung Cancer	-	Amiodarone treatment	pcqdnvzxpq(eveqwqexau) = mtzysisrju hyihwsaqke (kikuwheahe )	-	29 Aug 2022
				Amiodarone	pcqdnvzxpq(eveqwqexau) = pexjeqxsah hyihwsaqke (kikuwheahe )
ESC2022	Not Applicable	Toxicity	-	Amiodarone treatment	pkrmjlvqjn(ynkzhjgttk) = ogyzaoinzg gzfsqkuykf (qgqdljlihd )	-	29 Aug 2022
				Amiodarone	pkrmjlvqjn(ynkzhjgttk) = lksvuzlsul gzfsqkuykf (qgqdljlihd )

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