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1
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Ahmad J, Li YJ, Phillips E, Dellinger A, Hayashi PH, Chalasani N, Fontana RJ, Kleiner DE, Barnhart HX, Hoofnagle JH. Liver Injury due to Intravenous Methylprednisolone in the Drug-Induced Liver Injury Network. Liver Int 2025; 45:e16242. [PMID: 39803998 PMCID: PMC11790010 DOI: 10.1111/liv.16242] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/23/2024] [Accepted: 12/31/2024] [Indexed: 02/05/2025]
Abstract
BACKGROUND AND AIMS Short courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP-related DILI enrolled in the US DILI Network (DILIN). METHODS DILIN cases with MP as a suspected drug were reviewed. DILIN causality scoring was assigned on a 5-point scale (definite, highly likely, probable, possible, unlikely). All cases with MP causality scores of definite, highly likely or probable were analysed. HLA data from direct sequencing were analysed. RESULTS Eleven cases of definite, highly likely, or probable MP DILI were identified. The median age was 48 years; 73% were female; median latency to onset was 30 days; 55% were jaundiced; and all had hepatocellular injury with one patient requiring transplantation. Nine of the 11 cases were in patients with multiple sclerosis (MS). Liver biopsies in 7 cases revealed mild acute hepatitis with/without cholestasis. HLA data demonstrated that HLA-DRB1*15:01, the primary HLA class II allele associated with MS was over-represented. HLA-DQB1*06:02-HLA-DQA1*01:02 which is haplotypic with the HLA-DRB1*15 haplotype was more common in the MP DILI cases compared to other DILI controls (p = 0.03) and to DILI controls exposed to MP (p = 0.04). CONCLUSION MP DILI is characterised by hepatocellular injury, short latency and generally rapid recovery. There was no independent HLA haplotype associated with MP DILI.
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Affiliation(s)
- Jawad Ahmad
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York
| | - Yi-Ju Li
- Department of Biostatistics and Bioinformatics, Duke School of Medicine, Durham, NC
| | | | - Andrew Dellinger
- Department of Biostatistics and Bioinformatics, Duke School of Medicine, Durham, NC
| | - Paul H. Hayashi
- Food and Drug Administration, University of Michigan, Ann Arbor, MI
| | - Naga Chalasani
- Indiana University, University of Michigan, Ann Arbor, MI
| | - Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - David E. Kleiner
- Laboratory of Pathology, Intramural Division, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD
| | | | - Jay H. Hoofnagle
- Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD
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2
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Șorodoc V, Indrei L, Dobroghii C, Asaftei A, Ceasovschih A, Constantin M, Lionte C, Morărașu BC, Diaconu AD, Șorodoc L. Amiodarone Therapy: Updated Practical Insights. J Clin Med 2024; 13:6094. [PMID: 39458044 PMCID: PMC11508869 DOI: 10.3390/jcm13206094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/06/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Amiodarone, a bi-iodinated benzofuran derivative, is among the most commonly used antiarrhythmic drugs due to its high level of effectiveness. Though initially categorized as a class III agent, amiodarone exhibits antiarrhythmic properties across all four classes of antiarrhythmic drugs. Amiodarone is highly effective in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation while also playing a crucial role in preventing a range of ventricular arrhythmias. Amiodarone has a complex pharmacokinetic profile, characterized by a large volume of distribution and a long half-life, which can range from several weeks to months, resulting in prolonged effects even after discontinuation. Side effects may include thyroid dysfunction, pulmonary fibrosis, and hepatic injury, necessitating regular follow-ups. Additionally, amiodarone interacts with several drugs, including anticoagulants, which must be managed to prevent adverse effects. Therefore, a deep understanding of both oral and intravenous formulations, as well as proper dosage adjustments, is essential. The aim of this paper is to provide a comprehensive and updated review on amiodarone's indications, contraindications, recommended dosages, drug interactions, side effects, and monitoring protocols.
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Affiliation(s)
- Victorița Șorodoc
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Lucia Indrei
- Radiology and Medical Imaging Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Catinca Dobroghii
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Andreea Asaftei
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Alexandr Ceasovschih
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Mihai Constantin
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Cătălina Lionte
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Bianca Codrina Morărașu
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Alexandra-Diana Diaconu
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Laurențiu Șorodoc
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- Second Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, 700111 Iasi, Romania
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Shi H, Chen R, Li M, Ge J. Acute hepatotoxicity of intravenous amiodarone in a Becker muscular dystrophy patient with decompensated heart failing and ABCB4 gene mutation: as assessed for causality using the updated RUCAM. J Cardiothorac Surg 2024; 19:464. [PMID: 39044225 PMCID: PMC11265456 DOI: 10.1186/s13019-024-02869-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 06/14/2024] [Indexed: 07/25/2024] Open
Abstract
BACKGROUND Cardiac dysfunction, including arrhythmias, may be one of the main clinical manifestations of Becker muscular dystrophy (BMD). Amiodarone is widely used to treat arrhythmia. However, multi-systemic toxicity caused by amiodarone, especially hepatotoxicity, should not be neglected. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, renal and coagulation in BDM patient with ABCB4 gene mutation. CASE PRESENTATION We present a case of a 16-year-old boy admitted with heart failure and atrial fibrillation (AF). He was diagnosed with Becker muscular dystrophy (BMD) and gene testing showed comorbid mutations in gene DMD, ABCB4 and DSC2. Amiodarone was prescribed to control the paroxysmal atrial fibrillation intravenously. However, his liver enzyme levels were sharply elevated, along with cardiac shock, renal failure and coagulation disorders. After bedside continuous renal replacement therapy, the patient's liver function and clinical status rehabilitated. CONCLUSIONS ABCB4 gene mutation might be involved in amiodarone-induced hepatotoxicity. Studies in a cohort might help to prove this hypothesis in the future.
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Affiliation(s)
- Hui Shi
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, 1069 Xietu Road, Shanghai, 200032, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Ruizhen Chen
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, 1069 Xietu Road, Shanghai, 200032, China.
- National Clinical Research Center for Interventional Medicine, Shanghai, China.
| | - Minghui Li
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, 1069 Xietu Road, Shanghai, 200032, China.
- National Clinical Research Center for Interventional Medicine, Shanghai, China.
| | - Junbo Ge
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University, 1069 Xietu Road, Shanghai, 200032, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
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4
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Izquierdo-García E, Lázaro-Cebas A, Montero Pastor B, Such Díaz A, Álvaro-Alonso EA, López Guerra L, Escobar-Rodríguez I. Design of mobile and website health application devices for drug tolerability in hereditary fructose intolerance. Orphanet J Rare Dis 2024; 19:12. [PMID: 38183105 PMCID: PMC10770908 DOI: 10.1186/s13023-023-03011-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/19/2023] [Indexed: 01/07/2024] Open
Abstract
BACKGROUND Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance. RESULTS A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals. CONCLUSIONS IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.
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Affiliation(s)
- Elsa Izquierdo-García
- Pharmacy Department, Hospital Universitario Infanta Leonor, Av. Gran Vía del Este, 80, Madrid, 28031, Spain.
| | - Andrea Lázaro-Cebas
- Pharmacy Department, Hospital General Universitario Santa Lucía, Cartagena, Spain
| | - Berta Montero Pastor
- Pharmacy Department, Hospital Universitario Infanta Leonor, Av. Gran Vía del Este, 80, Madrid, 28031, Spain
| | - Ana Such Díaz
- Pharmacy Department, Hospital Universitario Infanta Leonor, Av. Gran Vía del Este, 80, Madrid, 28031, Spain
| | - Elena Alba Álvaro-Alonso
- Pharmacy Department, Hospital Universitario Infanta Leonor, Av. Gran Vía del Este, 80, Madrid, 28031, Spain
| | - Laura López Guerra
- Pharmacy Department, Hospital Universitario Infanta Leonor, Av. Gran Vía del Este, 80, Madrid, 28031, Spain
| | - Ismael Escobar-Rodríguez
- Pharmacy Department, Hospital Universitario Infanta Leonor, Av. Gran Vía del Este, 80, Madrid, 28031, Spain
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Comparative Pharmacokinetic of Curcuminoids Formulations with an Omega-3 Fatty Acids Monoglyceride Carrier: A Randomized Cross-Over Triple-Blind Study. Nutrients 2022; 14:nu14245347. [PMID: 36558506 PMCID: PMC9783836 DOI: 10.3390/nu14245347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/06/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
There is a growing interest for curcuminoids in the general population and the scientific research community. Curcuminoids, derived from turmeric spice, are lipophiles and therefore have a low solubility in water which hence have a low bioavailability in the human plasma. To circumvent this issue, a natural product developed by Biodroga Nutraceuticals combined curcuminoids with omega-3 fatty acids (OM3) esterified in monoglycerides (MAG). The objective was to perform a 24 h pharmacokinetics in humans receiving a single dose of curcuminoid formulated by three different means, and to compare their plasma curcuminoids concentration. Sixteen males and fifteen females tested three formulations: 400 mg of curcuminoids powder extract, 400 mg of curcuminoids in rice oil and 400 mg of curcuminoids with 1 g MAG-OM3. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 h post dose intake. Plasma samples were analyzed by ultra high-performance liquid chromatography with a triple quadrupole mass spectrometer (UPLC-MS/MS). Twenty-four hours after a single dose intake, the total plasma curcuminoids area under the curve (AUC) reached 166.8 ± 17.8 ng/mL*h, 134.0 ± 12.7 ng/mL*h and 163.1 ± 15.3 ng/mL*h when curcuminoids were provided with MAG-OM3, with rice oil or in powder, respectively. The Cmax of total curcuminoids reached between 11.9-17.7 ng/mL at around 4 h (Tmax). One-hour post-dose, the curcuminoids plasma concentration was 40% higher in participants consuming the MAG-OM3 compared to the other formulations. Thus, in a young population, plasma curcuminoids 24 h pharmacokinetics and its increase shortly after the single dose intake were higher when provided with MAG-OM3 than rice oil.
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Lopes dos Santos A, Lagarto M, Gouveia C. A Rare Case of Intravenous Amiodarone Toxicity. Cureus 2022; 14:e27958. [PMID: 36120239 PMCID: PMC9465810 DOI: 10.7759/cureus.27958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2022] [Indexed: 11/13/2022] Open
Abstract
Amiodarone is a highly effective treatment for life-threatening supraventricular and ventricular arrhythmias, namely in the setting of acutely decompensated heart failure. However, it could be associated with several serious adverse effects both in long-term oral therapy and in short-term use of intravenous (IV) preparation, including shock and liver injury. We report an unusual case of life-threatening refractory hypotension associated with acute hepatitis and renal failure a few hours after initiation of IV amiodarone. A 70-year-old man was admitted to the emergency department (ED) with dyspnea, chest discomfort, and a non-productive cough. Physical examination and complementary diagnostic tests helped diagnose acutely decompensated heart failure due to atrial fibrillation (AF) with a rapid ventricular response, and IV amiodarone was started. A few hours after initiating this drug, the patient developed hypotension with the need for inotropic therapy, acute elevation of amino transaminases, and renal failure. Renal function and liver transaminases returned to baseline after discontinuing amiodarone. A Roussel Uclaf Causality Assessment Method (RUCAM) score of 5 identifies our patient`s acute hepatitis as a possible adverse drug reaction. Refractory hypotension and liver injury with acute hepatitis after a short-term IV amiodarone therapy are extremely rare with few previously reported cases. Therefore, it is very important to perform continuous hemodynamic monitoring of the patient and liver function monitorization during short-term IV administration of this drug because these complications can be potentially fatal. A high index of suspicion is the key to functional organic recovery.
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Offenbacher J, Kazi F, Chen N, Mohamed M, Chacko J, Guttenplan N, Nguyen V. Immediate oral amiodarone re-challenge following the development of parenteral-induced acute liver toxicity. World J Emerg Med 2021; 12:321-323. [PMID: 34512831 DOI: 10.5847/wjem.j.1920-8642.2021.04.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 03/16/2021] [Indexed: 12/12/2022] Open
Affiliation(s)
- Joseph Offenbacher
- Department of Emergency Medicine, Jacobi and Montefiore Hospitals, Albert Einstein College of Medicine, Bronx 10461, USA
| | - Farnam Kazi
- Department of Emergency Medicine, Jacobi and Montefiore Hospitals, Albert Einstein College of Medicine, Bronx 10461, USA
| | - Niel Chen
- Department of Emergency Medicine, Jacobi and Montefiore Hospitals, Albert Einstein College of Medicine, Bronx 10461, USA
| | - Mohamed Mohamed
- Department of Emergency Medicine, Jacobi and Montefiore Hospitals, Albert Einstein College of Medicine, Bronx 10461, USA
| | - Jasmine Chacko
- Department of Pharmacy, Montefiore Medical Center, Bronx 10461, USA
| | - Nils Guttenplan
- Department of Medicine (Division of Cardiology), Montefiore Hospitals, Albert Einstein College of Medicine, Bronx 10461, USA
| | - Vincent Nguyen
- Department of Emergency Medicine, Jacobi Hospital, Albert Einstein College of Medicine, Bronx 10461, USA
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9
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His Bundle Pacing in Amiodarone-Induced Complete Heart Block, QT Prolongation, and Torsade de Pointes. JACC Case Rep 2020; 2:780-784. [PMID: 34317347 PMCID: PMC8302033 DOI: 10.1016/j.jaccas.2020.02.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 02/13/2020] [Indexed: 10/24/2022]
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Essrani R, Mehershahi S, Essrani RK, Ravi SJK, Bhura S, Sudhakaran A, Hossain M, Mehmood A. Amiodarone-Induced Acute Liver Injury. Case Rep Gastroenterol 2020; 14:87-90. [PMID: 32231507 PMCID: PMC7098330 DOI: 10.1159/000506184] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 01/27/2020] [Indexed: 11/24/2022] Open
Abstract
Amiodarone is a lipophilic structure with a half-life of 25–100 days. Long-term oral amiodarone is associated with photosensitivity, thyroid dysfunction, and pulmonary and hepatic toxicity. Intravenous amiodarone can lead to sweating, heating sensation, nausea, phlebitis at the injection site, and rarely acute hepatitis. This is a compelling case of a 60-year-old male who developed acute liver injury 24–36 h after starting amiodarone. All the possible causes of acute liver injury were ruled out, and his liver enzymes improved after discontinuing amiodarone.
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Affiliation(s)
- Rajesh Essrani
- Department of Internal Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
| | | | | | | | - Sajeer Bhura
- General Internal Medicine, State University of New York at Buffalo, Buffalo, New York, USA
| | - Anuraj Sudhakaran
- Department of Internal Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Muhammad Hossain
- Department of Internal Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Asif Mehmood
- Department of Internal Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
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Safety, Efficacy and Pharmacokinetics of Anidulafungin in Patients 1 Month to <2 Years of Age With Invasive Candidiasis, Including Candidemia. Pediatr Infect Dis J 2020; 39:305-309. [PMID: 32032174 PMCID: PMC7182240 DOI: 10.1097/inf.0000000000002568] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
Nineteen patients 1 month to <2 years of age with (n = 16) or at high risk of (n = 3) invasive candidiasis received anidulafungin for 5-35 days (3 mg/kg day 1, 1.5 mg/kg daily thereafter) followed by optional fluconazole (NCT00761267). Most treatment-emergent adverse events were mild/moderate, and no treatment-related deaths occurred. End of intravenous therapy global response success rate was 68.8%. Pharmacokinetics were similar to adult patients.
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12
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Ho YF, Chou HY, Chu JS, Lee PI. Comedication with interacting drugs predisposes amiodarone users in cardiac and surgical intensive care units to acute liver injury: A retrospective analysis. Medicine (Baltimore) 2018; 97:e12301. [PMID: 30212969 PMCID: PMC6156051 DOI: 10.1097/md.0000000000012301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Risk factors and underlying mechanisms for liver injury associated with amiodarone remain elusive. This study aimed to investigate the drug-related covariates for acute liver injury by amiodarone-an intriguing compound of high lipophilicity, with a long half-life and notable efficacy.The medical, pharmacy, and laboratory records of new amiodarone users admitted to the cardiac or surgical intensive care units of a medical center were examined retrospectively. A Cox regression model with time-varying dose-related variables of amiodarone was utilized to estimate the hazard ratio (HR) of amiodarone-associated liver injury while adjusting for concomitant therapy and relevant covariates.Of the 131 eligible patients among 6,572 amiodarone users (46,402 prescriptions), 6 were identified as amiodarone-associated liver injury cases. In comparison to controls (n = 125), this liver injury cohort (n = 6) had significantly higher numbers of amiodarone-interacting (2.7 ± 2.0 vs 0.9 ± 0.9 drugs, P = .02) and hepatotoxic (3.8 ± 0.8 vs 2.5 ± 1.7 drugs, P = .03) comedications. The number of comedications with amiodarone-interacting potential (HR 2.07, 95% confidence interval [CI] 1.02-4.22, P = .04) and amiodarone cumulative doses standardized by body surface area (HR 6.82, 95% CI 1.72-27.04, P = .01) were independent risk factors for liver injury associated with amiodarone.Drug-related (amiodarone cumulative dose, interacting drugs) factors were significant predictors of amiodarone-associated acute liver injury. A prudent evaluation of each medication profile is warranted to attain precision medicine at the level of patient care, especially for those treated by medications with complex physicochemical and pharmacokinetic properties, such as amiodarone.
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Affiliation(s)
- Yunn-Fang Ho
- Graduate Institute of Clinical Pharmacy
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Pharmacy
| | | | - Jan-Show Chu
- Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University; Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan
| | - Ping-Ing Lee
- Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University
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13
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The protective effect of grape seed and Ginkgo biloba against hepatotoxicity induced by the antidysrhythmic drug “amiodarone” in male albino rats. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2018. [DOI: 10.1016/j.bjbas.2017.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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14
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Abstract
Polysorbate 80 is a synthetic nonionic surfactant used as an excipient in drug formulation. Various products formulated with polysorbate 80 are used in the oncology setting for chemotherapy, supportive care, or prevention, including docetaxel, epoetin/darbepoetin, and fosaprepitant. However, polysorbate 80, like some other surfactants, is not an inert compound and has been implicated in a number of systemic and injection- and infusion-site adverse events (ISAEs). The current formulation of intravenous fosaprepitant has been associated with an increased risk of hypersensitivity systemic reactions (HSRs). Factors that have been associated with an increased risk of fosaprepitant-related ISAEs include the site of administration (peripheral vs. central venous), coadministration of anthracycline-based chemotherapy, number of chemotherapy cycles or fosaprepitant doses, and concentration of fosaprepitant administered. Recently, two polysorbate 80-free agents have been approved: intravenous rolapitant, which is a neurokinin 1 (NK-1) receptor antagonist formulated with the synthetic surfactant polyoxyl 15 hydroxystearate, and intravenous HTX-019, which is a novel NK-1 receptor antagonist free of synthetic surfactants. Alternative formulations will obviate the polysorbate 80-associated ISAEs and HSRs and should improve overall management of chemotherapy-induced nausea and vomiting.Funding Heron Therapeutics, Inc.
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Affiliation(s)
- Lee S Schwartzberg
- Division of Hematology/Oncology, Department of Medicine, University of Tennessee Health Science Center and West Cancer Center, Memphis, TN, USA.
| | - Rudolph M Navari
- Division of Hematology and Oncology, University of Alabama Birmingham, Birmingham, AL, USA
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Gayam V, Khalid M, Dahal S, Garlapati P, Gill A, Alex R, Mansour M. Fatal Acute Liver Failure With Intravenous Amiodarone: A Case Report and Literature Review. Gastroenterology Res 2018; 11:62-63. [PMID: 29511409 PMCID: PMC5827905 DOI: 10.14740/gr911w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 01/24/2018] [Indexed: 02/02/2023] Open
Abstract
Amiodarone is a drug which frequently causes elevated transaminases. However, acute liver failure has been rarely reported. Here, we present a case of fatal acute liver failure following the administration of intravenous amiodarone. It is important to be aware of this rare but potentially fatal complication of intravenous amiodarone so that it can be withdrawn immediately at the first sign of hepatic impairment.
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Affiliation(s)
- Vijay Gayam
- Interfaith Medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213, USA
| | - Mazin Khalid
- Interfaith Medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213, USA
| | - Sumit Dahal
- Interfaith Medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213, USA
| | - Pavani Garlapati
- Interfaith Medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213, USA
| | - Arshpal Gill
- Interfaith Medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213, USA.,American University of Antigua, Jabberwock Rd, Osbourn, Antigua and Barbuda
| | - Ragin Alex
- Interfaith Medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213, USA.,American University of Antigua, Jabberwock Rd, Osbourn, Antigua and Barbuda
| | - Mohammad Mansour
- Interfaith Medical Center, 1545 Atlantic Ave, Brooklyn, NY 11213, USA
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16
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Jaiswal P, Attar BM, Yap JE, Devani K, Jaiswal R, Wang Y, Szynkarek R, Patel D, Demetria M. Acute liver failure with amiodarone infusion: A case report and systematic review. J Clin Pharm Ther 2018; 43:129-133. [PMID: 28714083 DOI: 10.1111/jcpt.12594] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/20/2017] [Indexed: 11/28/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Amiodarone, a commonly used class III antiarrhythmic agent notable for a relatively long half-life of up to 6 months and its pronounced adverse effect profile, is used for both acute and chronic management of cardiac arrhythmias. Chronic use of amiodarone has been associated with asymptomatic hepatotoxicity; however, acute toxicity is thought to be uncommon. There are only six reported cases of acute liver failure (ALF) secondary to amiodarone. In all these cases the outcome of death during the same hospitalization resulted. We aimed to report the only case of acute liver failure secondary to amiodarone infusion in the existing literature where the patient survived. CASE SUMMARY A 79-year-old woman admitted with atrial flutter was being treated with intravenous (IV) amiodarone when she abruptly developed coagulopathy, altered mental status and liver enzyme derangement. She was diagnosed with acute liver failure (ALF) secondary to an amiodarone adverse drug reaction, with a calculated score of seven on the Naranjo adverse drug reaction probability scale. Amiodarone was immediately withheld, and N-acetylcysteine (NAC) was initiated. Clinical improvement was seen within 48 hours of holding the drug and within 24 hours of initiating NAC. On post-hospital follow-up visit she was reported to have complete recovery. WHAT IS NEW AND CONCLUSION This report emphasizes the importance of monitoring liver enzymes and mental status while a patient is being administered IV amiodarone. N-acetylcysteine administration may have possibly contributed to the early and successful recovery from ALF in our patient. To date, she is the only patient in the existing literature who has been reported to survive ALF secondary to amiodarone administration.
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Affiliation(s)
- P Jaiswal
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - B M Attar
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - J E Yap
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - K Devani
- Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA
| | - R Jaiswal
- Department of Internal Medicine, Forest Hills Hospital, Forest Hills, NY, USA
| | - Y Wang
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - R Szynkarek
- Department of Pharmacy, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - D Patel
- Department of Internal Medicine, Mercy Catholic Medical Center, Darby, PA, USA
| | - M Demetria
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
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17
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Gayam V, Khalid M, Shrestha B, Hossain MR, Dahal S, Garlapati P, Gill A, Mandal AK, Sangha R. Drug-Induced Liver Injury: An Institutional Case Series and Review of Literature. J Investig Med High Impact Case Rep 2018; 6:2324709618761754. [PMID: 29568780 PMCID: PMC5858623 DOI: 10.1177/2324709618761754] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 01/31/2018] [Accepted: 02/03/2018] [Indexed: 12/12/2022] Open
Abstract
Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the USA. DILI can be broadly classified as Intrinsic and Idiosyncratic. Identifying predictors and at-risk patients are challenging but can have a substantial clinical implication. This case report series demonstrates the importance of valproic acid, fluconazole, and amiodarone as potential hepatoxic agents of drug-induced liver injury leading to acute hepatic failure. The causality in all cases was established by Roussel Uclaf Causality Assessment Method/Council for International Organizations of Medical Sciences score and Naranjo Algorithm. Obesity, hypo-perfusion state, and concurrent hepatotoxic agent might identify at-risk patients. Further studies are required to understand the risk factors.
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Affiliation(s)
- Vijay Gayam
- Interfaith Medical Center, Brooklyn, NY, USA
| | | | | | | | - Sumit Dahal
- Interfaith Medical Center, Brooklyn, NY, USA
| | | | | | | | - Ruby Sangha
- Interfaith Medical Center, Brooklyn, NY, USA
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18
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Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone. Case Rep Crit Care 2016; 2016:5232804. [PMID: 27672457 PMCID: PMC5031827 DOI: 10.1155/2016/5232804] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 08/20/2016] [Accepted: 08/23/2016] [Indexed: 12/26/2022] Open
Abstract
Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.
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19
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Hashmi A, Keswani NR, Kim S, Graham DY. Hepatic Dysfunction in Patients Receiving Intravenous Amiodarone. South Med J 2016; 109:83-6. [PMID: 26840961 DOI: 10.14423/smj.0000000000000413] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Amiodarone is a commonly used antiarrhythmic drug. Hepatotoxicity following chronic oral administration occurs in 1% to 3% of patients. Hepatotoxicity following intravenous (IV) administration is infrequent but may be associated with dramatic increases in serum transaminases. We describe the incidence of liver toxicity among patients receiving IV amiodarone during a 5-year period. METHODS This was a single-center retrospective review of patients receiving IV amiodarone for any cause. The outcome measures were development of elevated serum transaminases and the relation of transaminitis to all-cause 30-day mortality. RESULTS A total of 1510 patients received amiodarone intravenously between 2005 and 2011; 77 (5%) developed elevated liver enzymes. Enzyme elevation was divided into mild (100-300 IU/L), moderate (300-1000 IU/L), and severe (>1000 IU/L). The median alanine aminotransferase was 189 (37-10,006) IU/L and aspartate aminotransferase was 253 (84-12,005) IU/L. The 30-day mortality among those with transaminitis was 22%; however, no patient died of amiodarone-related liver disease. CONCLUSIONS Amiodarone can cause severe elevation in liver enzymes. The incidence of severe transaminitis is low; deaths following IV amiodarone are rarely caused by drug-induced liver failure.
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Affiliation(s)
- Ali Hashmi
- From the Department of Medicine and Pharmacy Service, Michael E. DeBakey VA Medical Center, and Baylor College of Medicine, Houston, Texas
| | - Nicole R Keswani
- From the Department of Medicine and Pharmacy Service, Michael E. DeBakey VA Medical Center, and Baylor College of Medicine, Houston, Texas
| | - Sharon Kim
- From the Department of Medicine and Pharmacy Service, Michael E. DeBakey VA Medical Center, and Baylor College of Medicine, Houston, Texas
| | - David Y Graham
- From the Department of Medicine and Pharmacy Service, Michael E. DeBakey VA Medical Center, and Baylor College of Medicine, Houston, Texas
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20
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Diab OA, Kamel J, Abd-Elhamid AA. Predictors of intravenous amiodarone induced liver injury. Egypt Heart J 2016; 69:45-54. [PMID: 29622954 PMCID: PMC5839365 DOI: 10.1016/j.ehj.2016.05.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/04/2016] [Indexed: 11/27/2022] Open
Abstract
Background Intravenous (IV) amiodarone may be associated with liver injury that may necessitate drug discontinuation. The prediction of amiodarone induced liver injury (AILI) and its severity may help careful patient monitoring or the choice of other measures alternative to amiodarone in high risk patients. Little is known regarding predictors of AILI. Objectives To address the predictors of AILI and its severity. Methods The study included 180 patients indicated for IV amiodarone therapy who were divided into 2 groups: cases (90 patients) who developed AILI, and controls (90 patients) who did not develop AILI. AILI was defined as aminotransferase (ALT and AST) elevation by ⩾2 folds of baseline levels. Severe AILI was defined as enzyme elevation by >5 folds of baseline values. Results Multivariate analysis showed that the presence of cardiomyopathy (P = 0.032), congestive hepatomegaly (P = 0.001), increasing baseline total bilirubin (P < 0.0001), direct current cardioversion (P = 0.015), and increasing dose of amiodarone (P = 0.014) to be independent predictors for AILI. Regarding severity of AILI, inotropic support (P = 0.034), congestive hepatomegaly (P = 0.012), increasing baseline total bilirubin (P = 0.001), and increasing dose of amiodarone (P = 0.002) were found to be independent predictors for severe AILI. Among cases, linear regression analysis showed that baseline ALT was the only significant independent predictor of post-amiodarone ALT (P < 0.0001), while baseline AST (P < 0.0001) and EF (P = 0.012) were the only significant independent predictors of post-amiodarone AST. Conclusions Compromised cardiac, hepatic, and hemodynamic conditions, with increasing dose of IV amiodarone were associated with AILI. Severity of liver injury had linear relationship with baseline aminotransferase levels and left ventricular systolic function.
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Affiliation(s)
- O A Diab
- Department of Cardiology, Ain Shams University Hospital, Ain Shams University, Cairo, Egypt
| | - John Kamel
- Department of Cardiology, Ain Shams University Hospital, Ain Shams University, Cairo, Egypt
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21
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Fonseca P, Dias A, Gonçalves H, Albuquerque A, Gama V. Acute hepatitis after amiodarone infusion. World J Clin Cases 2015; 3:900-903. [PMID: 26488027 PMCID: PMC4607809 DOI: 10.12998/wjcc.v3.i10.900] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 04/18/2015] [Accepted: 08/11/2015] [Indexed: 02/05/2023] Open
Abstract
Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.
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22
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Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease. BIOMED RESEARCH INTERNATIONAL 2015; 2015:168905. [PMID: 26273591 PMCID: PMC4529891 DOI: 10.1155/2015/168905] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 01/27/2015] [Accepted: 02/04/2015] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI). The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.
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23
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Beaty EH, Ballany W, Trohman RG, Madias C. Ventricular tachycardia associated with radiation-induced cardiac sarcoma. Tex Heart Inst J 2014; 41:620-5. [PMID: 25593527 DOI: 10.14503/thij-13-3378] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Cardiac tumors can lead to distinct electrocardiographic changes and ventricular arrhythmias. Benign and malignant cardiac tumors have been associated with ventricular tachycardia. When possible, benign tumors should be resected when ventricular arrhythmias are intractable. Chemotherapy can shrink malignant tumors and eliminate arrhythmias. We report the case of a 52-year-old woman with breast sarcoma whom we diagnosed with myocardial metastasis after she presented with palpitations. The initial electrocardiogram revealed sinus rhythm with new right bundle branch block and ST-segment elevation in the anterior precordial leads. During telemetry, hemodynamically stable, sustained ventricular tachycardia with right ventricular localization was detected. Images showed a myocardial mass in the right ventricular free wall. Amiodarone suppressed the arrhythmia. To our knowledge, this is the first report of ventricular tachycardia associated with radiation-induced undifferentiated sarcoma. We discuss the distinct electrocardiographic changes and ventricular arrhythmias that can be associated with cardiac tumors, and we review the relevant medical literature.
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24
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Petrou E, Iakovou I, Boutsikou M, Girasis C, Mavrogeni S, Pavlides G. Acute epigastric and low back pain during amiodarone infusion; is it the drug or the vehicle to blame? Heart Lung 2013; 43:60-1. [PMID: 24239300 DOI: 10.1016/j.hrtlng.2013.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2013] [Revised: 09/24/2013] [Accepted: 09/25/2013] [Indexed: 10/26/2022]
Abstract
Amiodarone is a Class III antiarrhythmic agent used for cardioversion and prevention of recurrences of atrial fibrillation. However, its use is limited due to its side-effects resulting from the drug's long-term administration. We have described acute epigastric pain following treatment with intravenous amiodarone for atrial fibrillation in a previous report. Hereby, we describe a second patient who suffered acute epigastric pain, as well as one who suffered acute low back pain. Intravenous amiodarone has been related to a series of minor and major adverse reactions, indicating other constituents of the intravenous solution as the possible cause, possibly polysorbate-80. A possible correlation between acute epigastric and low back pain after intravenous amiodarone loading is unproven; however it is of crucial importance for clinicians to be aware of this phenomenon, and especially since an acute epigastric pain is implicated in the differential diagnosis of cardiac ischemia.
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Affiliation(s)
- Emmanouil Petrou
- First Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave., GR-17674 Kallithea, Athens, Greece.
| | - Ioannis Iakovou
- First Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave., GR-17674 Kallithea, Athens, Greece
| | - Maria Boutsikou
- First Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave., GR-17674 Kallithea, Athens, Greece
| | - Chrysafios Girasis
- First Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave., GR-17674 Kallithea, Athens, Greece
| | - Sophie Mavrogeni
- First Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave., GR-17674 Kallithea, Athens, Greece
| | - Gregory Pavlides
- First Cardiology Department, Onassis Cardiac Surgery Center, 356 Sygrou Ave., GR-17674 Kallithea, Athens, Greece
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25
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Nasser M, Larsen TR, Waanbah B, Sidiqi I, McCullough PA. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature. DRUG HEALTHCARE AND PATIENT SAFETY 2013; 5:191-8. [PMID: 24109195 PMCID: PMC3792591 DOI: 10.2147/dhps.s48640] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Amiodarone is a benzofuran class III antiarrhythmic drug used to treat a wide spectrum of ventricular tachyarrhythmias. The parenteral formulation is prepared in polysorbate 80 diluent. We report an unusual case of acute elevation of aminotransaminase concentrations after the initiation of intravenous amiodarone. An 88-year-old Caucasian female developed acute hepatitis and renal failure after initiating intravenous amiodarone for atrial fibrillation with a rapid ventricular response in the setting of acutely decompensated heart failure and hepatic congestion. Liver transaminases returned to baseline within 7 days after discontinuing the drug. Researchers hypothesized that this type of injury is related to liver ischemia with possible superimposed direct drug toxicity. The CIOMS/RUCAM scale identifies our patient's acute hepatitis as a highly probable adverse drug reaction. Future research is needed to understand the mechanisms by which hyperacute drug toxicity occurs in the setting of impaired hepatic perfusion and venous congestion.
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Affiliation(s)
- Mohammad Nasser
- Providence Hospitals and Medical Centers, Department of Medicine, Division of Cardiology, Southfield and Novi, MI, USA
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26
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Sahud MA, Caulfield M, Clarke N, Koch R, Bougie D, Aster R. Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins. Br J Haematol 2013; 163:260-7. [PMID: 23952260 DOI: 10.1111/bjh.12521] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 06/27/2013] [Indexed: 11/30/2022]
Abstract
Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone-dependent, platelet-reactive antibodies were identified using conventional serological techniques. However, water-insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug-dependent antibodies specific for platelet glycoproteins (GP)Ia/IIa (integrin α2 β1 ) in each patient and a second antibody specific for GPIIb/IIIa (αII b β3 integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2-30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug-dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug.
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Affiliation(s)
- Mervyn A Sahud
- Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA
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27
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Grecian R, Ainslie M. Acute hepatic failure following intravenous amiodarone. BMJ Case Rep 2012; 2012:bcr-2012-007080. [PMID: 23257638 DOI: 10.1136/bcr-2012-007080] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 73-year-old gentleman presented to the hospital after an episode of loss of consciousness. He had a defibrillator in situ, which on interrogation was found to have fired for an episode of ventricular fibrillation. As an inpatient he developed frequent episodes of self-terminating ventricular tachycardia, treated initially with oral amiodarone. A 24 h amiodarone infusion was started on day 3 of admission, following which the patient developed hyperventilation. Investigations revealed that this was secondary to acute hepatic and renal failure, requiring haemofiltration on the intensive care unit. Cessation of amiodarone was associated with normalisation of liver function over 48 h. The patient had normal blood and jugular venous pressures throughout days 1-4 of admission. We discuss the role of amiodarone as the predominant factor in the deterioration of this patient's liver function, versus the differential diagnosis of ischaemia-induced hepatotoxicity, citing recent research regarding this subject.
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28
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Kicker JS, Haizlip JA, Buck ML. Hepatotoxicity after continuous amiodarone infusion in a postoperative cardiac infant. J Pediatr Pharmacol Ther 2012; 17:189-95. [PMID: 23118673 DOI: 10.5863/1551-6776-17.2.189] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
A former 34-week-old female infant with Down syndrome underwent surgical correction of a congenital heart defect at 5 months of age. Her postoperative course was complicated by severe pulmonary hypertension and junctional ectopic tachycardia. Following treatment with amiodarone infusion, she developed laboratory indices of acute liver injury. At their peak, liver transaminase levels were 19 to 35 times greater than the upper limit of normal. Transaminitis was accompanied by coagulopathy, hyperammonemia, and high serum lactate and lipid levels. Hepatic laboratory abnormalities began to resolve within 48 hr of stopping amiodarone infusion. Heart rate control was achieved concurrently with discovery of laboratory test result abnormalities, and no further antiarrhythmic therapy was required. The intravenous formulation of amiodarone contains the diluent polysorbate 80, which may have hepatotoxic effects. Specifically, animal studies suggest that polysorbate 80 may destabilize cell membranes and predispose to fatty change within liver architecture. Polysorbate was implicated in infant fatalities from E-ferol use in the 1980s. This case illustrates a possible adverse event by the Naranjo probability scale. Given the extent of clinically apparent hepatic injury, this patient was not rechallenged with amiodarone during the remainder of her hospitalization. With amiodarone now used as first-line pharmacologic therapy for critical tachyarrhythmia in this population, the number of children exposed to this drug should be expected to increase. Laboratory indices of liver function should be evaluated at initiation of amiodarone therapy, as well as frequently throughout duration of therapy. Consideration should be given to polysorbate-free formulation of intravenous amiodarone for use in the cohort with congenital cardiac disease.
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Affiliation(s)
- Jennifer S Kicker
- Division of Pediatriac Critical Care, Department of Pediatrics, University of Virginia Children's Hospital, Charlottesville, Virginia
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29
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Lahbabi M, Aqodad N, Ibrahimi A, Lahlou M, Aqodad H. Acute hepatitis secondary to parenteral amiodarone does not preclude subsequent oral therapy. World J Hepatol 2012; 4:196-8. [PMID: 22761971 PMCID: PMC3388118 DOI: 10.4254/wjh.v4.i6.196] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2011] [Revised: 09/04/2011] [Accepted: 06/23/2012] [Indexed: 02/06/2023] Open
Abstract
Amiodarone chlorhydrate is a diiodated benzofuran derivative used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone and symptomatic hepatic dysfunction occurs in less than 1% to 3% of patients taking amiodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity. A 29 year old woman with normal liver function was given amiodarone intravenously to treat her atrial fibrillation. She developed acute toxic hepatitis after 24 h. The intravenous form of amiodarone was immediately avoided and replaced by the oral form, using conventional loading doses as soon as the deranged liver function tests had normalized, without recurrence of the hepatitis. These observations show that the occurrence of acute hepatic impairment with intravenous amiodarone does not necessarily preclude the use of this drug by mouth and the necessity of monitoring the hepatic function of patients treated with amiodarone.
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Affiliation(s)
- Mounia Lahbabi
- Mounia Lahbabi, Nouredine Aqodad, Adil Ibrahimi, Department of Hepato-Gastroenterology, Hassan II University Hospital, Fes 30000, Morocco
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30
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Thiele RH, Williams J, Moylan CA, Rao SV, Bennett-Guerrero E. CASE 6--2012: suspected amiodarone hepatotoxicity after cardiac surgery. J Cardiothorac Vasc Anesth 2012; 26:729-32. [PMID: 22516469 DOI: 10.1053/j.jvca.2012.02.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2012] [Indexed: 11/11/2022]
Affiliation(s)
- Robert H Thiele
- Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
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31
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Huang X, Yang Y, Zhu J, Gao X, Wang G, Tan H, Liang Y, Li J. Clinical Applications and Acute Hepatotoxicity of Intravenous Amiodarone. J Int Med Res 2009; 37:1928-36. [PMID: 20146893 DOI: 10.1177/147323000903700631] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
This cross-sectional, retrospective study was designed to evaluate the current clinical applications and acute hepatotoxicity of intravenous amiodarone administration at a hospital in China. Clinical data were collected from 1214 patients receiving intravenous amiodarone treatment between October 2003 and September 2005. Baseline patient characteristics, drug indications, administration records and acute hepatotoxicity associated with the drug were examined. Amiodarone was used primarily in arrhythmic patients with obvious cardiac dysfunction. Atrial fibrillation and ventricular arrhythmia were the two most commonly treated dysfunctions. Incorrect indications and administration methods were also noted. Hepatotoxicity occurred in 12.6% of the patients, but was mild in most cases. Males showed a higher incidence of hepatotoxicity than females. The use of amiodarone was considered to be reasonable and standardized, but there was still considerable room for improvement, particularly in the standardization of administration guidelines. Intravenous amiodarone can cause hepatotoxicity and hepatic function tests should be performed soon after giving amiodarone intravenously.
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Affiliation(s)
- X Huang
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Y Yang
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - J Zhu
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - X Gao
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - G Wang
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - H Tan
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Y Liang
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - J Li
- Emergency Centre of Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Llanos L, Moreu R, Peiró AM, Pascual S, Francés R, Such J, Horga JF, Pérez-Mateo M, Zapater P. Causality assessment of liver injury after chronic oral amiodarone intake. Pharmacoepidemiol Drug Saf 2009; 18:291-300. [PMID: 19165760 DOI: 10.1002/pds.1709] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIM The number of patients receiving amiodarone will increase in future years. As clinically significant hepatotoxicity associated with oral amiodarone is infrequent and difficult to predict, a new Bayesian-developed model is proposed to help in the causality assessment of amiodarone-induced liver injury. METHODS Incidence of abnormal liver enzymes in patients receiving amiodarone was obtained from placebo controlled clinical trials. Published case reports of amiodarone-induced hepatotoxicity were identified through a literature search. Maximum number of expected hepatotoxicity cases in amiodarone and placebo-treated patients was calculated using Poisson distribution. The calculated odds ratio was used as a Prior Odds (PrO) to subsequent quantification, using a Bayesian-approach, of individual amiodarone-induced hepatotoxicity likelihood. RESULTS PrO of amiodarone-induced hepatotoxicity was 0.48. Thirty nine amiodarone-associated hepatotoxicity case reports were retrieved. Half of published case reports developed an irreversible damage. The amiodarone Bayesian model combining information about latency period and period of remission, together with analytical parameters properly defines the toxicity profile shown in published case reports. The analytical pattern defined by this model is different from the one expected if liver injury in published cases was caused by other etiologies. CONCLUSIONS A method based on a Bayesian-approach, which links information from clinical trials with clinical hepatotoxicity profile from published case reports can be a useful tool for amiodarone-induced liver injury causality assessment. At present, this method is limited due to scarcity and quality of available data. Further efforts are needed to improve model ability in order to identify amiodarone-induced liver injury.
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Affiliation(s)
- Lucía Llanos
- Clinical Pharmacology Section, University General Hospital, Alicante, Spain.
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Hilkens M, Pickkers P, Peters WHM, van der Hoeven JG. No elevation of glutathione S-transferase-a1-1 by amiodarone loading in intensive care unit patients with atrial fibrillation. Anaesth Intensive Care 2009; 37:281-5. [PMID: 19400493 DOI: 10.1177/0310057x0903700204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Hepatocellular toxicity is a putative side-effect of amiodarone. The hepatic detoxification enzyme glutathione S-transferase-A1-1 (GSTA1-1) is a sensitive indicator of hepatocellular damage. We investigated the occurrence of subclinical liver injury, as measured by plasma GSTA1-1 in intensive care unit patients with atrial fibrillation receiving amiodarone. Sixteen haemodynamically stable intensive care unit patients with atrial fibrillation were treated with amiodarone intravenously. Patients were given a loading dose of 150 mg followed by another 150 mg followed by a continuous infusion of 1200 mg/hour if atrial fibrillation persisted. Blood samples for GSTA1-1 (measured by an enzyme-linked immunosorbent assay) were taken at zero, one, three, six, 12 and 24 hours, transaminases and bilirubin at zero, six, 12 and 24 hours. Blood pressure and heart rate were continuously monitored. Effects were analysed for time-dependent changes (one-way analysis of variance for repeated measures). Blood pressure increased from 125 +/- 8/60 +/- 3 mmHg at t = 0 to 144 +/- 9/66 +/- 4 mmHg at t = 24 hours (P < 0.05), heart rate decreased from atrial fibrillation 124 +/- 5 to sinus rhythm 86 +/- 6 beats per minute (P < 0.05). There was no significant elevation of GSTA1-1, transaminases or bilirubin during the observation period of 24 hours. Amiodarone does not cause elevation of GSTA1-1 as a marker of subclinical liver injury in haemodynamically stable intensive care unit patients with atrial fibrillation.
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Affiliation(s)
- M Hilkens
- Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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Abstract
Amiodarone is a class III antiarrhythmic agent with a long half-life which is used to control atrial and ventricular arrhythmias, including atrial flutter and fibrillation. We describe here the case of an elderly woman (77 years of age) who was hospitalized for acute atrial fibrillation, abdominal pain, and dyspnea. In the Emergency Department, treatment with intravenous amiodarone was begun. The following day, the patient developed acute liver damage; improved liver function occurred following the withdrawal of amiodarone. Complete recovery of liver function was documented after three weeks. Unfortunately, the patient died from a severe infectious disease, with multiple organ failure.
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Rizzioli E, Incasa E, Gamberini S, Savelli S, Zangirolami A, Tampieri M, Manfredini R. Acute toxic hepatitis after amiodarone intravenous loading. Am J Emerg Med 2007; 25:1082.e1-4. [PMID: 18022508 DOI: 10.1016/j.ajem.2007.02.045] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2007] [Accepted: 02/27/2007] [Indexed: 12/20/2022] Open
Affiliation(s)
- Emanuela Rizzioli
- Department of Internal Medicine, Hospital of the Delta, Lagosanto, Ferrara, Italy
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Kum LCC, Chan WWL, Hui HHY, Wong GWM, Ho SSS, Sanderson JE, Yu C, Fung JWH. Prevalence of amiodarone-related hepatotoxicity in 720 Chinese patients with or without baseline liver dysfunction. Clin Cardiol 2006; 29:295-9. [PMID: 16881537 PMCID: PMC6653912 DOI: 10.1002/clc.4960290705] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The prevalence of hepatotoxicity after longterm oral amiodarone therapy in Chinese patients with or without elevated liver enzymes at baseline is unknown. HYPOTHESIS Amiodarone may still be safely prescribed for Chinese patients who have baseline liver dysfunction. METHODS This is a retrospective cross-sectional study. Significant liver dysfunction (SLD) was defined as alanine aminotransferase (ALT) > 2 times upper limit of normal range. RESULTS Baseline liver function was checked in 628 of the 720 Chinese patients identified. The mean duration of amiodarone use was 615.9 +/- 703.1 days. Ninety patients (14.3%) had elevated baseline ALT. The prevalence of SLD was 3.7% (confidence interval [CI] 2.1-5.3%) and 4.4% (CI 0.2-8.6%) in patients with normal (n = 538) and elevated (n = 90) baseline ALT, respectively (p = 0.765). Therapy was continued in 42 patients with elevated baseline ALT until final follow-up. Eight of these (19.0%) had elevated ALT upon final follow-up, but the derangement was mild (mean ALT 134.8 +/- 145.9 IU/l, median 76 IU/l). During follow up, 24 patients developed SLD and half of these subsequently withdrew from therapy. The ALT levels at final follow-up had improved over time in both groups, but the mean difference was not significant (255.1 +/- 706.4 vs. 131.0 +/- 207.5 IU/l, p = 0.312). CONCLUSION The prevalence of SLD in Chinese patients taking oral amiodarone with or without elevated baseline ALT was similar (4.4 vs. 3.7%). It seems that amiodarone may be safely prescribed in patients with elevated baseline ALT.
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Affiliation(s)
- Leo C. C. Kum
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | | | - Helen H. Y. Hui
- School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace W. M. Wong
- School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, China
| | - Susan S. S. Ho
- School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, China
| | - John E. Sanderson
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - Cheuk‐Man Yu
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - Jeffery W. H. Fung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
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The Liver in Systemic Illness. ZAKIM AND BOYER'S HEPATOLOGY 2006. [PMCID: PMC7155679 DOI: 10.1016/b978-1-4160-3258-8.50061-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Rätz Bravo AE, Drewe J, Schlienger RG, Krähenbühl S, Pargger H, Ummenhofer W. Hepatotoxicity during rapid intravenous loading with amiodarone: Description of three cases and review of the literature. Crit Care Med 2005; 33:128-34; discussion 245-6. [PMID: 15644659 DOI: 10.1097/01.ccm.0000151048.72393.44] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Atrial fibrillation is the most common arrhythmia after cardiac surgery. Amiodarone can effectively prevent and control postoperative atrial and ventricular fibrillation. Acute hepatic damage after intravenous amiodarone, which can be fatal, is not well recognized. We describe three cases of acute hepatocellular injury after intravenous amiodarone administration in critically ill patients. Another 25 published cases and six cases reported to the Swiss Pharmacovigilance Center (Swissmedic) are discussed. DESIGN This study consisted of a series of three case reports and review of the literature. SETTING : This study was conducted at an operative critical care unit at the University Hospital Basel, Switzerland. PATIENTS Three hemodynamically compromised patients after open heart surgery developed significant increases of transaminases (up to more than 100-fold of the upper limit of normal) shortly after the introduction of intravenous amiodarone. INTERVENTIONS AND MEASUREMENT: Cessation of intravenous amiodarone and of other potentially hepatotoxic drugs. RESULTS Liver parameters significantly improved or returned to normal in all three patients, even after start of oral amiodarone in two patients. CONCLUSIONS Amiodarone is a highly effective antiarrhythmic agent for the treatment and prevention of atrial and ventricular arrhythmias. Acute liver damage after intravenous amiodarone, possibly induced by the solubilizer polysorbate 80, is rare but potentially harmful. Amiodarone loading should therefore be adapted to the necessity of an immediate effect of the drug, and liver function should be monitored closely in critically ill patients. Oral maintenance therapy with amiodarone is possible, even in patients who developed liver disease during intravenous loading.
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Affiliation(s)
- Alexandra E Rätz Bravo
- Division of Clinical Pharmacology & Toxicology, University Hospital of Basel, CH-4031 Basel, Switzerland
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Galilea AG, García Sánchez M, Mata García MDL, Fugarolas GM. Hepatitis tóxica aguda de instauración precoz por amiodarona intravenosa. GASTROENTEROLOGIA Y HEPATOLOGIA 2002. [DOI: 10.1016/s0210-5705(02)70272-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Luengo O, Montero J, Alegre J, Fernández Sevilla T. [Toxic hepatitis caused by intravenous amiodarone]. Med Clin (Barc) 2000; 115:798-9. [PMID: 11171458 DOI: 10.1016/s0025-7753(00)71696-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
Atrial tachyarrhythmias are the most frequent arrhythmias occurring in ICU patients, being particularly common in patients with cardiovascular and respiratory failure. Unlike ambulatory patients in whom atrial fibrillation/flutter (AF) is likely to be short lived, in the critically ill these arrhythmias are unlikely to resolve until the underlying disease process has improved. Urgent cardioversion is indicated for hemodynamic instability. Treatment in hemodynamically stable patients includes correction of treatable precipitating factors, control of the ventricular response rate, conversion to sinus rhythm, and prophylaxis against thromboembolic events in those patients who remain in AF. Diltiazem is the preferred agent for rate control, while procainamide and amiodarone are generally considered to be the antiarrhythmic agents of choice.
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Affiliation(s)
- Paul E. Marik
- From the Department of Internal Medicine, Washington Hospital Center, Washington, DC
| | - Gary P. Zaloga
- From the Department of Internal Medicine, Washington Hospital Center, Washington, DC
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López-Gómez D, Nicolás J, Frigola JM, Manito N, Esplugas E. [The use of oral amiodarone as a chronic treatment in a patient with prior fulminant hepatitis due to intravenous amiodarone]. Rev Esp Cardiol 1999; 52:201-3. [PMID: 10193175 DOI: 10.1016/s0300-8932(99)74896-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Acute hepatitis for intravenous amiodarone is an uncommon problem with scarce appearances in medical literature. Sometimes, it has postulated that the vehicle of the intravenous preparation and not the active principle is the possible cause of this complication. We report a patient with fulminating hepatitis and severe encephalopathy following the administration of intravenous amiodarone. We present also the clinical evolution of the patient after reintroduction of oral amiodarone. In the end, we make a review of the associated literature with our case.
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Affiliation(s)
- D López-Gómez
- Servicio de Cardiología, Ciudad Sanitaria, L'Hospitalet de Llobregat, Barcelona
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Dionísio J, Pereira I, Telo L, Amaral-Marques R. Amiodarona numa Unidade de Cuidados Intensivos Pneumológicos. Revisão de utilizaçao. REVISTA PORTUGUESA DE PNEUMOLOGIA 1998. [DOI: 10.1016/s0873-2159(15)31034-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Abstract
Amiodarone was introduced 30 years ago as an antianginal agent and subsequently has been used as an antiarrhythmic agent. This drug was initially used for patients with malignant ventricular arrhythmias; however, currently it is being used broadly for rate and rhythm control in patients with atrial fibrillation. At first, amiodarone was primarily used by cardiologists and today it is used throughout the medical profession. Amiodarone therapy can potentially result in a wide range of adverse effects. The majority of these adverse effects are dose related and reversible. The following is a review of the adverse effects and drug interactions of amiodarone along with recommendations for identification and management of these adverse effects.
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James PR, Hardman SM. Acute hepatitis complicating parenteral amiodarone does not preclude subsequent oral therapy. HEART (BRITISH CARDIAC SOCIETY) 1997; 77:583-4. [PMID: 9227310 PMCID: PMC484809 DOI: 10.1136/hrt.77.6.583] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- P R James
- Department of Academic and Clinical Cardiovascular Medicine, Whittington Hospital, London, United Kingdom
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48
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Abstract
While some of the adverse events caused by the administration of medicines are specifically attributable to the drug molecule, a proportion arises because of the chemical, biological and physical nature of the formulation. The effects may be compounded by certain patient factors, an incomplete understanding of the behaviour of the formulation or the coadministration of other drugs. This review examines adverse drug reactions and other adverse events arising from the nature of the dosage form or formulation used. These adverse effects may be the result of local irritation/toxicity, hypersensitivity or allergic reactions, systemic effects from essentially local therapies, or idiosyncratic reactions in a small number of individuals. In certain cases where the exact nature of the formulation is unknown, adverse events cannot be attributed to any single ingredient. In addition, the total of all ingredients of a formulation, even where details of the formulation are clear, may give rise to abnormal behaviour of the formulation in vivo. Often the desired objective of a particular specialised formulation leads to an unforseen but related adverse effect, and in certain instances these events are completely unpredictable and at variance with the perceived objectives of the formulation.
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Affiliation(s)
- I F Uchegbu
- The School of Pharmacy, University of London, England
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Leatham EW, Holt DW, McKenna WJ. Class III antiarrhythmics in overdose. Presenting features and management principles. Drug Saf 1993; 9:450-62. [PMID: 8129865 DOI: 10.2165/00002018-199309060-00008] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Class III (Vaughan-Williams classification) antiarrhythmic drugs prolong the cardiac action potential without affecting depolarisation. The 3 class III drugs currently in general use are amiodarone, sotalol and bretylium. The presenting features of acute toxicity are different for each agent and are, therefore, discussed separately. Several new class III antiarrhythmic agents are under development, including dofetilide and d-sotalol, but specific data on overdoses of these potent class III drugs are not yet available. Amiodarone toxicity following acute overdose is rare because poor bioavailability and a large volume of distribution limit the peak serum concentration. Toxicity is low even if high serum concentrations are reached. The major risks from acute overdose are hypotension (intravenous administration only) and arrhythmia if other factors, such as hypokalaemia or additional antiarrhythmic agents are present. Management is chiefly directed at reducing absorption with activated charcoal or cholestyramine, and monitoring for arrhythmia. Sotalol is a beta-blocker with additional class III activity. Oral bioavailability is high, and overdosed patients can present with bradycardia, hypotension and major haemodynamic collapse. The combination of bradycardia and prolongation of the QT interval is associated with malignant arrhythmias such as torsade de pointes. Management principles include observation and correction of bradycardia with endocardial pacing, intravenous adrenergic drugs and glucagon. The risk of arrhythmia can be substantially reduced by intravenous potassium and magnesium supplements. d-Sotalol is a potent class III drug devoid of beta-blocking activity and may be expected to share the proarrhythmic affects of the racemic mixture in overdose, without pronounced hypotension and bradycardia. Intravenous bretylium in overdose causes an initial hypertensive effect, followed by profound hypotension from systemic vasodilation. Management is directed at controlling hypotension with volume expansion and norepinephrine (noradrenaline).
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Affiliation(s)
- E W Leatham
- Department of Cardiological Sciences, St George's Hospital Medical School, London, England
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