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Schweizerische Medizinische... Dec 1988The extraordinary antiarrhythmic efficacy of amiodarone has been well documented in the last few years. Parallel investigations of the electrophysiologic influence of... (Review)
Review
The extraordinary antiarrhythmic efficacy of amiodarone has been well documented in the last few years. Parallel investigations of the electrophysiologic influence of this iodinated benzofuran derivative on myocardial tissue showed that repolarizing as well as depolarizing currents are inhibited. However, the detailed electrochemical aspects of these effects are only partly understood. Likewise, ideas on causes of the differences in hemodynamic and electrophysiologic actions of oral and intravenous amiodarone are still speculative. An understanding of the actions of amiodarone is particularly difficult to achieve because of the unique pharmacokinetics of the drug: it resides in extra-plasmatic compartments for months after discontinuation of treatment, a fact which explains, for example, the lack of an established dose/response relationship. Replacement of amiodarone by another antiarrhythmic drug in the same patient may be problematic, because pharmacokinetic and pharmacodynamic interactions of residual amiodarone with the new antiarrhythmic drug are to be expected. Therefore, amiodarone should be prescribed only in cases where other treatment has failed. This is also advisable in view of the long list of amiodarone-induced adverse reactions. Determinations of plasma concentrations of amiodarone and desethylamiodarone may be useful in some instances, but must never replace clinical evaluation of antiarrhythmic drug efficacy. Although the incidence of some amiodarone-induced adverse reactions increases with dosage and serum drug level, dose-independent factors may play a role in the rare but serious pulmonary and hepatic side effects.
Topics: Amiodarone; Drug Interactions; Heart Conduction System; Hemodynamics; Humans; Liver
PubMed: 3065934
DOI: No ID Found -
Cleveland Clinic Journal of Medicine Mar 1998Amiodarone is a potent and versatile antiarrhythmic. Despite side effects involving the lungs, heart, thyroid, and other organs, it is effective in the treatment of... (Review)
Review
Amiodarone is a potent and versatile antiarrhythmic. Despite side effects involving the lungs, heart, thyroid, and other organs, it is effective in the treatment of refractory atrial and ventricular arrhythmias and it has unique safety in patients with coronary disease and left ventricular dysfunction. This review discusses the evolving indications for amiodarone and management of toxicities and drug interactions.
Topics: Amiodarone; Anti-Arrhythmia Agents; Humans
PubMed: 9540249
DOI: 10.3949/ccjm.65.3.159 -
American Journal of Hospital Pharmacy Apr 1986The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or...
The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers; identical solutions were also mixed with either potassium chloride 20 meq, lidocaine hydrochloride 2000 mg, quinidine gluconate 500 mg, procainamide hydrochloride 2000 mg, verapamil hydrochloride 25 mg, or furosemide 100 mg. All admixtures were prepared in triplicate and stored for 24 hours at 24 degrees C. Amiodarone concentrations were determined using a stability-indicating high-performance liquid chromatographic assay immediately after admixture and at intervals during storage. Each solution was visually inspected and tested for pH. Amiodarone concentrations decreased less than 10% in all admixtures except those containing quinidine gluconate in polyvinyl chloride containers. The only visual incompatibility observed was in admixtures containing quinidine gluconate and 5% dextrose injection. In most solutions pH either decreased slightly or remained unchanged. Amiodarone hydrochloride is stable when mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers alone or with potassium chloride, lidocaine, procainamide, verapamil, or furosemide and stored for 24 hours at 24 degrees C. Amiodarone should not be mixed with quinidine gluconate in polyvinyl chloride containers.
Topics: Amiodarone; Benzofurans; Chromatography, High Pressure Liquid; Drug Stability; Hydrogen-Ion Concentration; Injections; Spectrophotometry, Ultraviolet; Time Factors
PubMed: 3706337
DOI: No ID Found -
Journal of Cardiovascular Pharmacology Oct 1996We investigated the in vitro and in vivo interaction between amiodarone and lidocaine. The interaction on a molecular level was first studied in microsomes from 11 human... (Clinical Trial)
Clinical Trial
We investigated the in vitro and in vivo interaction between amiodarone and lidocaine. The interaction on a molecular level was first studied in microsomes from 11 human livers. Close correlations between amiodarone N-monodesethylase activities and (a) the amounts of cytochrome P-4503A4 (CYP3A4), and (b) the rates of lidocaine N-monodesethylation were observed. Lidocaine inhibited amiodarone N-monodesethylation (Ki = 120 microM) competitively; inversely, amiodarone suppressed lidocaine N-monodesethylase activity in the same manner (Ki = 47 microM). Moreover, the metabolite N-monodesethylamiodarone (DEA) was stable and inhibited lidocaine metabolism in a concentration-dependent manner. The in vivo interaction was investigated in 6 cardiac patients. Each of them received a dose of 1 mg/kg lidocaine hydrochloride intravenously (i.v.) on three different occasions: before amiodarone treatment (control), and after cumulative doses of 3 g (phase I) and 13 g (phase II), respectively, amiodarone hydrochloride. The analysis of lidocaine pharmacokinetics showed an increase in lidocaine area under the curve (AUC) when amiodarone was administered, whereas that of N-monodesethylated lidocaine decreased. Moreover, the systemic clearance of lidocaine decreased, while the elimination half-life (t1/2) and the distribution volume at steady state of lidocaine remained unchanged. The pharmacokinetic parameters during phase II were the same as those during phase 1, indicating that the interaction had already occurred early in the loading phase of amiodarone administration. The interaction between amiodarone and lidocaine may be explained by the inhibition of CYP3A4 by amiodarone and/or by its main metabolite DEA.
Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Proteins; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Drug Therapy, Combination; Female; Humans; In Vitro Techniques; Kinetics; Lidocaine; Male; Microsomes, Liver; Middle Aged; Mixed Function Oxygenases; Protein Binding
PubMed: 8891878
DOI: 10.1097/00005344-199610000-00009 -
Journal of Cardiovascular Pharmacology Dec 2015Amiodarone (AMD), nifekalant (NIF), and lidocaine (LID) hydrochlorides are widely used for ventricular tachycardia/fibrillation (VT/VF). This study retrospectively... (Comparative Study)
Comparative Study Observational Study
BACKGROUND
Amiodarone (AMD), nifekalant (NIF), and lidocaine (LID) hydrochlorides are widely used for ventricular tachycardia/fibrillation (VT/VF). This study retrospectively investigated the NIF potency and the differential effects of 2 initial AMD doses (≤150 mg or 300 mg) in the Japanese SOS-KANTO 2012 study population.
METHODS AND RESULTS
From 16,164 out-of-hospital cardiac arrest cases, 500 adult patients using a single antiarrhythmic drug for shock-resistant VT/VF were enrolled and categorized into 4 groups (73 LID, 47 NIF, 173 AMD-≤150, and 207 AMD-300). Multivariate analyses evaluated the outcomes of NIF, AMD-≤150, or AMD-300 groups versus LID group. Odds ratios (ORs) for survival to admission were 3.21 [95% confidence interval (CI): 1.38-7.44, P < 0.01] in NIF and 3.09 (95% CI: 1.55-6.16, P < 0.01) in AMD-≤150 groups and significantly higher than those of the LID group. However, the OR was 1.78 (95% CI: 0.90-3.51, P = 0.10) in AMD-300 group and was not significant than LID group. ORs for 24-hour survival were 6.68 in NIF, 4.86 in AMD-≤150, and 2.97 in AMD-300, being significantly higher in these groups.
CONCLUSIONS
NIF and AMD result in similar improvements for 24-hour survival in cardiopulmonary arrest patients, and this suggest the necessity of a randomized control study.
Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Female; Humans; Japan; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Pyrimidinones; Survival Rate; Treatment Outcome
PubMed: 26317166
DOI: 10.1097/FJC.0000000000000310 -
Progress in Cardiovascular Nursing 2007
Review
Topics: Amiodarone; Anti-Arrhythmia Agents; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans
PubMed: 17786095
DOI: 10.1111/j.0889-7204.2007.07398.x -
Annales Pharmaceutiques Francaises Mar 2012Amiodarone hydrochloride, a class III antiarrhythmic agent, shows ß blocker-like and potassium channel blocker-like actions on the sinuatrial and atrioventricular...
Amiodarone hydrochloride, a class III antiarrhythmic agent, shows ß blocker-like and potassium channel blocker-like actions on the sinuatrial and atrioventricular nodes. It is given by mouth in the treatment of all forms of atrial, junctional and ventricular arrhythmias. Capsules for paediatric patients are not commercially available and must be prepared in the pharmacy department. The aim of the study was to evaluate the stability of amiodarone hydrochloride at different dosages, 10, 60 and 100 mg, in capsules for paediatric patients stored in three packages under dark conditions and at room temperatures over one year. At different intervals during the storage period, amiodarone hydrochloride concentration was tested using a high-performance liquid chromatography (HPLC) method. Amiodarone hydrochloride content remained greater than 95% of the initial concentration in all capsules at all dosages. The 10, 60 and 100 mg amiodarone paediatric capsules were stable for one year when stored in the three packages at ambient temperature and under dark conditions.
Topics: Amiodarone; Anti-Arrhythmia Agents; Capsules; Child; Chromatography, High Pressure Liquid; Confidence Intervals; Darkness; Drug Compounding; Drug Packaging; Drug Stability; Drug Storage; Humans; Powders; Reproducibility of Results; Temperature
PubMed: 22500960
DOI: 10.1016/j.pharma.2012.02.001 -
Revista Medico-chirurgicala a... 2016Drug release from modified-release matrix tablets made of Kollidon® SR and Chitosan is dependent on its degree of solubility in the dissolution medium as well as on the...
AIM
Drug release from modified-release matrix tablets made of Kollidon® SR and Chitosan is dependent on its degree of solubility in the dissolution medium as well as on the matrix forming polymer. By complexing hydrochloride amiodarone with hydroxypropyl-β-cyclodextrin, an inclusion complex was obtained, which showed an increase in solubility by more than 200%. The complex was used to obtain modified-release matrix tablets based on Kollidon® SR and Chitosan.
MATERIALS AND METHODS
Matrix tablets were obtained through direct compression method of non-complexed amiodarone and inclusion complex, and they were marked F1 and F10, respectively. The two formulations were studied comparatively in terms of release kinetics of the active substance through in vitro drug release tests. Those tests were conducted using a paddle apparatus II for 12 hours and two gastrointestinal simulation liquids with different pH values relevant for oral administration - 2 hours at pH 1.2 and 10 hours at pH 6.8. The release of hydrochloride amiodarone was quantified using a validated HPLC method. Two factors were calculated to assess the release profile of amiodarone: the similarity factor f1 and difference factor f2.
RESULTS
The increase in Kollidon® SR concentration resulted in a slower release of amiodarone at both pH values. The use of Chitosan resulted in a decrease of AMD release only at pH 6.8.
CONCLUSIONS
The similarities between the two release profiles of AMD were confirmed by the values of the similarity factor (f1 = 43.697) and difference factor f2 (f2 = 68.263).
Topics: Amiodarone; Chemistry, Pharmaceutical; Chitosan; Delayed-Action Preparations; Hydrogen-Ion Concentration; In Vitro Techniques; Povidone; Solubility; Tablets; beta-Cyclodextrins
PubMed: 30152660
DOI: No ID Found -
The Annals of Pharmacotherapy Jun 1996To review the clinical pharmacology, pharmacokinetics, and clinical efficacy and safety of intravenous amiodarone. (Review)
Review
OBJECTIVE
To review the clinical pharmacology, pharmacokinetics, and clinical efficacy and safety of intravenous amiodarone.
DATA IDENTIFICATION
Articles were identified through a computer search of the English-language literature using MEDLINE (KR Information OnDisc) and the search term amiodarone. Additional articles were identified through examination of the bibliographies of the articles initially retrieved.
STUDY SELECTION
Relevant or representative animal studies, clinical trials, and case reports were selected for evaluation. Particular emphasis was placed on studies pertaining to the use of intravenous amiodarone in treatment-refractory ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT).
DATA EXTRACTION
The literature was assessed for adequate description of patients, study methodologies (e.g., study design, number of patients), and outcomes.
DATA SYNTHESIS
Amiodarone is an unusual class III antiarrhythmic that produces each of the four main types of antiarrhythmic action in addition to other effects, such as vasodilatory, selective antithyroid, and other activities that may be therapeutically relevant. Amiodarone pharmacokinetics demonstrate extensive interpatient variability and are characterized by wide tissue distribution (steady-state volume of distribution 40-84 L/kg), slow total body clearance (90-158 mL/h/kg), long terminal elimination half-life (20-47 d), and extensive hepatic metabolism. The onset of maximal antiarrhythmic effect is a function of both amiodarone dosage and time. The high plasma concentrations achieved with intravenous dosing do not fully replicate the electrophysiologic effects observed following long-term oral administration, particularly with respect to class III activity. Available data suggest that intravenous amiodarone is associated with an efficacy rate of 50% or more in treatment-refractory VT/VF, and has a relatively rapid (2-24 h) onset of action. The drug is relatively well tolerated, but close hemodynamic, electrocardiographic, and hepatic function monitoring are required. The value of using amiodarone serum concentrations to guide therapy remains uncertain.
CONCLUSIONS
Intravenous amiodarone is an effective, relatively safe antiarrhythmic for the treatment of recurrent, hemodynamically unstable VT/VF refractory to other drug therapy in the acute care setting.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Humans; Injections, Intravenous
PubMed: 8792951
DOI: 10.1177/106002809603000612 -
British Medical Journal (Clinical... Jul 1983Amiodarone was administered to 80 patients with recurrent cardiac tachyarrhythmias previously resistant to drug treatment. Forty nine patients were treated for...
Amiodarone was administered to 80 patients with recurrent cardiac tachyarrhythmias previously resistant to drug treatment. Forty nine patients were treated for ventricular tachycardia or fibrillation and 31 for supra-ventricular arrhythmias. The mean (range six days to 51 months), permitting a total of 100 patient years of observation. Adverse reactions were observed in 69 patients. Severe side effects were encountered in 13: four patients developed interstitial pneumonitis, four patients developed incessant ventricular tachycardia, three patients taking amiodarone and digoxin sustained sinus node arrest with depression of escape foci, one patient developed hepatitis, and one patient developed hypercalcaemia with renal failure. Furthermore, a rise in the serum concentration of digoxin and potentiation of warfarin anticoagulation occurred in cases in which these agents were combined with amiodarone. Amiodarone was stopped in 14 patients because of side effects. Although amiodarone is effective in suppressing arrhythmias in most patients in whom extensive use of antiarrhythmic drugs has been unsuccessful, it is associated with diverse and serious toxicity. These observations suggest that at present the use of amiodarone should be reserved for patients with life threatening or seriously disabling arrhythmias in whom longer established drugs have been ineffective or are contraindicated.
Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Pulmonary Fibrosis; Recurrence; Respiratory Function Tests; Tachycardia
PubMed: 6409240
DOI: 10.1136/bmj.287.6386.175