Amiodarone Hcl-D5w (amiodarone HCl/dextrose 5 % in water)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Amiodarone is predominantly a class III antiarrhythmic agent, but the drug also appears to exhibit activity in each of the 4 Vaughn-Williams antiarrhythmic classes.
Amiodarone is considered a class III antiarrhythmic agent, but the drug also appears to exhibit activity in each of the four Vaughn-Williams antiarrhythmic classes. Like class I antiarrhythmic agents, amiodarone blocks sodium channels at rapid pacing frequencies and exerts antisympathetic action like class II antiarrhythmics. The principal effect of amiodarone on cardiac tissue is to lengthen the cardiac action potential, a class III effect.
The drug also exhibits negative chronotropic effects similar to class IV drugs. In addition to blocking sodium channels, amiodarone also blocks cardiac potassium channels, which slows cardiac conduction and prolongs the refractory period. The blocking of calcium and potassium channels and antisympathetic activity result in the negative dromotropic effects and slowing of conduction and prolongation of the refractory period in the atrioventricular (AV) node.
The vasodilatory effects of amiodarone also decrease cardiac workload and the consumption of myocardial oxygen. Amiodarone hydrochloride contains 37.3% iodine.
Amiodarone is slowly and variably absorbed from the GI tract following oral administration. The absolute bioavailability of commercially available amiodarone tablets averages approximately 50%. Food increases the rate and extent of absorption of amiodarone.
Results of a study in healthy adults indicate that administration of a single 600-mg oral dose of amiodarone after a high-fat meal increases the AUC and the peak plasma concentration of amiodarone by 2.3 (range: 1.7-3.6) and 3.8 (range: 2.7-4.4) times, respectively, compared with administration in the fasting state. Food also increases the rate of absorption of amiodarone; when administered with food, the time to achieve peak plasma concentration of unchanged drug is decreased by about 37% to 4.5 hours. The mean AUC and peak plasma concentrations of N-desethylamiodarone (the major metabolite) increase by about 55 and 32%, respectively; however, the time to peak plasma concentration of this metabolite remains unchanged in the presence of food.
Following oral administration, peak plasma amiodarone concentrations usually occur within 3-7 hours. Within the oral dosage range of 100-600 mg daily, steady-state plasma concentrations of the drug are approximately proportional to dosage, increasing by an average of 0.5 mcg/mL per 100-mg increment in dosage; however, there is considerable interindividual variation in plasma concentrations attained with a given dosage.
In a study of single-dose IV amiodarone hydrochloride (5 mg/kg over 15 minutes) in healthy individuals, peak drug concentration ranged from 5-41mcg/mL. Following 10-minute IV infusions of amiodarone hydrochloride at a dose of 150 mg in patients with ventricular fibrillation or hemodynamically unstable ventricular tachycardia, peak drug concentration ranged from 7-26 mcg/mL. Because of a rapid distribution phase, the concentration of amiodarone declines to 10% of peak values within 30-45 minutes after the end of the infusion.
In clinical trials after 48 hours of continuous IV infusions (125, 500, or 1000 mg daily) plus supplemental infusions (150 mg) as needed for recurrent arrhythmias, mean plasma concentrations of amiodarone ranged from 0.7-1.4 mcg/mL. Following administration of a single IV dose of amiodarone in patients with cirrhosis, lower peak and mean plasma concentrations of N-desethylamiodarone are observed; mean amiodarone concentration remains unchanged. Amiodarone is approximately 96% bound to plasma proteins.
Amiodarone and N-desethylamiodarone cross the placenta. Amiodarone and its major metabolite are distributed into human milk.
Amiodarone undergoes metabolism by cytochrome P-450 (CYP) isoenzymes 3A and 2C8 to form N-desethylamiodarone. The precise role of N-desethylamiodarone in the antiarrhythmic activity of amiodarone has not been clearly established. The development of maximal ventricular class III antiarrhythmic effects after oral amiodarone administration in humans correlates more closely with N-desethylamiodarone accumulation over time than with amiodarone accumulation.
In patients with severe left ventricular dysfunction, the pharmacokinetics of amiodarone are not significantly altered; however, the terminal elimination half-life of N-desethylamiodarone is prolonged in these patients. Amiodarone and N-desethylamiodarone are not dialyzable.
Plasma concentrations of amiodarone appear to decline in at least a biphasic manner. Following a single IV dose in healthy adults, the elimination half-life of amiodarone has been reported to range from 9-36 days. The elimination half-life of the major metabolite, N-desethylamiodarone, ranges from 9-30 days.
Following single-dose administration of amiodarone in a limited number of healthy individuals, amiodarone exhibits multicompartmental pharmacokinetics; the mean apparent terminal plasma elimination half-life of amiodarone and N-desethylamiodarone were 58 (range: 15-142) and 36 (range: 14-75) days, respectively. The drug appears to be eliminated in a biphasic manner with an initial 50% reduction in about 2.5-10 days, which is followed by a terminal elimination half-life averaging 53 days (range: 26-107 days), with most patients exhibiting a terminal elimination half-life in the range of 40-55 days. The mean elimination half-life of N-desethylamiodarone is approximately 61 days.
The elimination half-life of amiodarone was increased in geriatric individuals to 47 days, as compared with 20 days in younger individuals. Amiodarone is eliminated primarily via hepatic metabolism and biliary excretion with negligible amounts of amiodarone or N-desethylamiodarone found in urine.
Generic name: amiodarone HCl/dextrose 5 % in water
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Amiodarone Hcl-D5w
Indications
No indications are available for this drug.
Dosing
Amiodarone is a highly toxic drug, and the lowest effective dosage should be used to minimize the risk and occurrence of adverse effects. Dosage of amiodarone must be carefully adjusted according to the severity of the arrhythmia and clinical response.
Effects of amiodarone on abnormal heart rhythms are not usually observed before 2-3 days and often require 1-3 weeks of continued therapy, even when a loading-dose regimen is used; therapeutic effects may continue to increase even after this period with continuation of amiodarone. The time to onset of antiarrhythmic effects is shorter when a loading-dose regimen is used.
Amiodarone is available as amiodarone hydrochloride; dosage is expressed in terms of the salt.
Amiodarone hydrochloride is administered orally or by IV infusion. Amiodarone also has been administered by intraosseous (IO) injection+ in the setting of advanced cardiovascular life support (ACLS) if IV access cannot be obtained.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Amiodarone is metabolized by the cytochrome P-450 (CYP) microsomal enzyme system, principally the isoenzymes CYP3A and CYP2C8. In vitro, amiodarone and N-desethylamiodarone also potentially inhibit CYP2C9, CYP2C19, CYP2D6, CYP3A, CYP2A6, CYP2B6, CYP2C8, and transporters such as P-glycoprotein (P-gp) and organic cation transporter (OCT)2.
Because of the long and variable elimination half-life of amiodarone, the potential for interactions exists not only with concomitantly administered drugs but also with drugs administered after discontinuance of amiodarone therapy. Drug interactions should be expected to persist for weeks to months after discontinuation of amiodarone.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Cardiogenic shock.
*Use in patients with sick sinus syndrome, in patients with second- or third-degree AV block, and in patients with episodes of bradycardia that have caused syncope, except when used concomitantly with an artificial pacemaker.
*Known hypersensitivity to amiodarone or any ingredient in the formulation, including iodine.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects reported in >1% of patients receiving oral amiodarone tablets leading to discontinuation included pulmonary toxicity, paroxysmal ventricular tachycardia, congestive heart failure, and elevated liver enzymes.
The most common adverse effects reported in 1-2% of patients receiving IV amiodarone leading to discontinuation of therapy included hypotension, asystole/cardiac arrest/pulseless electrical activity, ventricular tachycardia, and cardiogenic shock.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of amiodarone in pediatric patients+ have not been established. In a clinical trial in pediatric patients 30 days to 15 years of age, hypotension (36%), bradycardia (20%), and AV block (15%) were common dose-related adverse effects, and in some cases were severe or life-threatening. In this trial, injection-site reactions were observed in 5 of 20 patients receiving IV amiodarone through a peripheral vein.
Each mL of the commercially available amiodarone hydrochloride IV injection contains 20.2 mg of benzyl alcohol as a preservative. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with ''gasping syndrome'' in neonates, characterized by striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse.
Postmarketing reports and published case series indicate that amiodarone use during pregnancy may increase the risk of fetal adverse effects, including neonatal hypo- and hyperthyroidism, neonatal bradycardia, neurodevelopmental abnormalities, preterm birth, and fetal growth restriction. Amiodarone and N-desethylamiodarone cross the placenta.
Reproduction studies in pregnant rats or rabbits receiving oral amiodarone dosages of 25 mg/kg daily (approximately 0.4 and 0.9 times, respectively, the maximum recommended human maintenance dosage of 600 mg for a 60-kg patient (calculated on the basis of body surface area)) revealed no evidence of harm to the fetus. However, in pregnant rabbits receiving oral amiodarone hydrochloride dosages of 75 mg/kg daily (approximately 2.7 times the maximum recommended human maintenance dosage of 600 mg for a 60-kg patient (calculated on the basis of body surface area)), abortions occurred in more than 90% of these rabbits. Slight displacement of the testes and an increased incidence of incomplete ossification of some skull and digital bones were reported in pregnant rats receiving oral amiodarone hydrochloride dosages of 50 mg/kg daily (approximately 0.8 times the maximum recommended human maintenance dosage of 600 mg for a 60-kg patient (calculated on the basis of body surface area)) or more. In addition, in rats receiving oral amiodarone hydrochloride dosages of 100 mg/kg daily (approximately 1.6 times the maximum recommended human maintenance dosage of 600 mg for a 60-kg patient (calculated on the basis of body surface area) or more, or 200 mg/kg daily (approximately 1.6 or 3.2 times the maximum recommended human maintenance dosage of 600 mg for a 60-kg patient (calculated on the basis of body surface area)), reduced fetal body weight or increased incidence of fetal resorptions, respectively, were observed. Adverse effects on fetal growth and survival also were reported in 1 of 2 strains of mice receiving oral amiodarone hydrochloride dosages of 5 mg/kg daily (approximately 0.04 times the maximum recommended human maintenance dosage of 600 mg for a 60-kg patient (calculated on the basis of body surface area)).
Untreated underlying arrhythmias, including ventricular arrhythmias, during pregnancy pose a risk to the mother and fetus. Ventricular tachycardia is more common and may be more symptomatic during pregnancy. Ventricular arrhythmias are most common in pregnant women with underlying cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse. The majority of ventricular tachycardia episodes are initiated by ectopic beats and the incidence of arrhythmia episodes may therefore increase during pregnancy because of the increased propensity for ectopic activity. Breakthrough arrhythmias can also develop due to differences in treatment levels that can occur during pregnancy. The risk of arrhythmia can also increase during labor and delivery.
Inform patients of the potential fetal risk from amiodarone exposure. Monitor pregnant patients receiving amiodarone continuously during labor and delivery.
Monitor newborns exposed to amiodarone in utero for symptoms of thyroid dysfunction and cardiac arrhythmias.
Amiodarone and its major metabolite N-desethylamiodarone are distributed into human milk at concentrations between 3.5 and 45% of the maternal weight-adjusted dosage. Cases of hypothyroidism and bradycardia have been reported in breastfed infants, although it is unclear if this was due to amiodarone exposure in breastmilk. Nursing offspring of lactating rats receiving amiodarone have been shown to be less viable and to have reduced body weight gains.
Because nursing may expose the infant to a substantial dose of amiodarone and its metabolite, it is recommended that nursing be discontinued during amiodarone therapy.
The manufacturer does not provide specific dosage recommendations in geriatric patients; however, close clinical monitoring is recommended in geriatric patients receiving amiodarone therapy. Dosage in general for geriatric patients should be selected carefully, usually starting at the low end of the dosage range, because these individuals frequently have decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
Adults >=65 years of age have shown lower clearance and an extended half-life of amiodarone compared to younger adults.
While clinical experience to date has not revealed age-related differences in response to amiodarone, clinical studies evaluating the drug have not included sufficient numbers of adults >=65 years of age to determine whether geriatric patients respond differently than younger adults.
The manufacturers state that the amiodarone dosage for geriatric patients should be selected carefully, usually starting at the low end of the dosage range, because these individuals frequently have decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. In addition, geriatric patients may be more susceptible to bradycardia and conduction disturbances induced by the drug. Close clinical monitoring is recommended.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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