Amiodarone - Cordarone ®
|The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.|
Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]
|[150 mg / 100 ml] [10 minutes]
(Glass bottle or polyolefin container)
Stability / Miscellaneous
|Recommended concentration: 1-6 mg/ml.
Central line is required for concentrations > 2 mg/ml.
[Supplied: 3 ml amp (50 mg/ml)].
Infusion: whenever possible administer through a central venous catheter. Also, an in-line filter should be used during administration. Cordarone I.V. concentrations greater than 3 mg/mL in D5W have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, Cordarone I.V. concentrations should not exceed 2 mg/mL unless a central venous catheter is used. Cordarone I.V. infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W. Use of evacuated glass containers for admixing Cordarone I.V. is not recommended as incompatibility with a buffer in the container may cause precipitation.
Amiodarone: I.V. DOSE RECOMMENDATIONS -- FIRST 24 HOURS -- Loading infusions. The recommended starting dose of Cordarone I.V. is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:
First Rapid: 150 mg over the FIRST - 10 minutes (15 mg/min). Add 3 mL of Cordarone I.V. (150 mg) to 100 mL D5W. Infuse 100 mL over 10 minutes.
Followed by Slow: 360 mg over the NEXT 6 hours (1 mg/min). Add 18 mL of Cordarone I.V. (900 mg) to 500 mL D5W (conc = 1.8 mg/mL).
Maintenance infusion: 540 mg over the REMAINING 18 hours (0.5 mg/min).
After the first 24 hours, the maintenance infusion rate of 0.5 mg/min (720 mg/24 hours) should be continued utilizing a concentration of 1 to 6 mg/mL (Cordarone I.V. concentrations greater than 2 mg/mL should be administered via a central venous catheter). In the event of breakthrough episodes of VF or hemodynamically unstable VT, Give 150-mg/100 ml D5W over 10 minutes to minimize potential for hypotension. The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression. The initial infusion rate should not exceed 30 mg/min. The maintenance infusion of up to 0.5 mg/min can be cautiously continued for 2 to 3 weeks regardless of the patient's age, renal function, or Left-ventricular function. There is limited experience in patients receiving Cordarone I.V. > 3 weeks.
RECOMMENDATIONS FOR ORAL DOSAGE AFTER I.V. INFUSION
Duration of Cordarone I.V. Infusion: 1 to 3 weeks
Duration of Cordarone I.V. Infusion: >3 weeks
Restated: Duration of IV infusion < 1 week: 800-1600mg/day po initially x 1-2 weeks or complete current week; 1-3 weeks: 600-800mg/day po initially - total therapy ~ 1 month counting IV infusion ; >3 weeks: 400mg po qd initially.
Oral Loading - Half-life elimination: 40-55 days (range: 26-107 days);
Recommendations for conversion to intravenous amiodarone after oral administration: During long-term amiodarone therapy (ie, 4 months), the mean plasma-elimination half-life of the active metabolite of amiodarone is 61 days. Replacement therapy may not be necessary in such patients if oral therapy is discontinued for a period <2 weeks, since any changes in serum amiodarone concentrations during this period may not be clinically significant.
Mechanisms of Action
Intravenous amiodarone administration prolongs intranodal conduction (Atrial-His, AH) and refractoriness of the atrioventricular node (ERP AVN), but has little or no effect on sinus cycle length (SCL), refractoriness of the right atrium and right ventricle (ERP RA and ERP RV), repolarization (QTc), intraventricular conduction (QRS), and infranodal conduction (His-ventricular, HV).
Pharmacokinetics and Metabolism
N-desethylamiodarone (DEA) is the major active metabolite of amiodarone in humans. DEA serum concentrations above 0.05 mg/L are not usually seen until after several days of continuous infusion but with prolonged therapy reach approximately the same concentration as amiodarone. Amiodarone is metabolized to desethylamiodarone by the cytochrome P450 (CYP450) enzyme group, specifically cytochrome P450 3A4 (CYP3A4) and CYP2C8. The CYP3A4 isoenzyme is present in both the liver and intestines. The highly variable systemic availability of oral amiodarone may be attributed potentially to large interindividual variability in CYP3A4 activity.
Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine. Neither amiodarone nor DEA is dialyzable. Amiodarone and DEA cross the placenta and both appear in breast milk.
The systemic availability of oral amiodarone in healthy subjects ranges between 33% and 65%. From in vitro studies, the protein binding of amiodarone is >96%.
In clinical studies of 2 to 7 days, clearance of amiodarone after intravenous administration in patients with VT and VF ranged between 220 and 440 mL/h/kg. Age, sex, renal disease, and hepatic disease (cirrhosis) do not have marked effects on the disposition of amiodarone or DEA. Renal impairment does not influence the pharmacokinetics of amiodarone. After a single dose of intravenous amiodarone in cirrhotic patients, significantly lower Cmax and average concentration values are seen for DEA, but mean amiodarone levels are unchanged. Normal subjects over 65 years of age show lower clearances (about 100 mL/hr/kg) than younger subjects (about 150 mL/hr/kg) and an increase in t1/2 from about 20 to 47 days. In patients with severe left ventricular dysfunction, the pharmacokinetics of amiodarone are not significantly altered but the terminal disposition t1/2 of DEA is prolonged. Although no dosage adjustment for patients with renal, hepatic, or cardiac abnormalities has been defined during chronic treatment with oral amiodarone, close clinical monitoring is prudent for elderly patients and those with severe left ventricular dysfunction.
There is no established relationship between drug concentration and therapeutic response for short-term intravenous use. Steady-state amiodarone concentrations of 1 to 2.5 mg/L have been associated with antiarrhythmic effects and acceptable toxicity following chronic oral amiodarone therapy.
Hypotension should be treated initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion. The initial rate of infusion should be monitored closely and should not exceed that prescribed in DOSAGE AND ADMINISTRATION.
In some cases, hypotension may be refractory resulting in fatal outcome (see package insert for ADVERSE REACTIONS, Postmarketing Reports).
Bradycardia and AV Block
Neonatal Hypo- or Hyperthyroidism
HOW SUPPLIED ----------------------
Store at 20° to 25°C (68° to 77°F)
Protect from light. Avoid excessive heat.
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. Read the disclaimer