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Amiodarone HCl Injection

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Amiodarone HCl Injection

Indications
Dosage
How Supplied

INDICATIONS

Amiodarone HCl injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy. Intravenous amiodarone also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with intravenous amiodarone, patients may be transferred to oral amiodarone therapy (see DOSAGE AND ADMINISTRATION).

Intravenous amiodarone should be used for acute treatment until the patient's ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but intravenous amiodarone may be safely administered for longer periods if necessary.

DOSAGE AND ADMINISTRATION

Amiodarone shows considerable inter-individual variation in response. Thus, although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose as needed is essential. The recommended starting dose of intravenous amiodarone is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:

AMIODARONE HCI INJECTION DOSE RECOMMENDATIONS
- FIRST 24 HOURS -

Loading infusions First Rapid: 150 mg over the FIRST 10 minutes (15 mg/min).
  Add 3 mL of Amiodarone HCl Injection (150 mg) to 100 mL D5W (concentration = 1.5 mg/mL). Infuse 100 mL over 10 minutes.
Followed by Slow: 360 mg over the NEXT 6 hours (1 mg/min).
  Add 18 mL of Amiodarone HCl Injection (900 mg) to 500 mL D5W (concentration = 1.8 mg/mL).
Maintenance infusion 540 mg over the REMAINING 18 hours (0.5 mg/min).
  Decrease the rate of the slow loading infusion to 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 (amiodarone HCl injection 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, 150 mg supplemental infusions of amiodarone HCl injection mixed in 100 mL of D5W may be administered. Such infusions should be administered over 10 minutes to minimize the potential for hypotension. The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression.

The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. The initial infusion rate should not exceed 30 mg/min.

Based on the experience from clinical studies of amiodarone injection, a 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 has been limited experience in patients receiving amiodarone injection for longer than 3 weeks.

The surface properties of solutions containing injectable amiodarone are altered such that the drop size may be reduced. This reduction may lead to underdosage of the patient by up to 30% if drop counter infusion sets are used. Amiodarone injection must be delivered by a volumetric infusion pump.

Amiodarone injection should, whenever possible, be administered through a central venous catheter dedicated to that purpose. An in-line filter should be used during administration.

Amiodarone injection loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death (see PRECAUTIONS, Liver Enzymes Elevations).

Amiodarone HCl injection 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, amiodarone HCl injection concentrations should not exceed 2 mg/mL unless a central venous catheter is used (See ADVERSE REACTIONS Postmarketing Reports).

Amiodarone HCl injection infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W. Use of evacuated glass containers for admixing amiodarone HCl injection is not recommended as incompatibility with a buffer in the container may cause precipitation.

It is well known that amiodarone adsorbs to polyvinyl chloride (PVC) tubing and the clinical trial dose administration schedule was designed to account for this adsorption. All of the clinical trials were conducted using PVC tubing and its use is therefore recommended. The concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect doses identified in these studies. It is important that the recommended infusion regimen be followed closely.

Intravenous amiodarone has been found to leach out plasticizers, including DEHP [di-(2-ethylhexyl) phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing intravenous amiodarone at higher concentrations and lower flow rates than provided in dosage and Administration.

Intravenous amiodarone does not need to be protected from light during administration.

AMIODARONE HCl SOLUTION STABILITY

Solution Concentration
(mg/mL)
Container Comments
5% Dextrose in Water (D5W) 1.0 - 6.0 PVC Physically compatible, with amiodarone loss < 10% at 2 hours at room temperature.
5% Dextrose in Water (D5W) 1.0 - 6.0 Polyolefin, Glass Physically compatible, with no amiodarone loss at 24 hours at room temperature.

Admixture Incompatibility

Amiodarone HCI injection in D5W is incompatible with the drugs shown below.

Y-SITE INJECTION INCOMPATIBILITY

Drug Vehicle Amiodarone Concentration Comments
Aminophylline D5W 4 mg/mL Precipitate
Cefamandole Nafate D5W 4 mg/mL Precipitate
Cefazolin Sodium D5W 4 mg/mL Precipitate
Mezlocillin Sodium D5W 4 mg/mL Precipitate
Heparin Sodium D5W -- Precipitate
Sodium Bicarbonate D5W 3 mg/mL Precipitate

Intravenous to Oral Transition

Patients whose arrhythmias have been suppressed by intravenous amiodarone may be switched to oral amiodarone. The optimal dose for changing from intravenous to oral administration of amiodarone will depend on the dose of intravenous amiodarone already administered, as well as the bioavailability of oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients.

Since there are some differences between the safety and efficacy profiles of the intravenous and oral formulations, the prescriber is advised to review the package insert for oral amiodarone when switching from intravenous to oral amiodarone therapy.

Since grapefruit juice is known to inhibit CYP3A4-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, grapefruit juice should not be taken during treatment with oral amiodarone (see PRECAUTIONS: DRUG INTERACTIONS).

The following table provides suggested doses of oral amiodarone to be initiated after varying durations of intravenous amiodarone administration. These recommendations are made on the basis of a comparable total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone.

RECOMMENDATIONS FOR ORAL DOSAGE AFTER I.V. INFUSION

Duration of Amiodarone injection Infusion# Initial Daily Dose of Oral Amiodarone
< 1 week 800-1600 mg
1-3 weeks 600-800 mg
> 3 weeks* 400 mg
# Assuming a 720 mg/day infusion (0.5 mg/min).
* Amiodarone Injection is not intended for maintenance treatment.

HOW SUPPLIED

Amiodarone Hydrochloride Injection, is supplied as:

NDC Syringe Packaging Factor
25021-302-73 Amiodarone Hydrochloride Injection 150 mg/3 mL (50 mg/mL) in 3 mL Single Use Syringe 10 Single Use Syringes per Carton

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light. Avoid excessive heat. Do not freeze.

Use carton to protect contents from light until used. LATEX-FREE

Mfg. for SAGENT Pharmaceuticals, Schaumburg, IL 60195 (USA). Mfg. by Gland Pharma, India. April 2008. FDA revision date: 2/4/2004

Last reviewed on RxList: 11/18/2008
This monograph has been modified to include the generic and brand name in many instances.

Indications
Dosage
How Supplied
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