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NEXTERONE is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. NEXTERONE 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 NEXTERONE, patients may be transferred to oral amiodarone therapy [see DOSAGE AND ADMINISTRATION].
Use NEXTERONE for acute treatment until the patient's ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but NEXTERONE may be safely administered for longer periods if necessary.
DOSAGE AND ADMINISTRATION
Amiodarone shows considerable interindividual variation in response. Although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose is essential. The recommended starting dose of NEXTERONE is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:
Table 1: NEXTERONE DOSE RECOMMENDATIONS: FIRST 24 HOURS
|Loading infusions||First Rapid:||150 mg over the FIRST 10 minutes (15 mg/min).|
|Add 3 mL of NEXTERONE (150 mg) to 100 mL D5W or normal saline (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 NEXTERONE (900 mg) to 500 mL D5W or normal saline (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, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) utilizing a concentration of 1 to 6 mg/mL (Use a central venous catheter for NEXTERONE concentrations greater than 2 mg/mL). The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression.
In the event of breakthrough episodes of VF or hemodynamically unstable VT, use 150 mg supplemental infusions of NEXTERONE (mixed in 100 mL of D5W or normal saline and infused over 10 minutes to minimize the potential for hypotension).
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. Do not exceed an initial infusion rate of 30 mg/min.
Based on the experience from clinical studies of intravenous amiodarone, a maintenance infusion of up to 0.5 mg/min can be 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 intravenous amiodarone for longer than 3 weeks.
Administer NEXTERONE, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration.
Intravenous amiodarone 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 WARNINGS AND PRECAUTIONS].
Intravenous amiodarone concentrations greater than 3 mg/mL 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, do not exceed NEXTERONE concentrations of 2 mg/mL, unless a central venous catheter is used [see ADVERSE REACTIONS].
NEXTERONE may be diluted in D5W or saline and administered in polyvinyl chloride (PVC), polyolefin, or glass containers.
Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation.
NEXTERONE does not need to be protected from light during administration.
NOTE: Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.
NEXTERONE in D5W is incompatible with the drugs shown in Table 2.
Table 2: Y-SITE INJECTION INCOMPATIBILITY
|Cefamandole Nafate||D5W||4 mg/mL||Precipitate|
|Cefazolin Sodium||D5W||4 mg/mL||Precipitate|
|Mezlocillin Sodium||D5W||4 mg/mL||Precipitate|
|Sodium Bicarbonate||D5W||3 mg/mL||Precipitate|
Intravenous to Oral Transition
Patients whose arrhythmias have been suppressed by NEXTERONE may be switched to oral amiodarone. The optimal dose for changing from intravenous to oral administration of amiodarone will depend on the dose of NEXTERONE already administered, as well as the bioavailability of oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients. See package insert for oral amiodarone.
Since grapefruit juice is known to inhibit CYP3A-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, do not drink grapefruit juice during treatment with oral amiodarone [see DRUG INTERACTIONS].
Table 3 provides suggested doses of oral amiodarone to be initiated after varying durations of NEXTERONE administration. These recommendations are made on the basis of a similar total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone.
Table 3: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS
|Duration of NEXTERONE 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).
* NEXTERONE is not intended for maintenance treatment.
Dosage Forms and Strengths
Injection, 50 mg/mL
NEXTERONE (amiodarone Hcl) is available in single-use glass vials packaged in individual cartons as follows:
150 mg/3 mL in a 5 mL vial NDC 43066 - 101 - 02
450 mg/9 mL in a 10 mL vial NDC 43066 - 101 - 03
900 mg/18 mL in a 20 mL vial NDC 43066 - 101 - 04
NEXTERONE (amiodarone HC1) is available in single-use glass prefilled syringes packaged in blister-packs as follows:
150 mg/3 mL in a 5 mL prefilled syringe NDC 43066 - 101 - 01
Store at 20° - 25°C (68° - 77°F); excursions permitted to 15° - 30°C (59° - 86°F). See USP Controlled Room Temperature.
Protect from light and excessive heat.
Use carton or blister pack to protect contents from light until used.
Stoppers and tip caps do not contain natural rubber latex
Vials manufactured by: HollisterStier Laboratories, LLC Spokane, WA 99207, Pre-filled Syringes manufactured by: Baxter Pharmaceutical Solutions, LLC Bloomington, IN 47403. For: Baxter Baxter Healthcare Corporation Deerfield, IL60015. Revised: December/2011
Last reviewed on RxList: 1/6/2012
This monograph has been modified to include the generic and brand name in many instances.
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