Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING NEXTERONE (amiodarone HCl) Premixed Injection is supplied as a ready-to-use, sterile, nonpyrogenic, iso-osmotic solution in 100 mL and 200 mL single-dose GALAXY containers packaged in individual cartons as follows: 150 mg/100 mL NDC 43066 – 150 – 10 360 mg/200 mL NDC 43066 – 360 – 20 Do not add supplementary medication to NEXTERONE Premixed Injection. 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. Protect from freezing. Use carton to protect contents from light until used.; PACKAGE LABELING - PRINCIPAL DISPLAY PANEL Container Label NDC 43066-360-20 Nexterone (amiodarone HCI) Premixed Injection 360 mg/200 mL (1.8 mg/mL) Rx Only For Intravenous Use Galaxy 200mL Single-Dose Container Discard unused portion Iso-osmotic solution in Dextrose Code 2G3450 Sterile, Nonpyrogenic Each mL contains: 1.8 mg amiodarone HCl, USP; 18 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 41.4 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. CAUTIONS: Check for minute leaks by squeezing bag firmly. If leaks are found, discard bag as sterility may be impaired. Do not use unless solution is clear. Do not add supplemental medication. Must not be used in series connections. Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Made in the USA 07-34-00-2401 Barcode 3 4306636020 7 Carton Label Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) Nexterone (amiodarone HCl) Premixed Injection 360 mg/200 mL (1.8 mg/mL) For Intravenous Use UNVARNISHED AREA FOR ON-LINE PRINTING OF LOT & EXP Barcode 3 4306636020 7 Iso-osmotic solution in Dextrose Sterile, Nonpyrogenic Each mL contains: 1.8 mg amiodarone HCl, USP; 18 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 41.4 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. Does not contain polysorbate 80 or benzyl alcohol. Dosage : See prescribing information. STORAGE: Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation Deerfield, IL 60015 USA 07-01-00-1679 Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) NDC 43066-360-20 Code 2G3450 Nexterone (amiodarone HCl) Premixed Injection 360 mg/200 mL (1.8 mg/mL) Rx Only For Intravenous Use USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE 1 Galaxy Single-Dose Container Discard unused portion Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Container Label Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) For Intravenous Use UNVARNISHED AREA FOR ON-LINE PRINTING OF LOT & EXP Barcode 3 4306615010 5 Iso-osmotic solution in Dextrose Sterile, Nonpyrogenic Each mL contains: 1.5 mg amiodarone HCl, USP; 15 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 42.1 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. Does not contain polysorbate 80 or benzyl alcohol. Dosage : See prescribing information. STORAGE: Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation Deerfield, IL 60015 USA 07-01-00-1735 Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) NDC 43066-150-10 Code 2G3451 Nexterone (amiodarone HCl) Premixed Injection 150 mg/100 mL (1.5 mg/mL) Rx Only For Intravenous Use USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE 1 Galaxy Single-Dose Container Discard unused portion Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Carton Label Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection 150 mg/100 mL (1.5 mg/mL) For Intravenous Use UNVARNISHED AREA FOR ON-LINE PRINTING OF LOT & EXP Lot ABXXXXXX EXP YYY-MM-DD *FOR BAR CODE POSITION ONLY (01) 00000000000000 (10)XX0000000 (21) 000000000000 (17)0000000000 Barcode 3 4306615010 5 Iso-osmotic solution in Dextrose Sterile, Nonpyrogenic Each mL contains: 1.5 mg amiodarone HCl, USP; 15 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 42.1 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. Does not contain polysorbate 80 or benzyl alcohol. DOSAGE : See prescribing information. STORAGE: Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation Deerfield, IL 60015 USA 07-01-00-1735 Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) NDC 43066-150-10 Code 2G3451 Nexterone (amiodarone HCl) Premixed Injection 150 mg/100 mL (1.5 mg/mL) Rx Only For Intravenous Use USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE 1 GALAXY Single-Dose Container Discard unused portion Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Representative Container for NDC 43066-360-20 1 of 2 Representative Container for NDC 43066-360-20 2 of 2 Representative Carton Label for NDC 43066-360-20 Representative Container Label for NDC 43066-150-10 1 of 2 Representative Container Label for NDC 43066-150-10 2 of 2 Representative Carton Label for NDC 43066-150-10
- 16 HOW SUPPLIED/STORAGE AND HANDLING NEXTERONE (amiodarone HCl) Premixed Injection is supplied as a ready-to-use, sterile, nonpyrogenic, iso-osmotic solution in 100 mL and 200 mL single-dose GALAXY containers packaged in individual cartons as follows: 150 mg/100 mL NDC 43066 – 150 – 10 360 mg/200 mL NDC 43066 – 360 – 20 Do not add supplementary medication to NEXTERONE Premixed Injection. 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. Protect from freezing. Use carton to protect contents from light until used.
- PACKAGE LABELING - PRINCIPAL DISPLAY PANEL Container Label NDC 43066-360-20 Nexterone (amiodarone HCI) Premixed Injection 360 mg/200 mL (1.8 mg/mL) Rx Only For Intravenous Use Galaxy 200mL Single-Dose Container Discard unused portion Iso-osmotic solution in Dextrose Code 2G3450 Sterile, Nonpyrogenic Each mL contains: 1.8 mg amiodarone HCl, USP; 18 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 41.4 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. CAUTIONS: Check for minute leaks by squeezing bag firmly. If leaks are found, discard bag as sterility may be impaired. Do not use unless solution is clear. Do not add supplemental medication. Must not be used in series connections. Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Made in the USA 07-34-00-2401 Barcode 3 4306636020 7 Carton Label Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) Nexterone (amiodarone HCl) Premixed Injection 360 mg/200 mL (1.8 mg/mL) For Intravenous Use UNVARNISHED AREA FOR ON-LINE PRINTING OF LOT & EXP Barcode 3 4306636020 7 Iso-osmotic solution in Dextrose Sterile, Nonpyrogenic Each mL contains: 1.8 mg amiodarone HCl, USP; 18 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 41.4 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. Does not contain polysorbate 80 or benzyl alcohol. Dosage : See prescribing information. STORAGE: Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation Deerfield, IL 60015 USA 07-01-00-1679 Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 360 mg/200 mL (1.8 mg/mL) NDC 43066-360-20 Code 2G3450 Nexterone (amiodarone HCl) Premixed Injection 360 mg/200 mL (1.8 mg/mL) Rx Only For Intravenous Use USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE 1 Galaxy Single-Dose Container Discard unused portion Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Container Label Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) For Intravenous Use UNVARNISHED AREA FOR ON-LINE PRINTING OF LOT & EXP Barcode 3 4306615010 5 Iso-osmotic solution in Dextrose Sterile, Nonpyrogenic Each mL contains: 1.5 mg amiodarone HCl, USP; 15 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 42.1 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. Does not contain polysorbate 80 or benzyl alcohol. Dosage : See prescribing information. STORAGE: Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation Deerfield, IL 60015 USA 07-01-00-1735 Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) NDC 43066-150-10 Code 2G3451 Nexterone (amiodarone HCl) Premixed Injection 150 mg/100 mL (1.5 mg/mL) Rx Only For Intravenous Use USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE 1 Galaxy Single-Dose Container Discard unused portion Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Carton Label Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection 150 mg/100 mL (1.5 mg/mL) For Intravenous Use UNVARNISHED AREA FOR ON-LINE PRINTING OF LOT & EXP Lot ABXXXXXX EXP YYY-MM-DD *FOR BAR CODE POSITION ONLY (01) 00000000000000 (10)XX0000000 (21) 000000000000 (17)0000000000 Barcode 3 4306615010 5 Iso-osmotic solution in Dextrose Sterile, Nonpyrogenic Each mL contains: 1.5 mg amiodarone HCl, USP; 15 mg Betadex Sulfobutyl Ether Sodium, NF; 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate, and 42.1 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. Does not contain polysorbate 80 or benzyl alcohol. DOSAGE : See prescribing information. STORAGE: Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30º C (59º to 86º F). See USP Controlled Room Temperature. Protect from freezing. Avoid excessive heat. USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE. Baxter, Galaxy and Nexterone are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation Deerfield, IL 60015 USA 07-01-00-1735 Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) Nexterone (amiodarone HCl) Premixed Injection For Intravenous Use 150 mg/100 mL (1.5 mg/mL) NDC 43066-150-10 Code 2G3451 Nexterone (amiodarone HCl) Premixed Injection 150 mg/100 mL (1.5 mg/mL) Rx Only For Intravenous Use USE CARTON TO PROTECT CONTENTS FROM LIGHT UNTIL USE 1 GALAXY Single-Dose Container Discard unused portion Baxter Logo Baxter Healthcare Corporation, Deerfield, IL 60015 USA Representative Container for NDC 43066-360-20 1 of 2 Representative Container for NDC 43066-360-20 2 of 2 Representative Carton Label for NDC 43066-360-20 Representative Container Label for NDC 43066-150-10 1 of 2 Representative Container Label for NDC 43066-150-10 2 of 2 Representative Carton Label for NDC 43066-150-10
Overview
NEXTERONE Premixed Injection contains amiodarone HCl (C 25 H 29 I 2 NO 3 •HCl), a class III antiarrhythmic drug. Amiodarone HCl is (2-butyl-3-benzo-furanyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone hydrochloride. Amiodarone HCl has the following structural formula: Amiodarone HCl is a white to slightly yellow crystalline powder and is very slightly soluble in water. It has a molecular weight of 681.78 and contains 37.3% iodine by weight. NEXTERONE Premixed Injection is a sterile clear, colorless to slightly yellow solution visually free from particulates. NEXTERONE Premixed Injection is available as a ready-to-use, nonpyrogenic, iso-osmotic solution for intravenous administration in 100-mL GALAXY containers with 150 mg of amiodarone HCl, USP (1.5 mg/mL) in dextrose, and 200-mL GALAXY containers with 360 mg of amiodarone HCl, USP (1.8 mg/mL) in dextrose. NEXTERONE Premixed Injection (150 mg/100 mL, 1.5 mg/mL): Each mL contains 1.5 mg of amiodarone HCl, USP, 15 mg Betadex Sulfobutyl Ether Sodium, NF, 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate and 42.1 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. NEXTERONE Premixed Injection (360 mg/200 mL, 1.8 mg/mL): Each mL contains 1.8 mg of amiodarone HCl, USP, 18 mg Betadex Sulfobutyl Ether Sodium, NF, 0.362 mg citric acid anhydrous, 0.183 mg sodium citrate dihydrate and 41.4 mg dextrose anhydrous in water for injection. Sodium hydroxide or hydrochloric acid may have been added to adjust pH. NEXTERONE Premixed Injection does not contain polysorbate 80 or benzyl alcohol. The GALAXY container is fabricated from a specially designed multilayered plastic. Solutions are in contact with the polyethylene layer of the container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability and safety of the plastic have been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies. Amiodarone HCl Structural Formula
Indications & Usage
NEXTERONE Premixed Injection 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 Premixed Injection is an antiarrhythmic agent indicated for treatment and prophylaxis of ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. (1)
Dosage & Administration
• The recommended starting dosing regimen is: (2) o Initial Load: 150 mg in 100 mL infused over 10 minutes o Followed by: 1 mg/min for 6 hours o Followed by: 0.5 mg/min thereafter • For breakthrough episodes of VF or hemodynamically unstable VT, repeat the Initial Load (2) 2.1 General Considerations Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit, solution should be clear. Visually inspect the container. If the administration port protector is damaged, detached or not present, discard the container as the solution path sterility may be compromised. Check for minute leaks prior to use by squeezing the bag firmly. If leaks are detected, discard solution as sterility may be impaired. Protect from light until ready to use. NEXTERONE Premixed Injection is available in GALAXY containers as a single-use, ready-to-use, iso-osmotic solution in dextrose for intravenous administration. No further dilution is required. Discard any unused portion after use. Administer NEXTERONE Premixed Injection, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration. 2.2 Recommended Dosage NEXTERONE Premixed Injection response can vary. Monitor patient response and adjust dose accordingly. In controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. Table 1: NEXTERONE Premixed Injection Dosage Recommendations Loading Infusion First Rapid 150 mg over the FIRST 10 minutes (15 mg/min). Directly infuse NEXTERONE Premixed Injection (150 mg/100 mL; 1.5 mg/mL) at a rate of 10 mL/min. Followed by Slow 360 mg over the NEXT 6 hours (1 mg/min). Directly infuse NEXTERONE Premixed Injection (360 mg/200 mL; 1.8 mg/mL) at a rate of 0.556 mL/min. 540 mg over the REMAINING 18 hours (0.5 mg/min ) Decrease the rate to 0.278 mL/min. Maintenance Infusion After the first 24 hours, continue the maintenance infusion 720 mg per 24 hour period (0.5 mg/min) Directly infuse NEXTERONE Premixed Injection (360 mg/200 mL; 1.8 mg/mL) at a rate of 0.278 mL/min). Breakthrough VF or Hemodynamically Unstable VT 150 mg supplemental infusion over 10 minutes (15 mg/min). Directly infuse NEXTERONE Premixed Injection (150 mg/100mL; 1.5 mg/mL) at a rate of 10 mL/min. Admixture Incompatibility Amiodarone in D 5 W Injection forms precipitates with the drugs shown in Table 2 . If co-administration of the following drugs is necessary, use separate intravenous administration lines. Table 2: Y-SITE INJECTION INCOMPATIBILITY D5W = Dextrose 5% in Sterile Water, NS = Normal Saline Drug Vehicle Amiodarone Concentration Aminophylline D5W; NS 4 mg/mL Amoxicillin Sodium-Clavulanic Acid unknown 12.5 mg/mL Ampicillin Sodium-Sulbactam Sodium NS 6 mg/mL Argatroban D 5 W 1.8 mg/mL Bivalirudin D 5 W 4 mg/mL Cefamandole Nafate D 5 W 4 mg/mL Cefazolin Sodium D 5 W 4 mg/mL Ceftazidime D 5 W 6 mg/mL Digoxin D 5 W 6 mg/mL Furosemide (10 mg/mL) D 5 W 6 mg/mL Mezlocillin Sodium D 5 W 4 mg/mL Heparin Sodium D 5 W -- Imipenem-Cilastin Sodium D 5 W 6 mg/mL Magnesium Sulfate (500 mg/mL) D 5 W 6 mg/mL Micafungin NS 4 mg/mL Piperacillin Sodium –Tazobactam Sodium D 5 W 6 mg/mL Potassium Phosphates D 5 W 6 mg/mL Sodium Bicarbonate D 5 W 3 mg/mL Sodium Nitroprusside D 5 W 1.5, 6 and 15 mg/mL Sodium Phosphates D 5 W 6 mg/mL 2.3 Transition From Intravenous Amiodarone to Oral Amiodarone Table 3 provides suggested doses of oral amiodarone to be initiated after varying durations of NEXTERONE infusion. Table 3: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS INFUSION Duration of Amiodarone Infusion Assuming a 720 mg/day infusion (0.5 mg/min). Initial Daily Dose of Oral Amiodarone Less than 1 week 800 to 1600 mg 1 to 3 weeks 600 to 800 mg More than 3 weeks Intravenous amiodarone is not intended for maintenance treatment. 400 mg
Warnings & Precautions
• Hypotension: Slow the infusion; as needed, add vasopressor drugs, positive inotropic agents, and volume expansion. (5.2) • Primary Graft Dysfunction (PGD) Post Cardiac Transplant ( 5.3 ) • Bradycardia and AV block: Slow the infusion or discontinue. ( 5.4 ) 5.1 Persistence of Adverse Effects Because of the long half-life of amiodarone (9 to 36 days) and its metabolite desethylamiodarone (9 to 30 days), adverse reactions or interactions, as well as observed adverse effects, can persist following amiodarone withdrawal. 5.2 Hypotension Hypotension, the most common adverse reaction seen with intravenous amiodarone seen most often in the first several hours of treatment and is likely related to the rate of infusion. In some cases, hypotension may be refractory and result in a fatal outcome. Hypotension necessitating alterations in intravenous amiodarone therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients. Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion . Monitor the initial rate of infusion closely and do not exceed the recommended rate [ see Dosage and Administration (2) ]. 5.3 Primary Graft Dysfunction (PGD) Post Cardiac Transplant In retrospective studies, amiodarone use in transplant recipients prior to heart transplants has been associated with an increased risk of PGD. PGD is a life-threatening complication of heart transplantation that presents as a left, right or biventricular dysfunction occurring within the first 24 hours of transplant surgery for which there is no identifiable secondary cause (see section 6.2 ). Severe PGD may be irreversible. For patients who are on the heart transplant waiting list, consideration should be given to use an alternative antiarrhythmic drug as early as possible before transplant. 5.4 Bradycardia and Atrioventricular Block NEXTERONE Premixed Injection causes bradycardia and AV block which may require slowing the infusion rate or discontinuing NEXTERONE. In some patients, inserting a pacemaker is required. Have a temporary pacemaker available when treating a patient predisposed to bradycardia or AV block. 5.5 Hepatic Injury Acute hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of intravenous amiodarone. Intravenous infusions at much higher concentrations and rates of infusion than those recommended appear to increase this risk [ see Dosage and Administration (2) ]. Carefully monitor patients receiving NEXTERONE Premixed Injection for evidence of progressive hepatic injury. Consider reducing the rate of administration or withdrawing NEXTERONE Premixed Injection if hepatic injury occurs. 5.6 Proarrhythmia NEXTERONE Premixed Injection may cause a worsening of existing arrhythmias or precipitate a new arrhythmia, sometimes leading to fatal outcomes [ see Adverse Reactions (6.2) ]. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation, by intravenous amiodarone. Although QTc prolongation occurred frequently in patients receiving intravenous amiodarone, TdP or new-onset VF occurred infrequently (less than 2%). Monitor patients for QTc prolongation during infusion with NEXTERONE Premixed Injection. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. Correct hypokalemia, hypomagnesemia or hypocalcemia whenever possible before initiating treatment with NEXTERONE Premixed Injection, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics and laxatives. 5.7 Pulmonary Injury Early-onset Pulmonary Toxicity There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings have included pulmonary infiltrates and masses on X-ray, pulmonary fibrosis, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy. Some cases have progressed to respiratory failure or death. Monitor for new respiratory symptoms and evaluate appropriately. Obtain a baseline chest X-ray and pulmonary function tests in patients who are expected to be receiving amiodarone chronically. 5.8 Loss of Vision Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment, have been reported in patients treated with oral amiodarone or intravenous amiodarone. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and neuritis may occur at any time following initiation of therapy. Perform an ophthalmic examination if symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision. Re-evaluate the necessity of amiodarone therapy if optic neuropathy or neuritis is suspected. 5.9 Thyroid Abnormalities NEXTERONE Premixed Injection inhibits peripheral conversion of throxine (T4) to triiodothyronine (T3) and may cause increased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Monitor thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Hyperthyroidism may induce arrhythmia breakthrough. If any new signs of arrhythmia appear, the possibility of hyperthyroidism should be considered. Antithyroid drugs, β-adrenergic blockers, temporary corticosteroid therapy may be necessary to treat the symptoms of hyperthyroidism. The action of antithyroid drugs may be delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. Radioactive iodine therapy is contraindicated because of the low radioiodine uptake associated with amiodarone-induced hyperthyroidism. NEXTERONE Premixed Injection induced hyperthyroidism may be followed by a transient period of hypothyroidism. In some clinically hypothyroid amiodarone-treated patients, free thyroxine index values may be normal. Manage hypothyroidism by reducing the dose of or discontinuing amiodarone and thyroid hormone supplementation. 5.10 Neonatal Injury Amiodarone can cause fetal harm when administered to a pregnant woman. Fetal exposure may increase the potential for adverse experiences including cardiac, thyroid, neurodevelopmental, neurological and growth effects in neonate. Inform the patient of the potential hazard to the fetus if NEXTERONE Premixed Injection is administered during pregnancy or if the patient becomes pregnant while taking NEXTERONE [ see Pregnancy (8.1) ]. 5.11 Hypersensitivity Reactions Anaphylactic/anaphylactoid reactions have been reported with intravenous amiodarone including shock (sometimes fatal), cardiac arrest, and the following manifestations: hypotension, tachycardia, hypoxia, cyanosis, rash, Stevens-Johnson syndrome, flushing, hyperhidrosis and cold sweat. 5.12 Phlebitis Infusion site phlebitis has occurred in patients receiving intravenous amiodarone. Intravenous amiodarone concentrations greater than 3 mg/mL have been associated with a high incidence of peripheral vein phlebitis.
Contraindications
NEXTERONE Premixed Injection is contraindicated in patients with: • Known hypersensitivity to any of the components of NEXTERONE Premixed Injection, including iodine [ see Warnings and Precautions (5.9) ]. • Cardiogenic shock. • Marked sinus bradycardia. • Second- or third-degree atrioventricular (AV) block unless a functioning pacemaker is available. NEXTERONE Premixed Injection, is contraindicated in patients with (4) : • Known hypersensitivity to any of the components of NEXTERONE Premixed Injection, including iodine • Cardiogenic shock • Marked sinus bradycardia • Second- or third-degree atrio-ventricular (AV) block unless a pacemaker is available.
Adverse Reactions
The following adverse reactions are described elsewhere in labeling: • Hypotension [ see Warnings and Precautions (5.2) ] • Primary Graft Dysfunction (PGD) Post Cardiac Transplant [ see Warnings and Precautions (5.3) ] • Hepatic injury [ see Warnings and Precautions (5.5) ] • Proarrhythmia [ see Warnings and Precautions (5.6) ] • Pulmonary injury [ see Warnings and Precautions (5.7) ] • Thyroid injury [ see Warnings and Precautions (5.9) ] • Hypersensitivity [ see Warnings and Precautions (5.11) ] • The most common adverse reactions (1-2%) leading to discontinuation of intravenous amiodarone therapy are hypotension, asystole/cardiac arrest/pulseless electrical activity, VT, and cardiogenic shock. (6) • Other important adverse reactions are torsade de pointes, congestive heart failure, and liver function test abnormalities. (6) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received intravenous amiodarone for at least one week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days. The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse reactions. The most common adverse reactions leading to discontinuation of intravenous amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%). Other adverse reactions reported in less than 2% of patients receiving intravenous amiodarone in controlled and uncontrolled studies included the following: abnormal kidney function, diarrhea, shock, sinus bradycardia, Stevens-Johnson syndrome, VF, and vomiting. 6.2 Post-Marketing Experience The following adverse reactions have been reported in the post-marketing experience during or in close temporal relationship to intravenous amiodarone administration. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: pancytopenia, neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia, and granulocytosis. Cardiac Disorders: sinus node dysfunction (sinus arrest, sinoatrial block), intraventricular conduction disorders including bundle branch block and infra-HIS block, bradycardia (sometimes fatal), ventricular extrasystoles, and antegrade conduction via an accessory pathway. Endocrine Disorders: syndrome of inappropriate antidiuretic hormone secretion (SIADH). Eye Disorders: visual field defect and blurred vision. Gastrointestinal Disorders: pancreatitis. General Disorders and Administration Site Conditions: infusion site reactions, including thombosis, phlebitis, thrombophlebitis, cellulitis, pain, induration, edema, inflammation, urticaria, pruritus, erythema, pigment changes, hypoesthesia, skin sloughing, extravasation possibly leading to venous/infusion site necrosis, and granuloma. Hepatobiliary Disorders: cholestasis, cirrhosis, jaundice, alkaline phosphatase and blood lactate dehydrogenase increase. Injury, poisoning and procedural complications: transplant dysfunction (primary graft dysfunction post cardiac transplant). Musculoskeletal and Connective Tissue Disorders: myopathy, muscle weakness, rhabdomyolysis, muscle spasms, and back pain. Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disorders: thyroid nodules/thyroid cancer. Nervous System Disorders: intracranial pressure increased, pseudotumor cerebri, tremor, dizziness and hypoesthesia. Psychiatric Disorders: confusional state, hallucination, disorientation, and delirium. Renal and Urinary Disorders: acute renal failure (sometimes fatal), renal impairment, renal insufficiency, and blood creatinine increased. Reproductive Disorders and Breast Disorders: Epididymitis Respiratory, Thoracic and Mediastinal Disorders: interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia (possibly fatal), pulmonary alveolar hemorrhage, pulmonary phospholipidoisis, pleural effusion, bronchospasm, dyspnea, cough, hemoptysis, wheezing, and hypoxia. Skin and Subcutaneous Tissue Disorders: toxic epidermal necrolysis (sometimes fatal), Stevens-Johnson syndrome, exfoliative dermatitis, erythema multiforme, skin cancer, pruritus, angioedema, and urticaria. Vascular Disorders: vasculitis and flushing.
Drug Interactions
Drug interactions with amiodarone are described in Table 4 below. Table 4: Amiodarone Drug Interactions Concomitant Drug Class/Name Examples Clinical Comment QT Prolonging Drugs class I and III antiarrhythmics, lithium, certain phenothiazines, tricyclic antidepressants, certain fluoroquinolone and macrolide antibiotics, azole antifungals, halogenated inhalation anesthetic agents Increased risk of Torsade de Pointes. Avoid concomitant use. Negative Chronotropes digoxin, beta blockers, verapamil, diltiazem, clonidine, ivabradine Potentiates the electrophysiologic and hemodynamic effects of amiodarone, resulting in bradycardia, sinus arrest and AV block. Monitor heart rate. CYP450 Inhibitors Grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine Increased exposure of amiodarone. Avoid concomitant use. CYP450 Inducers St. John’s Wort Reduced amiodarone serum levels Cyclosporine Increased plasma levels of cyclosporine have been reported resulting in elevated creatinine, despite reduction of cyclosporine dose. Monitor cyclosporine drug levels and renal function with concomitant use. Cholestyramine Reduced amiodarone serum levels Antiarrhythmics quinidine, procainamide, flecainide Reserve concomitant use for patients who are unresponsive to a single agent. Antiarrhythmic metabolism inhibited by amiodarone. Initiate antiarrhythmic at a lower than usual dose and monitor patient carefully. Reduce dose levels of previously administered antiarrhythmic by 30 to 50% for several days after transitioning to oral amiodarone. Evaluate continued need for antiarrhythmic. Digoxin Increased digoxin concentration. Reduce digoxin by half or discontinue. If continued, monitor for evidence of toxicity. HMG-CoA Reductase Inhibitors simvastatin, lovastatin, atorvastatin Increased plasma concentration of HMG-CoA reductase inhibitor. Limit the dose of lovastatin to 40 mg. Limit the coadministered dose of simvastatin to 20 mg. Lower starting dose of other CYP3A4 substrates may be required. Warfarin Potentiates anticoagulant response and can result in serious or fatal bleeding. Coadministration increases INR by 100% after 3 to 4 days. Reduce warfarin dose by one-third to one-half and monitor INR. Phenytoin Increased steady state levels of phenytoin. Monitor phenytoin levels. Hepatitis C direct acting antiviral Sofosbuvir Cases of symptomatic bradyarrhythmia requiring pacemaker insertion have been reported in patients on oral maintenance amiodarone who initiated therapy with Sofosbuvir. • Amiodarone is a substrate for CYP3A and CYP2C8, so inhibitors and inducers affect amiodarone exposure ( 7 ) • Amiodarone inhibits p-glycoprotein and CYP1A2, CYP2C9, CYP2D6, and CYP3A, increasing exposure to other drugs ( 7 )
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