AMIODARONE HYDROCHLORIDE (Page 5 of 5)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity studies were conducted with intravenous administration of amiodarone. However, oral amiodarone caused a statistically significant, dose-related increase in the incidence of thyroid tumors (follicular adenoma and carcinoma) in rats. The incidence of thyroid tumors in rats was greater than the incidence in controls even at the lowest dose level tested, i.e., 5 mg/kg/day (much less, on a body surface area basis, than the maximum recommended human maintenance dose of 600 mg/day).

Mutagenicity studies conducted with amiodarone HCl (Ames, micronucleus, and lysogenic induction tests) were negative.

No fertility studies were conducted with intravenous administration of amiodarone. However, in a study in which amiodarone HCl was orally administered to male and female rats, beginning 9 weeks prior to mating, reduced fertility was observed at a dose level of 90 mg/kg/day (approximately 1.4 times the maximum recommended human maintenance dose of 600 mg/day).

14 CLINICAL STUDIES

Apart from studies in patients with VT or VF, described below, there are two other studies of amiodarone showing an antiarrhythmic effect before significant levels of DEA could have accumulated. A placebo-controlled study of intravenous amiodarone (300 mg over 2 hours followed by 1200 mg/day) in post-coronary artery bypass graft patients with supraventricular and 2- to 3-consecutive-beat ventricular arrhythmias showed a reduction in arrhythmias from 12 hours on. A baseline-controlled study using a similar IV regimen in patients with recurrent, refractory VT/VF also showed rapid onset of antiarrhythmic activity; amiodarone therapy reduced episodes of VT by 85% compared to baseline.

The acute effectiveness of intravenous amiodarone in suppressing recurrent VF or hemodynamically unstable VT is supported by two randomized, parallel, dose-response studies of approximately 300 patients each. In these studies, patients with at least two episodes of VF or hemodynamically unstable VT in the preceding 24 hours were randomly assigned to receive doses of approximately 125 or 1000 mg over the first 24 hours, an 8-fold difference. In one study, a middle dose of approximately 500 mg was evaluated. The dose regimen consisted of an initial rapid loading infusion, followed by a slower 6-hour loading infusion, and then an 18-hour maintenance infusion. The maintenance infusion was continued up to hour 48. Additional 10-minute infusions of 150 mg intravenous amiodarone were given for “breakthrough” VT/VF more frequently to the 125 mg dose group, thereby considerably reducing the planned 8-fold differences in total dose to 1.8- and 2.6-fold, respectively, in the two studies.

The prospectively defined primary efficacy end point was the rate of VT/VF episodes per hour. For both studies, the median rate was 0.02 episodes per hour in patients receiving the high dose and 0.07 episodes per hour in patients receiving the low dose, or approximately 0.5 versus 1.7 episodes per day (p=0.07, 2-sided, in both studies). In one study, the time to first episode of VT/VF was significantly prolonged (approximately 10 hours in patients receiving the low dose and 14 hours in patients receiving the high dose). In both studies, significantly fewer supplemental infusions were given to patients in the high-dose group. At the end of double-blind therapy or after 48 hours, all patients were given open access to whatever treatment (including intravenous amiodarone) was deemed necessary. Mortality was not affected in these studies.

16 HOW SUPPLIED

Amiodarone Hydrochloride Injection, 50 mg/mL, is supplied as follows:

NDC 51662-1205-1 AMIODARONE HYDROCHLORIDE INJECTION 150mg/3mL (50mg/mL) VIAL

NDC 51662-1205-2 Pouch containing a single AMIODARONE HYDROCHLORIDE INJECTION 150mg/3mL (50mg/mL) VIAL

NCD 51662-1205-3 Case of 25 pouches — AMIODARONE HYDROCHLORIDE INJECTION 150mg/3mL (50mg/mL) VIAL

HF Acquisition Co LLC, DBA HealthFirst
Mukilteo, WA 98275

Also supplied in the following manufactures dosage forms

NDC 0143-9875-10 3 mL Single Dose Vials (Cartons of 10 vials)
NDC 0143-9875-25 3 mL Single Dose Vials (Cartons of 25 vials)

Store at 20º-25ºC (68º-77ºF) [See USP Controlled Room Temperature].

Protect from light and excessive heat.

Use carton to protect contents from light until time of use.

17 PATIENT COUNSELING INFORMATION

Amiodarone has the potential to cause serious side effects that limit its use to life-threatening and hemodynamically unstable cardiac arrhythmias. Advise female patients to discontinue nursing while being treated with amiodarone, as breast-feeding could expose the nursing infant to a significant dose of the drug. Recommend that patients avoid grapefruit juice, over-the-counter cough medicine (which commonly contain dextromethorphan), and St. John’s Wort. Inform patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone. Discuss the symptoms of hypo- and hyper-thyroidism, particularly if patients will be transitioned to oral amiodarone.

Manufactured by:
HIKMA FARMACEUTICA (PORTUGAL), S.A.
Estrada do Rio da Mo, nº 8, 8A e 8B — Fervença,
2705 — 906 Terrugem SNT
PORTUGAL

Manufactured by:
WEST-WARD
A HIKMA COMPANY
Eatontown, NJ 07724 USA

Revised: July 2016

PIN193-WES/4

PRINCIPAL DISPLAY PANEL, VIAL

NDC 0143-9875-01
AMIODARONE
HYDROCHLORIDE INJECTION
150 mg/3 mL
(50 mg/mL)
FOR IV USE ONLY
Rx ONLY

3 mL Single Dose Vial
MUST BE DILUTED BEFORE
USE.
USUAL DOSAGE: See package
insert.
Store at 20º to 25ºC (68º to 77ºF)
[See USP Controlled Room
Temperature].
Retain in carton until time of use.

VIAL
(click image for full-size original)

PRINCIPAL DISPLAY PANEL, SERIALIZED LABEL

SERIALIZED LABEL
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — NDC 51662-1205-3 SERIALIZED CASE LABEL

Serialized Case Label
(click image for full-size original)

PRINCIPAL DISPLAY LABEL — NDC 51662-1205-2 SERIALIZED POUCH LABEL

Serialized Pouch Label
(click image for full-size original)

PRINCIPAL DISPLAY LABEL — NDC 51662-1205-3 SERIALIZED RFID LABEL

Serialized RFID Label
(click image for full-size original)

AMIODARONE HYDROCHLORIDE amiodarone hydrochloride injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51662-1205(NDC:0143-9875)
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
AMIODARONE HYDROCHLORIDE (AMIODARONE) AMIODARONE HYDROCHLORIDE 50 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
BENZYL ALCOHOL 20.2 mg in 1 mL
POLYSORBATE 80 100 mg in 1 mL
WATER
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:51662-1205-1 3 mL in 1 VIAL, SINGLE-DOSE None
2 NDC:51662-1205-3 25 POUCH in 1 CASE contains a POUCH (51662-1205-2)
2 NDC:51662-1205-2 1 mL in 1 POUCH This package is contained within the CASE (51662-1205-3)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077234 09/19/2018
Labeler — HF Acquisition Co LLC, DBA HealthFirst (045657305)
Registrant — HF Acquisition Co LLC, DBA HealthFirst (045657305)
Establishment
Name Address ID/FEI Operations
HF Acquisition Co LLC, DBA HealthFirst 045657305 relabel (51662-1205)

Revised: 06/2020 HF Acquisition Co LLC, DBA HealthFirst

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.