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Name:Amiodarone Hydrochloride
Manufacturer:General Injectables & Vaccines, Inc.
Category:Prescription Marketed Drugs


Amiodarone Hydrochloride 50mg/ml 3ml Ampule

AMIODARONE HYDROCHLORIDE  - amiodarone hydrochloride injection, solution, concentrate 
General Injectables & Vaccines, Inc.

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Amiodarone Hydrochloride 50mg/ml 3ml Ampule

DESCRIPTION

Amiodarone hydrochloride injection (C25H29I2NO3 • HCl), is a class III antiarrhythmic drug.
Amiodarone HCl is (2-butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3,5-
diiodophenyl]methanone hydrochloride. Amiodarone HCl has the following structural formula:

Formula1

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. Amiodarone
HCl injection is a sterile clear, pale-yellow micellar solution visually free from particulates. Each
milliliter contains 50 mg of amiodarone HCl, 20.2 mg of benzyl alcohol, 100 mg of polysorbate
80, and water for injection.

Amiodarone HCl injection contains polysorbate 80, which is known to leach di-(2-
ethylhexyl)phthalate (DEHP) from polyvinylchloride (PVC) (see DOSAGE AND
ADMINISTRATION).

CLINICAL PHARMACOLOGY

Mechanisms of Action

Amiodarone is generally considered a class III antiarrhythmic drug, but it possesses
electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs,
amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, it exerts
a noncompetitive antisympathetic action. One of its main effects, with prolonged administration,
is to lengthen the cardiac action potential, a class III effect. The negative chronotropic effect of
amiodarone in nodal tissues is similar to the effect of class IV drugs. In addition to blocking
sodium channels, amiodarone blocks myocardial potassium channels, which contributes to
slowing of conduction and prolongation of refractoriness. The antisympathetic action and the
block of calcium and potassium channels are responsible for the negative dromotropic effects on
the sinus node and for the slowing of conduction and prolongation of refractoriness in the
atrioventricular (AV) node. Its vasodilatory action can decrease cardiac workload and
consequently myocardial oxygen consumption.

Amiodarone HCl injection 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 (Hisventricular,
HV). A comparison of the electrophysiologic effects of intravenous and oral
amiodarone HCl is shown in the table below.


EFFECTS OF INTRAVENOUS AND ORAL AMIODARONE HCL ON
ELECTROPHYSIOLOGIC PARAMETERS






ERP ERP ERP
Formulation SCL QRS QTc AH HV RA RV AVN
↔ No Change






I.V.
Oral

At higher doses (greater than10 mg/kg) of amiodarone HCl injection, prolongation of the ERP RV and
modest prolongation of the QRS have been seen. These differences between oral and intravenous
administration suggest that the initial acute effects of amiodarone injection may be
predominantly focused on the AV node, causing an intranodal conduction delay and increased
nodal refractoriness due to slow channel blockade (class IV activity) and noncompetitive
adrenergic antagonism (class II activity).

Pharmacokinetics and Metabolism

Amiodarone exhibits complex disposition characteristics after intravenous administration. Peak
serum concentrations after single 5 mg/kg 15-minute intravenous infusions in healthy subjects
range between 5 and 41 mg/L. Peak concentrations after 10-minute infusions of 150 mg
amiodarone HCl injection in patients with ventricular fibrillation (VF) or hemodynamically
unstable ventricular tachycardia (VT) range between 7 and 26 mg/L. Due to rapid distribution,
serum concentrations decline to 10% of peak values within 30 to 45 minutes after the end of the
infusion. In clinical trials, after 48 hours of continued infusions (125, 500, or 1000 mg/day) plus
supplemental (150 mg) infusions (for recurrent arrhythmias), amiodarone mean serum
concentrations between 0.7 to 1.4 mg/L were observed (n equal to 260).

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.

No data are available on the activity of DEA in humans, but in animals, it has significant
electrophysiologic and antiarrhythmic effects generally similar to amiodarone itself. DEA’s
precise role and contribution to the antiarrhythmic activity of oral amiodarone are not certain.
The development of maximal ventricular class III effects after oral amiodarone administration in
humans correlates more closely with DEA accumulation over time than with amiodarone
accumulation. On the other hand (see Clinical Trials), after intravenous amiodarone
administration, there is evidence of activity well before significant concentrations of DEA are
attained.

The following table summarizes the mean ranges of pharmacokinetic parameters of amiodarone
reported in single dose I.V. (5 mg/kg over 15 min) studies of healthy subjects.

PHARMACOKINETIC PROFILE AFTER O.V. AMIODARONE ADMINISTRATION

Drug Clearance (mL/h/kg) Vc Vss t1/2


(L/kg) (L/kg) (days)
Notes:  VC and Vss denote the central and steady-state volumes of distribution from I.V. studies.
"__" denotes not available.


Amiodarone 90-158 0.2 40-84 20-47
Desethylamiodarone 197-290 _ 68-168 greater than or equal to AMI t 1/2

Desethylamiodarone clearance and volume involve an unknown biotransformation factor.

The systemic availability of oral amiodarone in healthy subjects ranges between 33% and 65%.

From in vitro studies, the protein binding of amiodarone is greater than 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
amiodarone injection 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.

Pharmacodynamics

Amiodarone HCl injection has been reported to produce negative inotropic and vasodilatory
effects in animals and humans. In clinical studies of patients with refractory VF or
hemodynamically unstable VT, treatment-emergent, drug-related hypotension occurred in 288 of
1836 patients (16%) treated with amiodarone injection. No correlations were seen between the
baseline ejection fraction and the occurrence of clinically significant hypotension during infusion
of amiodarone injection.

Clinical Trials

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 ofI.V. 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 I.V. 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 amiodarone HCl injection 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 amiodarone HCl injection 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 equal to 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. Mortality was not affected
in these studies; at the end of double-blind therapy or after 48 hours, all patients were given open
access to whatever treatment (including amiodarone injection) was deemed necessary.

INDICATIONS AND USAGE

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. Amiodarone injection 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 injection patients may be transferred to
oral amiodarone therapy (see DOSAGE AND ADMINISTRATION).

Amiodarone HCl injection 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
amiodarone injection may be safely administered for longer periods if necessary.

CONTRAINDICATIONS

Amiodarone HCl injection is contraindicated in patients with known hypersensitivity to any of
the components of amiodarone injection, including iodine, or in patients with cardiogenic shock,
marked sinus bradycardia, and second- or third-degree AV block unless a functioning pacemaker
is available.

WARNINGS

Hypotension

Hypotension is the most common adverse effect seen with amiodarone injection. In clinical
trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288
(16%) of 1836 patients treated with amiodarone injection. Clinically significant hypotension
during infusions was seen most often in the first several hours of treatment and was not doserelated,
but appeared to be related to the rate of infusion. Hypotension necessitating alterations in
amiodarone injection therapy was reported in 3% of patients, with permanent discontinuation
required in less than 2% of patients. 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 ADVERSE
REACTIONS, Postmarketing Reports).

Bradycardia and AV Block

Drug-related bradycardia occurred in 90 (4.9%) of 1836 patients in clinical trials while they were
receiving amiodarone HCl injection for life-threatening VT/VF; it was not dose-related.
Bradycardia should be treated by slowing the infusion rate or discontinuing amiodarone
injection. In some patients, inserting a pacemaker is required. Despite such measures,
bradycardia was progressive and terminal in 1 patient during the controlled trials. Patients with a
known predisposition to bradycardia or AV block should be treated with amiodarone injection in
a setting where a temporary pacemaker is available.

Liver Enzyme Elevations

Elevations of blood hepatic enzyme values, alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and gamma-glutamyl transferase (GGT), are seen commonly in patients
with immediately life-threatening VT/VF. Interpreting elevated AST activity can be difficult
because the values may be elevated in patients who have had recent myocardial infarction,
congestive heart failure, or multiple electrical defibrillations. Approximately 54% of patients
receiving amiodarone HCl injection in clinical studies had baseline liver enzyme elevations, and
13% had clinically significant elevations. In 81% of patients with both baseline and on-therapy
data available, the liver enzyme elevations either improved during therapy or remained at
baseline levels. Baseline abnormalities in hepatic enzymes are not a contraindication to
treatment.

Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal
failure, and death has been associated with the administration of amiodarone injection at a much
higher loading dose concentration and much faster rate of infusion than recommended in
DOSAGE AND ADMINISTRATION. Therefore, the initial concentration and rate of infusion
should be monitored closely and should not exceed that prescribed in DOSAGE AND
ADMINISTRATION (see DOSAGE AND ADMINISTRATION ).

In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be
weighed against the potential benefit of amiodarone injection therapy, but patients receiving
amiodarone injection should be monitored carefully for evidence of progressive hepatic injury.
Consideration should be given to reducing the rate of administration or withdrawing amiodarone
injection in such cases.
Proarrhythmia

Like all antiarrhythmic agents, amiodarone HCl injection may cause a worsening of existing
arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsades de pointes (TdP),
has been associated with prolongation by amiodarone injection of the QTc interval to 500 ms or
greater. Although QTc prolongation occurred frequently in patients receiving amiodarone
injection, torsades de pointes or new-onset VF occurred infrequently (less than 2%). Patients
should be monitored for QTc prolongation during infusion with amiodarone injection.
Combination of amiodarone with other antiarrhythmic therapy that prolongs the QTc should be
reserved for patients with life-threatening ventricular arrhythmias who are incompletely
responsive to a single agent. Fluoroquinolones, macrolide antibiotics, and azoles are known to
cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in
patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were
administered concomitantly. (See Drug Interactions, Other reported interactions with
amiodarone.) The need to co-administer amiodarone with any other drug known to prolong the
QTc interval must be based on a careful assessment of the potential risks and benefits of doing so
for each patient.

A careful assessment of the potential risks and benefits of administering amiodarone HCl
injection must be made in patients with thyroid dysfunction due to the possibility of arrhythmia
breakthrough or exacerbation of arrhythmia, which may result in death, in these patients.

Pulmonary Disorders

Early-onset pulmonary toxicity

There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in
patients treated with amiodarone HCl injection. Findings have included pulmonary infiltrates
and/or mass on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and
hypoxia. Some cases have progressed to respiratory failure and/or death.

ARDS

Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS)
during clinical studies involving 48 hours of therapy. ARDS is a disorder characterized by
bilateral, diffuse pulmonary infiltrates with pulmonary edema and varying degrees of respiratory
insufficiency. The clinical and radiographic picture can arise after a variety of lung injuries, such
as those resulting from trauma, shock, prolonged cardiopulmonary resuscitation, and aspiration
pneumonia, conditions present in many of the patients enrolled in the clinical studies. There have
been postmarketing reports of ARDS in amiodarone HCl injection patients. Amiodarone HCl
injection may play a role in causing or exacerbating pulmonary disorders in those patients.

Postoperatively, occurrences of ARDS have been reported in patients receiving oral amiodarone
therapy who have undergone either cardiac or noncardiac surgery. Although patients usually
respond well to vigorous respiratory therapy, in rare instances the outcome has been fatal. Until
further studies have been performed, it is recommended that FiO2 and the determinants of
oxygen delivery to the tissues (e.g., SaO2, PaO2) be closely monitored in patients on
amiodarone.

Pulmonary fibrosis

Only 1 of more than 1000 patients treated with amiodarone HCl injection in clinical studies
developed pulmonary fibrosis. In that patient, the condition was diagnosed 3 months after
treatment with amiodarone HCl, during which time she received oral amiodarone. Pulmonary
toxicity is a well-recognized complication of long-term amiodarone HCl use (see labeling for
oral amiodarone).

Loss of Vision

Cases of optic neuropathy and/or optic neuritis, usually resulting in visual impairment, have been
reported in patients treated with oral amiodarone. In some cases, visual impairment has
progressed to permanent blindness. Amiodarone I.V. 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 and can also be used to treat
patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral
medication. Optic neuropathy and/or neuritis may occur at any time following initiation of
therapy. A causal relationship to the drug has not been clearly established. If symptoms of visual
impairment appear, such as changes in visual acuity and decreases in peripheral vision, prompt
ophthalmic examination is recommended. Appearance of optic neuropathy and/or neuritis calls
for re-evaluation of amiodarone therapy. The risks and complications of antiarrhythmic therapy
with amiodarone must be weighed against its benefits in patients whose lives are threatened by
cardiac arrhythmias. Regular ophthalmic examination, including fundoscopy and slit-lamp
examination, is recommended during administrations of amiodarone. (See ADVERSE
REACTIONS.)

Long-Term Use

See labeling for oral amiodarone. There has been limited experience in patients receiving
intravenous amiodarone injection for longer than 3 weeks.

Thyrotoxicosis

Amiodarone HCl-induced hyperthyroidism may result in thyrotoxicosis and/or the possibility of
arrhythmia breakthrough or aggravation. There have been reports of death associated with
Amiodarone-induced thyrotoxicosis. IF ANY NEW SIGNS OF ARRHYTHMIA APPEAR, THE
POSSIBILITY OF HYPERTHYROIDISM SHOULD BE CONSIDERED (see
PRECAUTIONS, Thyroid Abnormalities).

Neonatal Hypo- or Hyperthyroidism

Although amiodarone use during pregnancy is uncommon, there have been a small number of
published reports of congenital goiter/hypothyroidism and hyperthyroidism associated with its
oral administration. If intravenous amiodarone is administered during pregnancy, the patient
should be apprised of the potential hazard to the fetus.

PRECAUTIONS

Amiodarone injection should be administered only by physicians who are experienced in the
treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits
of amiodarone therapy, and who have access to facilities adequate for monitoring the
effectiveness and side effects of treatment.

Thyroid Abnormalities

Amiodarone HCl inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and
may cause increased thyroxine levels, decreased T3 levels, and increased levels of inactive
reverse T3 (rT3) in clinically euthyroid patients. It is also a potential source of large amounts of
inorganic iodine. Because of its release of inorganic iodine, or perhaps for other reasons,
Amiodarone HCl can cause either hypothyroidism or hyperthyroidism. Thyroid function should
be monitored 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. Because of the
slow elimination of Amiodarone HCl and its metabolites, high plasma iodide levels, altered
thyroid function, and abnormal thyroid-function tests may persist for several weeks or even
months following Amiodarone HCl withdrawal.

Hypothyroidism has been reported in 2 to 4% of patients in most series, but in 8 to 10% in some
series. This condition may be identified by relevant clinical symptoms and particularly by
elevated serum TSH levels. In some clinically hypothyroid amiodarone-treated patients, free
thyroxine index values may be normal. Hypothyroidism is best managed by Amiodarone HCl
dose reduction and/or thyroid hormone supplement.

Hyperthyroidism occurs in about 2% of patients receiving Amiodarone HCl, but the incidence
may be higher among patients with prior inadequate dietary iodine intake. Amiodarone HClinduced
hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism
because of the possibility of thyrotoxicosis and/or arrhythmia breakthrough or aggravation, all of
which may result in death. There have been reports of death associated with amiodarone-induced
thyrotoxicosis. IF ANY NEW SIGNS OF ARRHYTHMIA APPEAR, THE POSSIBILITY OF
HYPERTHYROIDISM SHOULD BE CONSIDERED.

Hyperthyroidism is best identified by relevant clinical symptoms and signs, accompanied usually
by abnormally elevated levels of serum T3 RIA, and further elevations of serum T4, and a
subnormal serum TSH level (using a sufficiently sensitive TSH assay). The finding of a flat TSH
response to TRH is confirmatory of hyperthyroidism and may be sought in equivocal cases.
Since arrhythmia breakthroughs may accompany Amiodarone HCl-induced hyperthyroidism,
aggressive medical treatment is indicated, including, if possible, dose reduction or withdrawal of
Amiodarone HCl.

The institution of antithyroid drugs, ß-adrenergic blockers and/or temporary corticosteroid
therapy may be necessary. The action of antithyroid drugs may be especially delayed in
amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid
hormones stored in the gland. There have been reports of death associated with amiodaroneinduced
thyrotoxicosis. Radioactive iodine therapy is contraindicated because of the low
radioiodine uptake associated with amiodarone-induced hyperthyroidism. Amiodarone HClinduced
hyperthyroidism may be followed by a transient period of hyperthyroidism (see
WARNINGS, Thyrotoxicosis).

When aggressive treatment of amiodarone-induced thyrotoxicosis has failed or amiodarone
cannot be discontinued because it is the only drug effective against the resistant arrhythmia,
surgical management may be an option. Experience with thyroidectomy as a treatment for
amiodarone-induced thyrotoxicosis is limited, and this form of therapy could induce thyroid
storm. Therefore, surgical and anesthetic management require careful planning.

There have been postmarketing reports of thyroid nodules/thyroid cancer in patients treated with
Amiodarone HCl. In some instances hyperthyroidism was also present (see WARNINGS and
ADVERSE REACTIONS).

Surgery

Close perioperative monitoring is recommended in patients undergoing general anesthesia who
are on amiodarone therapy as they may be more sensitive to the myocardial depressant and
conduction defects of halogenated inhalational anesthetics.

Corneal Refractive Laser Surgery

Patients should be advised that most manufacturers of corneal refractive laser surgery devices
contraindicate that procedure in patients taking amiodarone.

DRUG INTERACTIONS

Amiodarone is metabolized to desethylamiodarone by the cytochrome P450 (CYP450) enzyme
group, specifically cytochromes P450 3A4 (CYP3A4) and CYP2C8. The CYP3A4 isoenzyme is
present in both the liver and intestines (see CLINICAL PHARMACOLOGY, Pharmacokinetics
and Metabolism). Amiodarone is an inhibitor of CYP3A4 and p-glycoprotein. Therefore,
amiodarone has the potential for interactions with drugs or substances that may be substrates,
inhibitors or inducers of CYP3A4 and substrates of p-glycoprotein. While only a limited number
of in vivo drug-drug interactions with amiodarone have been reported, chiefly with the oral
formulation, the potential for other interactions should be anticipated. This is especially
important for drugs associated with serious toxicity, such as other antiarrhythmics. If such drugs
are needed, their dose should be reassessed and, where appropriate, plasma concentration
measured. In view of the long and variable half-life of amiodarone, potential for drug
interactions exists not only with concomitant medication but also with drugs administered after
discontinuation of amiodarone.

Since amiodarone is a substrate for CYP3A4 and CYP2C8, drugs/substances that inhibit these
isoenzymes may decrease the metabolism and increase serum concentration of amiodarone.
Reported examples include the following:

Protease Inhibitors:

Protease inhibitors are known to inhibit CYP3A4 to varying degrees. A case report of one patient
taking amiodarone 200 mg and indinavir 800 mg three times a day resulted in increases in
amiodarone concentrations from 0.9 mg/L to 1.3 mg/L. DEA concentrations were not affected.
There was no evidence of toxicity. Monitoring for amiodarone toxicity and serial measurement
of amiodarone serum concentration during concomitant protease inhibitor therapy should be
considered.

Histamine H1 antagonists:

Loratadine, a non-sedating antihistaminic, is metabolized primarily by CYP3A4. QT interval
prolongation and torsade de pointes have been reported with the co-administration of loratadine
and amiodarone.

Histamine H2 antagonists:

Cimetidine inhibits CYP3A4 and can increase serum amiodarone levels.

Antidepressants:

Trazodone, an antidepressant, is metabolized primarily by CYP3A4. QT interval prolongation
and torsade de pointes have been reported with the co-administration of trazodone and
amiodarone.

Other substances:

Grapefruit juice given to healthy volunteers increased amiodarone AUC by 50% and Cmax by
84%, resulting in increased plasma levels of amiodarone. Grapefruit juice should not be taken
during treatment with oral amiodarone. This information should be considered when changing
from intravenous amiodarone to oral amiodarone (see DOSAGE AND ADMINISTRATION,
Intravenous to Oral Transition).

Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2,
CYP2C9, CYP2D6, and CYP3A4. This inhibition can result in unexpectedly high plasma levels
of other drugs which are metabolized by those CYP450 enzymes or are substrates of pglycoprotein.
Reported examples of this interaction include the following:

Immunosuppressives:

Cyclosporine (CYP3A4 substrate) administered in combination with oral amiodarone has been
reported to produce persistently elevated plasma concentrations of cyclosporine resulting in
elevated creatinine, despite reduction in dose of cyclosporine.

HMG-CoA Reductase Inhibitors:

Simvastatin (CYP3A4 substrate) in combination with amiodarone has been associated with
reports of myopathy/rhabdomyolysis.

Cardiovasculars:

Cardiac glycosides: In patients receiving digoxin therapy, administration of oral amiodarone
regularly results in an increase in serum digoxin concentration that may reach toxic levels with
resultant clinical toxicity. Amiodarone taken concomitantly with digoxin increases the serum
digoxin concentration by 70% after one day. On administration of oral amiodarone, the need for
digitalis therapy should be reviewed and the dose reduced by approximately 50% or
discontinued. If digitalis treatment is continued, serum levels should be closely monitored and
patients observed for clinical evidence of toxicity. These precautions probably should apply to
digitoxin administration as well.

Antiarrhythmics: Other antiarrhythmic drugs, such as quinidine, procainamide, disopyramide,
and phenytoin, have been used concurrently with amiodarone. There have been case reports of
increased steady-state levels of quinidine, procainamide, and phenytoin during concomitant
therapy with amiodarone. Phenytoin decreases serum amiodarone levels. Amiodarone taken
concomitantly with quinidine increases quinidine serum concentration by 33% after two days.

Amiodarone taken concomitantly with procainamide for less than seven days increases plasma
concentrations of procainamide and n-acetyl procainamide by 55% and 33%, respectively.
Quinidine and procainamide doses should be reduced by one-third when either is administered
with amiodarone. Plasma levels of flecainide have been reported to increase in the presence of
oral amiodarone; because of this, the dosage of flecainide should be adjusted when these drugs
are administered concomitantly. In general, any added antiarrhythmic drug should be initiated at
a lower than usual dose with careful monitoring. Combination of amiodarone with other
antiarrhythmic therapy should be reserved for patients with life-threatening ventricular
arrhythmias who are incompletely responsive to a single agent or incompletely responsive to
amiodarone. During transfer to oral amiodarone, the dose levels of previously administered
agents should be reduced by 30 to 50% several days after the addition of oral amiodarone (see
DOSAGE AND ADMINISTRATION, Intravenous to Oral Transition). The continued need for
the other antiarrhythmic agent should be reviewed after the effects of amiodarone have been
established, and discontinuation ordinarily should be attempted. If the treatment is continued,
these patients should be particularly carefully monitored for adverse effects, especially
conduction disturbances and exacerbation of tachyarrhythmias, as amiodarone is continued. In
amiodarone-treated patients who require additional antiarrhythmic therapy, the initial dose of
such agents should be approximately half of the usual recommended dose.

Antihypertensives: Amiodarone should be used with caution in patients receiving β-receptor
blocking agents (e.g., propranolol, a CYP3A4 inhibitor) or calcium channel antagonists (e.g.,
verapamil, a CYP3A4 substrate, and diltiazem, a CYP3A4 inhibitor) because of the possible
potentiation of bradycardia, sinus arrest, and AV block; if necessary, amiodarone can continue to
be used after insertion of a pacemaker in patients with severe bradycardia or sinus arrest.

Anticoagulants: Potentiation of warfarin -type (CYP2C9 and CYP3A4 substrate) anticoagulant
response is almost always seen in patients receiving amiodarone and can result in serious or fatal
bleeding. Since the concomitant administration of warfarin with amiodarone increases the
prothrombin time by 100% after 3 to 4 days, the dose of the anticoagulant should be reduced by
one-third to one-half, and prothrombin times should be monitored closely.

Clopidogrel, an inactive thienopyridine prodrug, is metabolized in the liver by CYP3A4 to an
active metabolite. A potential interaction between clopidogrel and amiodarone resulting in
ineffective inhibition of platelet aggregation has been reported.

Some drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the
synthesis of CYP3A4 (enzyme induction). This may lead to low amiodarone serum levels and
potential decrease in efficacy. Reported examples of this interaction include the following:

Antibiotics:

Rifampin is a potent inducer of CYP3A4. Administration of rifampin concomitantly with oral
amiodarone has been shown to result in decreases in serum concentrations of amiodarone and
desethylamiodarone.

Other substances, including herbal preparations:

St. John’s Wort (Hypericum perforatum) induces CYP3A4. Since amiodarone is a substrate for
CYP3A4, there is the potential that the use of St. John’s Wort in patients receiving amiodarone
could result in reduced amiodarone levels.

Other reported interactions with amiodarone:

Fentanyl (CYP3A4 substrate) in combination with amiodarone may cause hypotension,
bradycardia, and decreased cardiac output.

Sinus bradycardia has been reported with oral amiodarone in combination with lidocaine
(CYP3A4 substrate) given for local anesthesia. Seizure, associated with increased lidocaine
concentrations, has been reported with concomitant administration of intravenous amiodarone.

Dextromethorphan is a substrate for both CYP2D6 and CYP3A4. Amiodarone inhibits CYP2D6.

Cholestyramine increases enterohepatic elimination of amiodarone and may reduce its serum
levels and t1/2.

Disopyramide increases QT prolongation which could cause arrhythmia.

Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There
have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when
fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly. (See
WARNINGS, Proarrhythmia.)

Hemodynamic and electrophysiologic interactions have also been observed after concomitant
administration with propranolol, diltiazem, and verapamil.

Volatile Anesthetic Agents: (see PRECAUTIONS, Surgery).

In addition to the interactions noted above, chronic (> 2 weeks) oral amiodarone administration
impairs metabolism of phenytoin, dextromethorphan, and methotrexate.

Electrolyte Disturbances

Patientswith hypokalemia or hypomagnesemia should have the condition corrected whenever
possible before being treated with amiodarone injection, as these disorders can exaggerate the
degree of QTc prolongation and increase the potential for TdP. Special attention should be given
to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in
patients receiving concomitant diuretics.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

No carcinogenicity studies were conducted with amiodarone HCl injection. However, oral
amiodarone caused a statistically significant, dose-related increase in the incidence of thyroid
tumors (follicular adenoma and/or 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
(approximately 0.08 times the maximum recommended human maintenance dose*).

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

No fertility studies were conducted with amiodarone HCl injection. However, in a study in which
amiodarone hydrochloride 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*).

*600 mg in a 50 kg patient (dose compared on a body surface area basis)

PREGNANCY

Category D. See WARNINGS, Neonatal Hypo- or Hyperthyroidism.

In addition to causing infrequent congenital goiter/hypothyroidism and hyperthyroidism,
amiodarone has caused a variety of adverse effects in animals.

In a reproductive study in which amiodarone was given intravenously to rabbits at dosages of 5,
10, or 25 mg/kg per day (about 0.1, 0.3, and 0.7 times the maximum recommended human dose
[MRHD] on a body surface area basis), maternal deaths occurred in all groups, including
controls. Embryotoxicity (as manifested by fewer full-term fetuses and increased resorptions
with concomitantly lower litter weights) occurred at dosages of 10 mg/kg and above. No
evidence of embryotoxicity was observed at 5 mg/kg and no teratogenicity was observed at any
dosages.

In a teratology study in which amiodarone was administered by continuous I.V. infusion to rats
at dosages of 25, 50, or 100 mg/kg per day (about 0.4, 0.7, and 1.4 times the MRHD when
compared on a body surface area basis), maternal toxicity (as evidenced by reduced weight gain
and food consumption) and embryotoxicity (as evidenced by increased resorptions, decreased
live litter size, reduced body weights, and retarded sternum and metacarpal ossification) were
observed in the 100 mg/kg group.

Amiodarone HCl injection should be used during pregnancy only if the potential benefit to the
mother justifies the risk to the fetus.

NURSING MOTHERS

Amiodarone and one of its major metabolites, desethylamiodarone (DEA), are excreted in human
milk, suggesting that breast-feeding could expose the nursing infant to a significant dose of the
drug. Nursing offspring of lactating rats administered amiodarone have demonstrated reduced
viability and reduced body weight gains. The risk of exposing the infant to amiodarone should be
weighed against the potential benefit of arrhythmia suppression in the mother. The mother
should be advised to discontinue nursing.

LABOR AND DELIVERY

It is not known whether the use of amiodarone during labor or delivery has any immediate or
delayed adverse effects. Preclinical studies in rodents have not shown any effect on the duration
of gestation or on parturition.

PEDIATRIC USE

The safety and efficacy of amiodarone in the pediatric population have not been established;
therefore, its use in pediatric patients is not recommended. In a pediatric trial of 61 patients, aged
30 days to 15 years, hypotension (36%), bradycardia (20%), and atrio-ventricular block (15%)
were common dose-related adverse events and were severe or life-threatening in some cases.
Injection site reactions were seen in 5 (25%) of the 20 patients receiving amiodarone HCl
injection through a peripheral vein irrespective of dose regimen.

Amiodarone HCl injection contains the preservative benzyl alcohol (see DESCRIPTION). There
have been reports of fatal“gasping syndrome” in neonates (children less than one month of age)
following the administration of intravenous solutions containing the preservative benzyl alcohol.
Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and
cardiovascular collapse.

GERIATRIC USE

Clinical studies of Amiodarone HCl injection did not include sufficient numbers of subjects aged
65 and over to determine whether they respond differently from younger subjects. Other reported
clinical experience has not identified differences in responses between the elderly and younger
patients. In general, dose selection for an elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or
cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received
amiodarone HCl injection for at least 1 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, without an increased incidence of
severe adverse reactions. The mean duration of therapy in these studies was 5.6 days; median
exposure was 3.7 days.

The most important treatment-emergent adverse effects were hypotension, asystole/cardiac
arrest/electromechanical dissociation (EMD), 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 effects. The most common adverse
effects leading to discontinuation of amiodarone injection therapy were hypotension (1.6%),
asystole/cardiac arrest/EMD (1.2%), VT (1.1%), and cardiogenic shock (1%).

The following table lists the most common (incidence ≥2%) treatment-emergent adverse events
during amiodarone injection therapy considered at least possibly drug-related. These data were
collected from Wyeth-Ayerst clinical trials involving 1836 patients with life-threatening VT/VF.
Data from all assigned treatment groups are pooled because none of the adverse events appeared
to be dose-related.

SUMMARY TABULATION OF TREATMENT-EMERGENT DRUG-RELATED STUDY EVENTS IN PATIENTS RECEIVING AMIODARONE HCL INJECTION IN CONTROLLED AND OPEN-LABEL STUDIES (GREATER THAN OR EQUAL TO 2% INCIDENCE)


Controlled Ope- Label

Studies Studies Total
Study Event (n equal to 814) (n equal to 1022) (n equal to 1836)
Body as a Whole


Fever 24 (2.9%) 13 (1.2%) 37 (2.0%)
Cardiovascular System


Bradycardia 49 (6.0%) 41 (4.0%) 90 (4.9%)
Congestive heart failure 18 (2.2%) 21 (2.0%) 39 (2.1%)
Heart arrest 29 (3.5%) 26 (2.5%) 55 (2.9%)
Hypotension 165 (20.2%) 123 (12.0%) 288 (15.6%)
Ventricular tachycardia 15 (1.8%) 30 (2.9%) 45 (2.4%)
Digestive System


Liver function tests abnormal 35 (4.2%) 29 (2.8%) 64 (3.4%)
Nausea 29 (3.5% 43 (4.2%) 72 (3.9%)
Other treatment-emergent possibly drug-related adverse events reported in less than 2% of
patients receiving amiodarone HCl injection in Wyeth-Ayerst controlled and uncontrolled studies
included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT,
increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder,
shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.

Postmarketing Reports

In postmarketing surveillance, hypotension (sometimes fatal), sinus arrest,
anaphylactic/anaphylactoid reaction (including shock), angioedema, hepatitis, cholestatic
hepatitis, cirrhosis, pancreatitis, renal impairment, renal insufficiency, acute renal failure,
bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and
ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, dyspnea, cough,
hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pleuritis, pseudotumor
cerebri, syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid
nodules/thyroid cancer, toxic epidermal necrolysis (sometimes fatal), erythema multiforme,
Stevens-Johnson syndrome, exfoliative dermatitis, skin cancer, vasculitis, pruritus, hemolytic
anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis,
granuloma, myophathy, muscle weakness, rhabdomyolysis, hallucination, confusional state,
disorientation, delirium, epididymitis, and impotence also have been reported with Amiodarone
therapy.

Also, in patients receiving recommended dosages of Amiodarone HCl injection, there have been
postmarketing reports of the following injection site reactions: pain, erythema, edema, pigment
changes, venous thrombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing
(see DOSAGE AND ADMINISTRATION ).

OVERDOSAGE

There have been cases, some fatal, of amiodarone overdose. Effects of an inadvertent overdose
of amiodarone HCl injection include hypotension, cardiogenic shock, bradycardia, AV block,
and hepatotoxicity. Hypotension and cardiogenic shock should be treated by slowing the infusion
rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume
expansion. Bradycardia and AV block may require temporary pacing. Hepatic enzyme
concentrations should be monitored closely. Amiodarone is not dialyzable.

DOSAGE AND ADMINISTRATION

Amiodarone shows considerable interindividual 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 amiodarone HCl
injection is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion
regimen:

AMIODARONE HCl 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 (1mg/min).
                                                Add 18 mL of amiodarone HCl injection (900 mg) to 500 mL D5W
                                                (concentration=1.8 mg/mL).
Maintenance infustion
                                                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 HCl 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 HCl injection must be delivered by a volumetric
infusion pump.

Amiodarone HCl 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 HCl 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 WARNINGS, Liver Enzyme 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 polyvinylchloride (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.

Amiodarone HCl injection 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 Amiodarone HCl injection at higher concentrations and lower flow rates
than provided in DOSAGE AND ADMINISTRATION. In addition, polysorbate 80, a
component of Amiodarone HCl injection, is also known to leach DEHP from PVC (see
DESCRIPTION). Therefore, it is important that the recommendations in DOSAGE AND
ADMINISTRATION be followed closely.

Amiodarone HCl injection does not need to be protected from light during administration.

AMIODARONE HCl SOLUTION STABILITY


Concentration

Solution (mg/mL) Container Comments
5% Dextrose in  1-6 PVC Physically compatible, with amiodarone loss less 
Water (D5@)

than 10% at 2 hours at room temperature
5% Dextrose in  1-6 Polyolefin,  Physically compatible, with amiodarone loss at 24
Water (D5@)
Glass hours at room temperature


Admixture Incompatibility

Amiodarone HCl 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 amiodarone HCl injection 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 HCl injection Infusion#                     Initial Daily Dose of Oral Amiodarone HCl
#Assuming a 720 mg/day infusion (0.5 mg/min).

*Amiodarone injection is not intended for maintenance treatment.
                     less than 1 week                                                                  800-1600 mg
                    1-3 weeks                                                                             600-800 mg
                    greater than 3 weeks*                                                            400 mg

Parenteral drug products should be inspected visually for particulate matter and discoloration
prior to administration whenever solution and container permit.

HOW SUPPLIED

Amiodarone HCl Injection is available in packages of 10 ampuls (2 trays each containing 5
ampuls), 3 mL each as follows: 50 mg per mL (List No. 4348).

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Protect from light.

Keep ampuls in tray until time of use.

Sample Outer Label

Label1


AMIODARONE HYDROCHLORIDE 
amiodarone hydrochloride injection, solution, concentrate
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:52584-348(NDC:0409-4348)
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
Product Characteristics
Color      Score     
Shape Size
Flavor Imprint Code
Contains     
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:52584-348-35 1 AMPULE ( AMPULE) in 1 BAG contains a AMPULE
1 3 mL in 1 AMPULE This package is contained within the BAG (52584-348-35)

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075955 03/01/2010

Labeler - General Injectables & Vaccines, Inc. (108250663)
Establishment
Name Address ID/FEI Operations
General Injectables & Vaccines, Inc. 108250663 relabel

Revised: 04/2011 General Injectables & Vaccines, Inc.



Source: http://dailymed.nlm.nih.gov
Reproduced with permission of U.S. National Library of Medicine


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