Dosing & Uses
Dosage Forms & Strengths
solution for injection
- 500mg/10mL (50mg/mL single-dose vial)
Ventricular Arrhythmia
Indicated for prophylaxis and treatment of ventricular fibrillation (VF); also indicated for treatment of life-threatening ventricular arrhythmias (eg, ventricular tachycardia [VT] unresponsive to first-line antiarrhythmic agents [eg, lidocaine])
Immediately life-threatening ventricular arrhythmias (eg, VF, unstable VT)
- Other usual cardiopulmonary resuscitative procedures, including electrical cardioversion, should be used prior to and following the injection in accordance with good medical practice
- Undiluted solution: 5 mg/kg IV by rapid injection; if arrhythmia persists, may increase dose to 10 mg/kg and repeat prn
- Diluted solution for continuous suppression: 1-2 mg/min IV; alternatively, 5-10 mg/kg IV over at least 8 min q6hr
Other ventricular arrhythmias
-
IV
- Use diluted solution
- 5-10 mg/kg IV over at least 8 min; may repeat dose at 1- to 2-hr intervals if arrhythmia persists
- Maintenance: 5-10 mg/kg IV over at least 8 min q6hr; alternatively, 1-2 mg/min IV continuous infusion
-
IM
- Use undiluted solution
- 5-10 mg/kg IM; may repeat dose at 1- to 2-hr intervals if arrhythmia persists
- Maintenance: 5-10 mg/kg IM q6-8hr
- Switch of oral antiarrhythmic agent as soon as possible for continued maintenance therapy
Dosage Modifications
Renal impairment
- Primarily excreted via kidneys; increase dosage interval in patients with impaired renal function
- Removed by hemodialysis
Dosing Considerations
Limit use to intensive care units, coronary care units, or other facilities where equipment and personnel for constant monitoring of cardiac arrhythmias and blood pressure are available
Following administration, onset of antiarrhythmic action may occur between 20 minutes and 2 hr; although, it appears to act within minutes in VF; delay in effect appears to be longer after IM than after IV injection
Dosage Modifications
Renal impairment
- Primarily excreted via kidneys; increase dosage interval in patients with impaired renal function
- Removed by hemodialysis
Dosing Considerations
Drug is substantially excreted by the kidneys, carefully select dose for geriatric patients; consider monitoring renal function
Limit use to intensive care units, coronary care units, or other facilities where equipment and personnel for constant monitoring of cardiac arrhythmias and blood pressure are available
Following administration, onset of antiarrhythmic action may occur between 20 minutes to 2 hr; although, it appears to act within minutes in ventricular fibrillation; delay in effect appears to be longer after IM than after IV injection
Safety and efficacy not established
Ventricular Arrhythmia
Indicated for prophylaxis and treatment of ventricular fibrillation (VF); also indicated for treatment of life-threatening ventricular arrhythmias (eg, ventricular tachycardia [VT] unresponsive to first-line antiarrhythmic agents [eg, lidocaine])
In general, dose selection for geriatric patients 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 drug therapy
Risk of orthostatic hypotension exists, particularly if administered IV at rate exceeding recommendations
Immediately life-threatening ventricular arrhythmias (eg, VF, unstable VT)
- Other usual cardiopulmonary resuscitative procedures, including electrical cardioversion, should be used prior to and following the injection in accordance with good medical practice
- Undiluted solution: 5 mg/kg IV by rapid injection; if arrhythmia persists, may increase dose to 10 mg/kg and repeat prn
- Diluted solution for continuous suppression: 1-2 mg/min IV; alternatively, 5-10 mg/kg IV over at least 8 min q6hr
Other ventricular arrhythmias (IV)
- Use diluted solution
- 5-10 mg/kg IV over at least 8 min; may repeat dose at 1- to 2-hr intervals if arrhythmia persists
- Maintenance: 5-10 mg/kg IV over at least 8 min q6hr; alternatively, 1-2 mg/min IV continuous infusion
Other ventricular arrhythmias (IM)
- Use undiluted solution
- 5-10 mg/kg IM; may repeat dose at 1- to 2-hr intervals if arrhythmia persists
- Maintenance: 5-10 mg/kg IM q6-8hr
- Switch of oral antiarrhythmic agent as soon as possible for continued maintenance therapy
Dosing Considerations
Drug is substantially excreted by the kidneys; carefully select dose for geriatric patients; consider monitoring renal function
Limit use to intensive care units, coronary care units, or other facilities where equipment and personnel for constant monitoring of cardiac arrhythmias and blood pressure are available
Following administration, onset of antiarrhythmic action may occur between 20 minutes and 2 hr; although, it appears to act within minutes in VF; delay in effect appears to be longer after IM than after IV injection
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Hypotension, some degree even while supine (50%)
<1%
~0.7%
- Vertigo
- Dizziness
- Lightheadedness
- Syncope
~0.2%
- Increased frequency of premature ventricular contractions
- Transitory hypertension
- Initial increase in arrhythmias
- Precipitation of anginal attacks
- Sensation of substernal pressure
~0.1%
- Renal dysfunction
- Diarrhea, abdominal pain
- Hiccups
- Erythematous macular rash
- Flushing
- Hyperthermia
- Confusion, paranoid psychosis, emotional lability, anxiety
- Lethargy
- Generalized tenderness
- Shortness of breath, diaphoresis, nasal stuffiness
- Mild conjunctivitis
Warnings
Contraindications
Digitalis-induced arrhythmias
Cautions
Hypotension
- Administration regularly results in postural hypotension, subjectively recognized by dizziness, lightheadedness, vertigo, or faintness
- Some degree of hypotension is present in ~50% of patients while they are supine
- Hypotension may occur at doses lower than those needed to suppress arrhythmias
- Keep patients in supine position until tolerance to hypotensive effect develops; tolerance occurs unpredictably, but may be present after several days
- Patients aged >65 years may be at increased risk of developing orthostatic hypotension, especially if recommended IV infusion exceeded
- Hypotension with supine systolic pressure >75 mm Hg need not be treated unless there are associated symptoms
- If supine systolic pressure falls below 75 mm Hg, dopamine or norepinephrine infusion may be used to raise blood pressure
- When catecholamines are administered, use a dilute solution and closely monitor blood pressure (pressor effects catecholamines enhanced by bretylium)
- Volume expansion with blood or plasma and correction of dehydration should be carried out where appropriate
Transient hypertension
- Bretylium causes an initial norepinephrine release from adrenergic postganglionic nerve terminals
- Transient hypertension or increased frequency of premature ventricular contractions and other arrhythmias may occur in some patients, especially after too vigorous a dosing
Fixed cardiac output
- Avoid use in patients with fixed cardiac output (eg, severe aortic stenosis or pulmonary hypertension) since severe hypotension may result from a fall in peripheral resistance without a compensatory increased cardiac output
- If survival is threatened by the arrhythmia, bretylium may be used, but vasoconstrictive catecholamines should be given promptly if severe hypotension occurs
Hyperthermia
- Hyperthermia, characterized by temperature excess of 106°F, reported; temperature rise can begin within 1 hr or later after administration and peak within 1-3 days
- If suspected or diagnosed, discontinue bretylium and institute treatment immediately
Drug interaction overview
-
Digoxin
- Initial release of norepinephrine caused by bretylium may aggravate digitalis toxicity
- When a life-threatening cardiac arrhythmia occurs in a digitalized patient, bretylium should be used only if the etiology of the arrhythmia does not appear to be digitalis toxicity and other antiarrhythmic drugs are not effective
- Avoid simultaneous initiation of therapy with digitalis glycosides and bretylium
-
Monoamine oxidase inhibitors (MAOIs)
- Bretylium produces release of catecholamines from nerve endings
- This increased catecholamine release is potentiated by MAOIs
-
Catecholamines
- If catecholamines (ie, dopamine, norepinephrine) are administered to treat systolic blood pressure <75 mm Hg, a dilute solution should be used and blood pressure monitored closely because the pressor effects of the catecholamines are enhanced by bretylium
Pregnancy & Lactation
Pregnancy
Unknown whether bretylium can cause fetal harm when administered to pregnant women or can affect reproduction capacity
Administer during pregnancy only if clearly needed
Animal reproduction studies have not been conducted
Lactation
Data are not available
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Accumulates in sympathetic ganglia and their postganglionic adrenergic neurons when administered slowly or incrementally, where it inhibits norepinephrine release by depressing adrenergic nerve terminal excitability
Also suppresses ventricular fibrillation (VF) and ventricular arrhythmias; mechanisms of antifibrillatory and antiarrhythmic actions are not established, although electrophysiologic actions have been described in animal studies
Electrophysiologic effects observed in animal studies
- Increased VF threshold
- Increased action potential duration and effective refractory period without changes in heart rate
- Little effect on the rate of rise or amplitude of the cardiac action potential (Phase 0) or in resting membrane potential (Phase 4) in normal myocardium; however, when cell injury slows the rate of rise, decreases amplitude, and lowers resting membrane potential, bretylium transiently restores these parameters toward normal
- In canine hearts with infarcted areas, bretylium decreases disparity in action potential duration between normal and infarcted regions
- Increased impulse formation and spontaneous firing rate of pacemaker tissue, as well as increased ventricular conduction velocity
Absorption
Onset of action: 20 minutes to 2 hr
Elimination
Half-life: 6-10 hr (normal renal function)
Excretion: Urine (80% within 24 hr; additional 10% within 96 hr)
Administration
IV Compatibility
D5W
0.9% NaCl
IV Preparation
Solution should appear clear; slight discoloration does not alter potency
Rapid IV bolus: Do NOT dilute solution
Continuous or intermittent IV infusion: Dilute 500 mg to a minimum of 50 mL with D52 or 0.9% NaCl
IM Preparation
Solution should appear clear; slight discoloration does not alter potency
Do NOT dilute solution
IV Administration
Patients should remain in supine position until tolerance to the hypotensive effect of bretylium develops; tolerance occurs unpredictably but may be present after several days
Immediately life-threatening ventricular arrhythmias
- Rapid IV bolus (undiluted drug): When used for immediately life-threatening ventricular arrhythmias (eg, VF, hemodynamically unstable VT), give rapid IV bolus and if continuous suppression needed, follow with continuous or intermittent IV infusion (dilute drug as described above)
- Continuous IV solution infusion: 1-2 mg/min
- Intermittent IV infusion: 5-10 mg/kg infused over at least 8 min q6hr
-
Rapid infusion
- More rapid infusion may cause nausea and vomiting, and possibly provoke hypertensive crisis
- May increase orthostatic hypotension risk, especially in patients aged ≥65 yr
IM Administration
Patients should be kept in supine position until tolerance to the hypotensive effect of bretylium develops; tolerance occurs unpredictably but may be present after several days
Do not dilute for IM injection
Do not inject directly into or near a major nerve
Rotate injection site if repeated
Do not exceed 5 mL/injection site
As soon as possible, and when indicated, change to oral antiarrhythmic agent for maintenance therapy
Storage
Store at 20-25°C (68-77°F)
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Formulary
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