bretylium (Rx)

>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

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

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.

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)

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)