Note: Onset of action may be delayed; do not use as a substitute for a rapidly acting antiarrhythmic agent. For short-term use only (3 to 5 days).
Ventricular arrhythmia (immediately life-threatening [eg, ventricular fibrillation]): IV: 5 mg/kg as rapid injection; if ventricular arrhythmia persists, may increase to 10 mg/kg and repeat at 15- to 30-minute intervals as necessary.
Other ventricular arrhythmias:
IV: 5 to 10 mg/kg over >8 minutes; may repeat dose in 1 to 2 hours if arrhythmia persists.
IM: 5 to 10 mg/kg; may repeat in 1 to 2 hours if arrhythmia persists, then maintain same dosage every 6 to 8 hours.
Maintenance dosing: IV:
Intermittent infusion: 5 to 10 mg/kg over >8 minutes every 6 hours.
Continuous infusion: 1 to 2 mg per minute.
While undergoing electrocardiographic monitoring, the dose should be reduced and discontinued in 3 to 5 days after initiation. Substitute other appropriate antiarrhythmic agents if indicated.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific dosage adjustments provided in the manufacturer's labeling; however, a longer dosage interval is recommended.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing. Use with caution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection, as tosylate [preservative free]:
Generic: 50 mg/mL (10 mL [DSC])
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection, as tosylate:
Generic: 50 mg/mL ([DSC])
IM: Administer undiluted; rotate injection sites. Do not administer >5 mL in one injection site and do not inject into or near a major nerve.
IV: Administer undiluted by rapid injection (for immediately life-threatening ventricular arrhythmia [eg, ventricular fibrillation]), or diluted by intermittent bolus infusion (over >8 minutes) or continuous infusion. Rapid administration may result in severe nausea/vomiting and should be avoided unless necessary (eg, ventricular fibrillation).
Ventricular arrhythmia: Prophylaxis and treatment of ventricular fibrillation; treatment of life-threatening ventricular arrhythmias (primarily ventricular fibrillation and hemodynamically unstable tachycardia) resistant to conventional antiarrhythmic therapy.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Cardiovascular: Hypotension (in supine positioning: ~50%)
1% to 10%: Gastrointestinal: Nausea and vomiting (3%)
<1%: Abdominal pain, angina pectoris, anxiety, bradycardia, cardiac arrhythmia, chest pressure (substernal), confusion, conjunctivitis (mild), diaphoresis, diarrhea, dizziness, dyspnea, emotional lability, erythematous maculopapular rash, flushing, generalized ache or pain, hiccups, hyperthermia, lethargy, nasal congestion, psychosis (paranoid), renal insufficiency, syncope, transient hypertension, ventricular premature contractions, vertigo
Frequency not defined: Cardiovascular: Orthostatic hypotension
Digitalis-induced arrhythmias.
Concerns related to adverse effects:
• Hypertension: Initially may cause transient hypertension or an increase in the frequency of premature ventricular contractions or other arrhythmias, particularly with concomitant use of inotropic catecholamines.
• Hyperthermia: Hyperthermia, with temperature >106°F, has been reported; may begin within 1 hour of administration and peak within 1 to 3 days. Discontinue for suspected or confirmed hyperthermia.
• Hypotension: May cause orthostatic hypotension even at subtherapeutic doses; maintain patient in supine position until tolerance to hypotensive effects develop. If needed, treat with vasopressors (eg, dopamine, norepinephrine) as clinically indicated and monitor closely.
Disease-related concerns:
• Cardiovascular disease: Avoid use in patients with fixed cardiac output (eg, severe aortic stenosis, severe pulmonary hypertension); fall in peripheral resistance without compensatory increase in cardiac output may result in severe hypotension. If bretylium must be used, treat severe hypotensive episodes with vasopressors immediately. Use caution in patients with bradycardia (may aggravate condition).
• Renal impairment: Use with caution in renal impairment; dose reduction may be necessary.
Special populations:
• Elderly: Use with caution in the elderly.
Concurrent drug therapy issues:
• Cardiac glycosides: Avoid concomitant use with cardiac glycosides (eg, digoxin). May consider use in digitalized patients with serious arrhythmias that are unrelated to digoxin toxicity and resistant to other therapy.
Other warnings/precautions:
• Appropriate use: Onset of action may be delayed 20 minutes and up to 6 hours. Consider as a last resort and reserve use for serious ventricular arrhythmias resistant to other antiarrhythmic agents. The 2010 American Heart Association Guidelines for CPR and Emergency Cardiovascular Care (ECC) based on the 2010 ILCOR International Consensus on CPR and ECC Science with Treatment Recommendations do not support the use of bretylium in this setting (AHA [Neumar 2010]).
None known.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Bretylium may enhance the therapeutic effect of Alpha-/Beta-Agonists (Direct-Acting). Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Cardiac Glycosides: Bretylium may enhance the adverse/toxic effect of Cardiac Glycosides. Management: Bretylium should only be used in digitalis-treated patients when other antiarrhythmic options are ineffective and when arrhythmia is not suspected to be related to digitalis toxicity. Bretylium is contraindicated in digitalis-induced arrhythmias. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Medical therapy for pregnant women with a cardiac emergency is generally the same as in nonpregnant women; medications other than bretylium may be preferred (AHA [Jeejeebhoy 2015]).
ECG, blood pressure; renal function; consult individual institutional policies and procedures.
Class III antiarrhythmic drug that prolongs the duration of the action potential and effective refractory period in Purkinje fibers and ventricular tissue (Heissenbuttel, 1979; Singh, 1974). Bretylium also accumulates in sympathetic ganglia and their postganglionic adrenergic neurons. Following an initial release of norepinephrine (sympathomimetic effect), bretylium inhibits norepinephrine release by reducing adrenergic nerve terminal excitability.
Onset of action: Delayed 20 minutes and up to 2 hours.
Distribution: Vdss: 3 to 7 L/kg; minimal distribution in CNS (Kowey 1997).
Protein binding: <5% (Kowey 1997).
Half-life elimination: 6 to 10 hours.
Excretion: Urine (80% to 90% as unchanged drug).
Solution (Bretylium Tosylate Injection)
50 mg/mL (per mL): $31.13
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