Bretylium is a parenteral Class III antiarrhythmic agent indicated for the treatment of ventricular arrhythmias. Bretylium is associated with a high incidence of hypotension, particularly in the postresuscitation setting. Bretylium was originally introduced as an antihypertensive but was abandoned because of erratic oral absorption, rapid tolerance to its antihypertensive effects, and proclivity to cause significant orthostatic hypotension. Bretylium was subsequently reintroduced as an antiarrhythmic agent. Previous advanced cardiac life support (ACLS) guidelines included bretylium in the ventricular fibrillation (VF)/pulseless ventricular tachycardia (pVT) algorithm; however, due to raw material shortage and unreliable supply, bretylium was removed from the algorithm although noted to remain acceptable for use with some studies questioning its efficacy. Current guidelines recommend amiodarone or lidocaine for VF/pVT that is unresponsive to defibrillation.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless solution is clear. Slight discoloration does not alter potency.
-Use bretylium only under constant electrocardiographic monitoring.
-Keep patients supine during the course of therapy or closely observe for postural hypotension.
Intravenous Administration
IV Bolus
-Administer undiluted by rapid IV injection.
Intermittent IV Infusion
-Dilute 500 mg of bretylium to a minimum of 50 mL with 5% Dextrose Injection or 0.9% Sodium Chloride Injection.
-Administer IV over more than 8 minutes to minimize orthostatic hypotension and nausea and vomiting.
Continuous IV Infusion
-Dilute 500 mg of bretylium to a minimum of 50 mL with 5% Dextrose Injection or 0.9% Sodium Chloride Injection.
-Administer at a rate of 1 to 2 mg/minute IV.
Intramuscular Administration
-Do not dilute.
-Do not inject more than 5 mL into a single site.
-Inject into a large muscle mass. Do not inject directly into or near a major nerve. Rotate injection sites.
Hypotension and orthostatic hypotension are the most frequently reported adverse reactions with bretylium. Dizziness, lightheadedness, faintness, vertigo, and syncope have been reported in about 0.7% of bretylium-treated patients. Approximately 50% of patients will present with some sort of hypotension while supine. Keep patients in the supine position until tolerance to the hypotensive effect of bretylium develops. Tolerance occurs unpredictably but may be present after several days. If the supine systolic pressure decreases below 75 mmHg, initiate a dopamine or norepinephrine infusion to increase blood pressure. Monitor blood pressure closely in patients receiving catecholamines for enhanced pressor effects due to bretylium. Consider volume expansion and correction of dehydration as clinically indicated.
Transient hypertension (0.2%), increased frequency of premature ventricular contractions (PVCs) (0.2%), and initial increase in arrhythmia exacerbation (0.2%) may occur in some patients due to the initial release of norepinephrine from adrenergic postganglionic nerve terminals caused by bretylium. Bradycardia, sensation of substernal pressure, and precipitation of angina have also have been reported with a frequency of approximately 0.2%.
Nausea and vomiting occurred in approximately 3% of bretylium-treated patients, primarily when administered rapidly by the intravenous route.
Renal dysfunction, diarrhea, abdominal pain, hiccups, erythematous macular rash, flushing, confusion, paranoid psychosis, emotional lability, lethargy, generalized tenderness, anxiety, shortness of breath (dyspnea), diaphoresis, nasal congestion, and mild conjunctivitis have been reported in approximately 0.1% of bretylium-treated patients; the relationship of bretylium to these reactions has not been clearly established.
In a small number of patients, hyperthermia, characterized by temperature above 106 degrees F, has been reported in association with bretylium. Temperature rise can begin within 1 hour or later after administration and reach a peak within 1 to 3 days. Discontinue bretylium and institute appropriate treatment immediately if hyperthermia is suspected or diagnosed.
Bretylium is contraindicated in patients with digitalis toxicity-induced cardiac arrhythmias. The initial release of norepinephrine caused by bretylium may aggravate digitalis toxicity.
Avoid bretylium in patients with fixed cardiac output (e.g., severe aortic stenosis or severe pulmonary hypertension). Severe hypotension may result from a fall in peripheral resistance without a compensatory increase in cardiac output. If bretylium must be used, promptly treat severe hypotension with vasopressors.
Increase bretylium dosage intervals in patients with renal impairment. Bretylium is primarily excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function, renal failure, and/or renal disease.
Clinical studies of bretylium did not include sufficient numbers of geriatric subjects to determine whether they respond differently to bretylium than younger subjects. Intravenous infusion of bretylium, especially beyond the recommended rate, may produce an increased risk of orthostatic hypotension in elderly 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, as well as concomitant disease or drug therapy. Bretylium is primarily excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
Bretylium use requires a specialized care setting; 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.
Use bretylium during pregnancy only if clearly needed. It is not known whether bretylium can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Animal reproduction studies have not been conducted with bretylium.
Other agents are preferred due to little published experience with bretylium during breast-feeding and its high frequency of adverse effects.
For the treatment of ventricular arrhythmias, such as ventricular fibrillation or ventricular tachycardia:
NOTE: Bretylium is for short-term use only; change patients to an oral antiarrhythmic for maintenance therapy when indicated as soon as possible.
-for the treatment of immediately life-threatening ventricular arrhythmias, such as ventricular fibrillation or hemodynamically unstable ventricular tachycardia, that have failed to respond to first-line therapy:
Intravenous dosage (intermittent bolus):
Adults: 5 mg/kg/dose IV. Increase dose to 10 mg/kg/dose IV and repeat as necessary if arrhythmia persists.
Intravenous dosage (intermittent infusion):
Adults: 5 to 10 mg/kg/dose administered over more than 8 minutes IV every 6 hours.
Intravenous dosage (continuous infusion):
Adults: 1 to 2 mg/minute continuous IV infusion.
-for the treatment of non-life-threatening ventricular arrhythmias:
Intravenous dosage:
Adults: 5 to 10 mg/kg/dose administered over more than 8 minutes IV; may repeat dose every 1 to 2 hours if arrhythmia persists. Then, maintain same dose every 6 to 8 hours, or alternately, 1 to 2 mg/minute continuous IV infusion.
Intramuscular dosage:
Adults: 5 to 10 mg/kg/dose IM; may repeat dose every 1 to 2 hours if arrhythmia persists. Then, maintain same dose every 6 to 8 hours.
Maximum Dosage Limits:
-Adults
10 mg/kg/dose IV; there is little experience with dosages more than 40 mg/kg/day IV.
-Geriatric
10 mg/kg/dose IV; there is little experience with dosages more than 40 mg/kg/day IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Increase the dosage interval in patients with impaired renal function.
*non-FDA-approved indication
Acebutolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acetaminophen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Acrivastine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Amphetamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Amphetamine; Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Atenolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Atenolol; Chlorthalidone: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Benzphetamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Beta-adrenergic blockers: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Betaxolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Bisoprolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Brimonidine; Timolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Brompheniramine; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Brompheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Carteolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Carvedilol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Cetirizine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Desloratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dexmethylphenidate: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Diethylpropion: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Digoxin: (Major) Avoid simultaneous initiation of bretylium and digoxin. Bretylium is contraindicated in digitalis-induced arrhythmias. In a digitalized patient, use bretylium only if the arrhythmia does not appear to be digitalis-induced and other antiarrhythmic agents are not effective. The initial release of norepinephrine cause by bretylium may aggravate digitalis toxicity.
Diphenhydramine; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dobutamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dofetilide: (Major) Withdraw bretylium at least 3 half-lives before starting dofetilide therapy.
Dopamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Dorzolamide; Timolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Doxapram: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Ephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Ephedrine; Guaifenesin: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Epinephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Esmolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Fexofenadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Fingolimod: (Contraindicated) Fingolimod is contraindicated in patients requiring treatment with bretylium, a Class III antiarrhythmic.
Guaifenesin; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Guaifenesin; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Ibutilide: (Major) Do not use bretylium concurrently with ibutilide or within 4 hours of ibutilide infusion due to the potential to prolong refractoriness. During ibutilide clinical trials, class III antiarrhythmics, such as bretylium, were withheld for at least 5 half-lives before ibutilide infusion and for 4 hours after dosing.
Isocarboxazid: (Minor) Monoamine oxidase inhibitors potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
Isoproterenol: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Labetalol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Levobunolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Lisdexamfetamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Loratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Methamphetamine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Methylphenidate: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Metoprolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Midodrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Monoamine oxidase inhibitors: (Minor) Monoamine oxidase inhibitors potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
Nadolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Nebivolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Nebivolol; Valsartan: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Norepinephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Phendimetrazine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Phenelzine: (Minor) Monoamine oxidase inhibitors potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
Phentermine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Phentermine; Topiramate: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Pindolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Promethazine; Phenylephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Propafenone: (Major) Avoid the use of propafenone with bretylium. Withhold bretylium for at least 5 half-lives before dosing with propafenone.
Propranolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Pseudoephedrine; Triprolidine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Racepinephrine: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Selegiline: (Minor) Selegiline, a monoamine oxidase type B inhibitor, might potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Sotalol: (Major) Discontinue bretylium at least 3 half-lives before dosing with sotalol. Class III antiarrhythmics, such as bretylium, are not recommended as concomitant therapy with sotalol due to the potential to prolong refractoriness. In addition, concomitant use may result in excessive reduction of resting sympathetic nervous tone increasing the risk for hypotension and marked bradycardia, which may produce syncope.
Sympathomimetics: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium.
Timolol: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Tranylcypromine: (Minor) Monoamine oxidase inhibitors potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
Bretylium is a Class III antiarrhythmic drug that prolongs the duration of the action potential and the effective refractory period in Purkinje and ventricular muscle fibers without changes in heart rate. Bretylium transiently restores the rate of rise, amplitude, and resting membrane potential when myocardial cell injury is present; the drug has little effect on normal myocardium. Restoration of injured myocardial cell electrophysiology toward normal as well as an increase in the action potential duration and effective refractory period without changing their ratio to each other may be key factors in suppressing reentry of aberrant impulses and decreasing induced dispersion of local excitable states. Bretylium selectively accumulates in sympathetic ganglia and their postganglionic adrenergic neurons. After an initial release of norepinephrine that may cause a transient increase in blood pressure and heart rate, bretylium inhibits norepinephrine release by depressing adrenergic nerve terminal excitability. Peripheral adrenergic blockade regularly causes orthostatic hypotension but has less effect on supine blood pressure.
Bretylium is administered intravenously or intramuscularly. Less than 5% of the drug is protein bound. Apparent Vd at steady-state is 3 to 7 L/kg. Bretylium is water-soluble with little CNS penetration. Bretylium is eliminated intact by the kidneys; 70% to 80% of the dose is excreted unchanged in the urine within 24 hours, and an additional 10% during the next 3 days. Total body clearance is 300 to 450 mL/minute. Elimination half-life is 6 to 10 hours.
Affected cytochrome P450 isoenzymes and drug transporters: none
Bretylium does not undergo biotransformation. There are no pharmacokinetic drug interactions.
-Route-Specific Pharmacokinetics
Intravenous Route
Antifibrillatory effects are rapid, usually occurring within minutes of intravenous injection. Arrhythmia suppression is slower, usually occurring 20 minutes to 2 hours after parenteral administration.
Intramuscular Route
Delay in effect is longer after intramuscular administration compared to intravenous administration. In a study of patients with frequent ventricular premature beats, Cmax and peak hypotensive effects were seen within 1 hour of intramuscular administration, most likely reflecting adrenergic neuronal blockade. Suppression of premature ventricular beats was not maximal until 6 to 9 hours after dosing, when the mean plasma concentration had declined to less than one-half of Cmax.
-Special Populations
Renal Impairment
Bretylium half-life is expected to be longer in patients with renal insufficiency. It can be removed from the body by hemodialysis.