Bretylium Tosylate

Pronouncation: (breh-TILL-ee-uhm TAH-sill-ate) Class: Antiarrhythmic agent Trade Names: Bretylium Tosylate in 5% Dextrose - Injection 2 mg/mL (500 mg/vial) - Injection 4 mg/mL (1000 mg/vial) Trade Names: Bretylium Tosylate - Injection 50 mg/mL

Mechanism of Action

Pharmacology
Causes a chemical sympathectomy-like state by inhibiting norepinephrine release and depressing adrenergic nerve terminal excitability; produces a positive inotropic effect on the myocardium.

Pharmacokinetics
Metabolism
No metabolites identified.

Elimination
Eliminated intact by the kidneys; t is about 7.8 hr.

Onset
Rapid, usually within minutes.

Special Populations
Renal Function Impairment The t is increased.

Indications and Usage

Prophylaxis and treatment of ventricular fibrillation; treatment of life-threatening ventricular arrhythmia that has failed to respond to first-line antiarrhythmic agents.

Unlabeled Uses
Second-line therapy (following lidocaine) for the treatment of ventricular arrhythmia during advanced cardiac life support in CPR.

Contraindications
Standard considerations.

Dosage and Administration

Life-Threatening Ventricular Arrhythmias Adults Initial dose IV 5 to 10 mg/kg (undiluted) by rapid IV injection; if arrhythmia persists, adjust dosage as necessary. Maintenance (for continuous suppression) IV Infuse diluted solution at 1 to 2mg/min. Alternately, infuse diluted solution at 5 to 10 mg/kg over more than 8 min q 6 hr. Children IV 5mg/kg/dose followed by 10mg/kg at 10 to 30 min intervals (max total dose, 30 mg/kg). Maintenance 5 to 10mg/kg/dose q 6 hr. Other Ventricular Arrhythmias Adults IV 5 to 10 mg/kg (diluted) over 8min; if arrhythmia persists, give subsequent doses q 1 to 2hr. Maintenance Administer same dose q 6 hr or infuse 1 to 2 mg/min. IM 5 to 10 mg/kg (undiluted); if arrhythmia persists, give subsequent doses at 1 to 2 hr intervals. Maintain same dosage q 6 to 8 hr. Children

5 to 10 mg/kg/dose q 6 hr.

General Advice
For maintenance administration, dilute each dose in at least 50 mL of 5% dextrose in water or 0.9% sodium chloride for injection. Larger amounts can be diluted in any amount of solution (1 g in 250 mL = 4mg/mL; 1 g in 500 mL = 2 mg/mL; 1 g in 1,000 mL = 1 mg/mL). Use slow injection (over 10 min) to prevent nausea and vomiting. Rotate IM injection sites frequently to prevent atrophy and necrosis of muscle tissue. Do not give more than 5 mL in any one site.

Storage/Stability
Store at room temperature. Protect from freezing.

Drug Interactions
Antihypertensives May cause severe hypotension. Catecholamines Enhance pressor effects of catecholamines. Digoxin May aggravate arrhythmias caused by digitalis toxicity.

Laboratory Test Interactions

None well documented.

Adverse Reactions
Cardiovascular
Orthostatic hypotension; bradycardia; increased premature ventricular contractions and other arrhythmias; transient hypertension; angina; sensation of substernal pressure.

CNS
Dizziness; lightheadedness; syncope; vertigo.

GI
Nausea and vomiting after rapid IV injection.

Precautions
Monitor
Monitor patient's vital signs frequently, including cardiac rhythm. Transient increase in arrhythmias and hypertension may occur within 1 hr after initial administration. Especially note slow or irregular pulse or significant hypotension. If BP is less than 75 mm Hg, notify health care provider.

Pregnancy
Category C .

Lactation
Undetermined.

Children
Safety and efficacy not established.

Renal Function
Increase dosage interval.

Fixed cardiac output

Because severe hypotension may occur, avoid use in patients with fixed cardiac output (eg, severe aortic stenosis, pulmonary hypertension). Orthostatic hypotension is common (50%); keep patient supine until tolerance develops or medication is withdrawn.

Overdosage
Symptoms
Hypertension followed by refractory hypotension.

Patient Information
Instruct patient to make position changes slowly and to request assistance with ambulation. Advise men to sit on toilet while urinating.