BRETYLIUM TOSYLATE IN DEXTROSE 5%
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BRETYLIUM TOSYLATE IN DEXTROSE 5% (BRETYLIUM TOSYLATE IN DEXTROSE 5%).
Bretylium tosylate is an antiarrhythmic agent that prolongs the action potential duration and refractory period in cardiac tissue. It initially causes release of norepinephrine from sympathetic nerve endings, followed by inhibition of norepinephrine release. It has class III antiarrhythmic properties and also exhibits adrenergic blockade.
| Metabolism | Bretylium is eliminated primarily by the kidneys unchanged. No significant hepatic metabolism. About 70-80% of a dose is excreted unchanged in urine within 24 hours. |
| Excretion | Primarily excreted unchanged by the kidneys via glomerular filtration and tubular secretion; >70% of an administered dose recovered in urine within 24 hours; negligible biliary/fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 7-11 hours in patients with normal renal function, but can be prolonged to >24 hours in renal impairment or anuria, necessitating dose adjustment. |
| Protein binding | Negligible; <1% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 1.3-5.4 L/kg; extensive distribution indicates accumulation in tissues, especially sympathetic nerve terminals. |
| Bioavailability | Intramuscular: approximately 80-90% bioavailability; intravenous: 100%. |
| Onset of Action | Intravenous administration: onset of antiarrhythmic effect occurs within 6-20 minutes; peak effect at 6-9 hours after intramuscular injection. |
| Duration of Action | Duration of antiarrhythmic effect lasts 6-24 hours after a single intravenous dose; longer duration in patients with renal impairment. Repeat dosing may be required due to short half-life. |
Intravenous: 5-10 mg/kg infused over 10-30 minutes, may repeat at 30-minute intervals up to a total of 30 mg/kg; maintenance: 1-2 mg/min as continuous IV infusion or 5-10 mg/kg every 6 hours by intermittent infusion. Intramuscular: 5-10 mg/kg undiluted, repeat every 1-2 hours as needed.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: administer 25-50% of normal dose; CrCl <10 mL/min: administer 10-25% of normal dose; dose interval may also be extended. |
| Liver impairment | No specific dose adjustment guidelines; caution in severe hepatic impairment due to potential increased toxicity. |
| Pediatric use | Not established; limited data: 2-5 mg/kg IV or IM, repeat every 6-8 hours; maximum 30 mg/kg total. |
| Geriatric use | Lower initial doses recommended due to age-related renal impairment; monitor for hypotension and dysrhythmias. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BRETYLIUM TOSYLATE IN DEXTROSE 5% (BRETYLIUM TOSYLATE IN DEXTROSE 5%).
| Breastfeeding | No human data on excretion in breast milk; M/P ratio unknown. Risk of infant bradycardia and hypotension if exposed. Use with caution; discontinue breastfeeding or drug based on importance to mother. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate human studies; animal studies show fetal harm including reduced fetal weight and increased resorptions at doses 2-3 times human dose. Second and third trimesters: Risk of maternal hypotension reducing placental perfusion; potential for fetal bradycardia due to adrenergic blockade. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to bretylium or any component of the formulation","Digitalis toxicity-induced arrhythmias (relative contraindication)"]
| Precautions | ["Hypotension: Both orthostatic and supine hypotension are common; may be severe. Monitor blood pressure closely.","Transient initial increase in arrhythmias: Due to initial norepinephrine release, may worsen ventricular arrhythmias.","Renal impairment: Dosage adjustment required in patients with renal insufficiency due to renal elimination.","Use in digitalis-induced arrhythmias: May be less effective and may aggravate toxicity; caution advised."] |
| Food/Dietary | No specific food interactions reported. However, because the drug is administered intravenously in a hospital setting, dietary restrictions are not typically relevant. General advice: avoid excessive caffeine and alcohol as they may exacerbate arrhythmias. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate continuously during infusion. Assess fetal heart rate and uterine activity if used for arrhythmias in pregnancy. Monitor maternal electrolytes and renal function. |
| Fertility Effects | No human data on fertility. Animal studies: no adverse effects on fertility at clinically relevant doses. |
| Clinical Pearls | Bretylium tosylate is a class III antiarrhythmic used for ventricular fibrillation and hemodynamically unstable ventricular tachycardia. It initially causes norepinephrine release, which can increase blood pressure and arrhythmias, followed by adrenergic blockade leading to hypotension. It is not a first-line agent; amiodarone is preferred. Renal function impacts dosing; reduce dose in creatinine clearance < 10 mL/min. Monitor blood pressure closely during infusion. |
| Patient Advice | This medication is used for serious heart rhythm problems and is given intravenously in a hospital setting. · You may experience a temporary increase in blood pressure or heart rhythm irregularities initially. · You may feel dizzy or faint due to low blood pressure; do not get up too quickly. · Report any chest pain, shortness of breath, or severe dizziness to your healthcare provider immediately. · Avoid driving or operating machinery until you know how this medication affects you. |