BRETYLIUM TOSYLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BRETYLIUM TOSYLATE (BRETYLIUM TOSYLATE).
Bretylium tosylate is a class III antiarrhythmic agent that prolongs the action potential duration and refractory period by blocking potassium channels. It also initially causes norepinephrine release, leading to transient hypertension and increased contractility, followed by adrenergic neuron blockade, resulting in hypotension and reduced contractility.
| Metabolism | Bretylium is not significantly metabolized; it is excreted unchanged primarily by the kidneys via glomerular filtration and tubular secretion. |
| Excretion | Renal: ~80% unchanged; biliary/fecal: <1% |
| Half-life | 5-10 hours; prolonged in renal impairment (up to 30 hours) |
| Protein binding | <1% (negligible binding to plasma proteins) |
| Volume of Distribution | 3-6 L/kg; large due to extensive tissue uptake, especially in adrenergic nerve endings |
| Bioavailability | Oral: <5% (not used clinically); IM: 100% |
| Onset of Action | IV: 1-2 minutes; IM: 10-30 minutes; Oral: not used |
| Duration of Action | IV: 4-6 hours; IM: 6-8 hours; prolonged in renal impairment |
For ventricular tachycardia/fibrillation: 5-10 mg/kg IV bolus over 1-2 minutes, may repeat every 15-30 minutes up to 30 mg/kg total. Maintenance: 5-10 mg/kg IV every 6 hours or 0.5-2 mg/min continuous infusion. Intramuscular: 5-10 mg/kg undiluted, may repeat every 1-2 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment. CrCl 10-50 mL/min: give 50% of standard dose. CrCl <10 mL/min: give 25% of standard dose. Dosing interval may be extended to every 12-24 hours in severe impairment. |
| Liver impairment | No specific recommendations for Child-Pugh classification; use with caution in severe hepatic impairment as bretylium is minimally metabolized by liver, but dose reduction may be considered due to potential volume of distribution changes. |
| Pediatric use | Loading dose: 5 mg/kg IV or IM every 6-8 hours, may increase to 10 mg/kg if needed. Subsequent doses: 5-10 mg/kg IV/IM every 6-8 hours. Maximum single dose: 30 mg/kg. Continuous IV infusion: 0.5-2 mg/kg/min. |
| Geriatric use | Initiate at lower end of dosing range (5 mg/kg) due to age-related decline in renal function; monitor for hypotension and arrhythmias; adjust dose based on renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BRETYLIUM TOSYLATE (BRETYLIUM TOSYLATE).
| Breastfeeding | It is not known whether bretylium is excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. M/P ratio: not available. |
| Teratogenic Risk | Bretylium tosylate is classified as FDA Pregnancy Category C. Animal studies have shown no teratogenic effects, but there are no adequate and well-controlled studies in pregnant women. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester: limited data preclude definitive risk assessment; second and third trimesters: potential for maternal hypotension leading to reduced uteroplacental perfusion, fetal hypoxia, and bradycardia. |
■ FDA Black Box Warning
Hypotension: Bretylium can cause severe and persistent hypotension, especially in patients with low baseline blood pressure. Use with caution and monitor blood pressure closely during therapy.
| Serious Effects |
["Known hypersensitivity to bretylium","Severe hypotension with compromised cardiac output","Acute myocardial infarction with hypotension","Uncontrolled heart failure"]
| Precautions | ["Hypotension (severe, postural)","Transient hypertension and increased arrhythmias after initial administration","Prolonged QT interval (risk of torsades de pointes)","Renal impairment (dose adjustment needed)","Use with caution in digitalis-induced arrhythmias","Not recommended for atrial arrhythmias"] |
| Food/Dietary | Avoid grapefruit juice, as it may increase QT prolongation risk. Limit or avoid alcohol due to enhanced hypotensive effect. No other specific food restrictions. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG continuously during therapy. Monitor fetal heart rate and uterine activity if used in labor and delivery. Assess for signs of maternal hypotension, bradycardia, or arrhythmias. Monitor serum electrolytes and renal function periodically. |
| Fertility Effects | No specific studies on fertility effects in humans have been conducted. Animal reproduction studies have not been reported to indicate impairment of fertility. |
| Clinical Pearls | Bretylium tosylate is a class III antiarrhythmic used for ventricular fibrillation and hemodynamically unstable ventricular tachycardia. It causes initial catecholamine release leading to transient hypertension and arrhythmia exacerbation, followed by profound hypotension. Use only when other agents fail. Monitor for orthostatic hypotension; patient must remain supine during infusion. Bretylium accumulates in sympathetic nerve endings and blocks norepinephrine release, producing chemical sympathectomy. Do not use with other drugs that prolong QT interval. |
| Patient Advice | This medication is given in a hospital setting only for life-threatening heart rhythm problems. · You will need to lie flat during and after the infusion due to risk of severe low blood pressure. · Report any fainting, dizziness, or irregular heartbeat immediately. · Do not drive or operate machinery until you are told it is safe. · Tell your healthcare provider about any other medicines you take, especially for heart rhythm or blood pressure. · Avoid grapefruit juice and alcohol while taking this medication. |