BRETYLIUM TOSYLATE IN DEXTROSE 5% IN PLASTIC CONTAINER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BRETYLIUM TOSYLATE IN DEXTROSE 5% IN PLASTIC CONTAINER (BRETYLIUM TOSYLATE IN DEXTROSE 5% IN PLASTIC CONTAINER).
Bretylium tosylate inhibits norepinephrine release from adrenergic nerve terminals by blocking neuronal reuptake and causing initial norepinephrine release followed by depletion. It also exhibits class III antiarrhythmic activity by prolonging the action potential duration and refractory period in cardiac Purkinje fibers and ventricular muscle.
| Metabolism | Metabolism is minimal; bretylium is primarily excreted unchanged in the urine. It is not significantly metabolized by the liver. |
| Excretion | Renal: >80% unchanged; biliary/fecal: minimal (<5%) |
| Half-life | Terminal half-life: 7-11 hours (normal renal function); prolonged in renal impairment (up to 16-32 hours in anuria) |
| Protein binding | <5% (not significantly bound; alpha1-acid glycoprotein not a major binding protein) |
| Volume of Distribution | Vd: 3-6 L/kg (large, extensive extravascular distribution including myocardium) |
| Bioavailability | IM: 80-90% (but not recommended due to local irritation); IV: 100% |
| Onset of Action | IV: 5-30 minutes; IM: 20-60 minutes |
| Duration of Action | IV: 6-8 hours (antiarrhythmic effect); IM: 6-24 hours (variable, may require repeat dosing) |
For ventricular tachycardia/fibrillation: 5 mg/kg IV over 8-10 minutes, then 5-10 mg/kg IV q6-8h. For continuous infusion: 1-2 mg/min IV.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: reduce dose by 25-50% and increase dosing interval to q12-18h. CrCl <10 mL/min: reduce dose by 50-75% and give q24-36h. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment due to potential electrolyte disturbances. Monitor serum potassium and magnesium levels. |
| Pediatric use | Ventricular arrhythmias: 5 mg/kg IV over 10-20 minutes, may repeat with 10 mg/kg; then 5-10 mg/kg IV q6-8h. Not recommended for patients <1 month. |
| Geriatric use | Start at lower end of dosing range due to age-related renal function decline; monitor for hypotension and orthostatic effects. 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 IN DEXTROSE 5% IN PLASTIC CONTAINER (BRETYLIUM TOSYLATE IN DEXTROSE 5% IN PLASTIC CONTAINER).
| Breastfeeding | Unknown if excreted in breast milk. M/P ratio not established. Caution: potential for hypotension in nursing infant due to drug effects. Avoid breastfeeding for 48 hours after administration if possible. |
| Teratogenic Risk | Pregnancy Category C. Animal studies show embryocidal effects at doses 7-10 times human dose. No adequate human studies. Use only if benefit outweighs risk; first trimester exposure may increase malformation risk but data limited. Second and third trimester: risk of maternal hypotension reducing uteroplacental perfusion. |
■ FDA Black Box Warning
Bretylium tosylate is indicated for the treatment of ventricular arrhythmias and should be used only in patients with life-threatening arrhythmias. Hypotension is a common adverse effect; patients must be monitored closely. Initial dose may cause transient hypertension and increased arrhythmias due to norepinephrine release.
| Serious Effects |
["Hypersensitivity to bretylium or any component of the formulation"]
| Precautions | ["Hypotension: Bretylium commonly causes orthostatic and supine hypotension due to peripheral adrenergic blockade. Patients should be kept in supine position and monitored closely.","Transient hypertension and increased arrhythmias: Initial norepinephrine release may cause transient hypertension, increased heart rate, and exacerbation of arrhythmias.","Renal impairment: Dose reduction is required in patients with renal impairment because the drug is excreted unchanged in urine.","Use in patients with digitalis toxicity: Bretylium may aggravate arrhythmias associated with digitalis toxicity.","Rapid administration: May cause nausea and vomiting; should be infused over at least 8 minutes."] |
| Food/Dietary |
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| Fetal Monitoring | Continuous ECG monitoring for arrhythmia and QT prolongation. Blood pressure monitoring for hypotension. Fetal heart rate monitoring during second and third trimester administration. Serum electrolytes, especially potassium and magnesium. |
| Fertility Effects | No human data. Animal studies: no impairment of fertility at doses up to 10 mg/kg/day. Theoretical risk of antiadrenergic effects on reproductive function. |
| No clinically significant food interactions. However, caffeine and alcohol may exacerbate arrhythmias; consult with clinician. |
| Clinical Pearls | Bretylium tosylate is a class III antiarrhythmic used for ventricular fibrillation/tachycardia refractory to other agents. Onset of action is delayed (minutes to hours) due to initial norepinephrine release causing transient hypertension and arrhythmias, followed by hypotension from adrenergic blockade. Do not mix with other drugs in IV line. Use with caution in digitalis toxicity due to increased ventricular arrhythmia risk. Monitor BP closely; have vasopressors ready for severe hypotension. Dosage adjustment needed in renal impairment. |
| Patient Advice | This medication is given intravenously in a hospital setting for serious heart rhythm problems. · You may experience a temporary increase in blood pressure and heart rate followed by low blood pressure, dizziness, or fainting. · Report any chest pain, palpitations, severe dizziness, or shortness of breath immediately. · Do not stop or change the dose without your doctor's approval. · Inform all healthcare providers that you are receiving this drug. |