Dilution Bretylium

BRETYLIUM TOSYLATE INJECTION

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Usual Diluents

D5W, NS

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

[500 mg] [50-100 ml] [Titrate]
[2 grams] [250 ml ] [Titrate]

Package insert guidelines (below)....

Stability / Miscellaneous

EXP: 1 Day (RT). Usual continuous infusion rate: 1-2 mg/min (0.5 to 4 mg/min).

Renal impairment: 10-50/ 50% of dose. <10/ 25% of dose. Side effects: bradycardia/hypotension/ N&V.

[Supplied: 500mg/ 10ml syringe]

Calculation of drip rate: (code blue: 1 gram/500 ml D5W: 1 mg/min= 30 ml/hr )

INDICATIONS
Bretylium Tosylate is indicated in the prophylaxis and therapy of ventricular fibrillation.

Bretylium tosylate is also indicated in the treatment of life-threatening ventricular arrhythmias, such as ventricular tachycardia, that have failed to respond to adequate doses of a first-line antiarrhythmic agent, such as lidocaine.

Use of BRETYLIUM TOSYLATE INJECTION should be limited 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.

Following injection of BRETYLIUM TOSYLATE INJECTION there may be a delay of 20 minutes to 2 hours in the onset of antiarrhythmic action, although it appears to act within minutes in ventricular fibrillation. The delay in effect appears to be longer after intramuscular than after intravenous injection.

WARNINGS
Hypotension: Administration of bretylium tosylate regularly results in postural hypotension, subjectively recognized by dizziness, light-headedness, vertigo or faintness. Some degree of hypotension is present in about 50% of patients while they are supine. Hypotension may occur at doses lower than those needed to suppress arrhythmias.

Patients should be kept in the supine position until tolerance to the hypotensive effect of bretylium develops. Tolerance occurs unpredictably but may be present after several days.

Patients over 65 years may be at increased risk of developing orthostatic hypotension, especially when the recommended rate of intravenous infusion is exceeded. See DOSAGE AND ADMINISTRATION BELOW.

Hypotension with supine systolic pressure greater than 75 mm Hg need not be treated unless there are associated symptoms. If supine systolic pressure falls below 75 mm Hg, an infusion of dopamine or norepinephrine may be used to raise blood pressure. When catecholamines are administered, a dilute solution should be employed and blood pressure monitored dosely because the pressor effects of the catecholamines are enhanced by bretylium. Volume expansion with blood or plasma and correction of dehydration should be carried out where appropriate.

Transient hypertension and increased frequency of arrhythmias: Due to the initial release of norepinephrine from adrenergic postganglionic nerve terminals by bretylium, transient hypertension or increased frequency of premature ventricular contractions and other arrhythmias may occur in some patients.

Caution during use with digitalis glycosides: The initial release of norepinephrine caused by bretylium may aggravate digitalis toxicity. When a life-threatening cardiac arrhythmia occurs in a digitalized patient, bretylium should be used only if the etiology of the arrhythmia does not appear to be digitalis toxicity and other antiarrhythmic drugs are not effective. Simultaneous initiation of therapy with digitalis glycosides and bretylium should be avoided.

Patients with fixed cardiac output: In patients with fixed cardiac output (i.e., severe aortic stenosis or severe pulmonary hypertension) bretylium should be avoided since severe hypotension may result from a fall in peripheral resistance without a compensatory increase in cardiac output. If survival is threatened by the arrhythmia, bretylium tosylate may be used but vasoconstrictive catecholamines should be given promptly if severe hypotension occurs.

Hyperthermia: In a small number of patients, hyperthermia, characterized by temperature in excess of 106°F, has been reported in association with bretylium tosylate administration. Temperature rise can begin within one hour or later after administration of drug, and reach a peak within 1 to 3 days. If hyperthermia is suspected or diagnosed, bretylium should be discontinued and appropriate treatment instituted immediately.

DOSAGE AND ADMINISTRATION
BRETYLIUM TOSYLATE INJECTION is to be used clinically only for treatment of life-threatening ventricular arrhythmias under constant electrocardiographic monitoring. The clinical use of BRETYLIUM TOSYLATE INJECTION is for short-term use only. Patients should either be kept supine during the course of bretylium therapy or be closely observed for postural hypotension. The optimal dose schedule for parenteral administration of the drug has not been determined. There is comparatively little experience with dosages greater than 40mg/kg/day, although such doses have been used without apparent adverse effects. The following schedules are suggested:

A. For immediately Life-threatening Ventricular Arrhythmias such as Ventricular Fibrillation or Hemodynamically Unstable Ventricular Tachycardia:

Administer undiluted BRETYLIUM TOSYLATE INJECTION at a dosage of 5mg/kg of body weight by rapid intravenous injection. Other usual cardiopulmonary resuscitative procedures, including electrical cardioversion, should be employed prior to and following the injection in accordance with good medical practice. If ventricular fibrillation persists, the dosage may be increased to 10mg/kg and repeated as necessary.

For continuous suppression, dilute Bretylium Tosylate Injection with Dextrose Injection, USP or Sodium Chloride Injection, USP using the table below and administer the diluted solution as a constant infusion of 1 to 2mg Bretylium Tosylate Injection per minute, (see Table below). When administering Bretylium Tosylate Injection (or any potent medication) by continuous intravenous infusion, it is advisable to use a precision volume control device. An alternative maintenance schedule is to infuse the diluted solution at a dosage of 5 to 10mg Bretylium Tosylate per kg body weight, over a period greater than 8 minutes, every 6 hours. More rapid infusion may cause nausea and vomiting, and in patients older than 65 years, may increase the risk of developing orthostatic hypotension.

B. Other ventricular arrhythmias:

1) Intravenous Use: Bretylium tosylate injection must be diluted as described above before intravenous use.

Administer the diluted solution at a dosage of 5 to 10mg bretylium tosylate per kg of body weight by intravenous infusion over a period greater than 8 minutes. More rapid infusion may cause nausea and vomiting, and in patients older than 65 years, may increase the risk of developing orthostatic hypotension. Subsequent doses may be given at 1 to 2 hour intervals if the arrhythmia persists.

For maintenance therapy, the same dosage may be administered every 6 hours, or a constant infusion of 1 to 2mg bretylium tosylate per minute may be given, (See following table).

Suggested Bretylium Tosylate Injection Admixture Dilution and Administration rates for Continuous Infusion Maintenance Therapy Arranged in Descending Order of Concentration.

PREPARATION /ADMINISTRATION
Amount of Bretylium Tosylate Injection	Volume of IV Fluid*	Final Volume	Final Conc. (mg/ mL)	Dose mg/ min	Microdrops per mm.	mL/ hour
FOR FLUID RESTRICTED PATIENTS:
				1.0	7	7
500mg (10mL)	50mL	60mL	8.3	1.5 2.0	11 14	11 14
2g (40mL) 1g (20mL)	500mL 250mL	540mL 270mL	3.7 3.7	1.0 1.5	16 24	16 24
				2.0	32	32
1g (20mL) 500mg (10mL)	500mL 250mL	520mL 260mL	1 .9 1 .9	1.0 1.5 2.0	32 47 63	32 47 63

*lV fluid may be either Dextrose Injection, USP or Sodium Chloride Injection, USP. This table does not consider the overfill volume present in the IV fluids.

2) For Intramuscular Injection: DO NOT DILUTE BRETYLIUM TOSYLATE INJECTION PRIOR TO INTRAMUSCULAR INJECTION.

Inject 5 to 10mg bretylium tosylate per kg of body weight. Subsequent doses may be given at 1 to 2 hour intervals if the arrhythmia persists. Thereafter, maintain the same dosage every 6 to 8 hours. Intramuscular injection should not be made directly into or near a major nerve, and the site of injection should be varied on repeated injection.

Not more than 5mL should be injected intramuscularly in one site. (See package insert for PRECAUTONS) As soon as possible, and when indicated, patients should be changed to an oral antiarrhythmic agent for maintenance therapy.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED
Bretylium Tosylate Injection, 50mg/mL
0517-8810-01 10mL Single Dose Vial Packaged individually
Store at controlled room temperature 15°-30°C(59°-86°F).

Source: [package insert]