FDA label 3b4e5ebf-a4a7-4614-8f28-4bd641d6bcfa

WARNINGS 1. Hypotension Administration of bretylium tosylate regularly results in postural hypotension, subjectively recognized by dizziness, lightheadedness, 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 tosylate 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 . 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 closely because the pressor effects of the catecholamines are enhanced by bretylium tosylate. Volume expansion with blood or plasma and correction of dehydration should be carried out where appropriate. 2. Transient Hypertension and Increased Frequency of Arrhythmias Due to the initial release of norepinephrine from adrenergic postganglionic nerve terminals by bretylium tosylate, transient hypertension or increased frequency of premature ventricular contractions and other arrhythmias may occur in some patients, especially after too vigorous a dosing. 3. Caution During Use With Digitalis Glycosides The initial release of norepinephrine caused by bretylium tosylate may aggravate digitalis toxicity. When a life-threatening cardiac arrhythmia occurs in a digitalized patient, bretylium tosylate 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 tosylate should be avoided. 4. Patients with Fixed Cardiac Output In patients with fixed cardiac output (i.e., severe aortic stenosis or severe pulmonary hypertension) bretylium tosylate 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. 5. Hyperthermia In a small number of patients, hyperthermia, characterized by temperature 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 1-3 days. If hyperthermia is suspected or diagnosed, bretylium tosylate should be discontinued and appropriate treatment instituted immediately.

<table width="100%"><col width="98%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Patients should be kept in the supine position until tolerance to the hypotensive effect of bretylium tosylate develops. Tolerance occurs unpredictably but may be present after several days.</paragraph></td></tr></tbody></table>

ADVERSE REACTIONS Hypotension and postural hypotension have been the most frequently reported adverse reactions (see WARNINGS ). Nausea and vomiting occurred in about three percent of patients, primarily when bretylium tosylate was administered rapidly by the intravenous route. Vertigo, dizziness, lightheadedness and syncope, which sometimes accompanied postural hypotension, have been reported with an incidence of about 0.7%. Bradycardia, increased frequency of premature ventricular contractions, transitory hypertension, initial increase in arrhythmias (see WARNINGS ), precipitation of anginal attacks and sensation of substernal pressure have also been reported in a small number of patients with an incidence of about 0.2%. Renal dysfunction, diarrhea, abdominal pain, hiccups, erythematous macular rash, flushing, hyperthermia, confusion, paranoid psychosis, emotional lability, lethargy, generalized tenderness, anxiety, shortness of breath, diaphoresis, nasal stuffiness and mild conjunctivitis have been reported with an incidence of about 0.1%. The relationship of bretylium tosylate administration to these reactions has not been clearly established. Hyperthermia has also been reported (see WARNINGS ). To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-800-308-6755 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.