"SILVER SPRING, MD â€” The US Food and Drug Administration (FDA) is warning of several treatment-related serious adverse events in association with implantable left ventricular assist devices (LVADs) in heart-failure patients.
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Hypotension: Administration of bretylium (bretylium tosylate injection ) 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 (bretylium tosylate injection ) develops. Tolerance occurs unpredictably but may be present after several days.
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 (bretylium tosylate injection ) . 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 (bretylium tosylate injection ) , 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 (bretylium tosylate injection ) may aggravate digitalis toxicity. When a life-threatening cardiac arrhythmia occurs in a digitalized patient, bretylium (bretylium tosylate injection ) 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 (bretylium tosylate injection ) should be avoided.
Patients with fixed cardiac output: In patients with fixed cardiac output (i.e., severe aortic stenosis or severe pulmonary hypertension) bretylium (bretylium tosylate injection ) 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 (bretylium tosylate injection ) 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 (bretylium tosylate injection ) 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 (bretylium tosylate injection ) should be discontinued and appropriate treatment instituted immediately.
Dilution for Intravenous use: One vial of BRETYLIUM (bretylium tosylate injection ) TOSYLATE INJECTION should be diluted with a minimum of 50 mL of Dextrose Injection 5%, USP, or Sodium Chloride Injection, USP, prior to intravenous use. Rapid intravenous administration may cause severe nausea and vomiting. Therefore, the diluted solution should be infused over a period greater than 8 minutes. In treating existing ventricular fibrillation bretylium (bretylium tosylate injection ) tosylate should be given as rapidly as possible and may be given without dilution.
Use various sites for intramuscular injection: When injected intramuscularly, not more than 5mL should be given in a site, and injection sites should be varied since repeated intramuscular injection into the same site may cause atrophy and necrosis of muscle tissue, fibrosis, vascular degeneration and inflammatory changes.
Reduce dosage in impaired renal function: Since bretylium (bretylium tosylate injection ) is excreted principally via the kidney, the dosage interval should be increased in patients with impaired renal function. See CLINICAL PHARMACOLOGY section for information of the effect of reduced renal function on half-life.
No data are available on potential for carcinogenicity, mutagenicity or impairment of fertility in animals or humans. Studies with solutions in polypropylene syringes have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.
Category C: Animal reproduction studies have not been conducted with bretylium (bretylium tosylate injection ) tosylate. It is also not known whether bretylium (bretylium tosylate injection ) tosylate can cause harm when administered to a pregnant woman or can affect reproduction capacity. Bretylium (bretylium tosylate injection ) tosylate should be given to pregnant women only if clearly needed.
The safety and effectiveness of Bretylium (bretylium tosylate injection ) Tosylate have not been established. Its limited use in pediatric patients has been inadequate to fully define proper dosage and limitations for use.
Clinical studies of bretylium (bretylium tosylate injection ) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or drug therapy.
Intravenous infusion, especially if administered at a rate beyond that recommended in the DOSAGE AND ADMNISTRATION section, may produce an increased risk of orthostatic hypotension in the elderly. See WARNINGS)
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function, See CLINICAL PHARMACOLOGY.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/8/2004
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