warnings and cautions
5 WARNINGS AND PRECAUTIONS Tissue Ischemia : Avoid extravasation of Norepinephrine Bitartrate Injection into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug. Infuse Norepinephrine Bitartrate Injection into a large vein. To prevent sloughing and necrosis in areas in which extravasation has taken place, the area should be infiltrated as soon as possible with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of an adrenergic blocking agent. ( 5.1 ) Hypotension After Abrupt Discontinuation : Sudden cessation of the infusion rate may result in marked hypotension. Reduce the Norepinephrine Bitartrate Injection infusion rate gradually. ( 5.2 ) Cardiac Arrhythmias: Norepinephrine Bitartrate Injection may cause arrhythmias. Monitor cardiac function in patients with underlying heart disease. ( 5.3 ) Allergic Reactions with Sulfite: Norepinephrine Bitartrate Injection contains sodium metabisulfite. Sulfite may cause allergic-type-reactions. ( 5.4 ) 5.1 Tissue Ischemia Administration of Norepinephrine Bitartrate Injection to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating Norepinephrine Bitartrate Injection [see Dosage and Administration (2.1) ]. Avoid Norepinephrine Bitartrate Injection in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction. Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients. Extravasation of Norepinephrine Bitartrate Injection may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation [see Dosage and Administration (2.1) ]. Emergency Treatment of Extravasation To prevent sloughing and necrosis in areas in which extravasation has occurred, infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. 5.2 Hypotension after Abrupt Discontinuation Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the Norepinephrine Bitartrate Injection infusion rate while expanding blood volume with intravenous fluids. 5.3 Cardiac Arrhythmias Norepinephrine Bitartrate Injection elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias. 5.4 Allergic Reactions Associated with Sulfite Norepinephrine Bitartrate Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.