NOREPINEPHRINE Drug Interactions: What You Need to Know

INTERACTIONS

• Monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants of the triptyline or imipramine types may result in hypertension. ( 7.1 , 7.2 )
• Antidiabetics: Norepinephrine can decrease insulin sensitivity and raise blood glucose ( 7.3 )
• Cyclopropane and halothane anesthetics increase cardiac autonomic irritability. ( 7.4 )

7.1 MAO-Inhibiting Drugs Co-administration of Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) can cause severe, prolonged hypertension. If administration of Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection cannot be avoided in patients who recently have received any of these drugs and in whom, after discontinuation, MAO activity has not yet sufficiently recovered, monitor for hypertension.

7.2 Tricyclic Antidepressants Co-administration of Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection with tricyclic antidepressants (including amitriptyline, nortriptyline, protriptyline, clomipramine, desipramine, imipramine) can cause severe, prolonged hypertension. If administration of Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection cannot be avoided in these patients, monitor for hypertension.

7.3 Antidiabetics Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection can decrease insulin sensitivity and raise blood glucose. Monitor glucose and consider dosage adjustment of antidiabetic drugs.

7.4 Halogenated Anesthetics Concomitant use of Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection with halogenated anesthetics (e.g., cyclopropane, desflurane, enflurane, isoflurane, and sevoflurane) may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics.

CONTRAINDICATIONS Norepinephrine should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed. If norepinephrine bitartrate injection is continuously administered to maintain blood pressure in the absence of blood volume replacement, the following may occur: severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, poor systemic blood flow despite “normal” blood pressure, tissue hypoxia, and lactate acidosis. Norepinephrine should also not be given to patients with mesenteric or peripheral vascular thrombosis (because of the risk of increasing ischemia and extending the area of infarction) unless, in the opinion of the attending physician, the administration of norepinephrine bitartrate injection is necessary as a life-saving procedure. Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or norepinephrine. Hence, the use of norepinephrine during cyclopropane and halothane anesthesia is generally considered contraindicated because of the risk of producing ventricular tachycardia or fibrillation. The same type of cardiac arrhythmias may result from the use of norepinephrine bitartrate injection in patients with profound hypoxia or hypercarbia.

AND PRECAUTIONS

• Tissue Ischemia : Infuse Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection into a large vein. To prevent sloughing and necrosis in areas in with extravasation, infiltrate the area with an adrenergic blocking agent in saline. ( 5.1 )
• Hypotension After Abrupt Discontinuation: Gradually taper a norepinephrine infusion to prevent hypotension. ( 5.2 )
• Cardiac Arrhythmias: Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection may cause arrhythmias. Monitor cardiac function in patients with underlying heart disease. ( 5.3 )
• Allergic Reactions with Sulfite : Norepinephrine Bitartrate in Sodium Chloride Injection contains sodium metabisulfite: Sulfite may cause allergic-type reactions. ( 5.4 )

5.1 Tissue Ischemia Administration of Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride 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 in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span>.

Avoid Norepinephrine

Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride 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 in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride 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 mg to 10 mg of phentolamine mesylate in 10 mL 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 in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride Injection infusion rate while expanding blood volume with intravenous fluids.

5.3 Cardiac Arrhythmias Norepinephrine Bitartrate in Dextrose Injection or Norepinephrine Bitartrate in Sodium Chloride 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 This product 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 and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.