Norepinephrine Bitartrate

Norepinephrine Bitartrate Injection is indicated to raise blood pressure in adult patients with severe, acute hypotension.

• Initial dose of 0.25 mL to 0.375 mL (from 8 mcg to 12 mcg of base) per minute, adjust the rate of flow to establish and maintain a low to normal blood pressure (usually 80 mm Hg to 100 mm Hg systolic) sufficient to maintain the circulation of vital organs.
  2.2 Dosage

  After an initial dosage of 8 to 12 mcg per minute via intravenous infusion, assess patient response and adjust dosage to maintain desired hemodynamic effect. Monitor blood pressure every two minutes until the desired hemodynamic effect is achieved, and then monitor blood pressure every five minutes for the duration of the infusion.

  
  
  

  Typical maintenance intravenous dosage is 2 to 4 mcg per minute.

  
  
  
• The average maintenance dose ranges from 0.0625 mL to 0.125 mL per minute (from 2 mcg to 4 mcg of base).
  2.2 Dosage

  After an initial dosage of 8 to 12 mcg per minute via intravenous infusion, assess patient response and adjust dosage to maintain desired hemodynamic effect. Monitor blood pressure every two minutes until the desired hemodynamic effect is achieved, and then monitor blood pressure every five minutes for the duration of the infusion.

  
  
  

  Typical maintenance intravenous dosage is 2 to 4 mcg per minute.

  
  
  

Injection: 4 mg/4 mL (1 mg/mL norepinephrine base) sterile, clear colorless to slightly yellow color solution in a single-dose amber glass vial.

• Elderly patients may be at greater risk of developing adverse reactions.
  8.5 Geriatric Use

  Clinical studies of norepinephrine bitartrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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 other drug therapy.
  
  
  
  Avoid administration of norepinephrine bitartrate into the veins in the leg in elderly patients

  [see Warnings and Precautions (5.1)].

• 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 Tissue Ischemia

  Administration of norepinephrine bitartrate 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

  [see Dosage and Administration (2.1)].

  Avoid norepinephrine bitartrate 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 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.
• 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 Hypotension after Abrupt Discontinuation

  Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the norepinephrine bitartrate infusion rate while expanding blood volume with intravenous fluids.
• Cardiac Arrhythmias:
  Norepinephrine Bitartrate may cause arrhythmias. Monitor cardiac function in patients with underlying heart disease.
  5.3 Cardiac Arrhythmias

  Norepinephrine Bitartrate elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias.
• Allergic Reactions with Sulfite:
  Norepinephrine Bitartrate contains sodium metabisulfite. Sulfite may cause allergic-type-reactions.
  5.4 Allergic Reactions Associated with Sulfite

  Norepinephrine Bitartrate 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.