• Hypotension

Levophed Generic Name & Formulations

General Description

Norepinephrine bitartrate 1mg/mL (equivalent of 1mg base of norepinephrine); soln for IV infusion after dilution; contains sulfites.

Pharmacological Class


How Supplied

Single-dose vials (4mL) or ampules (4mL)—10

How Supplied

Levophed (norepinephrine bitartrate) injection, USP, is a sterile, colorless solution for injection intended for intravenous use. It contains the equivalent of 1 mg of norepinephrine base per 1 mL (4 mg/4 mL). It is available as 4 mg/4 mL in single-dose amber glass vials and in single-dose clear glass ampules. Supplied as:

  • Unit of Sale: 10 vials in a carton. Concentration: 4 mg/4 mL (1 mg/mL).

  • Unit of Sale: 10 ampules in a carton. Concentration: 4 mg/4 mL (1 mg/mL).


Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.]

Store in original carton until time of administration to protect from light. Discard unused portion.


Levophed Indications


To raise blood pressure in adults with severe, acute hypotension.

Levophed Dosage and Administration

Prior to Treatment Evaluations

Address hypovolemia before initiation of Levophed therapy. If the patient does not respond to therapy, suspect occult hypovolemia. 


Correct hypovolemia before administration. Give by IV infusion after dilution into a large vein. Initially 0.25–0.375mL (or 8–12mcg of base) per minute; adjust flow rate to establish and maintain a low to normal BP (usually 80–100 mmHg systolic) sufficient to maintain the circulation of vital organs. Usual maintenance: 0.0625–0.125mL (or 2–4mcg of base) per minute. Withdraw gradually.


Not established.

Levophed Contraindications

Not Applicable

Levophed Boxed Warnings

Not Applicable

Levophed Warnings/Precautions


Risk of tissue ischemia. Avoid in those with mesenteric or peripheral vascular thrombosis. Occlusive or thrombotic vascular disease. Prolonged or high dose infusions. Avoid abrupt cessation. Withdraw gradually by reducing infusion rate. Risk of cardiac arrhythmias esp during hypoxia or hypercarbia. Perform continuous cardiac monitoring in those with arrhythmias. Avoid extravasation. Asthma. Sulfite sensitivity. Elderly: avoid infusion into leg veins. Pregnancy. Nursing mothers.


Tissue Ischemia

  • Administration of Levophed 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. 

  • Correct hypovolemia prior to initiating Levophed. Avoid use in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction.

  • Patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions have reported gangrene of the extremities. Monitor for changes to the skin of the extremities in susceptible patients.

  • Extravasation of Levophed 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.

  • 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. 

  • When discontinuing the infusion, gradually reduce the Levophed infusion rate while expanding blood volume with intravenous fluids.

Cardiac Arrhythmias

  • Levophed 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 Associated with Sulfite

  • 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.

Pregnancy Considerations

Risk Summary 

  • Limited published data have not identified an increased risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. 

  • There are risks to the mother and fetus from hypotension associated with septic shock, myocardial infarction and stroke which are medical emergencies in pregnancy and can be fatal if left untreated.

Clinical Considerations

  • Disease-associated maternal and/or embryo/fetal risk: If treatment is delayed in pregnant women with hypotension associated with septic shock, myocardial infarction and stroke, there is an Increased risk of maternal and fetal morbidity and mortality. 

  • Do not withhold life-sustaining therapy for the pregnant woman due to potential concerns regarding the effects of norepinephrine on the fetus.

Nursing Mother Considerations

Risk Summary

  • There are no data on the presence of norepinephrine in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Clinically relevant exposure to the infant is not expected based on the short half-life and poor oral bioavailability of norepinephrine.

Pediatric Considerations

Safety and effectiveness in pediatric patients have not been established.

Geriatric Considerations

Clinical studies of Levophed 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 Levophed into the veins in the leg in elderly patients.

Levophed Pharmacokinetics


Following initiation of intravenous infusion, the steady state plasma concentration is achieved in 5 min.


Plasma protein binding of norepinephrine is approximately 25%. It is mainly bound to plasma albumin and to a smaller extent to prealbumin and alpha 1-acid glycoprotein. The volume of distribution is 8.8 L. Norepinephrine localizes mainly in sympathetic nervous tissue. It crosses the placenta but not the blood-brain barrier. 


Norepinephrine is metabolized in the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and MAO. The major metabolites are normetanephrine and 3- methoxyl-4-hydroxy mandelic acid (vanillylmandelic acid, VMA), both of which are inactive. Other inactive metabolites include 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxymandelic acid, and 3,4- dihydroxyphenylglycol.


The mean half-life of norepinephrine is approximately 2.4 min. The average metabolic clearance is 3.1 L/min.

Noradrenaline metabolites are excreted in urine primarily as sulphate conjugates and, to a lesser extent, as glucuronide conjugates. Only small quantities of norepinephrine are excreted unchanged.

Levophed Interactions


Risk of ventricular tachycardia or fibrillation with halothaned anesthetics (eg, cyclopropane, desflurane, enflurane, isoflurane, sevoflurane); monitor cardiac rhythm. Concomitant MAOIs (eg, linezolid) or tricyclic antidepressants (eg, amitriptyline, nortriptyline, protriptyline, clomipramine, desipramine, imipramine) can cause severe, prolonged hypertension; if unavoidable, monitor BP. May decrease insulin sensitivity and raise blood glucose with antidiabetic drugs; monitor and consider dose adjustment of antidiabetics.

Levophed Adverse Reactions

Adverse Reactions

Ischemic injury, bradycardia, anxiety, transient headache, respiratory difficulty, extravasation necrosis at inj site; tissue ischemia.

Levophed Clinical Trials

See Literature

Levophed Note

Not Applicable

Levophed Patient Counseling

Patient Counseling

Risk of Tissue Damage

  • Advise the patient, family, or caregiver to report signs of extravasation urgently.