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Levophed Side Effects

Generic Name: norepinephrine

Note: This page contains information about the side effects of norepinephrine. Some of the dosage forms included on this document may not apply to the brand name Levophed.

For the Consumer

Applies to norepinephrine: parenteral injection

Side effects include:

May cause headache, anxiety, arrhythmias, bradycardia, respiratory difficulty, ischemic injury, or extravasation at the infusion site.

For Healthcare Professionals

Applies to norepinephrine: injectable solution, intravenous solution


While NE can cause hypertension, local vasoconstriction, and tissue hypoxia in any patient, those with hyperthyroidism or who are also taking certain medications are particularly at risk. These medications include cyclopropane or halothane anesthetics, guanethidine, and monoamine oxidase inhibitors (MAOIs).[Ref]

Cardiovascular side effects from norepinephrine (NE) can be serious. The drug can produce profound hypertension, local vasoconstriction, and tissue hypoxia. NE-induced hypertension typically presents as headache, photophobia, stabbing chest pain, pallor, intense sweating, and/or vomiting. Rare cases of coronary artery spasm have been associated with high doses of NE.

Adequate intravascular volume replacement is strongly recommended before, during, and upon withdrawal of therapy. Inadequate intravascular volume before and during NE therapy can result in decreased perfusion of vital organs, including the heart, liver, and kidney. Inadequate intravascular volume upon NE withdrawal can result in recurrent and profound hypotension. Hypotension, tissue hypoperfusion, and tissue hypoxia can produce ischemic injury and systemic lactic acidosis.

Other cardiovascular side effects include (reflex) bradycardia and arrhythmias.[Ref]

Nervous system

Nervous system side effects are usually a sign of NE-induced hypertension, and may indicate a need for dosage reduction. Side effects include headache, anxiety, and photophobia.[Ref]


Blanching along the course of the infused vein may indicate vasa vasorum constriction with increased venous permeability. This can lead to extravasation, local tissue necrosis, and--rarely--tissue sloughing.

Phentolamine is an effective antidote to norepinephrine (the active ingredient contained in Levophed) extravasation. To prevent sloughing and necrosis in areas in which extravasation has taken place, it is recommended that the area be infiltrated as soon as possible with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of phentolamine, an adrenergic receptor antagonist. A syringe with a fine hypodermic needle is recommended, with the solution being infiltrated liberally throughout the area, which is easily identified by its cold, hard, and pallid appearance. Phentolamine usually causes immediate and conspicuous local hyperemia if used within 12 hours of extravasation of norepinephrine. In rare cases, excision of necrosed tissue is necessary.[Ref]

Local intravenous site problems can be severe. Because NE can cause local vasoconstriction, extravasation of the drug at the IV site can cause local tissue necrosis and sloughing. If blanching occurs along the course of the infused vein, another IV site is recommended. Proximal, larger veins serve better than peripheral, smaller veins. Elderly patients, particularly if a leg vein is utilized, are at highest risk.[Ref]


Hypersensitivity reactions, described by a distinct entity called "adrenergic urticaria," have been reported. In these cases, elevated systemic levels of catecholamines have been associated with psychological stress and generalized urticaria. In some cases, provocation with intradermal norepinephrine (the active ingredient contained in Levophed) or epinephrine has resulted in flares and recurrences.[Ref]


1. Karch SB "Coronary artery spasm induced by intravenous epinephrine overdose." Am J Emerg Med 7 (1989): 485-8

2. Verrill PJ "Adverse reactions to local anaesthetics and vasoconstrictor drugs." Practitioner 214 (1975): 380-7

3. "Product Information. Levophed Bitartrate (norepinephrine)." Sanofi Winthrop Pharmaceuticals, New York, NY.

4. Muelheims GH, Entrup RW, Paiewonsky D, Mierzwiak DS "Increased sensitivity of the heart to catecholamine-induced arrhythmias following guanethidine." Clin Pharmacol Ther 6 (1965): 757-62

5. Oglesby JE, Baugh JH "Tissue necrosis due to norepinephrine." Am J Surg 115 (1968): 408-12

6. Ventura HO, Messerli FH, Barron RE "Norepinephrine-induced hypertension in Guillain Barre syndrome." J Hypertens 4 (1986): 265-7

7. Angelos MG, Ward KR, Beckley PD "Norepinephrine-induced hypertension following cardiac arrest - effects on myocardial oxygen use in a swine model." Ann Emerg Med 24 (1994): 907-14

8. Okada Y, Suzuki H, Ishiyama I "Fatal subarachnoid haemorrhage associated with dental local anaesthesia." Aust Dent J 34 (1989): 323-5

9. Haft JI "Cardiovascular injury induced by sympathetic catecholamines." Prog Cardiovasc Dis 17 (1974): 73-86

10. Tisdale JE, Patel RV, Webb Cr, Borzak S, Zarowitz BJ "Proarrhythmic effects of intravenous vasopressors." Ann Pharmacother 29 (1995): 269-81

11. Fritz H, Hagstam KE, Lindqvist B "Local skin necrosis after intravenous infusion of norepinephrine, and the concept of endotoxinaemia. A clinical study on 10 cases." Acta Med Scand 178 (1965): 403-16

12. Gylling U, Rintala A "Treatment of noradrenaline infusion necrosis." Ann Chir Gynaecol Fenn 55 (1966): 271-5

13. Haustein UF "Adrenergic urticaria and adrenergic pruritus." Acta Derm Venereol 70 (1990): 82-4

14. Shelley WB, Shelley ED "Adrenergic urticaria: a new form of stress-induced hives." Lancet 2 (1985): 1031-3

Not all side effects for Levophed may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

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