(nor ep i NEF rin)
- Levarterenol Bitartrate
- Noradrenaline Acid Tartrate
- Norepinephrine Bitartrate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Levophed: 1 mg/mL (4 mL) [contains sodium metabisulfite]
Generic: 1 mg/mL (4 mL); 16 mg/250 mL in Dextrose 5% (250 mL); 16 mg/250 mL in NaCl 0.9% (250 mL); 16 mg/500 mL in NaCl 0.9% (500 mL); 4 mg/250 mL in Dextrose 5% (250 mL); 4 mg/250 mL in NaCl 0.9% (250 mL); 4 mg/500 mL in Dextrose 5% (500 mL); 8 mg/250 mL in Dextrose 5% (250 mL); 8 mg/250 mL in NaCl 0.9% (250 mL)
Solution, Intravenous [preservative free]:
Generic: 1 mg/mL (4 mL)
Solution Prefilled Syringe, Intravenous:
Generic: 0.08 mg/10 mL in NaCl 0.9% (10 mL); 0.16 mg/10 mL in NaCl 0.9% (10 mL); 0.8 mg/50 mL in NaCl 0.9% (50 mL)
Brand Names: U.S.
- Alpha/Beta Agonist
Stimulates beta1-adrenergic receptors and alpha-adrenergic receptors causing increased contractility and heart rate as well as vasoconstriction, thereby increasing systemic blood pressure and coronary blood flow; clinically, alpha effects (vasoconstriction) are greater than beta effects (inotropic and chronotropic effects)
Via catechol-o-methyltransferase (COMT) and monoamine oxidase (MAO)
Urine (as inactive metabolites)
Onset of Action
Very rapid acting
Duration of Action
Vasopressor: 1 to 2 minutes
Use: Labeled Indications
Hypotension/shock: Treatment of shock which persists after adequate fluid volume replacement; severe hypotension
Note: Recommended as the first-choice vasopressor for the treatment of sepsis and septic shock in adult patients (Rhodes 2017)
Hypotension from hypovolemia except as an emergency measure to maintain coronary and cerebral perfusion until volume could be replaced; mesenteric or peripheral vascular thrombosis unless it is a lifesaving procedure; during anesthesia with cyclopropane (not available in US) or halothane (not available in US) anesthesia
Documentation of allergenic cross-reactivity for vasopressors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity can not be ruled out with certainty
Note: Dose is stated in terms of norepinephrine base.
Hypotension/shock: Continuous IV infusion:
Initial: 8 to 12 mcg/minute; titrate to desired response. Usual maintenance range: 2 to 4 mcg/minute; dosage range varies greatly depending on clinical situation. If patient remains hypotensive despite large doses, evaluate for occult hypovolemia and provide fluid resuscitation as appropriate.
ACLS dosing range (weight-based dosing): Post cardiac arrest care: Initial: 0.1 to 0.5 mcg/kg/minute (7 to 35 mcg/minute in a 70 kg patient); titrate to desired response (AHA 2010)
Sepsis and septic shock (weight-based dosing): Range from clinical trials: 0.01 to 3 mcg/kg/minute (0.7 to 210 mcg/minute in a 70 kg patient) (Hollenberg 2004)
Refer to adult dosing.
Note: Dose is stated in terms of norepinephrine base.
Hypotension/shock (off-label use): Infants, Children, and Adolescents: Continuous IV infusion: Initial: 0.05 to 0.1 mcg/kg/minute; titrate to desired effect; usual maximum dose: 2 mcg/kg/minute (Fuhrman 2011; PALS [Kleinman 2010]; Park 2014)
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer's labeling.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling.
Continuous IV infusion: Dilute with D5W, D5NS, or NS; dilution in NS is not recommended by the manufacturer; however, stability in NS has been demonstrated (Tremblay 2008). Concentrations ranging from 4 to 16 mcg/mL are typically used in clinical practice (Phillips 2011).
Administer as a continuous infusion via an infusion pump. Dilute prior to use. Central line administration is preferred; extravasation may cause severe ischemic necrosis. Do not administer sodium bicarbonate (or any alkaline solution) through an IV line containing norepinephrine; inactivation of norepinephrine may occur.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate phentolamine (or alternative) antidote. Apply dry warm compresses (Hurst 2004; Reynolds 2014).
Phentolamine: Dilute 5 to 10 mg in 10 to 20 mL NS and administer into extravasation site as soon as possible after extravasation; may readminister if patient remains symptomatic (Reynolds 2014) or dilute 5 to 10 mg in 10 mL NS and administer into extravasation area (within 12 hours of extravasation).
Alternatives to phentolamine:
Nitroglycerin topical 2% ointment (based on limited data):
Adults: Apply a 1-inch strip to the site of ischemia; may repeat every 8 hours as necessary (Reynolds 2014).
Pediatrics: Apply 4 mm/kg as a thin ribbon to the site of ischemia; may repeat after 8 hours if needed (Wong 1992) or apply a 1-inch strip to the site of ischemia; may repeat every 8 hours as necessary (Denkler 1989; Reynolds 2014).
Terbutaline (based on limited case reports): Infiltrate extravasation area using a solution of terbutaline 1 mg diluted in 10 mL NS (large extravasation site, administration volume varied from 3 to 10 mL) or 1 mg diluted in 1 mL NS (small/distal extravasation site, administration volume varied from 0.5 to 1 mL) (Reynolds 2014; Stier 1999).
Store at 20°C to 25°C (68°F to 77°F). Protect from light.
Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy
AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Benzylpenicilloyl Polylysine: Alpha-/Beta-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Consider therapy modification
Beta-Blockers: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Consider therapy modification
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy
Chloroprocaine: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Monitor therapy
CloZAPine: May diminish the therapeutic effect of Alpha-/Beta-Agonists. Monitor therapy
Cocaine: May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification
COMT Inhibitors: May decrease the metabolism of COMT Substrates. Monitor therapy
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy
Droxidopa: Norepinephrine may enhance the hypertensive effect of Droxidopa. Monitor therapy
Ergot Derivatives: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy
Hyaluronidase: May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Consider therapy modification
Inhalational Anesthetics: May enhance the arrhythmogenic effect of Norepinephrine. Avoid combination
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination
Ioflupane I 123: Norepinephrine may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy
Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Norepinephrine. Exceptions: Tedizolid. Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Consider therapy modification
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Management: Avoid, if possible, the use of direct-acting alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Consider therapy modification
Frequency not defined.
Cardiovascular: Bradycardia, cardiac arrhythmia, peripheral ischemia (digital)
Central nervous system: Anxiety, transient headache
Dermatologic: Skin necrosis (with extravasation)
Concerns related to adverse effects:
• Extravasation: Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation; infuse into a large vein if possible. Avoid infusion into leg veins. Monitor IV site closely. [US Boxed Warning]: If extravasation occurs, infiltrate the area with diluted phentolamine (5 to 10 mg in saline) with a fine hypodermic needle. Phentolamine should be administered as soon as possible after extravasation is noted to prevent sloughing /necrosis.
• Hypoxia/hypercarbia: Use in patients with profound hypoxia or hypercarbia may produce ventricular tachycardia or fibrillation; use with extreme caution.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Dosage form specific issues:
• Sodium metabisulfite: Product may contain sodium metabisulfite; use caution in patients with asthma or a sulfite allergy.
• Administration: Administer infusions into a large vein, particularly an antecubital vein; some clinicians have indicated that the femoral vein is also an acceptable route. Avoid catheter tie-in technique, if possible. Avoid leg veins in elderly patients or in those suffering from occlusive disorders (eg, atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger disease). Gangrene has been reported in a lower extremity when infusions were given in an ankle vein.
• Appropriate use: Assure adequate circulatory volume to minimize need for vasoconstrictors. Avoid hypertension; monitor blood pressure closely and adjust infusion rate.
Blood pressure (or mean arterial pressure), heart rate; cardiac output (as appropriate), intravascular volume status, pulmonary capillary wedge pressure (as appropriate); urine output, peripheral perfusion; monitor infusion site closely
Consult individual institutional policies and procedures.
Pregnancy Risk Factor
Animal reproduction studies have not been conducted. Norepinephrine is an endogenous catecholamine and crosses the placenta (Minzter 2010; Wang 1999). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Appropriate medications should not be withheld due to concerns of fetal teratogenicity. Norepinephrine use during the post-resuscitation phase may be considered; however, the effects of vasoactive medications on the fetus should also be considered. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines (Jeejeebhoy [AHA] 2015).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience dizziness, nausea, or anxiety. Have patient report immediately to prescriber significant injection site pain or irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
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- Drug class: catecholamines
- Norepinephrine Bitartrate (AHFS Monograph)
- Norepinephrine (FDA)
- Norepinephrine Injection Concentrate (FDA)
Other brands: Levophed