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Levophed
Levophed
Pharmacologic Category
Alpha-/Beta- Agonist
Dosing: Adult
Administration requires the use of an infusion pump.
Note: Norepinephrine dosage is stated in terms of norepinephrine base.
Hypotension/shock: Continuous IV infusion:
Initial: 8-12 mcg/minute; titrate to desired response. Usual maintenance range: 2-4
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: 0.1-0.5
mcg/kg/minute (7-35 mcg/minute in a 70 kg patient); titrate to desired response (AHA,
2010)
Sepsis and septic shock (weight-based dosing): Range from clinical trials: 0.01-3
mcg/kg/minute (0.7-210 mcg/minute in a 70 kg patient) (Hollenberg, 2004)
Dosing: Pediatric
(For additional information see "Norepinephrine (noradrenaline): Pediatric drug information")
Administration requires the use of an infusion pump.
Note: Norepinephrine dosage is stated in terms of norepinephrine base.
Hypotension/shock: Continuous IV infusion: Initial: 0.05-0.1 mcg/kg/minute; titrate to desired
effect; maximum dose: 2 mcg/kg/minute (AHA, 2010; Kleinman, 2007)
Dosing: Geriatric
Refer to adult dosing.
Administration
Administer as a continuous infusion with the use of an infusion pump. Dilute prior to use.
Administration via central line recommended (may cause severe ischemic necrosis if extravasated).
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.
Compatibility
Stable in D5LR, D51/2NS, D5NS, D5W, D10W, LR, NS; incompatible with alkaline solutions.
Y-site administration: Compatible: Amiodarone, anidulafungin, argatroban, bivalirudin,
caspofungin, cisatracurium, clonidine, dexmedetomidine, diltiazem, dobutamine, dopamine,
doripenem, epinephrine, esmolol, famotidine, fenoldopam, fentanyl, furosemide, haloperidol,
heparin, hetastarch in lactate electrolyte injection (Hextend), hydrocortisone sodium
succinate, hydromorphone, inamrinone, labetalol, lorazepam, meropenem, micafungin,
midazolam, milrinone, morphine, mycophenolate, nicardipine, nitroglycerin, nitroprusside,
potassium chloride, propofol, ranitidine, remifentanil, telavancin, tigecycline, vasopressin,
vecuronium, vitamin B complex with C.Incompatible: Drotrecogin alfa, insulin (regular),
thiopental. Variable (consult detailed reference): Furosemide, nesiritide, pantoprazole.
Compatibility in syringe: Incompatible: Pantoprazole.
Use
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 (Dellinger, 2013)
Contraindications
Hypersensitivity to norepinephrine, bisulfites (contains metabisulfite), or any component of the
formulation; 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
U.S.) or halothane (not available in U.S.) anesthesia (risk of ventricular arrhythmias)
Warnings/Precautions
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. [U.S. Boxed Warning]: If extravasation occurs, infiltrate
the area with diluted phentolamine (5-10 mg in 10-15 mL of saline) with a fine
hypodermic needle. Phentolamine should be administered as soon as possible
after extravasation is noted to prevent sloughing /necrosis.
Concurrent drug therapy issues:
Monoamine oxidase inhibitors (MAO-I): Use with extreme caution in patients taking MAOInhibitors; prolong hypertension may result from concurrent use.
Dosage form specific issues:
Sodium metabisulfite: Product may contain sodium metabisulfite.
Other warnings/precautions:
Appropriate use: Assure adequate circulatory volume to minimize need for vasoconstrictors.
Avoid hypertension; monitor blood pressure closely and adjust infusion rate.
Metabolism/Transport Effects
Substrate of COMT
Drug Interactions
(For additional information: Launch Lexi-Interact Drug Interactions Program)
Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly,
Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy
AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may
enhance the tachycardic effect of Sympathomimetics. Risk C: 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. Risk D: 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 (DirectActing), including anti-anaphylactic effects of epinephrine, may be diminished by BetaBlockers. 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. Risk D: Consider therapy modification
Cannabinoid-Containing Products: May enhance the tachycardic effect of
Sympathomimetics. Exceptions: Cannabidiol.Risk C: Monitor therapy
COMT Inhibitors: May decrease the metabolism of COMT Substrates. Risk C: Monitor therapy
Droxidopa: Norepinephrine may enhance the hypertensive effect of Droxidopa. Risk C: 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. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Inhalational Anesthetics: May enhance the arrhythmogenic effect of Norepinephrine. Risk X: Avoid
combination
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I
123. Risk X: Avoid combination
Ioflupane I 123: Norepinephrine may diminish the diagnostic effect of Ioflupane I 123. Risk C:
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. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the hypertensive effect of
Norepinephrine. Exceptions: Tedizolid. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/BetaAgonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect
of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor
therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C:
Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the
tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists (DirectActing). 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. Risk D:
Consider therapy modification
Pregnancy Implications
Animal reproduction studies have not been conducted. Norepinephrine is an endogenous
catecholamine and crosses the placenta (Minzter, 2010; Wang, 1999).
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
It is not known if norepinephrine is excreted in breast milk. The manufacturer recommends that
caution be exercised when administering norepinephrine to nursing women.
Pricing: U.S.
Solution (Levophed Injection)
1 mg/mL (4 mL): $17.88
Monitoring Parameters
Blood pressure (or mean arterial pressure), heart rate; cardiac output (as appropriate), intravascular
volume status, pulmonary capillary wedge pressure (as appropriate); monitor infusion site closely
Adine (CL);
Arespin (ID);
Arterenol (DE);
Cardiamed (MY);
Efrinalin (BR);
Fioritina (AR);
Levophed Bitartrate (AE, AU, BE, BH, CY, EG, GR, IL, IQ, IR, JO, KR, KW, LB, LY, MY, NZ,
OM, PH, QA, SA, SG, SY, TH, TW, YE);
N-Epi (TH);
Noradrenaline (GB);
Norepin (PH);
Norepine (TW);
Norphed (PH);
Rhinopront (LU);
Vascon (ID)
Mechanism of Action
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)
Aron DC, Bravo EL, and Kapcala LP, Erroneous Plasma Norepinephrine Levels With
Radioimmunoassay, Ann Intern Med, 1983, 98(6):1023.
2.
Brierley J, Carcillo JA, Choong K, et al, Clinical Practice Parameters for Hemodynamic
Support of Pediatric and Neonatal Septic Shock: 2007 Update from the American College of Critical
Care Medicine, Crit Care Med, 2009, 37(2):666-88. [PubMed 19325359]
3.
4.
Dellinger RP, Levy MM, Rhodes A, et al, Surviving Sepsis Campaign: International
Guidelines for Management of Severe Sepsis and Septic Shock, 2012, Crit Care Med, 2013,
41(2):580-637. [PubMed 23353941]
5.
Denkler KA and Cohen BE, Reversal of Dopamine Extravasation Injury With Topical
Nitroglycerin Ointment,Plast Reconstr Surg, 1989, 84(5):811-3. [PubMed 2510208]
6.
Field JM, Hazinski MF, Sayre MR, et al, Part 1: Executive Summary: 2010 American Heart
Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular
Care, Circulation, 2010, 122 (18 Suppl 3):640-56. [PubMed 20956217]
7.
Hollenberg SM, Ahrens TS, Annane D, et al, Practice Parameters for Hemodynamic
Support of Sepsis in Adult Patients: 2004 Update, Crit Care Med, 2004, 32(9):192848. [PubMed 15343024]
8.
9.
Institute for Safe Medication Practice (ISMP) and Vermont Oxford Network, Standard
Concentrations of Neonatal Drug Infusions, 2011. Available at
https://www.ismp.org/Tools/PediatricConcentrations.pdf
10.
Kleinman ME, Chameides L, Schexnayder SM, et al, Part 14: Pediatric Advanced Life
Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and
Emergency Cardiovascular Care,Circulation, 2010, 122(18 Suppl 3):876-908. [PubMed 20956230]
11.
12.
Minzter BH, Johnson RF, Paschall RL, et al, "The Diverse Effects of Vasopressors on the
Fetoplacental Circulation of the Dual Perfused Human Placenta," Anesth Analg, 2010, 110(3):85762. [PubMed 20032025]
13.
Nelson Textbook of Pediatrics, 18th ed, Kliegman RM, Behrman RE, Jenson HB, Stanton
BF, eds, Philadelphia, PA: WB Saunders Co, 2007.
14.
15.
Peberdy MA, Callaway CW, Neumar RW, et al, Part 9: Post Cardiac Arrest Care: 2010
American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care, Circulation, 2010, 122(18 Suppl 3):768-86. [PubMed 20956225]
16.
17.
Stier PA, Bogner MP, Webster K, et al, "Use of Subcutaneous Terbutaline to Reverse
Peripheral Ischemia," Am J Emerg Med, 1999, 17(1):91-4. [PubMed 9928712]
18.
19.
Wang L, Zhang W, and Zhao Y, "The Study of Maternal and Fetal Plasma Catecholamines
Levels During Pregnancy and Delivery," J Perinat Med, 1999, 27(3):195-8. [PubMed 10503181]
20.
Wong AF, McCulloch LM, and Sola A, Treatment of Peripheral Tissue Ischemia With
Topical Nitroglycerin Ointment in Neonates, J Pediatr, 1992, 121(6):980-3. [PubMed 1447671]