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Generic Name: norepinephrine
Brand and Other Names: levarterenol, Levophed
Drug Class: Alpha/Beta Adrenergic Agonists
What is norepinephrine, and what is it used for?
Norepinephrine is a natural substance known as catecholamine synthesized in the brain and present in the central and peripheral nervous systems. Norepinephrine is both a hormone and a nerve-signaling agent (neurotransmitter) that plays a vital role in the fight-or-flight response to perceived danger. Norepinephrine used as a medication is similar in structure to the natural norepinephrine and mimics its actions in the body.
Norepinephrine is used to treat severe low blood pressure (hypotension) caused by cardiac arrest, circulatory shock or septic shock. Norepinephrine increases blood pressure by constricting the peripheral blood vessels, increases cardiac output, and dilates the coronary arteries improving blood flow.
Norepinephrine works by stimulating alpha-1 and beta-1 adrenergic receptors. Adrenergic receptors are molecules on cell surfaces that are activated by norepinephrine and epinephrine, another catecholamine. Norepinephrine increases blood pressure by stimulating alpha-1 receptors in the peripheral blood vessels which causes them to constrict. It also stimulates beta-1 receptors in the heart and coronary arteries, which increases the heart rate and strength of heart contractions, and dilates coronary arteries, increasing blood flow.
Norepinephrine is approved for use in the following conditions:
- Cardiac arrest and profound hypotension
- Acute hypotension due to:
- Pheochromocytomectomy, surgical removal of pheochromocytoma, a type of catecholamine secreting tumor in the adrenal gland
- Sympathectomy, surgical removal of nerve cell clusters (ganglion) as a treatment for certain condition
- Poliomyelitis, a disease caused by polio virus infection
- Spinal anesthesia
- Heart attack (myocardial infarction)
- Septicemia
- Blood transfusion
- Drug reactions
Off-label uses include:
- Beta-blocker toxicity
- Calcium channel-blocker toxicity
- Tricyclic antidepressant toxicity
Warnings
- Do not administer norepinephrine in the following conditions:
- Hypersensitivity to norepinephrine or any of its components
- Hypotension from low blood volume (hypovolemia), except as an emergency measure to maintain blood flow to the brain and coronary arteries, until blood volume replacement is complete; norepinephrine administration in hypovolemic state can severely reduce blood flow to peripheral tissue and kidneys
- Blood clots (thrombosis) in the peripheral or intestinal (mesenteric) blood vessels, except as a life-saving procedure
- When using cyclopropane or halothane anesthetics (both are not available in the US), because it can cause rapid and irregular contractions of the ventricles (ventricular tachycardia or fibrillation)
- Profoundly low tissue levels of oxygen (hypoxia) and high carbon dioxide levels (hypercarbia); can result in irregular heart rhythms
- Use with extreme caution with concurrent monoamine oxidase inhibitor (MAOI) therapy or antidepressants of the triptyline or imipramine types; may result in severe and prolonged hypertension
- Norepinephrine bitartrate injection contains sodium metabisulfite that may cause allergic-type reactions including severe reactions (anaphylaxis) or asthmatic episodes in certain susceptible people
- Continuously monitor the patient while on norepinephrine therapy to avoid dangerously high blood pressure
- As far as possible, infuse norepinephrine into a large vein, frequently check for free flow and take care to avoid leakage from the vein (extravasation) which can locally constrict blood vessels and cause tissue death (necrosis); in case of extravasation, infiltrate the area as soon as possible with diluted phentolamine (5 to 10 mg in 10 to 15 mL of saline)
What are the side effects of norepinephrine?
Common side effects of norepinephrine include:
- Reflex slowing down of heart rate (bradycardia)
- Irregular heart rhythm (cardiac arrhythmia)
- Heart muscle disease (cardiomyopathy)
- Anxiety
- Confusion
- Restlessness
- Transient headache
- Tremor
- Shortness of breath (dyspnea)
- Sweating
- Urinary retention
- Peripheral vascular insufficiency due to blood vessel constriction
- Reduced peripheral blood flow (ischemia)
- Low oxygen saturation in tissue (hypoxia) and tissue injury from ischemia
- Peripheral tissue death due to ischemia (gangrene)
- Tissue injury from extravasation
This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.
Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.
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What are the dosages of norepinephrine?
Injectable solution
- 1 mg/mL
Adult
Acute Hypotension
- Initial: 8-12 mcg/minute intravenous (IV) infusion; titrate to effect
- Maintenance: 2-4 mcg/minute IV infusion
Cardiac Arrest
- Initial: 8-12 mcg/minute intravenous (IV) infusion; titrate to effect
- Maintenance: 2-4 mcg/minute IV infusion
- 0.01-3 mcg/kg/minute intravenous (IV) infusion
Beta Blocker Toxicity (Off-label)
- Should be titrated to age-appropriate blood pressure
Calcium Channel Blocker Toxicity (Off-label)
- Should be titrated to age-appropriate blood pressure
- Tricyclic Antidepressant Toxicity (Off-label)
- Should be titrated to age-appropriate blood pressure
Pediatric
Acute hypotension
- Initial: 0.05-0.1 mcg/kg/minute intravenous (IV) infusion; titrate to effect
- Maximum: 1-2 mcg/kg/minute
Cardiac Arrest
- Initial: 0.05-0.1 mcg/kg/minute intravenous (IV) infusion; titrate to effect
- Maximum: 1-2 mcg/kg/minute
Shock
- 0.05-0.1 mcg/kg/minute IV infusion; titrate to effect; not to exceed 2 mcg/kg/minute
Overdose
- Norepinephrine overdose may cause symptoms such as headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decrease in cardiac output.
- In case of overdose, discontinue norepinephrine until the patient stabilizes.
What drugs interact with norepinephrine?
Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.
- Severe interactions of norepinephrine include:
- isocarboxazid
- linezolid
- phenelzine
- procarbazine
- selegiline transdermal
- tranylcypromine
- Norepinephrine has serious interactions with at least 34 different drugs.
- Norepinephrine has moderate interactions with at least 261 different drugs.
- Mild Interactions of norepinephrine include:
- bendroflumethiazide
- bumetanide
- chlorothiazide
- chlorthalidone
- cyclopenthiazide
- desmopressin
- eucalyptus
- furosemide
- hydrochlorothiazide
- torsemide
The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.
It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information.
Check with your doctor or health care provider if you have any questions about the medication.
Pregnancy and breastfeeding
- No animal reproduction studies have been conducted and it is not known if norepinephrine can cause fetal harm; use in pregnancy only if clearly needed.
- It is not known if norepinephrine is excreted in breast milk; because many drugs are excreted in breast milk, use with caution in nursing women.