What is the complete drug information for Norepinephrine (Levophed)?

From the Guidelines

Norepinephrine is the first-choice vasopressor for treating hypotension in critically ill patients, particularly in septic shock, with a strong recommendation and moderate quality of evidence 1.

Indications and Usage

Norepinephrine is primarily used to treat hypotension in critically ill patients, particularly in septic shock, neurogenic shock, and other conditions with severe hypotension. The typical dosage ranges from 0.01-3 mcg/kg/minute administered as a continuous intravenous infusion, titrated to achieve a target mean arterial pressure (usually 65-75 mmHg) 1.

Mechanism of Action

Norepinephrine works by stimulating alpha-1 adrenergic receptors in blood vessels, causing vasoconstriction and increasing blood pressure. It also has some beta-1 adrenergic effects, providing mild cardiac stimulation 1.

Administration and Monitoring

The medication must be administered through a central venous catheter and requires continuous blood pressure monitoring. Common side effects include hypertension if dosed too high, bradycardia, arrhythmias, and tissue necrosis if extravasation occurs. Norepinephrine has a very short half-life (1-2 minutes), allowing for quick titration based on patient response 1.

Precautions and Contraindications

It should be used cautiously in patients with hypovolemia, as volume status should be addressed before or alongside vasopressor therapy. The medication is typically prepared in D5W or normal saline solutions and should be protected from light during administration. We recommend against using low-dose dopamine for renal protection (strong recommendation, high quality of evidence) 1.

Alternative and Combination Therapy

We suggest using dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (e.g., patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (weak recommendation, low quality of evidence) 1. We also suggest adding either vasopressin (up to 0.03 U/min) or epinephrine to norepinephrine with the intent of raising mean arterial pressure to target, or adding vasopressin to decrease norepinephrine dosage (weak recommendation, moderate quality of evidence) 1.

Additional Recommendations

We suggest using dobutamine in patients who show evidence of persistent hypoperfusion despite adequate fluid loading and the use of vasopressor agents (weak recommendation, low quality of evidence) 1. If initiated, vasopressor dosing should be titrated to an end point reflecting perfusion, and the agent reduced or discontinued in the face of worsening hypotension or arrhythmias. We also suggest that all patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (weak recommendation, very low quality of evidence) 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION Norepinephrine Bitartrate Injection is a concentrated, potent drug which must be diluted in dextrose containing solutions prior to infusion. DESCRIPTION Norepinephrine (sometimes referred to as l-arterenol/Levarterenol or l-norepinephrine) is a sympathomimetic amine which differs from epinephrine by the absence of a methyl group on the nitrogen atom

The complete drug information for norepinephrine includes:

• Drug Name: Norepinephrine (IV)
• Description: A sympathomimetic amine used to restore blood pressure in acute hypotensive states
• Dosage and Administration: Must be diluted in dextrose containing solutions prior to infusion, with an average dosage of 0.5 mL to 1 mL per minute (from 2 mcg to 4 mcg of base) 2
• Chemical Structure: (-)-α-(aminomethyl)-3,4-dihydroxybenzyl alcohol tartrate (1:1) (salt) monohydrate 2
• Solubility: Sparingly soluble in water, very slightly soluble in alcohol and ether, and readily soluble in acids
• pH: 3 to 4.5
• Storage: The air in the vials has been displaced by nitrogen gas 2

From the Research

Norepinephrine Drug Information

• Norepinephrine is a first-line agent recommended during resuscitation of septic shock to correct hypotension due to depressed vascular tone 3.
• The optimal blood pressure target for norepinephrine administration is a mean arterial pressure of at least 65 mmHg, with higher values recommended in cases of chronic hypertension 3, 4.
• Early administration of norepinephrine is beneficial for septic shock patients to restore organ perfusion, and the mean arterial pressure target should be individualized 3.
• In cases of refractory hypotension, increasing norepinephrine up to doses ≥1 µg/kg/min could be an option, or combining norepinephrine with other vasopressors such as vasopressin 4.

Comparison with Other Vasopressors

• Norepinephrine is currently the first-line vasopressor for septic shock, but vasopressin can be considered as a first-line vasopressor in septic shock patients with other risk factors that may contribute to renal failure requiring renal replacement therapy (RRT) 5.
• A network meta-analysis found that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications 6.
• Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, but was also associated with a higher incidence of cardiac arrhythmia 6.

Discontinuation of Vasopressors

• When discontinuing vasopressors in septic shock patients receiving concomitant norepinephrine and vasopressin treatment, discontinuing norepinephrine first may lead to a lower incidence of hypotension compared to discontinuing vasopressin first 7.
• However, the order of discontinuation did not significantly affect overall mortality, ICU mortality, or length of stay in the ICU 7.