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)

Hypotension or shock: Treatment of severe hypotension, cardiogenic shock, or septic shock (and other vasodilatory shock states) that persist after adequate fluid volume replacement.

There are no contraindications listed in the US manufacturer's labeling.

Dosing: Adult Cardiogenic shock Cardiogenic shock: Note: Optimal goal of therapy not well established, but typically titrate to maintain end-organ perfusion. Institutional protocols may vary with weight-based or non-weight-based dose regimens (Ref ). Continuous infusion: Weight-based dosing: IV: Initial: 0.05 mcg/kg/minute; titrate based on clinical end point (eg, BP, end-organ perfusion); usual dosage range: 0.05 to 0.4 mcg/kg/minute (Ref ). Non–weight-based dosing (based on ~80 kg patient): IV: Initial: 5 mcg/minute; titrate based on clinical end point (eg, BP, end-organ perfusion); usual dosage range: 5 to 30 mcg/minute (doses calculated and rounded for an 80 kg patient based on weight-based dosing using the referenced sources (Ref ). Hepatorenal syndrome type 1 or acute kidney injury, treatment Hepatorenal syndrome type 1 or acute kidney injury, treatment (alternative agent) (off-label use): Note: Alternative to terlipressin. Use in combination with albumin (Ref ). Continuous infusion : Non–weight-based dosing: IV: Initial: 5 to 8 mcg/minute; dose may be increased every 4 hours based on clinical end points (eg, increase mean arterial pressure of ~10 mm Hg from baseline, improved urine output); maximum dose: 10 mcg/minute non-ICU; 50 mcg/minute in ICU (Ref ). Post–cardiac arrest shock Post–cardiac arrest shock: Note: Optimal goal of therapy not well established, but typically titrate to mean arterial BP (MAP) >65 mm Hg and preferably systolic BP of 80 to 100 mm Hg to optimize cerebral and end-organ perfusion. Institutional protocols may vary with weight-based or non-weight-based dose regimens (Ref ). Continuous infusion: Weight-based dosing: IV: Initial: 0.05 to 0.15 mcg/kg/minute; titrate based on clinical end points (eg, MAP, end-organ perfusion); usual dosing range: 0.05 to 1 mcg/kg/minute; maximum dose range for refractory shock: 1 to 3.3 mcg/kg/minute (Ref ). Non–weight-based dosing (based on ~80 kg patient): IV: Initial: 5 to 15 mcg/minute; titrate based on clinical end points (eg, MAP, end-organ perfusion); usual dosing range: 5 to 80 mcg/minute; maximum dose range for refractory shock: 80 to 250 mcg/minute (doses calculated and rounded for an 80 kg patient based on weight-based dosing using the referenced sources (Ref ). Septic shock and other vasodilatory shock states Septic shock and other vasodilatory shock states: Note: In general, used to maintain goal MAP (eg, ~65 mm Hg); consider use if patient is in shock or has hypoperfusion during or after fluid resuscitation (Ref ). Institutional protocols may vary with weight-based or non-weight-based dose regimens. Continuous infusion: Weight-based dosing: IV: Initial: 0.05 to 0.15 mcg/kg/minute; titrate to goal MAP; usual dose range: 0.025 to 1 mcg/kg/minute; maximum dose range for refractory shock: 1 to 3.3 mcg/kg/minute (Ref ). Note: While available data describe a wide range of initial dosing (0.01 to 0.5 mcg/kg/minute), initial dosing provided is a reasonable starting point for most patients. Non–weight-based dosing (based on ~80 kg patient): IV: Initial: 5 to 15 mcg/minute; titrate to goal MAP; usual dose range: 2 to 80 mcg/minute; maximum dose range for refractory shock: 80 to 250 mcg/minute (doses calculated and rounded for an 80 kg patient based on weight-based dosing using the referenced sources (Ref ). Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

IV: Administer as a continuous infusion via an infusion pump. Dilute vials prior to use; a 4 mg per 250 mL and an 8 mg per 250 mL premixed solution are also available for IV infusion. Central line administration is preferred; extravasation may cause severe ischemic necrosis. If central line is not available, may administer for a short duration (<72 hours) through a peripheral IV catheter placed in a large vein at a proximal site (eg, in or proximal to antecubital fossa). Frequent monitoring of the IV catheter site is recommended to rapidly identify extravasation (Ref ). Refer to institutional policies and procedures; catheter placement/size and vasopressor concentration may vary depending on institution. Administration through midline catheters may also be an option (Ref ). Do not administer sodium bicarbonate (or any alkaline solution) through an IV line containing norepinephrine; inactivation of norepinephrine may occur. Avoid abrupt withdrawal; reduce infusion flow rate slowly.

Very rapid acting.

Sublingual powder

Vasopressor: 1 to 2 minutes.

Adverse Reactions The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined: Cardiovascular: Bradycardia, cardiac arrhythmia, cardiomyopathy (stress), peripheral vascular insufficiency Central nervous system: Anxiety, transient headache Respiratory: Dyspnea <1%, postmarketing, and/or case reports: Peripheral gangrene, peripheral ischemia (digital [Daroca-Pérez 2017])

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. If extravasation occurs, infiltrate the area with diluted phentolamine (5 to 10 mg in 10 to 20 mL saline in adult patients) with a fine hypodermic needle. Phentolamine should be administered as soon as possible after extravasation is noted to prevent sloughing /necrosis. Disease-related concerns: • Hypovolemia: Address hypovolemia before initiating therapy; patients who are hypotensive from hypovolemia may experience severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite normal BP. • Hypoxia/hypercarbia: Use in patients with profound hypoxia or hypercarbia may produce ventricular tachycardia or fibrillation; use with extreme caution. Dosage form specific issues: • Sodium metabisulfite: Product may contain sodium metabisulfite. Use caution in patients with asthma or a sulfite allergy; allergic-type reactions, including anaphylactic symptoms and life-threatening asthmatic episodes, may occur. Other warnings/precautions: • Abrupt discontinuation: Gradually reduce infusion rate while expanding blood volume with IV fluids during discontinuation of therapy; severe hypotension may occur with abrupt discontinuation. • Appropriate use: Assure adequate circulatory volume to minimize need for vasoconstrictors. Avoid hypertension; monitor BP closely and adjust infusion rate. Avoid in patients with mesenteric or peripheral vascular thrombosis; use may increase ischemia and extend the area of infarction.