Levofed2 mg/2 ml

Established / FDA-approved uses

• Severe, acute hypotension: Levofed is indicated to raise blood pressure in adult patients with severe, acute hypotension, including hypotension associated with septic shock, cardiogenic shock, and other distributive or vasodilatory shock states.
• Septic shock (guideline-supported, generally preferred first-line agent): International critical care guidelines (e.g. the Surviving Sepsis Campaign) recommend Levofed as the first-line vasopressor of choice for adults with septic shock who remain hypotensive despite adequate fluid resuscitation.

Adjunct / combination use

• As an adjunct to appropriate intravenous fluid resuscitation and, when needed, other vasopressors (e.g. vasopressin) or inotropes (e.g. dobutamine) added to Levofed in refractory shock.
• Adjunctive use during resuscitation from cardiac arrest to support blood pressure after return of spontaneous circulation, per advanced cardiac life support protocols.

Off-label uses (commonly used, not formally FDA-approved for these)

• Hypotension during spinal or general anesthesia.
• Support of blood pressure in neurogenic shock and other refractory hypotensive states in intensive care, based on clinical judgment.

Levofed does not treat the underlying cause of shock; it is used for temporary hemodynamic support while the underlying condition is treated.

Each mL of injectable solution typically contains Norepinephrine bitartrate equivalent to 1 mg of Norepinephrine base (common presentations include 1 mg/mL and 4 mg/4 mL ampoules/vials, sold as a sterile concentrate for dilution). Some formulations contain sodium metabisulfite or sodium bisulfite as an antioxidant preservative.

Norepinephrine is supplied as a sterile, clear, colorless-to-faintly-yellow aqueous solution for intravenous infusion after dilution; it is not available as an oral formulation.

Levofed (also known as noradrenaline) is an endogenous catecholamine and a potent, direct-acting sympathomimetic amine. As a medicine, Levofed is used as a vasopressor to restore adequate blood pressure and perfusion of vital organs in patients with severe, acute hypotension and shock, most commonly septic shock.

Levofed is administered only as a continuous intravenous infusion in a closely monitored hospital setting (intensive care unit or equivalent), because of its potency and narrow margin between therapeutic effect and toxicity.

Vasopressor / Sympathomimetic (adrenergic) agent — Levofed belongs to the catecholamine class of drugs used for hemodynamic (blood pressure) support.

Mechanism

Norepinephrine is a direct-acting agonist at adrenergic receptors. It stimulates alpha-1 adrenergic receptors predominantly, producing potent vasoconstriction of arterioles and venules, which increases systemic vascular resistance and raises both systolic and diastolic blood pressure. Norepinephrine also has modest beta-1 adrenergic agonist activity, producing a mild positive inotropic effect on the heart, though heart rate often falls (reflex bradycardia) due to baroreceptor-mediated vagal response to the rise in blood pressure. Norepinephrine has minimal beta-2 activity.

Pharmacokinetics

Norepinephrine has a rapid onset of action (within minutes) when given intravenously and a short elimination half-life (approximately 2–2.5 minutes), so its hemodynamic effects resolve quickly once the infusion is stopped or the rate reduced. It is metabolized primarily by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), mainly in the liver and other tissues, and excreted in urine as inactive metabolites.

• Levofed is for intravenous infusion only — never given orally, intramuscularly, or as a bolus injection.
• Dilute the concentrate in 5% dextrose, dextrose-saline, or normal saline as directed before infusing; use only clear, particulate-free solution.
• Administer using a calibrated infusion pump into a large vein, preferably a secure central venous catheter, to reduce the risk of extravasation.
• Continuously monitor blood pressure (checking every 2–3 minutes until stable, then at regular intervals), heart rate, and cardiac rhythm throughout the infusion.
• Do not stop the infusion abruptly; reduce the rate gradually while monitoring for rebound hypotension.
• Inspect the infusion site frequently for signs of extravasation (blanching, swelling, pain); if extravasation occurs, stop the infusion at that site immediately and seek prompt medical management (see Precautions and Warnings).

• Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants: Can markedly and unpredictably potentiate the pressor (blood-pressure-raising) effect of Levofed, risking severe, prolonged hypertension; substantially reduced Levofed doses and very close monitoring are required if co-administration cannot be avoided.
• Halogenated general anesthetics (e.g. halothane, cyclopropane): Sensitize the myocardium to catecholamines, increasing the risk of serious ventricular arrhythmias when combined with Levofed.
• Other vasopressors/sympathomimetics: Concurrent use can have additive cardiovascular effects; combination should be managed only under specialist critical-care supervision.
• Oxytocic drugs: May potentiate the vasopressor effect, increasing the risk of severe hypertension.
• Antidiabetic agents (insulin, oral hypoglycemics): Levofed can raise blood glucose and reduce insulin sensitivity; blood glucose should be monitored during co-administration.

Common

• Bradycardia (reflex slowing of heart rate) or, less commonly, tachycardia
• Headache
• Anxiety, restlessness
• Palpitations
• Hypertension (including excessive blood pressure elevation with overly rapid titration)

Less common / serious

• Cardiac arrhythmias (including ventricular arrhythmias)
• Peripheral (limb, digital) ischemia with prolonged or high-dose use, rarely progressing to gangrene
• Extravasation-related local tissue necrosis and sloughing at or around the infusion site (see Precautions and Warnings)
• Reduced organ (renal, mesenteric) perfusion with excessive vasoconstriction
• Metabolic acidosis with prolonged high-dose use

Pregnancy: Data on Levofed use in pregnancy are limited. Levofed should be used in pregnancy only if clearly needed and the potential maternal benefit justifies the potential risk to the fetus, such as in life-threatening maternal emergencies (e.g. septic shock, severe hemorrhage, or hypotension refractory to fluids). Levofed can reduce placental blood flow through vasoconstriction, so it should be used at the lowest effective dose with close fetal and maternal monitoring; a physician must weigh risks and benefits in each case.

Lactation: There is limited information on Levofed in breast milk. Because Levofed has a very short half-life and poor oral bioavailability, clinically significant exposure to a breastfeeding infant is not expected; however, Levofed is used only in acute, monitored hospital settings, so a physician should advise on breastfeeding timing based on the mother's overall clinical condition.

• Monitored setting required: Levofed must be administered only in a closely monitored setting (ICU/critical care) with continuous blood pressure and cardiac monitoring by trained personnel; it is not a medicine that can be used unsupervised.
• Extravasation risk (vesicant): Extravasation can cause severe local tissue necrosis. Infuse through a secure, preferably central, intravenous line and inspect the infusion site frequently. If extravasation occurs, stop the infusion at that site immediately and infiltrate the affected area promptly with phentolamine (a local antidote) as directed by a physician.
• Correct hypovolemia concurrently: Levofed does not replace adequate fluid/blood volume resuscitation in shock; volume status should be corrected together with, not instead of, Levofed therapy.
• Cardiac arrhythmias: Levofed can provoke or worsen cardiac arrhythmias; use with particular caution and continuous ECG monitoring in patients with underlying heart disease.
• Drug interactions: Concurrent MAOIs or tricyclic antidepressants can markedly potentiate the pressor effect of Levofed, requiring substantially reduced doses (see Interactions).
• Sulfite sensitivity: Some formulations contain sulfite preservatives, which can cause allergic-type reactions, including anaphylactic symptoms, in susceptible (particularly asthmatic) patients.
• Avoid abrupt discontinuation: Stopping Levofed suddenly can cause marked rebound hypotension; taper the infusion gradually while monitoring blood pressure.

Overdose or excessively rapid administration of Levofed can cause severe hypertension, marked reflex bradycardia, decreased cardiac output, severe headache, photophobia, chest pain, pallor, profuse sweating, and vomiting, and may precipitate serious arrhythmias.

Suspected Levofed overdose is a medical emergency that occurs in a hospital/ICU setting where the infusion can be stopped or reduced immediately; if any overdose is suspected, staff should seek immediate senior/emergency medical assistance or contact a poison control center for further guidance. Do not attempt home management — Levofed is only ever given under direct medical supervision.

Levofed injection should be stored at controlled room temperature, 20–25°C (68–77°F), protected from light, and kept in its original carton until the time of use. Do not use if the solution is discolored (pinkish, yellowish-brown) or contains a precipitate. Keep out of reach of children. Discard any unused, diluted solution as per hospital protocol; do not use if not clear and colorless to slightly yellow.

• Elderly: No specific dose adjustment is established, but elderly patients may be more sensitive to the cardiovascular effects of Levofed and may have more underlying cardiac disease; use with caution and close monitoring.
• Renal impairment: No specific dosage adjustment is established; Levofed is titrated to clinical (blood pressure) response under continuous monitoring regardless of renal function.
• Hepatic impairment: No specific dosage adjustment is established; use with caution and titrate to effect, since Levofed is metabolized via COMT/MAO enzymes present in the liver, among other tissues.
• Pregnancy and lactation: See Pregnancy and Lactation section.
• Pediatric patients: See Pediatric Uses section.

Levofed is used for as short a duration as clinically necessary — typically hours to a few days — for as long as the patient remains in shock or severe acute hypotension and requires vasopressor support. There is no fixed maximum duration; the infusion is continuously titrated and is tapered off gradually as the patient's hemodynamic status improves and underlying causes are treated, under continuous intensive-care monitoring.

Norepinephrine belongs to the catecholamine class of drugs; therapeutically it is classified as a vasopressor and an adrenergic (sympathomimetic) agonist, chemically related to epinephrine and dopamine.

Norepinephrine acts predominantly as a potent alpha-1 adrenergic receptor agonist, causing marked vasoconstriction of arterioles and veins, which raises systemic vascular resistance and blood pressure. It also has mild beta-1 adrenergic agonist activity, producing a modest increase in myocardial contractility, though heart rate typically decreases due to a compensatory (baroreceptor-mediated) reflex response to the rise in blood pressure. Its predominant vascular action distinguishes it from purely inotropic agents and underlies its role as a first-line vasopressor in septic and other distributive shock states.

C

Safety and efficacy of Levofed have not been formally established in controlled pediatric trials; the labeling position for Levofed in pediatric patients is conservative. Nonetheless, Levofed is widely and routinely used off-label in pediatric intensive care for septic shock and other hypotensive states unresponsive to fluid resuscitation, based on extensive clinical experience and pediatric critical-care guidelines (e.g. Surviving Sepsis Campaign guidance for children).

When used in children, Levofed is dosed by body weight, typically starting around 0.05–0.1 mcg/kg/min IV as a continuous infusion and titrated carefully to the target blood pressure/perfusion response, always in a pediatric intensive care unit with continuous invasive monitoring by clinicians experienced in pediatric critical care.