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Indications & Uses
Indication information is not available for this brand yet.
Pharmacology
Norepinephrine is a direct-acting sympathomimetic, which means it works straight on the receptors and stimulates β1- and α-adrenergic receptors. Through its α-agonist action it narrows the blood vessels (vasoconstriction). This raises both the systolic and the diastolic BP, and the heart rate slows down reflexly as a result.
Dosage Reference
Reference Information Only
Dosages shown are general references from official sources. Always consult your doctor or pharmacist for personalized dosing.
Adults:
An infusion of Norepinephrine should be given into a large vein.
Restoration of Blood Pressure in Acute Hypotensive States
Blood volume depletion should always be corrected as fully as possible before any vasopressor is given. In an emergency, when intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, Norepinephrine can be given before and together with blood volume replacement.
Diluent
Norepinephrine should be diluted in 5 percent dextrose injection or 5 percent dextrose and sodium chloride injections. These dextrose containing fluids protect against significant loss of potency due to oxidation. Saline solution alone is not recommended. If whole blood or plasma is needed to increase blood volume, give it separately (for example, with a Y-tube and individual containers if both are given at the same time).
Average Dosage
Add the content of the ampoule (4 mg/4 ml) of Norepinephrine to 1,000 mL of a 5 percent dextrose containing solution. Each ml of this dilution contains 4 mcg of the base of Norepinephrine, and it is given by intravenous infusion. Pass a plastic intravenous catheter through a suitable bore needle, well advanced centrally into the vein, and fix it securely with adhesive tape. If possible, avoid a catheter tie-in technique, as this promotes stasis. An IV drip chamber or other suitable metering device is essential, so that the rate of flow in drops per minute can be estimated accurately.
Start with 2 ml to 3 ml (from 8 mcg to 12 mcg of base) per minute and watch the response. Then adjust the rate of flow to establish and maintain a low normal blood pressure (usually 80 mm Hg to 100 mm Hg systolic), enough to maintain the circulation to vital organs. In patients who were hypertensive before, the blood pressure should be raised no higher than 40 mm Hg below the preexisting systolic pressure. The average maintenance dose ranges from 0.5 ml to 1 ml per minute (from 2 mcg to 4 mcg of base).
High Dosage
In all cases, the dose of Norepinephrine should be titrated according to the patient's response. Occasionally much larger or even enormous daily doses (as high as 68 mg base or 17 ampoules) may be necessary if the patient stays hypotensive. Even so, occult blood volume depletion should always be suspected and corrected when present. Central venous pressure monitoring is usually helpful in detecting and treating this situation.
Fluid Intake
How much the solution is diluted depends on the clinical fluid volume requirements. If large volumes of fluid (dextrose) are needed at a flow rate that would mean an excessive dose of the pressor agent per unit of time, use a solution more dilute than 4 mcg per ml. On the other hand, when large volumes of fluid are clinically undesirable, a concentration greater than 4 mcg per ml may be necessary.
Duration of Therapy
Continue the infusion until adequate blood pressure and tissue perfusion are maintained without therapy. Reduce the infusion gradually and avoid abrupt withdrawal. In some of the reported cases of vascular collapse due to acute myocardial infarction, treatment was required for up to six days.
Adjunctive Treatment in Cardiac Arrest
Norepinephrine infusions are usually given intravenously during cardiac resuscitation, to restore and maintain an adequate blood pressure after an effective heartbeat and ventilation have been established by other means. Its powerful beta-adrenergic stimulating action is also thought to increase the strength and effectiveness of systolic contractions once they occur.
Average Dosage
To maintain systemic blood pressure during the management of cardiac arrest, Norepinephrine is used in the same manner as described under Restoration of Blood Pressure in Acute Hypotensive States. Do not use the solution if its color is pinkish or darker than slightly yellow, or if it contains a precipitate. Avoid contact with iron salts, alkalis, or oxidizing agents.
Side Effects
In the body as a whole, Norepinephrine Tartrate can cause ischemic injury, because of its potent vasoconstrictor action and tissue hypoxia. Cardiovascular system: bradycardia, probably as a reflex result of a rise in blood pressure, and arrhythmias. Nervous system: anxiety and transient headache. Respiratory system: respiratory difficulty. Skin and appendages: extravasation necrosis at the injection site. Prolonged use of any potent vasopressor may lead to plasma volume depletion, and this should be corrected continuously with appropriate fluid and electrolyte replacement therapy. If plasma volumes are not corrected, hypotension may recur when Norepinephrine Tartrate is stopped. Or blood pressure may be maintained at the risk of severe peripheral and visceral vasoconstriction (for example, decreased renal perfusion). That brings less blood flow and tissue perfusion, then tissue hypoxia and lactic acidosis, and possible ischemic injury. Gangrene of the extremities has been reported rarely. Overdoses, or even conventional doses in hypersensitive persons (for example, hyperthyroid patients), cause severe hypertension with violent headache, photophobia, stabbing retrosternal pain, pallor, intense sweating and vomiting.
Cautions & Contraindications
Warnings & Precautions
Avoid hypertension Norepinephrine Tartrate is a potent medicine, and people respond differently to pressor substances. So there is always a chance that an overdose will push the blood pressure dangerously high. Blood pressure should be recorded every two minutes from the time the infusion starts until the desired blood pressure is reached, and then every five minutes for as long as the infusion continues. The rate of flow must be watched constantly. The patient should never be left alone while receiving Norepinephrine Tartrate. Headache may be a symptom of hypertension caused by overdosage. Site of infusion Whenever possible, give the infusion into a large vein, particularly an antecubital vein, because the risk of necrosis of the overlying skin from prolonged vasoconstriction is apparently very slight when the drug goes into this vein. Some authors have said the femoral vein is also an acceptable route. A catheter tie-in technique should be avoided if possible, since blocked blood flow around the tubing may cause stasis and a higher local concentration of the drug. Occlusive vascular diseases (for example, atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger's disease) are more likely to occur in the lower than in the upper extremity. So the veins of the leg should be avoided in elderly patients or in those with such disorders. Gangrene has been reported in a lower extremity when infusions of Norepinephrine Tartrate were given in an ankle vein. Extravasation Check the infusion site often for free flow. Take care to avoid extravasation into the tissues, as local necrosis might follow because of the vasoconstrictive action of the drug. Blanching along the course of the infused vein, sometimes without obvious extravasation, has been attributed to vasa vasorum constriction with increased permeability of the vein wall, which lets some leakage through. On rare occasions this may progress to superficial slough, particularly during infusion into leg veins in elderly patients or in those with obliterative vascular disease. So if blanching occurs, consider changing the infusion site at intervals so that the effects of local vasoconstriction can subside. Antidote for extravasation ischemia To prevent sloughing and necrosis where extravasation has taken place, infiltrate the area as soon as possible with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of phentolamine, an adrenergic blocking agent. Use a syringe with a fine hypodermic needle and infiltrate the solution liberally throughout the area, which is easily identified by its cold, hard and pallid appearance. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. So phentolamine should be given as soon as possible after the extravasation is noticed.
Contraindications
Norepinephrine should not be given to patients who are hypotensive because of a blood volume deficit. The one exception is as an emergency measure, to keep blood flowing to the coronary and cerebral arteries until blood volume replacement therapy is complete. If Norepinephrine is given continuously to hold up blood pressure without replacing the blood volume, several things may follow: severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, poor systemic blood flow despite a "normal" blood pressure, tissue hypoxia, and lactate acidosis. Patients with mesenteric or peripheral vascular thrombosis should not receive it either, because it risks increasing ischemia and extending the area of infarction. The only exception is when the attending physician decides that Norepinephrine is necessary as a life-saving procedure. Cyclopropane and halothane anesthetics increase cardiac autonomic irritability, so they seem to sensitize the myocardium to intravenously given epinephrine or norepinephrine. For this reason, using Norepinephrine during cyclopropane or halothane anesthesia is generally considered contraindicated, since it can produce ventricular tachycardia or fibrillation. The same kind of cardiac arrhythmias may result when Norepinephrine is used in patients with profound hypoxia or hypercarbia.
Pregnancy & Breastfeeding
Norepinephrine is listed as Pregnancy Category C. No animal reproduction studies have been done with Norepinephrine, so nobody knows whether it can harm the baby when given to a pregnant woman, or whether it affects the ability to have children. A pregnant woman should receive Norepinephrine only if it is clearly needed.
It is also not known whether this medicine passes into human milk. Many drugs do, so caution is needed when Norepinephrine is given to a woman who is breastfeeding.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Use in Special Populations
Use in children and adolescents: Safety and effectiveness of Norepinephrine Tartrate in pediatric patients have not been established. Geriatric use: Clinical studies of Norepinephrine Tartrate did not include enough subjects aged 65 and over to show whether they respond differently from younger subjects. Other reported clinical experience hasn't found any difference in response between elderly and younger patients. In general, the dose for an elderly patient should be chosen with caution, usually starting at the low end of the dosing range. This is because decreased hepatic, renal or cardiac function is more common in older people, and so are other diseases and other drug therapy. Norepinephrine Tartrate infusions should not be given into the veins in the leg in elderly patients. Carcinogenesis, mutagenesis, impairment of fertility: Studies have not been performed.
Overdose
Too much Norepinephrine Tartrate can cause headache, severe hypertension, reflex bradycardia, a marked increase in peripheral resistance and a drop in cardiac output. If it is given by accident in excess, you will see it as an excessive rise in blood pressure. In that case, stop Norepinephrine Tartrate until the patient's condition has stabilized.
⚠️ In an emergency call 999 or go to the nearest hospital emergency department.
Storage
Keep Norepinephrine Tartrate in a dry place where the temperature stays at or below 30°C, and protect it from light.
Drug Interactions
Common questions about Levofed DS 4 mg/4 ml
What is Levofed DS 4 mg/4 ml IV Infusion?
Levofed DS 4 mg/4 ml IV Infusion is a medicine that contains Norepinephrine Tartrate. It is made by Beacon Pharmaceuticals PLC. It belongs to the Alpha and Beta-adrenergic agonist group of medicines.
What are the side effects of Levofed DS?
In the body as a whole, Norepinephrine Tartrate can cause ischemic injury, because of its potent vasoconstrictor action and tissue hypoxia. Cardiovascular system: bradycardia, probably as a reflex result of a rise in blood pressure, and arrhythmias.
Can I take Levofed DS during pregnancy or while breastfeeding?
Norepinephrine is listed as Pregnancy Category C. No animal reproduction studies have been done with Norepinephrine, so nobody knows whether it can harm the baby when given to a pregnant woman, or whether it affects the ability to have children. Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
What happens if I take too much Levofed DS?
Too much Norepinephrine Tartrate can cause headache, severe hypertension, reflex bradycardia, a marked increase in peripheral resistance and a drop in cardiac output. If it is given by accident in excess, you will see it as an excessive rise in blood pressure. In an emergency call 999 or go to the nearest hospital emergency department.
How should I store Levofed DS?
Keep Norepinephrine Tartrate in a dry place where the temperature stays at or below 30°C, and protect it from light.
Can I take other medicines with Levofed DS?
Some medicines can interact with Norepinephrine Tartrate, for example: Halothane, Adrenaline, Imipramine Hydrochloride. Tell your doctor or pharmacist about every medicine you take.
Do I need a prescription for Levofed DS?
Levofed DS is a prescription (Rx) medicine. Take it as your doctor advises.