Levophed SF

Levophed SF

norepinephrine

Manufacturer:

Hospira

Distributor:

Hospira
Full Prescribing Info
Contents
Noradrenaline bitartrate.
Description
Each ampule of Levophed SF contains noradrenaline 2 mg in 2 mL (1:1000), present as noradrenaline acid tartrate 4 mg in 2 mL.
It also contains the following excipients: Sodium chloride 17 mg/2 mL for tonicity and water for injection up to 2 mL. Sodium hydroxide and/or hydrochloric acid may be used for pH adjustment.
Noradrenaline acid tartrate is (1R)-2-amino-1-(3,4-dihydroxyphenyl)ethanol hydrogen (2R,3R)-2,3-dihydroxybutanedioate monohydrate.
Molecular Formula: C12H17NO9·H2O. Molecular Weight: 337.3.
Levophed SF is supplied in sterile concentrated solution for injection. Noradrenaline is a white or almost white crystalline powder. It is freely soluble in water and slightly soluble in ethanol (96%). Noradrenaline has a pH of 3-4.
Action
Pharmacology: Noradrenaline, a sympathomimetic amine, acts predominantly on α- and β-receptors in the heart. It therefore causes peripheral vasoconstriction (α-adrenergic action), and a positive inotropic effect on the heart and dilation of coronary arteries (β-adrenergic action). These actions result in an increase in systemic blood pressure and coronary artery blood flow. In myocardial infarction accompanied by hypotension, noradrenaline usually increases aortic blood pressure, coronary artery blood flow, and myocardial oxygenation, thereby helping to limit the area of myocardial ischemia and infarction. Venous return is increased and the heart tends to resume a more normal rate and rhythm than in the hypotensive state. In hypotension that persists after correction of blood volume deficits, noradrenaline helps raise the blood pressure to an optimal level and establish a more adequate circulation.
Indications/Uses
Emergency measure in blood pressure restoration in cases of acute hypotension.
Dosage/Direction for Use
Average Dosage: Add 2 mL of the 1:1000 solution of Levophed SF to 500 mL, (or Levophed SF 4 mL to 1 L) of glucose 5% solution. Each 1 mL of this dilution contains 4 mcg of noradrenaline (equivalent to 8 mcg of the acid tartrate). Give this dilution IV via a catheter well advanced centrally into the vein and securely fixed, if possible, avoiding a catheter tie-in technique as it promotes stasis. A drip bulb is necessary to permit an accurate estimation of the rate of flow in drops per minute. After observing the response to an initial dose of 2-3 mL/min (8-12 mcg of base), adjust the rate of flow to establish and maintain a low normal blood pressure (usually 80-100 mm Hg systolic) sufficient to maintain the circulation to vital organs. In previously hypertensive patients, it is recommended that the blood pressure should be raised no higher than 40 mm Hg below the preexisting systolic pressure. The average maintenance dose ranges from 0.5-1 mL/min (2-4 mcg of base). Occasionally, much larger daily doses (as high as 68 mg base or 34 ampules) may be necessary if the patient remains hypotensive, but occult blood volume depletion should always be suspected and corrected when present. Dilution can be varied depending on the clinical fluid volume requirement.
Duration of Therapy: The infusion should be continued until adequate blood pressure and tissue perfusion are maintained without therapy. The infusion rate should then be reduced gradually, avoiding abrupt withdrawal. In some of the reported cases of vascular collapse due to acute myocardial infarction, treatment was required for up to 6 days.
Overdosage
Overdosage with norepinephrine may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance and decreased cardiac output. Headache may indicate severe hypertension.
In case of accidental overdosage, as evidenced by excessive blood pressure elevation, discontinue norepinephrine until the condition of the patient stabilizes.
Contraindications
Levophed SF should not be given to patients who are hypotensive from hypovolemia, except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed. If Levophed SF is continuously administered to maintain blood pressure in the absence of blood volume replacement, the following may occur: Severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, poor systemic blood flow despite "normal" blood pressure, tissue hypoxia and lactate acidosis.
Levophed SF should not be given to patients with mesenteric or peripheral vascular thrombosis (because of the risk of increasing ischemia and extending the area of infarction) unless, in the opinion of the attending physician, the administration of Levophed SF is necessary as a life-saving procedure.
Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of IV administered epinephrine or norepinephrine. Hence, the use of Levophed SF during cyclopropane and halothane anesthesia is generally considered contraindicated because of the risk of producing ventricular tachycardia or fibrillation.
The same type of cardiac arrhythmias may result from the use of Levophed SF in patients with profound hypoxia or hypercarbia.
Warnings
Norepinephrine should be used with extreme caution in patients receiving MAOIs or antidepressants of the triptyline or imipramine types, because severe, prolonged hypertension may result.
Special Precautions
Avoid Hypertension: Because of the potency and varying responses to Levophed SF, the possibility exists that hypertension may be produced with overdoses of this pressor agent. Hence, it is desirable to record the blood pressure every 2 min from the time administration is started until the desired blood pressure is obtained, and then every 5 min if administration is to be continued. The rate of flow must be watched constantly and the patient should never be left unattended while receiving norepinephrine. Headache may be a symptom of hypertension due to overdosage.
Hypersensitivity: Certain patients may be hypersensitive to the effects of Levophed SF eg, hyperthyroidism patients (see Adverse Reactions).
Site of Infusion: Levophed SF should be given into a large vein, particularly an antecubital vein, because when administered into this vein, the risk of necrosis of the overlying skin from prolonged vasoconstriction is apparently very slight. The femoral vein is also an acceptable route of administration. A catheter tie-in technique should be avoided, if possible, since the obstruction to blood flow around the tubing may cause stasis and increased local concentration of Levophed SF. As occlusive vascular diseases (eg, atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger's disease) are more likely to occur in the lower rather than in the upper extremity, the leg veins in elderly patients or in those suffering from such disorders should be avoided. Gangrene has been reported in lower extremity when infusions of Levophed were given in an ankle vein.
Extravasation: The infusion site should be checked frequently for free flow. Care should be taken to avoid extravasation of norepinephrine into the tissues, as local necrosis might ensue due to the vasoconstrictive action of Levophed SF. 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, permitting some leakage.
This may also progress on rare occasions to superficial slough, particularly during infusion into leg veins in elderly patients or in those suffering from obliterative vascular disease. Hence, if blanching occurs, consideration should be given to changing the infusion site at intervals to allow the effects of local vasoconstriction to subside.
Antidote for Extravasation Ischemia: To prevent sloughing and necrosis in areas in which extravasation has occurred, the area should be infiltrated as soon as possible with 10-15 mL of saline solution containing 5-10 mg of phentolamine, an adrenergic-blocking agent. Using a syringe with a fine hypodermic needle, the solution is infiltrated 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 hrs. Therefore, phentolamine should be given as soon as possible after the extravasation is noted.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Studies have not been performed.
Use in pregnancy: Animal reproduction studies have not been conducted with norepinephrine. It is also not known whether norepinephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Norepinephrine should be given to a pregnant woman only if clearly needed.
Use in lactation: It is not known whether Levophed SF is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when norepinephrine is administered to a nursing woman.
Use in children: Safety and effectiveness in children have not been established.
Use in the elderly: Clinical studies of norepinephrine did not include sufficient numbers of subjects ≥65 years to determine whether they respond differently from younger subjects. Although clinical experience has not identified, differences in responses between the elderly and younger patients, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other therapy.
Norepinephrine infusions should not be administered into the veins in the leg in elderly patients.
Use In Pregnancy & Lactation
Use in pregnancy: Animal reproduction studies have not been conducted with norepinephrine. It is also not known whether norepinephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Norepinephrine should be given to a pregnant woman only if clearly needed.
Use in lactation: It is not known whether Levophed SF is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when norepinephrine is administered to a nursing woman.
Adverse Reactions
Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy. If plasma volumes are not corrected, hypotension may recur when Levophed SF is discontinued, or blood pressure may be maintained at the risk of severe peripheral and visceral vasoconstriction (eg, decreased renal perfusion) with diminution in blood flow and tissue perfusion with subsequent tissue hypoxia and lactic acidosis and possible ischemic injury. Gangrene of extremities has been rarely reported.
Overdoses or conventional doses in hypersensitive persons (eg, hyperthyroid patients) cause severe hypertension with violent headache, photophobia, stabbing retrosternal pain, pallor, intense sweating and vomiting.
The following reactions can occur: Body as a Whole: Ischemic injury due to potent vasoconstrictor action and tissue hypoxia.
Cardiovascular System: Bradycardia, probably as a reflex result of a rise in blood pressure, arrhythmias.
Nervous System: Anxiety, transient headache.
Respiratory System: Respiratory difficulty.
Skin and Appendages: Extravasation necrosis at injection site.
Drug Interactions
Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of IV administered epinephrine or norepinephrine. Hence, the use of norepinephrine during cyclopropane and halothane anesthesia is generally considered contraindicated because of the risk of producing ventricular tachycardia or fibrillation. The same type of cardiac arrhythmias may result from the use of norepinephrine in patients with profound hypoxia or hypercarbia.
Extreme caution should be exercised in patients receiving monoamine oxidase inhibitors (MAOIs) or antidepressants of the triptyline or imipramine types (see Warnings) because severe, prolonged hypertension may result.
Incompatibilities: Levophed SF solutions should not be mixed with other medicines. Infusion solutions containing noradrenaline acid tartrate have been reported to be incompatible with alkalis and oxidizing agents, barbiturates, chlorpheniramine, chlorothiazide, nitrofurantoin, phenytoin, sodium bicarbonate, sodium iodide, streptomycin, sulfadiazine and sulfafurazole.
Caution For Usage
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use, whenever solution and container permit.
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.
Levophed SF should be administered in glucose 5% solution in distilled water or glucose 5% in saline solution. Administration in saline solution alone is not recommended. Whole blood or plasma, if indicated to increase blood volume, should be administered separately. Levophed SF contains no antimicrobial preservative. It is for single-use only. Discard any residue.
MIMS Class
ATC Classification
C01CA03 - norepinephrine ; Belongs to the class of adrenergic and dopaminergic cardiac stimulants excluding glycosides. Used in the treatment of hypotension.
Presentation/Packing
Infusion conc 1 mg/mL (amp) x 2 mL x 5's, 4 mL x 5's.
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