Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Norepinephrine Bitartrate Injection, USP, is a sterile, colorless to pale yellow solution for injection intended for intravenous use. It contains the equivalent of 1 mg of norepinephrine base per 1 mL (4 mg/4 mL). It is available as 4 mg/4 mL in single-dose amber glass vials. Supplied as: Unit of Sale Concentration NDC 43066-997-10 Single-dose vials in boxes of 10 4 mg/4 mL (1 mg/mL) Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Store in original carton until time of administration to protect from light. Discard unused portion.; PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Container Label NDC 43066-997-01 Rx Only NORepinephrine Injection, USP 4 mg/4 mL (1mg/mL) FOR INTRAVENOUS INFUSION ONLY DILUTE BEFORE USE. Warning: Contains Sulfites. 4 mL Single-Dose Vial Each mL contains: norepinephrine bitartrate USP equal to 1 mg norepinephrine base. PROTECT FROM LIGHT. Code No.: TS/DRUGS/2/2015 LAB-021081-00 07-09-00-1148 (01)0034306697014 Lot: Exp.: Baxter Logo Manufactured for Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in India Carton Label GTIN 20343066997100 NDC 43066-997-10 NORepinephrine Bitartrate Injection, USP 4 mg/4 mL (1 mg.mL) Warning: This is a potent drug. Dosage should be controlled by frequent determination of blood pressure. Do not leave patient unattended during administration. Avoid extravasation. Read package insert carefully. FOR INTRAVENOUS INFUSION ONLY DILUTE BEFORE USE. DISCARD UNUSED PORTION. PROTECT FROM LIGHT. STERILE INJECTION 10 X 4 mL Single-Dose Vials Warning: Contains Sulfites. Rx only 07-03-00-0874 CAR-010360-00 NDC 43066-997-10 NORepinephrine Bitartrate Injection, USP 4 mg/4 mL (1 mg/mL) Manufactured for Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in India Baxter Logo Code No.: TS/DRUGS/2/2015 Each mL contains norepinephrine bitartrate USP, equivalent to 1 mg norepinephrine base, sodium chloride for isotonicity with not more than 0.2 mg sodium metabisulfite as antioxidant. The air in the vials has been displaced by nitrogen gas. Usual Dosage and Dilution Information: See package insert. 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. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Discard unused portion. NDC 43066-997-10 NORepinephrine Bitartrate Injection, USP 4 mg/4 mL (1 mg/mL) (01)20343066997100 Norepinephrine Representative Container Label 43066-997-01 Norepinephrine Representative Label 43066-997-10 1 of 4 Norepinephrine Representative Label 43066-997-10 2 of 4 Norepinephrine Representative Label 43066-997-10 3 of 4 Norepinephrine Representative Label 43066-997-10 4 of 4
- 16 HOW SUPPLIED/STORAGE AND HANDLING Norepinephrine Bitartrate Injection, USP, is a sterile, colorless to pale yellow solution for injection intended for intravenous use. It contains the equivalent of 1 mg of norepinephrine base per 1 mL (4 mg/4 mL). It is available as 4 mg/4 mL in single-dose amber glass vials. Supplied as: Unit of Sale Concentration NDC 43066-997-10 Single-dose vials in boxes of 10 4 mg/4 mL (1 mg/mL) Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Store in original carton until time of administration to protect from light. Discard unused portion.
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Container Label NDC 43066-997-01 Rx Only NORepinephrine Injection, USP 4 mg/4 mL (1mg/mL) FOR INTRAVENOUS INFUSION ONLY DILUTE BEFORE USE. Warning: Contains Sulfites. 4 mL Single-Dose Vial Each mL contains: norepinephrine bitartrate USP equal to 1 mg norepinephrine base. PROTECT FROM LIGHT. Code No.: TS/DRUGS/2/2015 LAB-021081-00 07-09-00-1148 (01)0034306697014 Lot: Exp.: Baxter Logo Manufactured for Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in India Carton Label GTIN 20343066997100 NDC 43066-997-10 NORepinephrine Bitartrate Injection, USP 4 mg/4 mL (1 mg.mL) Warning: This is a potent drug. Dosage should be controlled by frequent determination of blood pressure. Do not leave patient unattended during administration. Avoid extravasation. Read package insert carefully. FOR INTRAVENOUS INFUSION ONLY DILUTE BEFORE USE. DISCARD UNUSED PORTION. PROTECT FROM LIGHT. STERILE INJECTION 10 X 4 mL Single-Dose Vials Warning: Contains Sulfites. Rx only 07-03-00-0874 CAR-010360-00 NDC 43066-997-10 NORepinephrine Bitartrate Injection, USP 4 mg/4 mL (1 mg/mL) Manufactured for Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in India Baxter Logo Code No.: TS/DRUGS/2/2015 Each mL contains norepinephrine bitartrate USP, equivalent to 1 mg norepinephrine base, sodium chloride for isotonicity with not more than 0.2 mg sodium metabisulfite as antioxidant. The air in the vials has been displaced by nitrogen gas. Usual Dosage and Dilution Information: See package insert. 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. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Discard unused portion. NDC 43066-997-10 NORepinephrine Bitartrate Injection, USP 4 mg/4 mL (1 mg/mL) (01)20343066997100 Norepinephrine Representative Container Label 43066-997-01 Norepinephrine Representative Label 43066-997-10 1 of 4 Norepinephrine Representative Label 43066-997-10 2 of 4 Norepinephrine Representative Label 43066-997-10 3 of 4 Norepinephrine Representative Label 43066-997-10 4 of 4
Overview
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. Norepinephrine Bitartrate is (-)-α-(aminomethyl)-3,4-dihydroxybenzyl alcohol tartrate (1:1) (salt) monohydrate (molecular weight 337.3 g/mol) and has the following structural formula: Norepinephrine Bitartrate Injection, USP is supplied in a sterile aqueous solution in the form of the bitartrate salt to be administered by intravenous infusion. Norepinephrine is sparingly soluble in water, very slightly soluble in alcohol and ether, and readily soluble in acids. Each mL contains 1 mg of norepinephrine base (equivalent to 1.89 mg of norepinephrine bitartrate, anhydrous basis), sodium chloride for isotonicity, not more than 0.2 mg (vials) of sodium metabisulfite as an antioxidant. It has a pH of 3.0 to 4.5. The air in the containers has been displaced by nitrogen gas. Norepinephrine Structural Formula
Indications & Usage
Norepinephrine Bitartrate Injection is indicated to raise blood pressure in adult patients with severe, acute hypotension. Norepinephrine Bitartrate Injection is a catecholamine indicated for restoration of blood pressure in adult patients with acute hypotensive states. ( 1 )
Dosage & Administration
• Initial dose of 0.25 mL to 0.375 mL (from 8 mcg to 12 mcg of base) per minute, adjust the rate of flow to establish and maintain a low to normal blood pressure (usually 80 mm Hg to 100 mm Hg systolic) sufficient to maintain the circulation of vital organs. (2.2 ) • The average maintenance dose ranges from 0.0625 mL to 0.125 mL per minute (from 2 mcg to 4 mcg of base). ( 2.2 ) 2.1 Important Dosage and Administration Instructions Correct Hypovolemia Address hypovolemia before initiation of norepinephrine bitartrate injection therapy. If the patient does not respond to therapy, suspect occult hypovolemia [see Warnings and Precautions (5.1) ]. Administration Dilute norepinephrine bitartrate injection prior to use [see Dosage and Administration (2.3) ] . Infuse norepinephrine bitartrate injection into a large vein. Avoid infusions into the veins of the leg in the elderly or in patients with occlusive vascular disease of the legs [see Warnings and Precautions (5.1) ]. Avoid using a catheter-tie-in technique . Discontinuation When discontinuing the infusion, reduce the flow rate gradually. Avoid abrupt withdrawal. 2.2 Dosage After an initial dosage of 8 to 12 mcg per minute via intravenous infusion, assess patient response and adjust dosage to maintain desired hemodynamic effect. Monitor blood pressure every two minutes until the desired hemodynamic effect is achieved, and then monitor blood pressure every five minutes for the duration of the infusion. Typical maintenance intravenous dosage is 2 to 4 mcg per minute. 2.3 Preparation of Diluted Solution Visually inspect norepinephrine bitartrate injection for particulate matter and discoloration prior to administration (the solution is colorless) . Do not use the solution if its color is pinkish or darker than slightly yellow or if it contains a precipitate. Add the content of one norepinephrine bitartrate injection vial (4 mg in 4 mL) to 1,000 mL of 5% Dextrose Injection, USP or Sodium Chloride Injection solutions that contain 5% dextrose to produce a 4 mcg per mL dilution. Dextrose reduces loss of potency due to oxidation. Administration in saline solution alone is not recommended. Use higher concentration solutions in patients requiring fluid restriction. Prior to use, store the diluted norepinephrine bitartrate injection solution for up to 24 hours at room temperature [20°C to 25°C (68°F to 77°F)] and protect from light. 2.4 Drug Incompatibilities Avoid contact with iron salts, alkalis, or oxidizing agents. Whole blood or plasma, if indicated to increase blood volume, should be administered separately.
Warnings & Precautions
• Tissue Ischemia: Avoid extravasation of norepinephrine bitartrate into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug. Infuse norepinephrine bitartrate into a large vein. To prevent sloughing and necrosis in areas in which extravasation has taken place, the area should be infiltrated as soon as possible with10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of an adrenergic blocking agent. ( 5.1 ) • Hypotension After Abrupt Discontinuation: Sudden cessation of the infusion rate may result in marked hypotension. Reduce the norepinephrine bitartrate infusion rate gradually. ( 5.2 ) • Cardiac Arrhythmias: Norepinephrine Bitartrate may cause arrhythmias. Monitor cardiac function in patients with underlying heart disease. ( 5.3 ) • Allergic Reactions with Sulfite: Norepinephrine Bitartrate contains sodium metabisulfite. Sulfite may cause allergic-type-reactions. ( 5.4 ) 5.1 Tissue Ischemia Administration of norepinephrine bitartrate to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating norepinephrine bitartrate [see Dosage and Administration (2.1) ]. Avoid norepinephrine bitartrate in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction. Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients. Extravasation of norepinephrine bitartrate may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation [see Dosage and Administration (2.1) ]. Emergency Treatment of Extravasation To prevent sloughing and necrosis in areas in which extravasation has occurred, infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. 5.2 Hypotension after Abrupt Discontinuation Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the norepinephrine bitartrate infusion rate while expanding blood volume with intravenous fluids. 5.3 Cardiac Arrhythmias Norepinephrine Bitartrate elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias. 5.4 Allergic Reactions Associated with Sulfite Norepinephrine Bitartrate Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.
Contraindications
None. None ( 4 )
Adverse Reactions
The following adverse reactions are described in greater detail in other sections: • Tissue Ischemia [see Warnings and Precautions (5.1) ] • Hypotension [see Warnings and Precautions (5.2) ] • Cardiac Arrhythmias [see Warnings and Precautions (5.3) ] The most common adverse reactions are hypertension and bradycardia. The following adverse reactions can occur: Nervous system disorders: Anxiety, headache Respiratory disorders: Respiratory difficulty, pulmonary edema Most common adverse reactions are ischemic injury, bradycardia, anxiety, transient headache, respiratory difficulty, and extravasation necrosis at injection site. (6) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 866-770-7144 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions
• Monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types may result in hypertension. ( 7.1 ) • Cyclopropane and halothane anesthetics increase cardiac autonomic irritability. ( 7.4 ) 7.1 MAO-Inhibiting Drugs Co-administration of norepinephrine bitartrate with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) can cause severe, prolonged hypertension. If administration of norepinephrine bitartrate cannot be avoided in patients who recently have received any of these drugs and in whom, after discontinuation, MAO activity has not yet sufficiently recovered, monitor for hypertension. 7.2 Tricyclic Antidepressants Co-administration of norepinephrine bitartrate with tricyclic antidepressants (including amitriptyline, nortriptyline, protriptyline, clomipramine, desipramine, imipramine) can cause severe, prolonged hypertension. If administration of norepinephrine bitartrate cannot be avoided in these patients, monitor for hypertension. 7.3 Antidiabetics Norepinephrine Bitartrate can decrease insulin sensitivity and raise blood glucose. Monitor glucose and consider dosage adjustment of antidiabetic drugs. 7.4 Halogenated Anesthetics Concomitant use of norepinephrine bitartrate with halogenated anesthetics (e.g., cyclopropane, desflurane, enflurane, isoflurane, and sevoflurane) may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics.
Similar Drugs
Related medications based on brand, generic name, substance, active ingredients.