norepinephrine (as bitartrate) 4 MG per 4 ML Injection

Details

Generic Name: NOREPINEPHRINE BITARTRATE

Brand Name: Norepinephrine bitartrate

Substance Name(s):
NOREPINEPHRINE BITARTRATE

WARNINGS

Norepinephrine should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe, prolonged hypertension may result.

DRUG INTERACTIONS

Drug Interactions: Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously 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. Norepinephrine should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe, prolonged hypertension may result.

OVERDOSAGE

Overdosage with norepinephrine may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. In case of accidental overdosage, as evidenced by excessive blood pressure elevation, discontinue norepinephrine until the condition of the patient stabilizes.

DESCRIPTION

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 and has the following structural formula: Norepinephrine is supplied in sterile aqueous solution in the form of the bitartrate salt to be administered by intravenous infusion following dilution. Norepinephrine is sparingly soluble in water, very slightly soluble in alcohol and ether, and readily soluble in acids. Each mL contains the equivalent of 1 mg base of norepinephrine, sodium chloride for isotonicity. It has a pH of 3 to 4.5. The air in the ampules has been displaced by nitrogen gas. Norephinephrine structure

HOW SUPPLIED

Norepinephrine Bitartrate Injection, USP, contains the equivalent of 4 mg base of norepinephrine per each 4 mL ampule (1 mg/mL), and is available as follows: NDC 36000-162-10 Ampules of 4 mL in shelf carton of 10 Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Retain in carton until time of use. Protect from light.

GERIATRIC USE

Geriatric Use: Clinical studies of norepinephrine bitartrate injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, 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 drug therapy. Norepinephrine infusions should not be administered into the veins in the leg in elderly patients (see PRECAUTIONS, General).

INDICATIONS AND USAGE

For blood pressure control in certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, myocardial infarction, septicemia, blood transfusion, and drug reactions). As an adjunct in the treatment of cardiac arrest and profound hypotension.

PEDIATRIC USE

Pediatric Use: Safety and effectiveness in pediatric patients has not been established.

PREGNANCY

Pregnancy Category C: 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.

NUSRING MOTHERS

Nursing Mothers: It is not known whether this drug 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.

BOXED WARNING

IMPORTANT- Antidote for Extravasation Ischemia: To prevent sloughing and necrosis in areas in which extravasation has taken place, the area should be infiltrated 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. A syringe with a fine hypodermic needle should be used, with the solution being 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 hours. Therefore, phentolamine should be given as soon as possible after the extravasation is noted.

DOSAGE AND ADMINISTRATION

Norepinephrine Bitartrate Injection is a concentrated, potent drug which must be diluted in dextrose containing solutions prior to infusion. An infusion of norepinephrine should be given into a large vein (see PRECAUTIONS). Restoration of Blood Pressure in Acute Hypotensive States Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, norepinephrine can be administered before and concurrently 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 are protection against significant loss of potency due to oxidation. Administration in saline solution alone is not recommended. Whole blood or plasma, if indicated to increase blood volume, should be administered separately (for example, by use of a Y-tube and individual containers if given simultaneously). Average Dosage: Add a 4 mL ampul (4 mg) 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. Give this solution by intravenous infusion. Insert a plastic intravenous catheter through a suitable bore needle well advanced centrally into the vein and securely fixed with adhesive tape, avoiding, if possible, a catheter tie-in technique as this promotes stasis. An IV drip chamber or other suitable metering device is essential to permit an accurate estimation of the rate of flow in drops per minute. After observing the response to an initial dose of 2 mL to 3 mL (from 8 mcg to 12 mcg of base) per minute, adjust the rate of flow to establish and maintain a low normal blood pressure (usually 80 mm Hg to 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 mL to 1 mL per minute (from 2 mcg to 4 mcg of base). High Dosage: Great individual variation occurs in the dose required to attain and maintain an adequate blood pressure. In all cases, dosage of norepinephrine should be titrated according to the response of the patient. Occasionally much larger or even enormous daily doses (as high as 68 mg base or 17 ampules) may be necessary if the patient remains hypotensive, but 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: The degree of dilution depends on clinical fluid volume requirements. If large volumes of fluid (dextrose) are needed at a flow rate that would involve an excessive dose of the pressor agent per unit of time, a solution more dilute than 4 mcg per mL should be used. 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: The infusion should be continued until adequate blood pressure and tissue perfusion are maintained without therapy. Infusions of norepinephrine should 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 six days. Adjunctive Treatment in Cardiac Arrest Infusions of norepinephrine are usually administered intravenously during cardiac resuscitation to restore and maintain an adequate blood pressure after an effective heartbeat and ventilation have been established by other means. [Norepinephrine’s 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. 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.