Norepirin

Norepinephrine Bitartrate 8 mg/4 mL (as Norepinephrine contains 4 mg/4 mL).

Pharmacology: Pharmacodynamics: Norepinephrine functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action).
Norepirin Injection belongs to a group of medicines called sympathomimetic and vasoconstriction.
Pharmacokinetics: Absorption: Norepinephrine is ineffective orally, and subcutaneous absorption is poor. As a result, it is recommended that norepinephrine be administered only via the intravenous route. Following IV administration, the onset of activity is rapid, with a short duration of action of only 1-2 minutes after the infusion is discontinued.
Distribution: Norepinephrine localizes mainly in sympathetic nervous tissue. The drug crosses the placenta but not the blood-brain barrier.
Elimination: The pharmacologic actions of norepinephrine are terminated primarily by uptake and metabolism in sympathetic nerve endings. The drug is metabolized in the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). The major metabolites are normetanephrine and 3-methoxy-4-hydroxy mandelic acid (vanillylmandelic acid, VMA), both of which are inactive. Other inactive metabolites include 3-methoxy-4-hydroxyphenylglycol,3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylglycol. Norepinephrine metabolites are excreted in urine primarily as the sulfate conjugates and, to a lesser extent, as the glucuronide conjugates. Only small quantities of norepinephrine are excreted unchanged.

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 adjunction in the treatment of cardiac arrest and profound hypotension.

Acute hypotension: For single dose, dilute 8 mg of norepinephrine bitartrate (eq. to norepinephrine 4 mg) in 1,000 mL of dextrose 5% injection or 0.9% normal saline, and administer in a ratio of 2-3 mL/min by intravenous drip. Monitor closely while administering and increase or decrease the dose. The maintenance dose is 0.5-1.0 mL/min and this is different with each individual.
As a result of the in-use stability test, it can be kept 24 hours after mixing at the temperature 30°C.
Cardiac arrest: During the cardiac resuscitation, secure effective heart beat with ventilation, then administer intravenously same as for acute hypotension.
Geriatric patient: Clinical studies of norepinephrine bitartrate did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. Clinical experience to date has not identified any differences in responses between geriatric and younger patients. If norepinephrine is used in geriatric patients, dosage should be selected carefully, usually starting at the low end of the dosage range, since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group. Norepinephrine infusions should not be administered into leg veins in geriatric patients.

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

Hypotension from hypovolemia except as an emergency measure to maintain coronary and cerebral perfusion until volume could be replaced.
Mesenteric or peripheral vascular thrombosis unless it is a lifesaving procedure.
During anesthesia with cyclopropane or halothane anesthesia.
Documentation of allergenic cross-reactivity for vasopressors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity can not be ruled out with certainty.

Norepinephrine bitartrate injection 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.
Assure adequate circulatory volume to minimize need for vasoconstrictors.
Avoid hypertension; monitor blood pressure closely and adjust infusion rate.
Use in patients with profound hypoxia or hypercarbia may produce ventricular tachycardia or fibrillation; use with extreme caution.
Vesicant; ensure proper needle or catheter placement prior to and during infusion.
Avoid extravasation; infuse into a large vein if possible. Avoid infusion into leg veins. Monitor IV site closely.
If extravasation occurs, infiltrate the area with diluted phentolamine (5 to 10 mg in saline) with a fine hypodermic needle. Phentolamine should be administered as soon as possible after extravasation is noted to prevent sloughing/necrosis.
Product contains sodium metabisulfite; use caution in patients with asthma or a sulfite allergy.
Administer infusions into a large vein, particularly an antecubital vein; some clinicians have indicated that the femoral vein is also an acceptable route. Avoid catheter tie-in technique, if possible.
Avoid leg veins in elderly patients or in those suffering from occlusive disorders (eg, atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger disease).
Gangrene has been reported in a lower extremity when infusions were given in an ankle vein.
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy.

Pregnancy: Animal reproduction studies have not been performed with norepinephrine, and it also is not known whether the drug can cause fetal harm when administered to pregnant women or can affect reproduction capacity. The drug should be used during pregnancy only when clearly needed.
Lactation: It is not known whether norepinephrine is distributed into human milk. Because many drugs are distributed into milk, the manufacturer recommends that the drug be used with caution in nursing women.

Cardiovascular: Bradycardia, cardiac arrhythmia, cardiomyopathy (stress), peripheral vascular insufficiency.
Central nervous system: Anxiety, transient headache.
Respiratory: Dyspnea.
Rare but important or life-threatening: Peripheral gangrene, peripheral ischemia.

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 bitartrate injection 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 bitartrate injection in patients with profound hypoxia or hypercarbia.
Norepinephrine bitartrate injection 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.
The levels/effects of Norepinephrine may be increased by Serotonin/Norepinephrine Reuptake Inhibitors.
The levels/effects of Norepinephrine may be decreased by Spironolactone.

Store below 30°C.
Store in the light protected hermetically sealed container.

Vasoconstrictors

C01CA03 - norepinephrine ; Belongs to the class of adrenergic and dopaminergic cardiac stimulants excluding glycosides. Used in the treatment of hypotension.

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