Active substanceNorepinephrineNorepinephrine
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  • Dosage form: & nbspconcentrate for solution for intravenous administration
    Composition:

    Composition per ml:

    Ingredient name

    Number of

    Feature Function

    Active substance

    Norepinephrine hydrotartrate monohydrate in terms of anhydrous substance

    1.0 mg or 2.0 mg

    Active substance

    Excipients

    Sodium chloride

    8.4 mg

    Isotonic agent

    Sodium hydroxide or

    Alkalizing agent

    hydrochloric acid

    pH from 3.0 to 4.5

    Acidifying agent

    Water for injections

    Up to 1 ml

    Solvent

    Each ml of Noradrenaline concentrate for the preparation of a solution for intravenous administration of 1 mg / ml contains 1 mg of norepinephrine hydrotartrate, equivalent to 0.5 mg of norepinephrine base.

    Each ml of Noradrenaline concentrate for the preparation of a solution for intravenous administration of 2 mg / ml contains 2 mg of norepinephrine hydrotartrate, equivalent to 1 mg of norepinephrine base.

    Description:Transparent, colorless or slightly brownish-yellow liquid.
    Pharmacotherapeutic group:Alpha-adrenomimetic.
    ATX: & nbsp

    C.01.C.A.03   Norepinephrine

    Pharmacodynamics:

    Norepinephrine is a biogenic amine, a neurotransmitter.

    Has a powerful stimulating effect on α-adrenoceptors and moderately stimulating ß1-adrenoceptors.

    Getting into the blood, even in small concentrations, causes generalized vasoconstriction, with the exception of coronary vessels, which expand due to indirect effects (due to increased oxygen consumption), which leads to increased strength and (in the absence of vagotonia) myocardial contraction rates, increasing the shock and minute volume heart. Causes an increase in blood pressure (BP), both systolic and diastolic, increases the overall peripheral vascular resistance (OPSS) and central venous pressure.

    Cardiotropic action of norepinephrine is associated with its stimulating effect on ß1- adrenoreceptors of the heart.

    Pharmacokinetics:

    Suction. After intravenous administration, the effects of norepinephrine develop rapidly. Norepinephrine has a short duration of action. The half-life of the plasma is about 1 to 2 minutes.

    Distribution. Norepinephrine is rapidly eliminated from the plasma by re-uptake and metabolism. Poorly penetrates the blood-brain barrier.

    Metabolism. Metabolised in the liver and other tissues by methylation with catechol-O-methyltransferase (COMT) and deamylation with monoamine oxidase. The final metabolite is 4-hydroxy-3-methoxymandelic acid. Intermediate metabolites: Normetanephrine and 3,4-dihydroxymandelic acid.

    Excretion. Metabolites of norepinephrine are mainly excreted by the kidneys along with urine in the form of sulfate conjugates and to a lesser extent in the form of glucuronide conjugates.

    Indications:Rapid recovery of blood pressure in acute reduction.
    Contraindications:

    - marked hypersensitivity to the components of the drug;

    - arterial hypotension caused by hypovolemia (except when norepinephrine is used to maintain cerebral and coronary blood flow before the end of therapy aimed at replenishing the volume of circulating blood);

    - carrying out halotane and cyclopropane general anesthesia (in connection with the risk of heart arrhythmia);

    - pronounced hypoxia and hypercapnia.

    Carefully:

    - severe left ventricular failure, acute heart failure, recent myocardial infarction, Prinzmetal angina;

    - thrombosis of coronary, mesenteric or peripheral vessels (risk of worsening of ischemia and increased infarction zone), insufficient blood circulation.

    Pregnancy and lactation:

    Norepinephrine can interfere with the perfusion of the placenta and cause bradycardia of the fetus. Norepinephrine can cause uterine contraction and lead to fetal asphyxia late in pregnancy.

    The drug norepinephrine during breastfeeding should be used with caution, since there is no evidence of its ability to penetrate into breast milk.

    The use of Noradrenaline during pregnancy is possible if the expected benefit for the mother exceeds the possible risk to the fetus.

    Dosing and Administration:

    Enter only intravenously.

    Individual dose of the drug Noradrenaline is established by the doctor depending on the clinical condition of the patient.

    Noradrenaline should be administered via central venous access devices, in order to reduce the risk of extravasation and subsequent tissue necrosis.

    Breeding:

    - For injection with a syringe infusion pump, add 4 ml of Noradrenalin 1 mg / ml with 46 ml of a 5% dextrose solution. Do not mix with other drugs.

    - For administration with a dropper, add 460 ml of 5% dextrose solution to 40 ml of Noradrenaline 1 mg / ml. Do not mix with other drugs.

    In both methods of dilution, the final concentration of the resulting solution for intravenous administration should be 80 mg / l, which is equivalent to 40 mg / l of norepinephrine base.

    The recommended initial dose of norepinephrine and the rate of reference is 0.1 to 0.3 μg / kg / minute. The infusion rate is progressively increased by titration step-by-step, at 0.05 to 0.1 μg / kg / min, according to the observed pressor effect until the desired normotonia is achieved. There are individual differences in the dose necessary to achieve and maintain normotonia. The goal is to reach the lower limit of the norm of systolic pressure (100 - 120 mm Hg) or to reach a sufficient level of the average value (above 65 - 80 mm Hg, depending on the patient's condition).

    - Before or during therapy, correction of hypovolemia, hypoxia, acidosis, hypercapnia is necessary.

    - Norepinephrine should be used concomitantly with adequate replenishment of the circulating blood volume.

    Arterial pressure:

    The duration, rate of administration and dosing of the solution of Norepinephrine are determined by cardiac monitoring data and under compulsory medical control of blood pressure (every 2 minutes until normotonia, after every 5 minutes during the entire infusion) to avoid the occurrence of hypertension.

    Discontinuation of therapy:

    Therapy Norepinephrine should be reduced in stages, as abrupt reversal can lead to acute hypotension.

    The course of treatment can last from several hours to 6 days.

    It is necessary to guard against the introduction of norepinephrine solution under the skin and in the muscles because of the danger of developing necrosis (See section "Special instructions").

    Side effects:From the side of the cardiovascular system: arterial hypertension and tissue hypoxia; ischemic impairment (caused by severe vasoconstriction, which can lead to pallor and coldness of limbs and face); tachycardia, bradycardia (probably reflexively as a result of increased blood pressure), arrhythmias, palpitations, increased contractility of the heart muscle as a result beta-adrenergic effect on the heart (inotropic and chronotropic), acute heart failure.

    With rapid administration there is: headache, chills, cooling of the extremities, tachycardia.

    From the central nervous system: anxiety, insomnia, headache, psychotic conditions, cephalgia, weakness, tremor, confusion, decreased attention, nausea, vomiting, anorexia.

    From the respiratory system: shortness of breath, pain in the sternum and mediastinum, difficulty in breathing, respiratory failure.

    From the urinary system: retention of urination.

    On the part of the organs of vision: acute glaucoma (in patients with anatomical predisposition - with the closing angle of the anterior chamber of the eyeball).

    From the immune system: when hypersensitivity to one of the ingredients of the drug, allergic reactions and difficulty in breathing are possible.

    Local reactions: irritation at the site of injection or development of necrosis (See section "Special instructions").

    Continuous introduction of a vasopressor to maintain blood pressure in the absence of recovery of the circulating blood volume can cause the following side effects:

    - severe peripheral and visceral angiospasm;

    - decreased renal blood flow;

    - tissue hypoxia;

    - increased serum lactate levels;

    - decreased urine production.

    In case of hypersensitivity: at use of high doses or usual there is a pronounced increase in blood pressure (accompanied by headache, photophobia, stabbing chest pain, pallor of the skin, increased sweating and vomiting); dyspeptic phenomena.

    Overdose:

    There may be spasms of skin vessels, collapse, anuria, marked increase in blood pressure.

    Treatment: When there are dose-related symptoms of an overdose, if possible, reduce the dose of the drug.

    Interaction:

    When norepinephrine is used simultaneously with cardiac glycosides, quinidine, tricyclic antidepressants, the risk of arrhythmias increases.

    Alpha-blockers (doxazosin, labetalol, phenoxybenzamine, phentolamine, prazozin, terazosin, thalazosin) and other drugs possessing alpha-adrenergic blocking activity (haloperidol, loxapine, phenothiazines, thioxanthenes), counteract the vasoconstrictor effect.

    Means for inhalation of general anesthesia (chloroform, enflurane, halothane, cyclopropane, isoflurane and methoxyflurane) - risk of ventricular arrhythmia.

    Tricyclic antidepressants and maprotiline - it is possible to increase cardiovascular effects, pressor action, tachycardia and arrhythmias.

    Hypotensive drugs and diuretics - reduction of the effect of norepinephrine.

    Beta-blockers - mutual weakening of the action.

    Cocaine, doxapram - mutual reinforcement of hypertensive action.

    MAO inhibitors, furazolidone, procarbazine and selegiline - it is possible to extend and strengthen the pressor effect.

    Nitrates - Weakening of antianginal action.

    Ergot alkaloids or oxytocin can enhance vasopressor and vasoconstrictor effects.

    Thyroid hormones - risk of coronary insufficiency on the background of angina pectoris.
    Special instructions:

    It is not recommended simultaneous reception of Noradrenaline and MAO inhibitors of imipramine and triptyline type (risk of development of pronounced and prolonged BP increase).

    With prolonged use of the drug, a decrease in plasma volume may be observed (correction is necessary to avoid recurrent hypotension when the drug is withdrawn).

    Elderly patients may be particularly sensitive to the effects of norepinephrine.

    During the infusion, the blood pressure and flow rate should be checked frequently (every 2 minutes) to avoid hypertension.

    If there is a disturbance of the heart rhythm during the infusion - the dose should be reduced.

    Care should also be taken when using Noradrenaline in patients with hyperthyroidism and diabetes.
    Particular care should be taken for patients with thrombosis of coronary, mesenteric or peripheral vessels, since noradrenaline may lead to increased ischemia and an increased infarction zone.
    For patients with hypotension after myocardial infarction and patients with Prinzmetal angina, care should also be taken.
    Risk of extravasation:
    In order to reduce the risk of extravasation and subsequent necrosis of tissues, constant monitoring of the needle position in the vein with the administration of Noradrenaline is necessary. The place of infusion should be frequently checked for the appearance of free flow (infiltration). Care should be taken to avoid leakage from the vessel (extravasation).Due to the vasoconstriction of the veins with increased permeability, Noradrenaline may flow in the tissues surrounding the vein used for infusion, in this case the place of infusion should be changed in order to weaken the effect of local vasoconstriction.
    Treatment of ischemia caused by extravasation:
    When the Noradrenaline drug is flowing from the vessel or injecting past the vein, blanching and later destruction of the tissues as a result of vasoconstrictive action of the drug on the vessels may occur.
    If the drug gets past the venous blood flow, 5-10 ml of phentolamine mesylate in 10-15 ml of physiological solution is injected into the injection site, topically.
    After dilution of Noradrenaline concentrate, the resulting solution must be used within 12 hours.

    Form release / dosage:

    concentrate for solution for intravenous administration

    Packaging:

    By 2 ml, 4 ml or 8 ml into ampoules from a neutral colorless glass of grade HC-1 or HC-3. 5 or 10 ampoules are placed in a contour cell packaging (tray) made of polyvinyl chloride according to GOST 25250-88 or imported or film of polyethylene terephthalate TURB 00916408002-94 or imported, approved for use in the Russian Federation, or paper packaging with a polymer coating or uncoated.

    For 1 or 2 packs (5 or 10 ampoules) together with the instructions for use and a knife ampoule, according to TU 400-6-169-85 or ampoule scanner according to TU 64-1-994-79 or according to TU 9432-001-14783767- 2003, put in a pack of cardboard. When packing ampoules with incisions, rings or break points, scarifiers or ampoule knives do not.

    Storage conditions:

    Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002774
    Date of registration:19.12.2014
    The owner of the registration certificate:ESCO PHARMA, LLCESCO PHARMA, LLC
    Manufacturer: & nbsp
    Information update date: & nbsp07.08.2015
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