Active substanceNimodipineNimodipine
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  • Nimodipine-native
    solution d / infusion 
    NATIVA, LLC     Russia
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  • Dosage form: & nbspsolution for infusions
    Composition:

    Composition per ml:

    Component name / Amount, mg

    Active substance:

    Nimodipine 0.2

    Excipients:

    Ethanol 96% 200.0

    Macrogol-400 170.0

    Sodium citrate dihydrate 2.0

    Citric acid monohydrate 0.33

    Water for injection.

    Description:Transparent colorless or slightly yellowish solution.
    Pharmacotherapeutic group:The blocker of "slow" calcium channels (BCCI)
    ATX: & nbsp

    C.08.C.A   Dihydropyridine derivatives

    C.08.C.A.06   Nimodipine

    Pharmacodynamics:

    Nimodipine has cerebrovazodilatiruyuschim action, prevents or eliminates spasm of blood vessels, provoked by various vasoactive substances (including serotonin, prostaglandins and histamine), has neuro- and psychotropic activity.

    In patients with acute disorders of the cerebral circulation nimodipine, expanding the vessels of the brain, improves cerebral circulation.At the same time, improvement of blood circulation, as a rule, is more pronounced in the area of ​​damaged and previously inadequately blood-filled areas of the brain. The use of nimodipine significantly reduces the mortality rate and the incidence of ischemic neurological disorders that occur as a result of subarachnoid hemorrhage.

    Pharmacokinetics:

    Suction

    With continuous infusion at a rate of 0.03 mg / kg / h, the average stable concentration of nimodipine in the blood plasma is 17.6-26.6 ng / ml. After intravenous bolus infusion, there is a two-phase reduction in nimodipine plasma concentration after 5-10 minutes and after about 60 minutes.

    Distribution

    The volume of nimodipine distribution is 0.9-1.6 l / kg. Nimodipine intensively binds to blood plasma proteins (97-99%). Penetrates through the placental barrier. The concentration of nimodipine and its metabolites in breast milk is significantly higher than the concentration in the blood plasma.

    After intravenous administration, the concentration of nimodipine in the cerebrospinal fluid is about 0.5% of the concentration in the blood plasma.

    Metabolism

    Nimodipine is metabolized by dehydrogenation of the dihydropyridine ring and oxidative cleavage of the esters.The three main metabolites found in the blood plasma do not have clinically significant pharmacological activity. The effect of nimodipine on the activity of liver enzymes has not been studied.

    Excretion

    The total clearance of nimodipine is 0.6-1.9 l / h / kg. At the person metabolites on 50 % are excreted by the kidneys and by 30% with bile.

    Indications:

    Prophylaxis and treatment of ischemic neurological disorders caused by spasm of cerebral vessels on the background of subarachnoid hemorrhage due to aneurysm rupture.

    Contraindications:

    - Hypersensitivity to any component of the drug.

    - Age to 18 years.

    Carefully:

    A drug Nimodipine-native should be used with caution in the following diseases and conditions: severe bradycardia, arterial hypotension (systolic blood pressure less than 100 mm Hg), myocardial ischemia, severe heart failure, increased intracranial pressure, generalized cerebral edema, hepatic and renal insufficiency.

    In patients with unstable angina or within the first 4 weeks after acute myocardial infarction, an assessment of the ratio of potential risk(decreased blood flow to the coronary arteries and myocardial ischemia) and benefits (improvement of blood supply to the brain).

    A drug Nimodipine-native contains 23.7% by volume of ethanol, which should be taken into account when prescribing patients suffering from alcoholism with a decrease in the intensity of the metabolism of ethanol in the body, pregnant and lactating women, patients with liver disease, epilepsy.

    Pregnancy and lactation:

    Application of the drug Nimodipine-native during pregnancy requires a careful evaluation of the ratio of factors of use and risk, taking into account the severity of the clinical picture. Because the nimodipine and its metabolites in breast milk are contained in significantly higher concentrations than in the blood plasma of the mother, at the time of application of the drug Nimodipine-native Breastfeeding should be discontinued.

    Fertility

    In some cases, when carrying out fertilization in vitro Against the background of using blockers of "slow" calcium channels, reversible chemical changes in the head of spermatozoa were observed, which can lead to a decrease in fertility.
    Dosing and Administration:

    Intravenous infusion

    The following dosing regimen is recommended.

    At the beginning of therapy for 2 hours, 1 mg nimodipine per hour (5 ml infusion solution of the drug Nimodipine-native), about 15 μg / kg / hr. With good tolerability (especially in the absence of a marked decrease in blood pressure), after 2 hours the dose is increased to 2 mg of nimodipine per hour (approximately 30 μg / kg / h). The initial dose for patients with a body weight of well below 70 kg or labile blood pressure should be 0.5 mg nimodipine per hour.

    Application for the prevention of ischemic neurological disorders

    Intramuscular therapy with nimodipine should begin no later than 4 days after hemorrhage, and continue throughout the period of maximum risk of vasospasm development, that is, up to 10-14 days after subarachnoid hemorrhage. After the end of the infusion therapy for the next 7 days, oral intake of the tablet form of nimodipine at a dose of 60 mg 6 times a day (every 4 hours) is recommended.

    Application for the treatment of ischemic neurological disorders

    If there are already ischemic neurological disorders,caused by vasospasm due to subarachnoid hemorrhage, infusion therapy should be started as early as possible and conducted for at least 5 days, but not more than 14 days. After the end of the infusion therapy for the next 7 days, oral intake of the tablet form of nimodipine at a dose of 60 mg 6 times a day (every 4 hours) is recommended.

    If during the use of the drug Nimodipine-native surgical treatment of hemorrhage, intravenous therapy with nimodipine should be continued for at least 5 days after surgery.

    Introduction to brain cisterns

    During the surgical intervention, freshly prepared nimodipine solution (1 ml infusion solution of the drug Nimodipine-native and 19 ml Ringer's solution), warmed to the average body temperature, can be administered intracisternally.

    The solution should be used immediately after preparation.

    Use in special patient groups

    If the patient develops unwanted reactions to the drug Nimodipine-native, should either reduce the dose, or stop therapy with nimodipine.

    Patients with hepatic impairment

    In severe liver function disorders, especially with liver cirrhosis, the bioavailability of nimodipine can be increased due to a decrease in the intensity of primary metabolism and a slowing of metabolic inactivation. A consequence of this can be an aggravation of both the main and side effects of nimodipine, in particular, its hypotensive effect. In such cases, the dose of the drug should be reduced, based on the degree of reduction in blood pressure; If necessary, treatment should be interrupted.

    Patients with impaired renal function

    In patients with renal failure, treatment should be carefully monitored. If there is a violation of kidney function, taking the drug Nimodipine-native should be discontinued.

    Method of application of the infusion solution, compatible solutions and equipment

    Infusion solution Nimodipine-native is used for continuous intravenous administration through a central catheter using an infusion pump and a three-channel stopcock simultaneously with one of the following solutions:

    5 % dextrose, 0,9 % sodium chloride, Ringer's solution, Ringer's solution with magnesium, a solution of dextran 40 or 6% hydroxyethyl starch in a ratio of approximately 1: 4 (Nimodipine-native : another solution).As a concomitant infusion solution can also be used mannitol, human albumin or blood. Solution Nimodipine-native Do not add to the infusion vessel or mix with other medications. It is recommended to continue the administration of nimodipine during anesthesia, surgery and angiography.

    For the connection of a polyethylene tube, through which a solution Nimodipine-native, channel of admission of the concomitant solution and the central catheter, it is necessary to use a three-channel stopcock.

    Nimodipine is sensitive to light, so you should avoid direct exposure to sunlight: use glass syringes and connecting tubes black, brown, yellow or red; In addition, it is advisable to wrap the infusion pump and tubes with opaque paper. With diffuse daylight or artificial light, the solution Nimodipine-native can be used for 10 hours without special protective measures. Nimodipine, the active substance of the infusion solution Nimodipine-native, absorbed by polyvinyl chloride, for its parenteral administration, only systems with polyethylene tubes can be used.

    Side effects:

    The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems. The incidence of undesirable reactions is estimated as follows: "very often" arising -> 10%; "often" -> 1% and 10%, "infrequently" -> 0.1% and <1%, "rarely" -> 0.01% and <0.1%, "very rarely" - 0.01%, including individual messages.

    Disorders from the blood and lymphatic system: infrequently - thrombocytopenia.

    Immune system disorders: infrequently - allergic reactions, rash.

    Disturbances from the nervous system: infrequently - headache.

    Disorders from the heart: infrequently - tachycardia; rarely bradycardia.

    Vascular disorders: infrequently - decrease in arterial pressure, vasodilation.

    Disorders from the gastrointestinal tract: infrequently - nausea; rarely - intestinal obstruction.

    Laboratory and instrumental data: rarely - transient elevation of hepatic enzyme levels.

    General disorders and disorders at the site of administration: rarely - reactions at the injection or infusion site, thrombophlebitis at the site of administration.

    Overdose:

    Symptoms

    In acute overdose with nimodipine, the following symptoms may occur: significant lowering of blood pressure, tachycardia, or bradycardia.

    Treatment

    When symptoms of acute overdose occur, the use of nimodipine should be stopped immediately. Measures for emergency care in case of an overdose are determined by its symptoms. If there is a significant drop in blood pressure, you should enter intravenously dopamine or norepinephrine. Since specific antidotes of nimodipine are not known, further therapy of other adverse reactions should be symptomatic.

    Interaction:

    Prolonged use of nimodipine with fluoxetine leads to an increase in the concentration of nimodipine in blood plasma by an average of 50%. The concentration of fluoxetine is significantly reduced, while the active metabolite content of fluoxetine - norfluoxetine does not change.

    Simultaneous long-term use of nimodipine and nortriptyline leads to a slight increase in the concentration of nimodipine (the concentration of nortriptyline in blood plasma does not change).

    In patients on long-term therapy with haloperidol, no drug interaction of nimodipine with haloperidol was observed.

    Simultaneous intravenous administration of zidovudine and nimodipine results in a significant increase in the area under the concentration-time curve (AUC) for zidovudine and a decrease in the volume of its distribution and clearance.

    In combination with drugs that reduce blood pressure:

    - diuretics;

    - beta-blockers;

    - angiotensin-converting enzyme (ACE) inhibitors;

    - antagonists of angiotensin II receptors;

    - other blockers of "slow" calcium channels (BCCI);

    - methyldopa;

    - inhibitors of phosphodiesterase

    Nimodipine may enhance the hypotensive effect of these drugs.

    Simultaneous therapy with potentially nephrotoxic drugs (eg, aminoglycosides, cephalosporins, furosemide) can cause renal dysfunction. Therefore, in the case of such treatment, and in patients with renal insufficiency, treatment should be carefully monitored. If a kidney dysfunction is detected, nimodipine should be discontinued.

    Infusion solution of the drug Nimodipine-native contains 23.7 percent by volume of ethanol, it is necessary to take into account possible interactions of ethanol with other drugs.

    Special instructions:

    It is advisable to use caution when handling the contents of the vial to avoid contact with the skin, mucous membranes of the eyes.

    It is recommended to carefully monitor patients with heart disease.

    When the drug is prescribed Nimodipine-native patients with liver disease should regularly carry out clinical tests of peripheral blood and liver enzymes.

    In patients with renal failure, treatment should be carefully monitored. If there is a violation of kidney function, taking the drug Nimodipine-native should be discontinued.

    A drug Nimodipine-native contains 23.7% by volume of ethanol, this should be taken into account when appointing patients suffering from alcoholism with a decrease in the intensity of the metabolism of ethanol in the body, pregnant and lactating women and patients with liver disease, epilepsy.

    Effect on the ability to drive transp. cf. and fur:

    In case of development of such undesirable reactions as decrease in arterial pressure, it is necessary to refrain from controlling vehicles and mechanisms, as well as from engaging in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Solution for infusions, 0.2 mg / ml.

    Packaging:

    For 50 ml of the drug in the bottles of dark glass of the first hydrolytic class, hermetically sealed with bromobutyl rubber stoppers of type I, closed with aluminum-plastic caps. The labels are glued on the vials.

    For 1 or 5 bottles, along with the instructions for use, put in a pack of cardboard.

    Storage conditions:

    In the 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 after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-004203
    Date of registration:20.03.2017
    Expiration Date:20.03.2022
    The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp17.04.2017
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