Nitseromaks liofit. for solution for infection. 4 mg fl. No. 4

Translation of the instruction Mose

NITsEROMAKS lyophilisate for solution for injections of 4 mg

Instruction

On medical use of medicine

Nitseromaks

(niceromax)

Ingredients:

Active ingredient: nicergoline;

1 bottle contains 4 mg of a nitsergolin;

excipients: lactoses monohydrate, tartaric acid.

Dosage form.

Lyophilisate for solution for injections.

Main physical and chemical properties: the lyophilized white porous mass or powder of white color.

Pharmacotherapeutic group.

Peripheral vazodilatator. ergot alkaloids.

ATX C04A E02 Code.

Pharmacological properties.

Pharmacodynamics.

Nitsergolin is derivative an ergolina with the alpha 1-adrenergic blocking activity when it is used parenterally. After oral administration nitsergolin gives in to fast and extensive metabolism with formation of a number of metabolites at the expense of which the activity at the different levels of the central nervous system is also observed.

At oral administration nitsergolin shows multiple neuropharmacological effects: it not only increases receipt and consumption of glucose in a brain, increases biosynthesis of protein and nucleic acids, but also influences different neurotransmitterny systems.

Nitsergolin improves cerebral cholinergic functions at old animals. Long use of medicament of a nitsergolin at old rats interfered with the decrease in level of acetylcholine connected with age (in bark and a corpus striatum) and also reduced release of acetylcholine (in a hippocampus) in the conditions of in vivo. After prolonged oral administration of a nitsergolin the increase in activity sincaline-acetyltransferase and density of muskarinovy receptors was also observed. Moreover, as in the researches in vitro, and in vivo nitsergolin significantly reduced activity of acetylcholinesterase. In these pilot studies the neurochemical effects were observed along with steady improvement of behavioural reactions, for example, in the test with a labyrinth, at mature animals to which applied nitsergolin for a long time, observed development of the reactions similar to reactions in young animals.

during use of a nitsergolin for animals also managed to reduce manifestations of insufficiency of cognitive function which was induced by several agents (hypoxia, electro-convulsive therapy (EKT), Scopolaminum). Oral administration of medicament of a nitsergolin in low doses increases exchange of dopamine at mature animals, in particular in the mesolimbic site probably by modulation of dofaminergichesky receptors. Nitsergolin improves mechanisms of intercellular signaling at mature animals. Both after disposable, and at long oral administration of medicament the increase in exchange of a basal and agonistchuvstvitelny fosfoinozitid is observed. Nitsergolin also increases activity and transferring to the site of a membrane of kaltsiyzavisimy isoforms of a protein kinase of Page. These enzymes take part in the mechanism of secretion of the soluble amyloid predecessor of a protein that leads to strengthening of its release and to decrease in products of pathological beta amyloid that was shown on the culture of a human neuroblastoma.

Thanks to the antioxidant effect and ability to activate detoxication enzymes nitsergolin the death of neurons owing to an oxidatic stress warns and also prevents emergence of apoptosis in in vivo and in vitro experimental models. Nitsergolin weakens age reduction of an expression of mRNK of neuronalny synthase of nitrogen oxide that can also influence improvement of cognitive function.

Pharmakodinamichesky researches at the person with use of computer techniques of removal of an electroencephalography (EEG) were conducted by

with participation of young volunteers and volunteers of advanced age and also with participation of patients of advanced age with cognitive disorders. Nitsergolin had the normalizing impact on results of EEG at patients of advanced age and adults of young age in a hypoxia, raising α- and β-activity and also reducing δ- and θ-activity. Positive changes in the relation of evoked potential and answers to irritations were registered at patients with dementia of easy and moderate degree of a different etiology (as a result of Alzheimer's disease and multiinfarctive dementia); after long-term treatment nitsergoliny (2–6 months) these changes correlate with improvement of clinical symptoms.

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Proceeding from the aforesaid, it is obvious what nitsergolin works by modeling of a wide range of the cellular and molecular mechanisms involved in dementia pathophysiology.

In clinical trials with participation of more than 1500 patients with dementia (like Alzheimer, the vascular and mixed type) who received nitsergolin in a dose 60 mg a day or placebo. After long-term treatment nitsergoliny continuous reduction of the cognitive disturbances and behavior disorders connected with dementia was observed. Changes could be observed after 2 months of treatment, and they sokhranlis for one year of treatment.

Pharmacokinetics.

After introduction of 2 mg of H ³ - a nitsergolina to 3 healthy patients by intravenous infusion lasting about 10 minutes nitsergolin gave in to fast hydrolysis of radio communication with formation of a metabolite 1-methyl-10-metoksidigidrolizergola (MMDL). As a result of further loss of methyl group in position of 1 structure of an ergolin the main metabolite 10-metoksidigidrolizergol is formed (MDL). Not changed nitsergolin came to light at all three patients throughout the period up to 90 minutes after infusion with the average levels in blood plasma about 4.5 ng/ml in 20 minutes with the subsequent fast decrease connected with elimination half-life less than 30 minutes. The maximum concentration of MMDL was observed in 20 minutes after administration of drug, and its levels quickly decreased after that throughout the period till 8 o'clock. The maximum concentration of MDL made about 2.2 ng/ml in 4 hours after the end of infusion with the subsequent slower phase of decrease, than such MMDL. About 50% and 10% of the entered radioactive material were removed with urine for 4 days and with excrements for 7 days respectively.

Special groups of patients.

Influence of renal failures on pharmacokinetics of a nitsergolin estimated at patients with the lung (KLkr (clearance of creatinine) of 60-80 ml/min.) moderated (KLkr 30–50 ml/min.) and heavy (KLkr of 10-25 ml/min.) a renal failure. At patients with the lung (n = 5) moderated (n = 5) and heavy (n = 4) a renal failure observed considerable differences in the amount of MDL that it was allocated with urine for 120 hours after reception of a nitsergolin in a dose 30 mg orally (38.1%, 42.6% and 25.7% of a dose of medicament respectively); for MMDL corresponding values made 1.7%, 0.6% and 0.2% respectively. At patients with a heavy renal failure the significant disturbance of removal of MDL with urine in comparison with other two groups was observed. Besides, at patients with a slight, moderate and heavy renal failure the average decrease in removal of MDL with urine (0–72 hours) for 32%, 32% and 59% in comparison with patients with normal renal function in other research at reception of tablets on 30 mg was observed.

Pharmacokinetics of a nitsergolin was not studied by

at patients with an abnormal liver function.

Pharmacokinetics of a nitsergolin was not studied by

at children.

Pharmacokinetics of a nitsergolin at patients of advanced age is completely not studied by

.

Clinical characteristics.

Indication.

Acute and chronic cerebrovascular disorders of metabolism owing to atherosclerosis, thrombosis and an embolism of cerebral vessels, tranzitorny disturbances of cerebral blood circulation (tranzitorny ischemic attacks).

Headache.

Additional therapy for treatment of arterial hypertension.

Contraindication.

Hypersensitivity to active agent, alkaloids of an ergot or to any component of drug. recently postponed myocardial infarction, acute bleeding, orthostatic hypotension, heavy bradycardia. concomitant use of sympathomimetics (agonists alpha or beta receptors).

Interaction with other medicines and other types of interactions.

needs to use Drug with care together with:

• antihypertensive medicaments (nitsergolin can exponentiate their action). Nitsergolin can exponentiate influence of β-blockers on heart;
• sympathomimetic means (alpha and beta): nitsergolin can counteract vasopressor effects of sympathomimetic medicaments as has the alpha and adrenergic blocking effect (see the section "Features of Use");
• medicaments which are metabolized by CYP2D6 isoenzyme: as nitsergolin it is metabolized by CYP2D6 isoenzyme, it is impossible to exclude interactions with other medicines which are metabolized in the same way;
• antiagregant and anticoagulants (for example acetylsalicylic acid): nitsergolin increases influence on a hemostasis in this connection the bleeding time can be extended;
• medicaments influencing metabolism of uric acid: nitsergolin can lead to asymptomatic increase in level of uric acid in blood plasma.

Feature of use.

Research with appointment single or repeated doses of a nitsergolin was shown that nitsergolin can reduce systolic arterial blood pressure and, to a lesser extent, diastolic arterial blood pressure at normotonichny patients and patients with the increased arterial blood pressure. such influence of a nitsergolin on arterial blood pressure can vary as in other researches changes of systolic or diastolic arterial blood pressure were not shown.

Sympathomimetic agonists (alpha and a beta) needs to be used with care to patients who receive nitsergolin (see the section "Interaction with Other Medicines and Other Types of Interactions").

generally in the recommended therapeutic doses nitsergolin does not cause changes of arterial blood pressure, however in patients with arterial hypertension, medicament can gradually reduce the level of arterial blood pressure.

Nitsergolin should appoint

with care to patients with a hyperuricemia or gout in the anamnesis and/or during the accompanying treatment by medicaments which can influence metabolism and excretion of uric acid.

Developing of fibrosis (for example a pneumosclerosis, heart, heart valves and retroperitoneal fibrosis) was associated with use of some alkaloids of an ergot having agonistic activity to 5-HT _2β - to serotonin receptors.

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It was reported about emergence of symptoms of an ergotism (including nausea, vomiting, diarrhea, abdominal pain and peripheral vasoconstriction) at use of some alkaloids of an ergot and their derivatives.

Before purpose of this class of medicines to doctors needs to get acquainted with signs and symptoms of overdose of an ergot.

Use during pregnancy or feeding by a breast.

Pregnancy

Nitsergolin had no toxic effect on reproductive function of pregnant females of rats and rabbits. The research at pregnant women was not conducted. In view of the approved indications, medicament use by pregnant women and to the women nursing it is improbable. Nitsergolin it is possible to use during pregnancy only provided that the potential advantage for the woman prevails over potential risk for a fruit.

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a breast

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Does not know Feeding whether gets nitsergolin into milk therefore medicine should not be applied to women who nurse.

Fertility

In researches on rats nitsergolin did not affect fertility.

Ability to influence speed of response at control of motor transport or other mechanisms.

Though clinical effect of medicament nitseromaks is directed to

to improvement of vigilance and concentration, influence of medicament on speed of response at control of motor transport or in operating time with other mechanisms at the same time was not investigated. anyway it is necessary to show care, in view of a basic disease of the patient.

during control of vehicles or works with mechanisms should consider that from time to time there can be dizziness or drowsiness (see the section "Side reactions").

Route of administration and doses.

Intramuscular injections: 2–4 mg (2–4 ml) twice a day (to dissolve lyophilisate with water for injections or normal saline solution to 2–4 ml).

Slow intravenous infusion: 4–8 mg dissolved in 100 ml of normal saline solution or solution of glucose. According to the decision of the doctor this dose can be reused several times per day.

experience of use of a nitsergolin by an intra arterial injection Exists: 4 mg dissolved in 10 ml of normal saline solution within 2 minutes.

dosing Mode, duration of treatment and a way of introduction depends on an individual clinical situation. It is in certain cases reasonable to begin treatment with administration of medicament parenterally, and then to pass to long oral administration. The effect of treatment is shown gradually. As therapy, as a rule, is long, the doctor needs to carry out the assessment of expediency of continuation of treatment through certain periods, but at least each 6 months.

Adult patients and patients of advanced age. According to results of pharmacokinetic researches and researches of tolerance of drug, adult patients and patients of advanced age should not carry out dose adjustment.

Patients with a renal failure. As removal with urine is the main way of elimination (80%) of a nitsergolin and its metabolites, it is recommended to reduce a medicament dose for patients with renal failures (creatinine level in blood serum ≥ 2 mg/ml) (see the section "Pharmacokinetics").

Children.

Safety and efficiency of a nitsergolin at children was not established to

. data are absent.

Overdose.

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At use of a nitsergolin in high doses the temporary lowering of arterial pressure can be observed. special treatment usually is not required, several minutes are enough to lie down. in exceptional cases at development of the significant insufficiency of blood supply of a brain and heart the purpose of sympathomimetics and continuous monitoring of indicators of arterial blood pressure is recommended.

Side reactions.

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gave side reactions on classes of systems of bodies and as reduction of their severity Below. frequency is determined as follows: very often (≥ 1/10); often (from ≥ 1/100 to

Disorder from mentality: infrequently agitation, confusion of consciousness, insomnia.

Disorder from nervous system: infrequently: drowsiness, dizziness, headache; frequency is unknown: feeling of heat.

Vascular disorders: infrequently: arterial hypotension, inflows.

Disorder from digestive tract: often: discomfort in a stomach; infrequently: diarrhea, nausea, constipation.

Disorder from skin and hypodermic cellulose: infrequently: itching; frequency is unknown: rash.

General disorders and reactions in the injection site: frequency is unknown: fibrosis.

Results of researches: infrequently: increase in level of uric acid in blood.

Message about the suspected side reactions. Messages about the suspected side reactions after registration of medicine is an important action. It allows to continue monitoring of a ratio advantage/risk at medicament use. Doctors are offered to report about any suspected side reactions.

Expiration date.

2 years.

Storage conditions.

to Store

in original packing at a temperature not higher than 25 wasps.

to Store

out of children's reach.

Incompatibility.

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For intravenous injections / infusions uses normal saline solution or solution of glucose.

not to mix

with other medicines. To use only the recommended solvents.

Packing.

On 1 or on 4 bottles with lyophilisate in blister strip packaging, on 1 blister strip packaging in a cardboard pack.

Category of release.

According to the prescription.

Producer.

Ltd company "pharmex groups".

Location of the producer and address of the place of implementation of its activity.

Ukraine, 08301, Kiev Region, Boryspil, st. of Shevchenko, house 100.