Niceromax lyophilized powder for solution for injection 4 mg vial No. 4

Translation of the instructions can be

Instruction

For medical use of the medicinal product

Niceromax

(Niceromax)

Composition:

Active ingredient: nicergoline;

1 vial contains 4 mg of nicergoline;

excipients: lactose, tartaric acid.

Dosage form.

Lyophilisate for solution for injection.

Main physicochemical properties: lyophilized white porous mass or white powder.

Pharmacotherapeutic group.

Peripheral vasodilators. Ergot alkaloids.

PBX code C04A E02.

Pharmacological properties.

Pharmacodynamics.

Nicergoline is an ergoline derivative with alpha-1-adrenergic blocking properties when used parenterally. After oral administration, nicergoline undergoes rapid and extensive metabolism to form a number of metabolites, which also exert activity at various levels of the central nervous system.

When administered orally, nicergoline exhibits multiple neuropharmacological effects: it not only increases the uptake and consumption of glucose in the brain, increases the biosynthesis of protein and nucleic acids, but also affects various neurotransmitter systems.

Nicergoline improves cerebral cholinergic functions in old animals. Long-term use of the drug nicergoline in old rats prevented the age-related decline in acetylcholine levels (in the cortex and striatum) and reduced acetylcholine release (in the hippocampus) in vivo. After long-term oral administration of nicergoline, an increase in choline acetyltransferase activity and muscarinic receptor density was also observed. Moreover, both in vitro and in vivo studies, nicergoline significantly reduced acetylcholinesterase activity. In these experimental studies, neurochemical effects were observed simultaneously with a stable improvement in behavioral responses, for example, in the maze test, in mature animals that were given nicergoline for a long time, the development of responses similar to those in young animals was observed.

When using nicergoline in animals, it was also possible to reduce the manifestations of cognitive dysfunction, which was induced by several agents (hypoxia, electroconvulsive therapy (ECT), scopolamine). Oral administration of the drug nicergoline in low doses increases dopamine metabolism in mature animals, in particular in the mesolimbic region, probably by modulating dopaminergic receptors. Nicergoline improves the mechanisms of intercellular signal transmission in mature animals. Both after a single and long-term oral administration of the drug, an increase in the metabolism of basal and agonist-sensitive phosphoinositide is observed. Nicergoline also increases the activity and transfer to the membrane site of calcium-dependent isoforms of protein kinase C. These enzymes are involved in the mechanism of secretion of soluble amyloid precursor protein, which leads to increased release and a decrease in the production of pathological beta-amyloid, which was demonstrated in human neuroblastoma culture.

Due to its antioxidant effect and ability to activate detoxification enzymes, nicergoline prevents the death of nerve cells due to oxidative stress, and also prevents the occurrence of apoptosis in in vivo and in vitro experimental models. Nicergoline attenuates the age-related decrease in the expression of neuronal nitric oxide synthase mRNA, which may also affect the improvement of cognitive function.

Pharmacodynamic studies in humans using computer-based electroencephalography (EEG) techniques were conducted in young and elderly volunteers, as well as in elderly patients with cognitive impairment. Nicergoline had a normalizing effect on EEG results in elderly and young adults under hypoxia, increasing α- and β-activity and decreasing δ- and θ-activity. Positive changes in evoked potential and response to stimulation were recorded in patients with mild to moderate dementia of various etiologies (as a result of Alzheimer's disease and multi-infarct dementia); after long-term treatment with nicergoline (2-6 months), these changes correlated with improvement in clinical symptoms.

Based on the above, it is clear that nicergoline works by modulating a wide range of cellular and molecular mechanisms involved in the pathophysiology of dementia.

In clinical studies involving more than 1500 patients with dementia (Alzheimer's type, vascular and mixed type) who received nicergoline at a dose of 60 mg per day or placebo. After long-term treatment with NICERGOLINE, a continuous decrease in cognitive impairment and behavioral disorders associated with dementia was observed. Changes were observed after 2 months of treatment and were maintained for one year of treatment.

After administration of 2 mg of H3-nicergoline to 3 healthy subjects by intravenous infusion over approximately 10 minutes, nicergoline underwent rapid hydrolysis of the ester bond to form the metabolite 1-methyl-10-methoxydihydrolysergol (MMDL). Subsequent loss of the methyl group at position 1 of the ergoline structure resulted in the formation of the major metabolite 10-methoxydihydrolysergol (MDL). Unchanged nicergoline was detected in all three subjects for up to 90 minutes after infusion with mean plasma levels of approximately 4.5 ng/mL at 20 minutes followed by a rapid decline associated with a half-life of less than 30 minutes. The maximum concentration of MMDL was observed as early as 20 minutes after administration, and its levels declined rapidly thereafter for up to 8 hours. The maximum concentration of MDL was approximately 2.2 ng/mL 4 hours after the end of the infusion, followed by a slower decline phase than that of MMDL. Approximately 50% and 10% of the administered radioactivity was excreted in the urine within 4 days and in the feces within 7 days, respectively.

Special patient groups.

The effect of renal impairment on the pharmacokinetics of nicergoline was evaluated in patients with mild (CLcr (creatinine clearance) 60-80 ml/min), moderate (CLcr 30-50 ml/min) and severe (CLcr 10-25 ml/min) renal impairment. In patients with mild (n = 5), moderate (n = 5) and severe (n = 4) renal impairment, significant differences were observed in the amount of MDL excreted in the urine within 120 hours after taking nicergoline at a dose of 30 mg orally (38.1%, 42.6% and 25.7% of the drug dose, respectively); for MMDL, the corresponding values were 1.7%, 0.6% and 0.2%, respectively. In patients with severe renal impairment, a significant impairment in the excretion of MDL in the urine was observed compared to the other two groups. In addition, patients with mild, moderate, and severe renal impairment had a mean decrease in urinary MDL excretion (0-72 hours) of 32%, 32%, and 59% compared to patients with normal renal function in another study when taking 30 mg tablets.

The pharmacokinetics of nicergoline have not been studied in patients with impaired liver function.

The pharmacokinetics of nicergoline have not been studied in children.

The pharmacokinetics of nicergoline in elderly patients has not been fully studied.

Clinical characteristics.

Indication.

Acute and chronic cerebrovascular metabolic disorders due to atherosclerosis, thrombosis and embolism of cerebral vessels, transient disorders of cerebral circulation (transient ischemic attacks).

Headache.

Adjunctive therapy for the treatment of arterial hypertension.

Contraindication.

Hypersensitivity to the active substance, ergot alkaloids or to any component of the drug. recent myocardial infarction, acute bleeding, orthostatic hypotension, severe bradycardia. simultaneous use of sympathomimetics (alpha or beta receptor agonists).

Interaction with other drugs and other types of interactions.

The drug should be used with caution together with:

sympathomimetic agents (alpha and beta): nicergoline can counteract the vasoconstrictor effects of sympathomimetic drugs, as it has an alpha-adrenergic blocking effect (see the section "Features of use");

Application features.

Studies with single or multiple doses of nicergoline have demonstrated that nicergoline can reduce systolic blood pressure and, to a lesser extent, diastolic blood pressure in normotensive and hypertensive patients. This effect of nicergoline on blood pressure may vary, as other studies have not demonstrated changes in systolic or diastolic blood pressure.

Sympathomimetic agonists (alpha and beta) should be used with caution in patients receiving nicergoline (see section “Interaction with other medicinal products and other types of interactions”).

In general, at recommended therapeutic doses, nicergoline does not cause changes in blood pressure, however, in patients with arterial hypertension, the drug may gradually lower blood pressure.

Nicergoline should be administered with caution to patients with a history of hyperuricemia or gout and/or during concomitant treatment with drugs that may affect the metabolism and excretion of uric acid.

The occurrence of fibrosis (e.g. fibrosis of the lungs, heart, heart valves and retroperitoneal fibrosis) has been associated with the use of certain ergot alkaloids that have agonist activity at 5-HT 2β serotonin receptors.

Before prescribing this class of medications, doctors should be familiar with the signs and symptoms of ergot overdose.

Use during pregnancy or breastfeeding.

pregnancy

Nicergoline had no reproductive toxicity in pregnant rats and rabbits. Studies in pregnant women have not been conducted. Given the approved indications, the use of the drug by pregnant and lactating women is unlikely. Nicergoline should be used during pregnancy only if the potential benefit to the woman outweighs the potential risk to the fetus.

Breastfeeding

It is not known whether nicergoline passes into milk, so the drug should not be used by women who are breastfeeding.

fertility

In studies in rats, nicergoline did not affect fertility.

The ability to influence the reaction speed when driving vehicles or other mechanisms.

Although the clinical effect of Niceromax is aimed at improving alertness and concentration, the effect of the drug on the reaction rate when driving or working with other mechanisms has not been studied. In any case, caution should be exercised, taking into account the patient's underlying disease.

When driving vehicles or operating machinery, it should be taken into account that dizziness or drowsiness may occasionally occur (see section "Adverse reactions").

Method of administration and doses.

Intramuscular injections: 2-4 mg (2-4 ml) twice a day (lyophilisate diluted with water for injection or saline to 2-4 ml).

Slow intravenous infusion: 4-8 mg dissolved in 100 ml of saline or glucose solution. This dose may be repeated several times a day at the discretion of the physician.

There is experience in using nicergoline by intra-arterial injection: 4 mg dissolved in 10 ml of saline, over 2 minutes.

The dosage regimen, duration of treatment and route of administration depend on the individual clinical situation. In some cases, it is advisable to start treatment with parenteral administration of the drug, and then switch to long-term oral administration. The effect of treatment appears gradually. Since therapy is usually long-term, the doctor must assess the feasibility of continuing treatment at certain intervals, but not less than every 6 months.

Adult and Elderly Patients: Based on pharmacokinetic and tolerability studies, no dose adjustment is necessary for adult and elderly patients.

Patients with renal impairment. Since urinary excretion is the main route of elimination (80%) of nicergoline and its metabolites, it is recommended to reduce the dose of the drug for patients with renal impairment (serum creatinine level ≥ 2 mg/ml) (see Section "Pharmacokinetics").

Children.

The safety and efficacy of nicergoline in children have not been established. Data are lacking.

Overdose.

When using nicergoline in high doses, a temporary decrease in blood pressure may be observed. Special treatment is usually not required, it is enough to lie down for a few minutes. In exceptional cases, with the development of severe insufficiency of blood supply to the brain and heart, the appointment of sympathomimetics and constant monitoring of blood pressure indicators is recommended.

Adverse reactions.

Adverse reactions are listed below by system organ class and in order of decreasing seriousness. The frequency is defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/100);

Psychiatric disorders: infrequently agitation, confusion, insomnia.

Nervous system disorders: uncommon: drowsiness, dizziness, headache; frequency unknown: feeling hot.

Vascular disorders: uncommon: hypotension, hot flashes.

Gastrointestinal disorders: common: abdominal discomfort; uncommon: diarrhea, nausea, constipation.

Skin and subcutaneous tissue disorders: uncommon: pruritus; frequency unknown: rash.

General disorders and administration site conditions: frequency unknown: fibrosis.

Research findings: uncommon: increased blood uric acid levels.

Reporting of suspected adverse reactions. Reporting of suspected adverse reactions after the registration of a medicinal product is an important measure. This allows for continued monitoring of the benefit/risk ratio of the drug. Physicians are encouraged to report any suspected adverse reactions.

Expiration date.

2 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 degrees Celsius.

Keep out of reach of children.

Incompatibility.

For intravenous injections/infusions, saline or glucose solution is used.

Do not mix with other medications. Use only recommended solvents.

Packaging.

1 or 4 vials of lyophilisate in a blister, 1 contour cell pack in a cardboard pack.

Vacation category.

According to the recipe.

Producer.

"Pharmex Group" LLC.

Location of the manufacturer and address of its place of business.

Ukraine, 08301, Kyiv region, Boryspil city, Shevchenko st., building 100.