Neurocytin®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NEUROCITIN®

Composition:

Active substances:

1 ml of solution contains: citicoline sodium (calculated as citicoline) – 10 mg, sodium chloride – 6 mg, potassium chloride – 0.4 mg, calcium chloride dihydrate – 0.27 mg, sodium lactate – 3.2 mg. Theoretical osmolarity – 299.2 mOsmol/L;

Excipient: water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear, colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Solutions for intravenous use. Electrolytes in combination with other agents. ATC code B05B B04.

Pharmacological Properties

Pharmacodynamics

Neurocitin® is an electrolyte solution with a balanced content of electrolytes and citicoline.

Citicoline stimulates the biosynthesis of structural phospholipids in neuronal membranes, thereby improving membrane functions, including the activity of ion-exchange pumps and neuroreceptors. Due to its membrane-stabilizing effect, citicoline possesses anti-edematous properties and thus reduces cerebral edema. Research findings have shown that citicoline inhibits the activity of certain phospholipases, prevents the residual formation of free radicals, protects membrane systems from damage, and maintains the body's antioxidant defense system.

Citicoline reduces the volume of damaged tissue by preventing cell death through modulation of apoptotic mechanisms and improves cholinergic transmission. Citicoline also exerts a preventive neuroprotective effect in focal cerebral strokes.

Citicoline promotes rapid functional recovery of patients with acute cerebrovascular disorders by reducing ischemic brain tissue damage, as confirmed by radiological findings.

In traumatic brain injuries, citicoline shortens the duration of the recovery period and reduces the severity of post-traumatic syndrome.

Citicoline enhances cerebral activity, reduces the level of amnesia, and improves the condition in cognitive, sensory, and motor disorders observed in cerebral ischemia.

The drug replenishes the deficit of circulating blood volume. Lactate, a component of the medicinal product, is metabolized into bicarbonate anions, which slightly shifts blood pH toward the alkaline side. The solution also has a detoxifying effect due to reduced concentration of toxic substances in the blood and activation of diuresis.

Pharmacokinetics

Citicoline is well absorbed following oral, intramuscular, and intravenous administration. After administration, a significant increase in plasma choline levels is observed. Studies have shown that bioavailability via oral and parenteral routes is practically equivalent.

The drug is metabolized in the intestine and liver, forming choline and cytidine. After administration, citicoline is taken up by brain tissues, where choline acts on phospholipids and cytidine on cytidine nucleotides and nucleic acids. Citicoline rapidly reaches brain tissue and actively incorporates into cell membranes, cytoplasm, and mitochondria, stimulating phospholipid activity.

Only a small amount of the administered dose is excreted in urine and feces (less than 3%). Approximately 12% of the administered dose is excreted via the respiratory tract. Elimination of the drug in urine and through the respiratory tract occurs in two phases: the first phase—rapid elimination (in urine—within the first 36 hours, via respiratory tract—within the first 15 hours), the second phase—slow elimination. The majority of the citicoline dose is incorporated into metabolic processes.

Other components of the drug (anions, cations) are excreted in urine.

Clinical characteristics.

Indications.

• Acute phase of cerebral circulation disorders, complications and sequelae of cerebral circulation disorders.
• Traumatic brain injury and its consequences.
• Neurological disorders (cognitive, sensory, motor) caused by cerebrovascular pathology of degenerative and vascular origin.

Contraindications.

• Hypersensitivity to the components of the medicinal product;
• increased parasympathetic nervous system tone;
• hypervolemia, hypernatremia, hyperkalemia, hypercalcemia, hyperchloremia, alkalosis, lactic acidosis;
• severe arterial hypertension, decompensated heart failure;
• oliguria, anuria;
• hepatic insufficiency (due to reduced bicarbonate formation from lactate);
• acute renal failure;
• extracellular hyperhydration;
• pulmonary edema, cerebral edema.

Interaction with other medicinal products and other types of interactions.

Citicoline potentiates the effect of levodopa.

The drug should not be administered simultaneously with medicinal products containing meclofenoxate.

When potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, and potassium-containing drugs are used, the risk of developing hyperkalemia increases. When the drug is used concomitantly with cardiac glycosides, the toxicity of the latter is enhanced due to the presence of Ca++ ions in the solution.

The drug is incompatible with cefamandole, amphotericin, ethyl alcohol, thiopental, aminocaproic acid, metaraminol, ampicillin, vibramycin, and monocycline. Possible increased sodium retention in the body when used concomitantly with the following medicinal products: nonsteroidal anti-inflammatory drugs, androgens, anabolic hormones, estrogens, corticotropin, mineralocorticoids, vasodilators, or ganglion blockers.

Due to the presence of lactate, which alkalinizes pH, Neurocytin® should be used with caution in combination with medicinal products whose renal elimination depends on pH. Renal clearance of salicylates, barbiturates, and lithium may decrease, while that of sympathomimetics and stimulants (such as dextroamphetamine sulfate, phenfluramine hydrochloride) may increase.

Special precautions for use

In case of persistent intracranial hemorrhage, the dose should not exceed 100 mL per day and the intravenous infusion rate should not exceed 30 drops per minute.

Monitoring of blood electrolyte levels, pH, pCO₂, and lactate should be performed.

Administration of intravenous solutions may lead to fluid and/or solution overload, hyperhydration, congestion, and pulmonary edema. The risk of dilution is inversely proportional to the electrolyte concentration. The risk of solution overload causing congestion with peripheral edema and pulmonary edema is directly proportional to the electrolyte concentration.

If any signs of hypersensitivity reactions occur, administration of the solution must be stopped immediately and appropriate treatment initiated.

Since the medicinal product contains sodium lactate, it should be used with particular caution in patients predisposed to hypernatremia (e.g., those with adrenocortical insufficiency, non-diabetic hyperglycemia, or extensive tissue injury) and in patients with cardiac disorders. Due to its sodium ion content, the solution should be administered with caution to elderly patients, patients with arterial hypertension, renal or cardiovascular insufficiency, congestive heart failure (especially in the postoperative period), patients with hypoxia or hepatic insufficiency, as well as patients with clinical conditions associated with sodium retention and edema, and patients receiving corticosteroids or corticotropin.

Due to potassium content, caution is required when administering the solution to patients with cardiac disorders and clinical conditions associated with potassium retention in the body.

When administering calcium, cardiac function should be monitored via ECG, especially in patients receiving digitalis. Serum calcium levels do not always reflect tissue calcium levels.

In patients with impaired renal excretory function, administration of the solution may lead to sodium or potassium retention.

Due to the presence of calcium ions in the medicinal product, caution is required when co-administering with blood products due to the potential risk of coagulation.

Parenteral administration of calcium to patients receiving cardiac glycosides should be performed with particular caution.

Lactate is a substrate for gluconeogenesis; therefore, blood glucose levels should be carefully monitored in patients with type II diabetes mellitus.

Sodium and potassium content

This medicinal product contains:

• 7.53 mmol (or 173 mg) of sodium per 50 mL dose;
• 15.05 mmol (or 346 mg) of sodium per 100 mL dose;
• 30.10 mmol (or 692 mg) of sodium per 200 mL dose.

Caution should be exercised when administering to patients on a sodium-controlled diet.

This medicinal product contains:

• 0.265 mmol (or 10.5 mg) of potassium per 50 mL dose, i.e., practically potassium-free;
• 0.53 mmol (or 21 mg) of potassium per 100 mL dose, i.e., practically potassium-free;
• 1.06 mmol (or 42 mg) of potassium per 200 mL dose.

Caution should be exercised when administering to patients with impaired renal function or those on a potassium-controlled diet.

Use during pregnancy or breastfeeding

There are no data on the use of Neurocytin® in pregnant women. Data on excretion of the drug in breast milk and its effects on the fetus are unknown. Therefore, the medicinal product should be administered during pregnancy or breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus.

Ability to influence reaction speed when driving or operating machinery

In individual cases, certain adverse reactions from the central nervous system may affect the ability to drive vehicles or operate machinery.

Dosage and Administration

For intravenous use.

The recommended dose for adults is 50 ml to 200 ml per day administered as intravenous infusion (40–60 drops per minute).

Treatment: during the first 2 weeks, 50–100 ml twice daily intravenously. Maximum daily dose – 200 ml.

In acute and emergency conditions, maximum therapeutic effect is achieved when the medicinal product is administered within the first 24 hours.

Dosage and duration of treatment depend on the severity of brain damage and are determined individually by the physician.

Elderly patients

Dose adjustment is not required.

Children

There is insufficient data on the use of this medicinal product in children.

Overdose

Overdose or too rapid administration of the solution may lead to disturbances in water-electrolyte balance, manifestations of alkalosis, and cardiorespiratory decompensation. In such cases, administration of the medicinal product must be stopped immediately. Symptomatic therapy should be administered.

Excessive lactate administration may lead to development of metabolic alkalosis, which in turn may be accompanied by hypokalemia.

Symptoms: mood changes, fatigue, dyspnea, muscle weakness, polydipsia, polyuria, cognitive disturbances, arrhythmia. Muscle hypertonia, twitching, and tetanic seizures may develop in patients with hypocalcemia.

Adverse reactions.

Psychiatric disorders: hallucinations, panic attack.

Central nervous system disorders: severe headache, dizziness, vertigo.

Cardiovascular disorders: arterial hypertension, arterial hypotension, tachycardia.

Respiratory system disorders: dyspnea.

Gastrointestinal disorders: nausea, vomiting, diarrhea.

Electrolyte imbalance: changes in serum electrolyte levels (potassium, calcium, sodium, chloride), metabolic alkalosis, chloride acidosis.

General disorders: hypervolemia.

Immune system disorders: chills, edema, allergic reactions, including: rash, purpura, pruritus, angioneurotic edema, anaphylactic shock; increased body temperature, excessive sweating, cough, sneezing, breathing difficulty, localized or generalized urticaria.

Local reactions at infusion site: inflammation, swelling, rash, pruritus, erythema, pain, burning, numbness at the infusion site.

If adverse reactions occur, infusion should be discontinued immediately, the patient's condition should be assessed, and appropriate medical management provided.

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 30 °C in the original packaging. Keep out of reach of children.

Incompatibility.

The drug must not be mixed with other medicinal products in the same container, including phosphate- and carbonate-containing solutions.

Packaging.

50 ml, 100 ml, or 200 ml in a bottle; 1 bottle per carton.

Prescription status. Prescription only.

Manufacturer.

Yuria-Pharm LLC.

Manufacturer's address and location of business activity.

108, Kozbirska St., Cherkasy, Cherkasy region, 18030, Ukraine. Tel.: (044) 281-01-01.