Axotilin

INSTRUCTIONS for medical use of the medicinal product AXOTILIN (AXOTILIN)

Composition:

Active substance: citicoline;

1 ml of solution contains citicoline in the form of citicoline sodium 100 mg;

Excipients: glycerin, sodium saccharin, sorbitol (E 420), sodium citrate, citric acid monohydrate, methylparahydroxybenzoate (E 218), propylparahydroxybenzoate (E 216), potassium sorbate, purified water.

Pharmaceutical form. Oral solution.

Main physicochemical characteristics: clear, colorless liquid.

Pharmacotherapeutic group. Other psychostimulants and nootropic agents. ATC Code N06BX06.

Pharmacological properties.

Pharmacodynamics.

Citicoline stimulates the biosynthesis of structural phospholipids in neuronal membranes. Citicoline improves the function of membrane mechanisms such as ion pumps and receptors, the regulation of which is essential for normal nerve impulse conduction. Due to its stabilizing effect on neuronal membranes, citicoline exhibits anti-edematous properties that promote reabsorption of cerebral edema.

Citicoline inhibits the activation of certain phospholipases (A1, A2, C, and D), reducing the formation of free radicals, preventing the destruction of membrane systems, and preserving antioxidant defense systems such as glutathione.

Citicoline preserves neuronal energy reserves, inhibits apoptosis, and thereby enhances cholinergic transmission.

Citicoline also exerts a preventive neuroprotective effect in focal cerebral ischemia.

Citicoline significantly increases functional recovery rates in patients with acute cerebrovascular disorders, which correlates with slowing the progression of ischemic brain damage as shown by neuroimaging. In patients with traumatic brain injury, citicoline accelerates recovery and reduces the duration and severity of post-traumatic syndrome.

Citicoline improves levels of attention and consciousness, promotes reduction of amnesia symptoms, and ameliorates cognitive and other neurological deficits associated with cerebral ischemia.

Pharmacokinetics.

Citicoline is well absorbed after oral, intramuscular, and intravenous administration. Plasma choline levels increase significantly after administration by the aforementioned routes. Oral absorption is nearly complete, and bioavailability is practically equivalent to that achieved with intravenous administration.

Depending on the route of administration, the drug is metabolized in the intestine and liver to choline and cytidine. After administration, citicoline is widely distributed throughout brain structures, with rapid incorporation of the choline fraction into structural phospholipids and the cytidine fraction into cytidine nucleotides and nucleic acids. Upon reaching the brain, citicoline integrates into cellular, cytoplasmic, and mitochondrial membranes, participating in the formation of phospholipid fractions.

Only a small amount of the dose is excreted in urine and feces (less than 3%). Approximately 12% of the dose is excreted as exhaled CO₂. Renal excretion of the drug occurs in two phases: the first phase lasts approximately 36 hours, during which the excretion rate rapidly decreases, and the second phase, during which the excretion rate declines much more slowly. The same biphasic pattern is observed in CO₂ excretion: the rate of exhaled CO₂ excretion rapidly decreases after approximately 15 hours, then declines much more slowly.

Clinical characteristics.

Indications.

• Stroke, acute phase of cerebral circulation disorders and treatment of complications and consequences of cerebral circulation disorders.
• Traumatic brain injury and its neurological consequences.
• Cognitive disorders and behavioral disturbances due to chronic vascular and degenerative cerebral disorders.

Contraindications.

• Hypersensitivity to any component of the drug.
• Increased tone of the parasympathetic nervous system.

Interaction with other medicinal products and other types of interactions.

The drug should not be used simultaneously with preparations containing meclofenoxate. Enhances the effect of levodopa.

Special precautions for use.

The medicinal product contains sorbitol (E 420); therefore, patients with hereditary fructose intolerance should not use Axotilin oral solution.

Methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216) contained in the product may cause allergic reactions (usually delayed-type).

This medicinal product contains 0.306 mmol of sodium in 5 ml of oral solution. Caution is advised when administering to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

There are insufficient data on the use of citicoline in pregnant women. Data on the excretion of citicoline in breast milk and its effects on the fetus are lacking. Therefore, during pregnancy or breastfeeding, the drug should be prescribed only when the expected benefit to the mother outweighs the potential risk to the fetus or infant.

Ability to influence reaction speed when driving or operating machinery.

In individual cases, certain adverse reactions affecting the central nervous system may impair the ability to drive or operate machinery.

Method of administration and dosage.

Orally.

The recommended dose for adult patients is from 500 mg (5 mL) to 2000 mg (20 mL) per day, divided into 2–3 doses. May be taken independently of food intake.

The medication should be diluted in a small amount of water prior to administration and taken using a dosing device. After each administration, the dosing device should be rinsed with water.

The duration of treatment depends on the severity of brain involvement and is determined individually by the physician.

Dose adjustment is not required for elderly patients.

Children.

Experience with the use of the medication in children is limited.

Overdose.

Cases of overdose have not been reported.

Adverse Reactions.

Nervous system and psychiatric disorders: severe headache, vertigo, hallucinations.

Cardiovascular system: arterial hypertension, arterial hypotension, tachycardia.

Respiratory system: dyspnea.

Gastrointestinal tract: nausea, vomiting, occasional diarrhea.

Skin and subcutaneous tissue: allergic reactions, including hyperemia, rash, exanthema, purpura, urticaria, pruritus, angioneurotic edema, anaphylactic shock.

General reactions: chills, edema.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after registration of the medicinal product is of great importance. It enables ongoing monitoring of the benefit-risk balance of the use of this medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

In the original packaging at a temperature not exceeding 25 °C. Do not freeze or refrigerate. Slight opalescence may occur during storage, which disappears when the preparation is kept at room temperature (≈ 20 °C).

Shelf life after first opening – 10 days.

Keep out of reach and sight of children.

Packaging.

50 ml in a bottle, 1 bottle with a dosing device in a carton.

Prescription status. Prescription only.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Borshchahivskyy Chemical-Pharmaceutical Plant".

Manufacturer's address and place of business.

17, Miru Street, Kyiv, 03134, Ukraine.