Axotilin

INSTRUCTION for medical use of the medicinal product AXOTILIN

Composition:

Active substance: citicoline;

1 ampoule (4 ml) contains 500 (1000) mg of citicoline (as citicoline sodium);

Excipients: hydrochloric acid or sodium hydroxide for pH adjustment, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical characteristics: clear, colorless liquid.

Pharmacotherapeutic group. Psychostimulants, agents used in attention deficit hyperactivity disorder (ADHD), nootropic agents. Other psychostimulant and nootropic agents.

ATC Code N06BX06.

Pharmacological Properties

Pharmacodynamics

Citicoline stimulates the biosynthesis of structural phospholipids in neuronal membranes. By enhancing the function of membrane mechanisms such as ion pumps and neurotransmitter receptors—whose regulation is essential for normal nerve impulse transmission—citicoline supports proper neuronal activity. Due to its stabilizing effect on neuronal membranes, citicoline exhibits anti-edematous properties that promote the reabsorption of cerebral edema.

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

Citicoline preserves neuronal energy reserves, inhibits apoptosis, and stimulates the synthesis of acetylcholine.

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

Citicoline significantly improves functional recovery rates in patients with acute cerebrovascular disorders, which correlates with a slowed progression of ischemic brain lesions as demonstrated 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, and helps reduce symptoms of amnesia as well as cognitive and neurological deficits associated with cerebral ischemia.

Pharmacokinetics

After administration, a significant increase in plasma choline levels is observed. The drug is metabolized in the intestine and liver, forming choline and cytidine.

Following administration, citicoline is widely distributed into brain structures, with rapid incorporation of the choline fraction into structural phospholipids and the cytidine fraction into cytidine nucleotides and nucleic acids. In the brain, citicoline integrates into cellular, cytoplasmic, and mitochondrial membranes, becoming part of the phospholipid fraction.

Only a small amount of the administered dose is excreted in urine and feces (less than 3%). Approximately 12% of the dose is eliminated as exhaled CO₂. Renal excretion occurs in two phases: the first phase lasts up to 36 hours, during which elimination rate decreases rapidly, and the second phase, during which elimination proceeds at a much slower rate. A similar biphasic pattern is observed in elimination via the respiratory tract: the rate of CO₂ elimination decreases rapidly within approximately 15 hours, followed by a much slower decline thereafter.

Clinical characteristics.

Indications.

• Stroke, acute phase of cerebral circulation disorders, and 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.

Enhances the effect of levodopa.

Citicoline can be used simultaneously with hemostatic, anti-edematous agents, and perfusion solutions.

The drug should not be used simultaneously with medications containing meclophenoxate.

Special precautions for use.

When administered intravenously, the drug should be injected slowly (over 3–5 minutes, depending on the dose administered). In the case of intravenous infusion, the infusion rate should be 40–60 drops per minute.

In severe and acute cases or in the presence of progressive changes in consciousness, the drug may be used concomitantly with hemostatic agents, agents that reduce intracranial pressure, and perfusion solutions.

In cases of pronounced cerebral edema, it is necessary to simultaneously administer agents that reduce intracranial pressure, such as mannitol and corticosteroids.

In the presence of intracranial hemorrhage, the intravenous infusion rate should not exceed 30 drops per minute; high doses should be avoided (more than 500 mg in a single dose or more than 1000 mg per day), as increased cerebral blood flow may occur. In such cases, dividing the daily dose into 2–3 administrations is recommended.

Citicoline should not be used as monotherapy; it should be combined with various therapeutic treatment methods indicated for the different pathological conditions for which it is prescribed.

Use during pregnancy or breastfeeding.

There is insufficient data on the use of citicoline in pregnant women. Data regarding excretion of citicoline in breast milk and its effects on the fetus are unknown. During pregnancy or breastfeeding, the medicinal product should be prescribed only if the expected therapeutic benefit for the mother outweighs the potential risk to the fetus or infant.

Ability to affect reaction speed when driving or operating machinery.

In individual cases, certain adverse reactions involving the central nervous system may affect the ability to drive a vehicle or operate complex machinery.

Method of Administration and Dosage.

The recommended dose for adults is from 500 mg to 2000 mg per day depending on the severity of symptoms.

The drug is intended for intramuscular or intravenous administration. For intravenous use, the drug may be administered slowly as an injection (over 3-5 minutes depending on the dose administered) or by infusion (rate: 40-60 drops per minute).

Maximum daily dose – 2000 mg.

The duration of treatment depends on the course of the disease and is determined by the physician.

Elderly patients do not require dose adjustment.

The injection solution is intended for single use only. The drug should be used immediately after opening the ampoule. Any unused portion must be discarded. The drug may be mixed with all isotonic solutions for intravenous administration, as well as with hypertonic glucose solution.

If necessary, treatment may be continued with the oral solution formulation of the drug.

Children.

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

Overdose.

There have been no reports of overdose. In case of accidental overdose, symptomatic treatment should be administered.

Adverse reactions.

Nervous system: severe headache, vertigo, hallucinations.

Cardiovascular system: arterial hypertension, arterial hypotension, tachycardia.

Respiratory system: dyspnea.

Gastrointestinal tract: nausea, vomiting, diarrhea.

Immune system: allergic reactions, including: rash, hyperemia, exanthema, urticaria, purpura, pruritus, angioedema, anaphylactic shock.

General reactions: chills, increased body temperature, increased sweating, local reactions at the injection site.

Shelf life.

3 years.

Storage conditions.

In the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children!

Incompatibility.

Do not use solvents not specified in the section "Administration and dosage".

Packaging.

4 ml in ampoules; 5 ampoules in a cassette; 1 or 2 cassettes per pack.

Prescription category. Prescription only.

Manufacturer.

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

Manufacturer's location and address of business activity.

17, Miru Street, Kyiv, 03134, Ukraine.