Axotilin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AXYOTILIN (AXOTILIN)

Composition:

Active substance: citicoline;

One tablet contains citicoline (as citicoline sodium) — 500 mg;

Excipients: microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous silicon dioxide, hydrogenated castor oil, talc, magnesium stearate;

Coating: polyvinyl alcohol, titanium dioxide (E 171), talc, sodium bicarbonate, polyethylene glycol (4000) (macrogol), methacrylate copolymer (type A).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: oval-shaped, biconvex tablets, film-coated, white in color.

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

ATC code N06B X06.

Pharmacological properties.

Pharmacodynamics.

Citicoline stimulates the biosynthesis of structural phospholipids in neuronal membranes, as confirmed by magnetic resonance spectroscopy data. Due to this mechanism of action, citicoline enhances the functioning of membrane mechanisms such as ion pump activity and receptors, the modulation of which is necessary for normal nerve impulse conduction. Thanks to its stabilizing effect on neuronal membranes, citicoline exhibits anti-edematous properties that promote reabsorption of brain edema.

Experimental studies have shown that 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 stimulates acetylcholine synthesis.

It has been experimentally proven that citicoline also exerts a preventive neuroprotective effect in models of focal cerebral ischemia.

Clinical studies have shown that citicoline significantly improves functional recovery parameters in patients with acute ischemic stroke, which correlates with a slowing of ischemic brain lesion progression 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, alleviates cognitive and neurological disorders associated with cerebral ischemia, and helps reduce symptoms of amnesia.

Pharmacokinetics.

Citicoline is well absorbed after oral administration. Following administration, a significant increase in plasma choline levels is observed. After oral intake, the drug is almost completely absorbed. Studies have shown that bioavailability after oral and intravenous administration is practically equivalent.

The drug is metabolized in the intestine and liver, forming choline and cytidine.

After 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 becomes incorporated into cellular, cytoplasmic, and mitochondrial membranes, becoming part of the phospholipid fraction.

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. Urinary excretion of the drug occurs in two phases: the first phase lasts 36 hours, during which the elimination rate decreases rapidly, and the second phase, in which the elimination rate decreases much more slowly. The same biphasic pattern is observed in elimination via the respiratory tract. The rate of CO₂ excretion decreases rapidly within approximately 15 hours, then declines much more slowly thereafter.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to citicoline or other components of the medicinal product.
• High parasympathetic nervous system tone.

Interaction with other medicinal products and other forms of interaction.

Citicoline enhances the effect of levodopa.

It should not be administered simultaneously with medicinal products containing meclofenoxate.

Special precautions for use.

The medicinal product contains hydrogenated castor oil, which may cause stomach discomfort and diarrhea. Therefore, patients with inflammatory bowel diseases should use the drug with special caution.

Use during pregnancy or breastfeeding.

There are insufficient data on the use of citicoline in pregnant women. Citicoline should not be used during pregnancy except in cases of urgent medical need. The drug should be prescribed during pregnancy only when the expected therapeutic benefit outweighs the potential risk. There is no data available on the passage of citicoline into breast milk or its effects on the fetus.

Ability to influence reaction rate when driving or operating machinery.

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

Method of administration and dosage.

The recommended dose is 500 to 2000 mg per day (1–4 tablets), depending on the severity of symptoms and the patient's condition.

Dosage and duration of treatment are determined by a physician.

Elderly patients do not require dose adjustment.

Children. Experience with the use of citicoline in children is limited; therefore, the medicinal product should be prescribed only when the expected benefit outweighs any potential risk.

Overdose.

Cases of overdose have not been reported.

Adverse reactions.

Adverse reactions occur very rarely (<1/10,000), including single cases.

Psychiatric disorders: hallucinations.

Nervous system disorders: severe headache, dizziness.

Cardiovascular disorders: arterial hypertension, arterial hypotension.

Respiratory system disorders: dyspnea.

Gastrointestinal disorders: nausea, vomiting, occasional diarrhea.

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

General disorders: chills, swelling.

Shelf life.

2 years.

Storage conditions.

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

Keep out of reach of children!

Packaging. 10 tablets per blister; 3 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer.

Public joint-stock company "Scientific and Production Center "Borshchahivskyy Chemical and Pharmaceutical Plant".

Manufacturer's address and place of business activity.

17 Myru Street, Kyiv, 03134, Ukraine.