Ticolin®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Ticolin® (Ticolin)

Composition:

Active substance: citicoline;

1 ml of the preparation contains 130.625 mg of citicoline sodium, equivalent to 125 mg of citicoline, or 261.25 mg of citicoline sodium, equivalent to 250 mg of citicoline;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group.

Psychostimulants. Drugs 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, as confirmed by magnetic resonance spectroscopy data. Due to this mechanism of action, citicoline improves the functioning of membrane mechanisms such as ion pump activity and receptors, modulation of which is necessary for normal nerve impulse conduction.

Thanks to its stabilizing effect on neuronal membranes, citicoline exhibits anti-edematous properties, which contribute to reducing cerebral edema.

Experimental studies have shown that citicoline inhibits the activation of certain phospholipases (A1, A2, C, and D), reduces free radical formation, prevents the destruction of membrane systems, and preserves 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 focal cerebral ischemia.

Clinical studies have shown that citicoline significantly enhances functional recovery in patients with acute ischemic cerebrovascular disorders, which correlates with a slowing of the growth in volume of ischemic brain damage 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, as well as cognitive and neurological disorders associated with cerebral ischemia, and helps reduce symptoms of amnesia.

Pharmacokinetics.

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

After administration, citicoline is widely distributed in 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 incorporated into the phospholipid fraction.

Only a small amount of the dose is found in urine and feces (less than 3%). Approximately 12% of the dose is excreted as exhaled CO₂. During elimination of the drug in urine, two phases are observed: the first phase—within 36 hours—during which the elimination rate decreases rapidly, and the second phase, during which the elimination rate decreases much more slowly. The same biphasic pattern is observed in elimination via the respiratory tract. The rate of CO₂ elimination decreases rapidly, approximately within 15 hours, after which it 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 disorders due to chronic vascular and degenerative cerebral disorders.

Contraindications.

• Hypersensitivity to citicoline or to other components of the drug;
• increased parasympathetic nervous system tone.

Interaction with other medicinal products and other types of interactions.

Citicoline enhances the effect of levodopa.

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

Special precautions for use.

When administered intravenously, the drug should be injected slowly (over 3–5 minutes, depending on the dose administered).

When administered intravenously by drip infusion, the infusion rate should be 40–60 drops per minute.

In case of persistent intracranial hemorrhage, the dose should not exceed 1000 mg per day and the intravenous infusion rate (30 drops per minute) should not be exceeded.

Use during pregnancy or breastfeeding.

There is 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 unknown.

During pregnancy or breastfeeding, the medicinal product should be prescribed only if the expected therapeutic benefit to the mother outweighs the potential risk to 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.

Dosage and Administration.

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

The medicinal product is intended for intramuscular or intravenous administration. For intravenous use, the medicinal product may be administered slowly by 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: dosage adjustment is not required.

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

Children.

Experience with the use of the medicinal product in children is limited.

Overdose.

Cases of overdose have not been reported.

Side effects.

Side effects occur very rarely (< 1/10000), including isolated cases.

Central and peripheral nervous system disorders: severe headache, vertigo, hallucinations.

Cardiovascular disorders: arterial hypertension, arterial hypotension, tachycardia.

Respiratory system disorders: dyspnea.

Gastrointestinal disorders: nausea, vomiting, diarrhea.

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

General disorders: chills, reactions at the site of injection.

Shelf life.

1.5 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging. Keep out of reach of children.

Incompatibilities.

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

Packaging.

4 ml in clear glass ampoules, 5 ampoules (5×1) in a cassette in a cardboard pack or 4 ml in clear glass ampoules, 10 ampoules (5×2) in cassettes in a cardboard pack.

Prescription category.

Prescription only.

Manufacturers.

Private Joint-Stock Company "Lekhym-Kharkiv" (responsible for manufacturing and batch control/testing, excluding batch release).

LLC NPF "MIKROKHEM" (responsible for batch release, excluding batch control/testing).

Addresses of manufacturers and locations of their operations.

Ukraine, 61115, Kharkiv region, city of Kharkiv, Severin Pototskogo Street, 36 (Private Joint-Stock Company "Lekhym-Kharkiv").

Ukraine, 93000, Luhansk region, city of Rubizhne, Lenin Street, 33

(LLC NPF "MIKROKHEM").

Marketing Authorization Holder.

LLC NPF "MIKROKHEM".

Address of the Marketing Authorization Holder.

Ukraine, 93000, Luhansk region, city of Rubizhne, Lenin Street, 33.

Adverse events associated with the use of this medicinal product should be reported by calling +38 (050) 309-83-54 (24/7).