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. Solution for injection.

Basic physico-chemical properties: clear, colorless solution.

Pharmacotherapeutic group

Psychoanaleptics. Psychostimulants. Medicinal products used in attention deficit hyperactivity disorder (ADHD), nootropic agents. Other psychostimulant and nootropic agents. Citicoline.

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 function of membrane mechanisms such as ion pump activity and receptors, the modulation of which is necessary for normal nerve impulse conduction.

Due to its stabilizing effect on neuronal membranes, citicoline exhibits anti-edematous properties that contribute to reducing brain edema.

Experimental studies have shown that citicoline inhibits the activation of certain phospholipases (A1, A2, C, and D), reduces the formation of free radicals, prevents the destruction of membrane systems, and preserves antioxidant defense systems such as glutathione.

Citicoline preserves neuronal energy stores, inhibits apoptosis, and stimulates acetylcholine synthesis.

It has been experimentally demonstrated 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 stroke, which correlates with a slowed progression 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 deficits associated with cerebral ischemia, and helps reduce symptoms of amnesia.

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.

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 integrates into cellular, cytoplasmic, and mitochondrial membranes, becoming incorporated into the phospholipid fraction.

Only a small amount of the dose is detected in urine and feces (less than 3%). Approximately 12% of the dose is excreted as exhaled CO₂. The elimination of the drug in urine occurs in two phases: the first phase lasts up to 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 excretion 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 disturbances due to chronic vascular and degenerative cerebral disorders.

Contraindications

• Hypersensitivity to citicoline or to any of the excipients.
• Increased parasympathetic nervous system tone.

Interaction with other medicinal products and other forms of interaction

Citicoline enhances the effect of levodopa.

The medicinal product should not be administered concurrently with medicinal products containing meclofenoxate.

Special precautions for use

When administered intravenously, the medicinal product should be given slowly (over 3–5 minutes, depending on the dose administered).

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

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

This medicinal product contains 1.96 mmol (or 45 mg) of sodium per 1000 mg dose of citicoline. Caution should be exercised when administering the medicinal product to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Adequate data on the use of citicoline in pregnant women are lacking.

Data regarding 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 when the expected therapeutic benefit to the mother outweighs the potential risk to the fetus.

Ability to affect the speed of reactions 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.

Administration and Dosage

The recommended dose for adults is 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 bolus 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

Due to the low toxicity of the medicinal product Ticolin®, intoxication is not expected, even if therapeutic doses have been accidentally exceeded.

In case of accidental overdose, symptomatic treatment should be administered.

Side effects

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

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

Psychiatric disorders: hallucinations.

Cardiovascular disorders: arterial hypertension, arterial hypotension.

Respiratory system disorders: dyspnea.

Gastrointestinal disorders: nausea, vomiting, intermittent diarrhea.

Immune system disorders: rash, hyperemia, exanthema, purpura.

General disorders: chills, edema.

Reporting suspected side effects. Reporting of suspected side effects after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Incompatibilities

Do not use solvents not specified in the section "Dosage and administration".

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 status

Prescription only.

Manufacturer

MICROKHIM LLC (responsible for batch release, excluding batch control/testing).

JSC "Halychpharm" according to technology and at the order of MICROKHIM LLC (responsible for manufacturing and batch control/testing, excluding batch release).

Manufacturer's address and location of its business activities

5, Budynsturii Street, Kyiv, 01013, Ukraine.

6/8 Opryshkovska Street, Lviv, 79024, Ukraine.

Marketing authorization holder

MICROKHIM LLC.

Address of the marketing authorization holder

5, Budynsturii Street, Kyiv, 01013, Ukraine.

You can report an adverse event associated with the use of the medicinal product to the pharmacovigilance system of MICROKHIM LLC by calling +38 (050) 309-83-54 (24/7) or emailing [email protected]