CYTIMAX-DARNITSA

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CYTOMAX-DARNITSA (CITIMAX-DARNITSA)

Composition:

Active substance: citicoline;

1 ml of solution contains sodium citicoline equivalent to 250 mg of citicoline;

1 ampoule (2 ml) contains sodium citicoline equivalent to 500 mg of citicoline;

1 ampoule (4 ml) contains sodium citicoline equivalent to 1000 mg of citicoline;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear colorless or slightly yellowish 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.

The active ingredient of the medicinal product, 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-exchange pumps and receptors, the modulation of which is essential for normal nerve impulse conduction.

Thanks to its stabilizing effect on neuronal membranes, citicoline exhibits anti-edematous properties, which contribute to a reduction in cerebral 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 reserves, inhibits apoptosis, and stimulates acetylcholine synthesis.

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

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

Pharmacokinetics.

After administration of the medicinal product, 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 throughout 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 found in urine and feces (less than 3%). Approximately 12% of the dose is excreted as exhaled CO₂. During excretion 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 excretion via the respiratory tract. The rate of CO₂ elimination decreases rapidly, within approximately 15 hours, and 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 consequences.
• Cognitive disorders and behavioral disturbances due to chronic vascular and degenerative cerebral disorders.

Contraindications.

• Hypersensitivity to the active substance or to other components of the medicinal product.
• Increased parasympathetic nervous system tone.

Interaction with other medicinal products and other types of interactions.

When citicoline and levodopa are used concomitantly, the effect of levodopa is enhanced.

The medicinal product should not be administered simultaneously with medicinal products containing meclophenoxate.

Special precautions for use.

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

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

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

This medicinal product contains sodium; therefore, caution should be exercised when administering it to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

There are insufficient data on the use of this medicinal product in pregnant women. It is not known whether citicoline passes into breast milk. The medicinal product should be used during pregnancy or breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus.

Ability to affect reaction speed when driving or operating machinery.

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

Method of Administration and Dosage.

The medicinal product should be administered intravenously or intramuscularly. In case of intravenous administration, the drug should be given as a slow intravenous injection (over 3–5 minutes depending on the dose administered) or by intravenous infusion (40–60 drops per minute).

The recommended dose for adults is 500–2000 mg per day depending on the severity of symptoms. The maximum daily dose is 2000 mg.

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

Dose adjustment is not required for elderly patients.

The medicinal product should be used immediately after opening the ampoule. The ampoule is intended for single use only. Any unused portion of the medicinal product should be discarded.

The medicinal product 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 drug in the form of an oral solution.

Children.

There is insufficient data on the use of citicoline in children. The medicinal product should be used only in urgent cases when the expected benefit outweighs the potential risk.

Overdose.

There are no data on cases of overdose with this medicinal product.

Side effects.

Side effects occur very rarely (<1/10,000), including isolated cases.

Respiratory system, thoracic organs and mediastinum: dyspnea.

Gastrointestinal tract: nausea, vomiting, diarrhea.

Nervous system: severe headache, vertigo, hallucinations.

Cardiovascular system: arterial hypertension, arterial hypotension, tachycardia.

Immune system: hypersensitivity reactions including angioneurotic edema, anaphylactic shock.

Skin and subcutaneous tissue: rash, purpura, pruritus, hyperemia, exanthema, urticaria.

General disorders and administration site reactions: chills, edema, increased body temperature, increased sweating, changes at the injection site.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibility.

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

Packaging.

2 ml (500 mg) or 4 ml (1000 mg) in an ampoule; 3 ampoules in a blister pack; 1 blister pack in a carton; 5 ampoules in a blister pack; 1 blister pack in a carton; 5 ampoules in a blister pack; 2 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical company "Darnytsia".

Manufacturer's address and location of business activity.

13, Boryspilska Street, Kyiv, 02093, Ukraine.