Neurodar

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

Composition:

Active substance: citicoline;

1 ampoule (4 ml) contains citicoline sodium equivalent to citicoline 500 mg or 1000 mg;

Excipients: water for injections, concentrated phosphoric acid for pH adjustment.

Pharmaceutical form. Solution for injection.

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 N06B X06.

Pharmacological properties.

Pharmacodynamics.

Citicoline stimulates the biosynthesis of neuronal membrane structural phospholipids, as confirmed by magnetic resonance spectroscopy data. Due to this mechanism of action, citicoline improves the functioning of membrane mechanisms such as ion exchange pumps and receptors, modulation of which is necessary for proper nerve impulse conduction.

Thanks to its stabilizing effect on neuronal membranes, citicoline exhibits anti-edematous properties that 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 preventive neuroprotective effect in focal cerebral ischemia.

Clinical studies have shown that citicoline significantly enhances functional recovery in patients with acute ischemic cerebrovascular events, which correlates with a slowing of the growth of the ischemic brain lesion volume 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.

Citicoline is well absorbed following oral, intramuscular, and intravenous administration. After administration, a significant increase in plasma choline levels is observed. Following oral administration, the drug is almost completely absorbed. Studies have shown that bioavailability following oral and parenteral 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 integrates into cellular, cytoplasmic, and mitochondrial membranes, becoming incorporated into the phospholipid fraction structure.

Only a small amount of the dose is found in urine and feces (less than 3%). Approximately 12% of the dose is excreted as CO₂ in exhaled air. During elimination via 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 during elimination via the respiratory tract. The rate of CO₂ excretion 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 neurological consequences.
• Cognitive and behavioral disorders due to chronic vascular and degenerative cerebral disorders.

Contraindications.

Hypersensitivity to the components of the drug, increased parasympathetic nervous system tone.

Interaction with other medicinal products and other forms of interaction.

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

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

In the presence of intracranial hemorrhage, the dose should not exceed 500 mg per single administration and 1000 mg per day, and the intravenous infusion rate should not exceed 30 drops per minute, due to the potential risk of increasing cerebral blood flow.

Citicoline should be integrated with various therapeutic approaches indicated for the different pathological conditions for which it is used.

Use during pregnancy or breastfeeding.

There are insufficient data on the use of citicoline in pregnant women. There are no data regarding the excretion of citicoline in breast milk or its effects on the fetus.

Although teratogenic effects of citicoline have not been observed, the drug should be used during pregnancy and breastfeeding only if absolutely necessary, when the expected benefit to the mother outweighs the potential risk to the fetus, and under strict medical supervision.

Ability to affect reaction speed when driving or operating machinery.

In individual cases, certain adverse reactions from the central nervous system (CNS) may affect the ability to drive 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 should be administered by intramuscular or intravenous injection.

Intravenously, 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 use in children is limited.

Overdose.

Cases of overdose have not been reported.

Adverse Reactions

Adverse reactions occur very rarely (< 1/10,000), 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, increased body temperature, excessive sweating, local reactions at the site of administration.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach and sight of children.

Incompatibilities.

The medicinal product must not be mixed with other medicinal products in the same container. Do not use solvents other than those specified in section "Instructions for use and dosage".

Packaging.

500 mg/4 ml: 4 ml of solution in an ampoule, 5 ampoules in a blister pack,

1 pack in a cardboard box.

1000 mg/4 ml: 4 ml of solution in an ampoule, 5 ampoules in a blister pack,

1 pack in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Laboratorio Farmaceutico C.T. S.r.l.

Manufacturer's address and place of business.

Via Dante Alighieri, 71 – 18038 San Remo (IM), Italy.

Marketing Authorization Holder.

Amaxa LTD.

Address of the Marketing Authorization Holder.

31 John Islip Street, London SW1P 4FE, United Kingdom.