DIPHOSPHOCIN

INSTRUCTION for medical use of the medicinal product DIFOSFOCIN (DIFOSFOCIN)

Composition:

Active substance: citicoline (as citicoline sodium);

1 ampoule (4 ml of solution) contains 500 mg or 1000 mg of citicoline (as citicoline sodium);

Excipients: sodium hydroxide (for pH adjustment), water for injections.

Medicinal form. Injection solution.

Main physicochemical characteristics: clear, colorless solution.

Pharmacotherapeutic group. Other psychostimulants and nootropics. Citicoline.

ATC code N06B X06.

Pharmacological Properties.

Pharmacodynamics.

Difosfocin is a preparation containing a synthetic analogue of the natural nucleoside citicoline (cytidine 5'-diphosphocholine), which is a precursor of phosphatidylcholine and other phospholipids that are components of cellular membranes. It has been shown that citicoline improves cerebral blood flow and oxygen supply to the brain, thereby promoting the restoration of normal cerebral metabolism. In addition, due to its protective effect on dopaminergic neurons, citicoline enhances dopamine levels and increases the sensitivity of dopamine receptors.

Pharmacokinetics.

After intramuscular administration of 1000 mg citicoline, maximum plasma concentrations of its main metabolite—choline—are observed within 0.4 hours, reaching levels of 25 μmol/L. Citicoline is metabolized in the liver to form free choline, which is further incorporated into the cycles of lecithin and membrane lipid synthesis. Elimination of citicoline occurs primarily via the respiratory tract (12% excreted in fully metabolized form), and to a lesser extent through urine and feces.

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 other components of the drug.
• Increased tone of the parasympathetic nervous system.

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.

In cases of severe cerebral edema, drugs for reducing intracranial pressure, such as mannitol and corticosteroids, should be administered.

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

When the drug is 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 should not exceed 30 drops per minute.

Use during pregnancy or breastfeeding.

Adequate data on the use of citicoline in pregnant women are lacking. Data regarding 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 for the mother outweighs the potential risk to the fetus.

Ability to affect reaction rate when driving or operating machinery.

In individual cases, certain adverse reactions from the central nervous system may affect 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 medication is intended for intramuscular or intravenous administration. For intravenous use, the drug may be administered by slow 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 medication 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.

Children.

Experience with use in children is limited.

Overdose.

No cases of overdose have been reported.

Side effects.

Side effects 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, angioneurotic edema, anaphylactic shock.

General disorders: chills, reactions at the injection site.

Shelf life. 5 years.

Do not use after the expiry date stated on the packaging.

Storage conditions. Store at a temperature not exceeding 25°C. Keep out of the reach of children.

Incompatibility.

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

Packaging. 4 ml of solution for injection in an ampoule; 3 ampoules with a dosage of 1000 mg or 5 ampoules with a dosage of 500 mg in a blister pack in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Mitim S.r.l.

Address of manufacturer and location of its business activity.
Via Cacciamali, 34-38 – 25125 Brescia, Italy.

Marketing authorization holder. Magis Farmaceutici S.r.l.

Address. Via Cefalonia 70 – 25124 Brescia, Italy.