CYTOFLAVIN solution for intravenous administration

General characteristics. Structure:

Active ingredient: 1 l of solution contains active components: succinic acid of 100 g, niacinamide of 10 g, inosine (inosine) of 20 g, Riboflavinum mononucleotide (Riboflavinum) of 2 g; excipients: N-metilglyukamin (меглумин) 165 g, sodium hydroxide of 34 g, water for injections.

Description: transparent liquid of yellow color.

Pharmacological properties:

Pharmacodynamics. Pharmacological effects are caused by combined effect of the components which are a part of the drug TSITOFLAVIN®. ЦИТОФЛАВИН® promotes activation of aerobic metabolism of cells that leads to increase in level of utilization of glucose, promotes the increased level of beta oxidation of fatty acids and resynthesis of γ-aminobutyric acid of acid in neurons. ЦИТОФЛАВИН® increases resistance of membranes of nervous and glial cells to influence of ischemia that is expressed in decrease in concentration of the neurospecific proteins characterizing the level of destruction of the main structural components of nervous tissue. ЦИТОФЛАВИН® improves coronary and brain blood-grooves, activates metabolic processes in the central nervous system, recovers the broken consciousness, promotes regress of neurologic symptomatology and improvement of cognitive functions of a brain. Possesses the bystry awakening action at postanesthetic oppression of consciousness. At use of the drug TSITOFLAVIN® in the first 12 hours from the beginning of development of a stroke the favorable course of ischemic and necrotic processes in a defeat zone (reduction of the center), recovery of the neurologic status and decrease in level of an invalidism in the remote period is observed.

Pharmacokinetics. At intravenous infusion with a speed about 2 ml/min. (in terms of undiluted ЦИТОФЛАВИН®) succinic acid and inosine are utilized almost instantly and in a blood plasma are not defined. Succinic acid - the peak of concentration decides within the first minute after introduction, on further bystry decrease without cumulation and return of its level to background values owing to a metabolization to water and carbon dioxide. Inosine is metabolized in a liver with formation of an inozinmonofosfat with the subsequent its oxidation to uric acid. In insignificant quantity it is removed by kidneys. Niacinamide is quickly distributed in all fabrics, gets through a placenta and into breast milk, is metabolized in a liver with formation of N-metilnikotinamida, removed by kidneys. Plasma elimination half-life makes about 1,3 hours, the equilibrium volume of distribution – about 60 liters, the general clearance – about 0,6 l/min. Riboflavinum is distributed unevenly: the greatest number in a myocardium, a liver, kidneys. Plasma elimination half-life makes about 2 hours, the equilibrium volume of distribution – about 40 liters, the general clearance – about 0,3 l/min. Gets through a placenta and into breast milk. Communication with proteins of plasma – 60%. It is removed by kidneys, partially in the form of a metabolite; in high doses – it is preferential in not changed look.

 

Indications to use:

At adults in complex therapy: 1. Acute disorder of cerebral circulation. 2. Effects of cerebrovascular diseases (brain heart attack effect, cerebral atherosclerosis). 3. Toxic and hypoxemic encephalopathy at acute and chronic poisonings, endointoxications, postanesthetic oppression of consciousness, and also for prevention and treatment of hypoxemic encephalopathy at cardiac operations with use of artificial circulation. At children (including 28-36 weeks, premature with term of a gestation) in complex therapy in the neonatality period: 1. At cerebral ischemia.

Route of administration and doses:

ЦИТОФЛАВИН® apply only intravenously kapelno in cultivation on 100-200 ml 5-10% of solution of a dextrose or 0,9% of solution of sodium of chloride. 1. At an acute disorder of cerebral circulation the drug is administered in the earliest terms from the beginning of development of a disease of 10 ml on introduction with an interval of 8-12 hours within 10 days. At a severe form of a course of a disease the single dose is increased to 20 ml. 2. At effects of cerebrovascular diseases (a brain heart attack effect, cerebral atherosclerosis) the drug is administered of 10 ml on introduction within 10 days once a day. 3. At toxic and hypoxemic encephalopathy the drug is administered of 10 ml on introduction by two times a day in 8-12 hours within 5 days. At coma of 20 ml on introduction in cultivation on 200 ml of solution of a dextrose. At a postanesthetic depression once in the same doses. At cardiac operations with use of artificial circulation enter into therapies of hypoxemic encephalopathy on 20 ml of drug in cultivation on 200 ml 5% of solution of a dextrose in 3 days prior to operation, in day of operation, 3 days after operation. At children (including premature) in the neonatality period with cerebral ischemia the daily dose of the drug TSITOFLAVIN® makes 2 ml/kg/days. The calculated daily dose of drug is entered intravenously kapelno (slowly) after cultivation into 5% or 10% dextrose solution (in the ratio not less than 1:5). Time of the first introduction – the first 12 hours after the birth; optimum time to start therapy are the first 2 hours of life. It is recommended to enter the prepared solution by means of the infusional pump with a speed from 1 to 4 ml/hour, providing uniform intake of drug in a blood stream within a day, depending on the settlement daily volume of solutions for basic therapy, a condition of a hemodynamics of the patient and indicators of an acid-base state. The course of treatment averages 5 days.

Features of use:

To newborn (premature) children to carry out administration of drug under control of indicators of an acid-base condition of capillary blood at least 2 times a day (both before the beginning, and in the course of therapy). Whenever possible it is necessary to control an indicator of a serumal lactate and glucose. Rate of administering of the solution containing ЦИТОФЛАВИН® should be reduced or to temporarily stop infusion at newborn (premature) children: - being on artificial ventilation of the lungs, at emergence of signs of the mixed (respiratory and metabolic) alkalosis threatened on development of disturbances of cerebral circulation; - at the kept spontaneous breath and respiratory support by CPAP method or at the laboratory signs of the metabolic alkalosis threatened on emergence or increase of attacks of apnoea receiving air-oxygen mix through a mask at emergence. At patients with a diabetes mellitus to carry out treatment under control of an indicator of glucose of blood. Perhaps intensive coloring of urine in yellow color. ЦИТОФЛАВИН® does not exert impact on ability to manage vehicles.

Side effects:

At bystry drop introduction emergence of the undesirable reactions which are not demanding drug withdrawal is possible: a hyperemia of integuments of various degree of manifestation, feeling of heat, bitterness and dryness in a mouth, irritation in a throat. Treat rare undesirable reactions: short-term pains and discomfort in epigastric area and area of a thorax, breath difficulty, nausea, a headache, dizziness, "tingling" in a nose, a dysosmia, blanching of integuments of various degree of manifestation. Allergic reactions in the form of a skin itch, a tranzitorny hypoglycemia, a hyperuricemia, an exacerbation of gout are also possible. At children (including premature) in the period of a neonatality development of disturbances from acid-base balance is possible (alkalosis).

Interaction with other medicines:

Succinic acid, inosine, niacinamide, are compatible to other medicines. Riboflavinum: Reduces activity of doxycycline, tetracycline, Oxytetracyclinum, erythromycin and lincomycin. It is not compatible to streptomycin. Chlorpromazinum, Imipraminum, amitriptyline due to blockade of a flavinokinaza, break inclusion of Riboflavinum in флавинаденинмононуклеотид and флавинадениндинуклеотид and increase its removal with urine. Thyroid hormones accelerate Riboflavinum metabolism. Reduces and prevents side effects of chloramphenicol (disturbance of a hemogenesis, an optic neuritis). Let's combine with the drugs stimulating a hemogenesis, antigipoksant, anabolic steroids.

Contraindications:

Individual intolerance of components of drug, pregnancy, lactation period. It is not appointed to the patients (except the neonatality period) who are in a critical state before stabilization of the central hemodynamics and/or at decrease in partial pressure of oxygen in an arterial blood less than 60 mm Hg.

Overdose:

Cases of overdose were not observed. At overdose to carry out symptomatic therapy.

Storage conditions:

In the place protected from light at a temperature of 0 - 25 ºС. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous administration in ampoules on 5 or 10 ml from colourless or brown glass. On 5 ampoules in a unilateral blister strip packaging, the blister strip packaging opened or which is thermostuck together with a cover film or aluminum foil on 1 or 2 planimetric packagings together with the application instruction in a cardboard pack.