Cytoflavin, 50 pcs.

Pharmacodynamics

Pharmacological effects are due to the complex action of the ingredients of the drug CITOFLAVIN®.

CITOFLAVIN® promotes activation of aerobic cell metabolism which results in increase of glucose utilization, promotes increased level of beta-oxidation of fatty acids and resynthesis of γ-aminobutyric acid in neurons.

CITOFLAVIN® increases resistance of nerve and glial cell membranes to ischemia, which is manifested by a decrease in the concentration of neuro-specific proteins characterizing the level of destruction of the main structural components of nervous tissue.

CITOFLAVIN® improves coronary and cerebral blood flow, activates metabolic processes in the central nervous system, restores disturbed consciousness, facilitates regress of neurological symptoms and improves cognitive functions of the brain. It has a fast awakening effect in post-arrest depression of consciousness.

When administering CITOFLAVIN® during the first 12 hours from the beginning of stroke a favorable course of ischemic and necrotic processes in the affected area (decrease of the focus), recovery of neurological status and decrease of disability level in a long-term period are observed.

Pharmacokinetics

In intravenous infusion at the rate of about 2 ml/min (in terms of undiluted CITOFLAVIN®) succinic acid and inosine are utilized almost immediately and are not determined in blood plasma.

Amber acid – peak concentration is determined during the first minute after administration, with its further rapid decrease without cumulation and return to the background level due to metabolism to water and carbon dioxide.
Inosine is metabolized in the liver to form inosine monophosphate with its subsequent oxidation to uric acid. A small amount is excreted by the kidneys.

Nicotinamide is rapidly distributed in all tissues, passes through the placenta and into the breast milk, is metabolized in the liver to form N-methylnicotinamide, and is excreted by the kidneys. Period of half-life from plasma is about 1.3 hours, equilibrium volume of distribution – about 60 liters, total clearance – about 0.6 l/min.

Riboflavin is unevenly distributed: most of it in myocardium, liver and kidneys. Half-life from plasma is about 2 hours, the equilibrium volume of distribution is about 40 liters, total clearance is about 0.3 l/min. It penetrates through the placenta and into the breast milk. Binding with plasma proteins is 60%. It is excreted by the kidneys, partially as a metabolite; in high doses it is mainly unchanged.

Indications

As part of complex therapy in adults:

consequences of cerebral infarction;

cerebrovascular diseases (cerebral atherosclerosis, hypertensive encephalopathy);

neurasthenia (increased irritability, fatigue, loss of ability for prolonged mental and physical stress);

diabetic polyneuropathy;

prevention of cognitive disorders after major surgical interventions in elderly patients.

Pharmacological effect

Pharmacological effects are due to the complex action of the components that make up the drug Cytoflavin®.

Succinic acid is an endogenous intracellular metabolite of the Krebs cycle, which performs a universal energy-synthesizing function in the cells of the body. With the participation of the coenzyme flavin adenine dinucleotide (FAD), succinic acid is quickly transformed by the mitochondrial enzyme succinate dehydrogenase into fumaric acid and then into other metabolites of the tricarboxylic acid cycle. Stimulates aerobic glycolysis and ATP synthesis in cells. The end product of succinic acid metabolism in the Krebs cycle is carbon dioxide and water. Succinic acid improves tissue respiration by activating electron transport in mitochondria.

Riboflavin (vitamin B2) is a flavin coenzyme (FAD) that activates succinate dehydrogenase and other redox reactions of the Krebs cycle.

Nicotinamide (vitamin PP), nicotinic acid amide. Nicotinamide in cells through a cascade of biochemical reactions is transformed into the form of nicotinamide adenine dinucleotide (NAD) and its phosphate (NADP), activating nicotinamide-dependent enzymes of the Krebs cycle, necessary for cellular respiration and stimulation of ATP synthesis.

Inosine is a purine derivative, a precursor to ATP. It has the ability to activate a number of Krebs cycle enzymes, stimulating the synthesis of key nucleotide enzymes – FAD and NAD.

Thus, all components of the drug Cytoflavin® are natural metabolites of the body and stimulate tissue respiration. Metabolic energy correction, antihypoxic and antioxidant activity of the drug, which determine the pharmacological properties and therapeutic effectiveness of the components, is due to the complementary action of succinic acid, inosine, nicotinamide and riboflavin.

When treating diabetic polyneuropathy, the antioxidant effect of the drug is realized. The drug Cytoflavin® includes coenzymes of mitochondrial complexes (riboflavin, nicotinamide), inosine (ATP precursor) and succinic acid (succinate, a component of the Krebs cycle), promotes the activation of aerobic cell metabolism, which leads to an increase in the level of glucose utilization. The use of succinic acid preparations in experimental diabetes mellitus in rats was accompanied by a decrease in the level of circulating products of lipid peroxidation and LDL cholesterol. Derivatives of 3-hydroxypyridine and succinic acid are not inferior to alpha-lipoic acid in the effectiveness of experimental treatment of behavioral disorders and conditioned reflex learning in alloxan-induced diabetes. Against the background of a course of succinic acid in the acute period of alloxan diabetes, hyperglycemia decreased and triglyceride levels normalized.

Preclinical safety data

Preclinical safety studies, including studies of repeated dose toxicity, genotoxicity, reproductive toxicity, and studies of allergenic properties, did not reveal any toxic or potentially dangerous effects for humans.

Pharmacokinetics

Special instructions

The drug should be used with caution:

for diseases of the digestive system (erosion, gastric and/or duodenal ulcers, gastritis and duodenitis (in the acute stage));
with arterial hypotension;
with nephrolithiasis;
with concomitant gout;
with hyperuricemia;
patients who have undergone cardiac surgery using a heart-lung machine (due to the lack of clinical studies in this group of patients).

In case of arterial hypertension, dose adjustment of antihypertensive drugs may be required.

In patients with diabetes mellitus, treatment should be carried out under the control of blood glucose concentrations.

During the treatment period, urine may become intensely yellow.

Impact on the ability to drive vehicles and machinery

Cytoflavin® does not affect the ability to drive vehicles and machines.

Active ingredient

Inosine, Nicotinamide, Riboflavin, Succinic acid

Composition

Succinic acid – 0.3 g.
Riboxin (inosine) – 0.05 g.
Nicotinamide – 0.025 g.
Riboflavin mononucleotide (riboflavin) – 0.005 g.
Excipients:
medium molecular weight polyvinylpyrrolidone (povidone).
calcium stearate.
copolymer of methacrylic acid and ethyl acrylate.
1,2-propylene glycol.
acid red 2C.

Pregnancy

Pregnancy
The safety of using the drug Cytoflavin® in pregnant women has not been studied, therefore the use of the drug during pregnancy is not recommended.

Breastfeeding period
There is no information on the penetration of the drug Cytoflavin® into human breast milk, therefore the use of the drug during breastfeeding is not recommended.

Fertility
No effects on fertility in animal studies.

Contraindications

hypersensitivity to the active substances or any of the excipients included in the drug;
children and adolescents under 18 years of age (due to the lack of data on effectiveness and safety).

The drug should be used with caution when:

diseases of the digestive system (erosion, gastric and/or duodenal ulcers, gastritis and duodenitis (in the acute phase));
arterial hypotension;
nephrolithiasis;
concomitant gout;
hyperuricemia;
in patients who have undergone cardiac surgery using a heart-lung machine, due to the lack of clinical studies in this group of patients.
Use for liver dysfunction
There is no data on the adverse effect of the drug Cytoflavin® on liver function. There is no data on the need for dose adjustment in persons with impaired liver function. There is no data on the adverse effect of Cytoflavin® on liver function. There are no data on the need for dose adjustment in persons with impaired liver function.

Side Effects

The results of preclinical and clinical studies and the results of monitoring the tolerability of the drug in circulation indicate good tolerability of the drug. The most frequently reported adverse reactions include: urticaria, itching, rash (rash, rash itchy, rash macular). These adverse drug reactions do not lead to serious consequences, in most cases resolve independently or with the prescription of desensitizing therapy, occur more often in patients with a burdened allergic history, do not have a significant negative impact on patients, and are very rare (less than 1 case per 10,000 patients).

Adverse reactions are classified according to their frequency of development as follows: very often (≥1/10); often (≥1/100-<1/10); uncommon (≥1/1000-<1/100); rare (≥1/10000-<1/1000); very rare (< 1/10000); frequency unknown (frequency cannot be determined from available data).

Organ system
Frequency
Adverse reactions
Metabolism
very rarely
transient hypoglycemia,
hyperuricemia,
exacerbation of concomitant gout
From the nervous system
very rarely
headache
From the side of blood vessels
very rarely
hyperemia
From the gastrointestinal tract
very rarely
pain in the epigastric region,
discomfort in the epigastric region,
nausea
From the skin and subcutaneous tissues
very rarely
itching
urticaria,
rash

Interaction

Succinic acid, inosine and nicotinamide are compatible with other drugs.

Riboflavin reduces the activity of some antibiotics (tetracyclines, erythromycin, lincomycin), and is incompatible with streptomycin.

Chlorpromazine, imipramine, amitriptyline, by blocking flavinokinase, disrupt the incorporation of riboflavin into flavin adenine mononucleotide and flavin adenine dinucleotide and increase its excretion in the urine.

Thyroid hormones accelerate the metabolism of riboflavin.

Reduces and prevents the side effects of chloramphenicol (disturbance of hematopoiesis, optic neuritis).

Compatible with drugs that stimulate hematopoiesis, antihypoxants, anabolic steroids.

Overdose

To date, no cases of overdose of the drug Cytoflavin® have been identified.

Storage conditions

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25°C.

Shelf life

Shelf life – 3 years. Do not use after the expiration date indicated on the package.

Manufacturer

Polisan NTFF LLC, Russia