Composition, form of production and packaging
Lyophilizate for the preparation of a solution for the / m introduction in the form of lyophilized mass of pink color; The reconstituted solution is a transparent, pink color.
1 amp.
trifosadenine disodium trihydrate 10 mg
cocarboxylase 50 mg
cyanocobalamin 0.5 mg
nicotinamide 20 mg
Excipients: glycine - 105.875 mg, methylparahydroxybenzoate - 0.6 mg, propyl parahydroxybenzoate - 0.15 mg.
Solvent in ampoules: lidocaine hydrochloride - 10 mg, water d / and - up to 2 ml.
187.125 mg - ampoules of dark glass (3) - packings of cellular contour (1) complete with a solvent (2 ml in ampoules) (3 pcs.) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
The drug is a rationally selected complex of metabolic substances and vitamins.
Trifosadenin is a derivative of adenosine, it stimulates metabolic processes. Has a vasodilating effect, incl. on the coronary and cerebral arteries. Improves metabolism and energy supply of tissues. Has antihypertensive and antiarrhythmic action. Under the influence of ATP there is a decrease in blood pressure, relaxation of smooth muscles, improving the conduct of nerve impulses.
Kokarboksilaza - coenzyme, formed in the body from the external thiamine (vitamin B 1 ). It is part of the enzyme carboxylase, catalyzing carboxylation and decarboxylation-keto acids. Mediates the synthesis of nucleic acids, proteins and lipids indirectly. Reduces the concentration of lactic and pyruvic acids in the body, promotes the absorption of glucose. Improves the trophism of nervous tissue.
Cyanocobalamin (vitamin B 12 ) in the body is converted to methylcobalamin and 5-deoxyadenosyl cobalamin. Methylcobalamin is involved in the reaction of homocysteine ​​to methionine and S-adenosylmethionine - the key reactions of the metabolism of pyrimidine and purine bases (and, consequently, DNA and RNA). If the vitamin is deficient in this reaction, it can be replaced by methyltetrahydrofolic acid, with folic acid reactions of metabolism being disturbed.
5-deoxyadenosylcobalamin serves as a cofactor in the isomerization of L-methylmalonyl-CoA in succinyl-CoA, an important carbohydrate and lipid metabolism reaction. Deficiency of vitamin B 12 leads to a violation of the proliferation of rapidly dividing cells of the hematopoietic tissue and epithelium, as well as to the violation of the formation of the myelin sheath of neurons.
Nicotinamide is one of the forms of vitamin PP, it participates in oxidation-reduction processes in the cell, improves carbohydrate and nitrogen metabolism, regulates tissue respiration.
PHARMACOKINETICS
Trifosadenin
After parenteral administration, it penetrates into the cells of the organs, where it is split into adenosine and inorganic phosphate with the release of energy.Subsequently, decay products are included in the resynthesis of ATP.
Cocarboxylase
Quickly absorbed after the / m introduction. Penetrates into most body tissues. It is subject to metabolic decomposition. Metabolism products are excreted mainly by the kidneys.
Cyanocobalamin
In the blood, cyanocobalamin binds to transcobalamins I and II, which transport it to tissues. It is deposited mainly in the liver. Relationship with plasma proteins 0.9%. Quickly and fully absorbed after IM and / or injection. C max after the / m introduction is achieved after 1 h. From the liver is excreted bile in the intestine and again absorbed into the blood. T 1/2 - 500 days. It is excreted at normal kidney function - 7-10% by kidneys, about 50% - by the intestine. With reduced renal function - 0-7% kidney, 70-100% - intestine. Penetrates through the placental barrier, into breast milk.
Nicotinamide
Quickly distributed into all tissues. Penetrates through the placental barrier and into breast milk. Metabolized in the liver with the formation of nicotinamide-N-methyl nicotinamide. It is excreted by the kidneys.
T 1/2 from the plasma is about 1.3 hours, stationary Vd is about 60 liters, the total ground clearance is about 0.6 liters per minute.
INDICATIONS
- Symptomatic treatment of diabetic polyneuropathy.
DOSING MODE
The drug is injected deep in the / m (in the gluteus muscle). In cases of severe pain, it is advisable to start treatment with a / m injection of 1 amp. (2 ml) / day until acute symptoms are removed. Duration of application - 9 days.
After improvement of symptoms or in cases of moderate symptoms of polyneuropathy: 1 amp. 2-3 times a week for 2-3 weeks. The recommended course of treatment is 3-9 injections, depending on the severity of the disease. The duration of treatment and the holding of repeated courses is determined by the doctor depending on the nature and severity of the disease.
Use in children
Data on the efficacy and safety of the drug Kokarnita children are absent.
SIDE EFFECT
The incidence of adverse reactions is given in accordance with the WHO classification: very often (more than 1/10); often (less than 1/10, but more than 1/100);infrequently (less than 1/100, but more than 1/1000); rarely (less than 1/1000, but more than 1/10 000); very rarely (less than 1/10 000), including individual cases;frequency is unknown.
From the immune system: rarely - allergic reactions (skin rash, shortness of breath, anaphylactic shock, Quincke's edema).
From the nervous system: very rarely - dizziness, headache, agitation, confusion.
From the heart: very rarely - tachycardia; in some cases, bradycardia, arrhythmia; frequency unknown - pain in the heart.
From the side of the vessels: the frequency is unknown - redness of the skin of the face and upper half of the trunk with a sensation of tingling and burning, "hot flashes".
From the digestive tract: very rarely - vomiting, diarrhea.
From the skin and subcutaneous tissues: very rarely - increased sweating, acne, itching, urticaria.
From the osteomuscular and connective tissue: very rarely - convulsions.
General disorders and disorders at the injection site: very rarely - irritation, pain and burning at the injection site, weakness may occur.
If any of these unwanted reactions worsen or any other unwanted reactions appear that are not listed in the instructions, you should notify the doctor.
With the development of severe undesirable reactions, the drug is canceled.
CONTRAINDICATIONS
- hypersensitivity to any component of the drug or
a solvent;
cardiovascular diseases: acute heart failure, acute myocardial infarction, uncontrolled arterial hypertension, arterial hypotension, severe forms of bradyarrhythmias, II-III degree AV blockade, chronic heart failure (NYHA III-IV stage), cardiogenic shock and others types of shocks, prolongation syndrome QT, thromboembolism, hemorrhagic stroke;
- Inflammatory lung diseases, COPD, bronchial asthma;
- pregnancy, the period of breastfeeding;
- children's age till 18 years;
- Hypercoagulation (including acute thrombosis), erythremia,
erythrocytosis;
- Stomach ulcer or duodenal ulcer in the stage of exacerbation;
- gout;
- Hepatitis, cirrhosis.
Carefully Use the drug for angina pectoris.
PREGNANCY AND LACTATION
It is not recommended to use Cockarnit during pregnancy. It is recommended to stop breastfeeding for the duration of treatment with the drug.
APPLICATION FOR CHILDREN
Contraindicated use of the drug for children and adolescents under the age of 18 years.
SPECIAL INSTRUCTIONS
With aggravation of the symptoms of the disease or lack of effect after 9 days, correction of the course of treatment is necessary.
When using the drug Cockarnit proper selection of a dose of hypoglycemic drug and adequate control of the course of diabetes.
The color of the prepared solution should be pink. Do not use the drug if the color of the solution has changed.
The solution must be used immediately after its preparation!
Influence on ability to drive vehicles, mechanisms
In the event of side effects from the central nervous system (dizziness, confusion), it is recommended to refrain from controlling vehicles and other mechanisms.
OVERDOSE
Components of the drug Cockarnit have a wide therapeutic range.
Overdose Symptoms
Trifosadenin: exceeding the maximum daily dose (about 600 mg for an adult) can lead to the development of the following symptoms: dizziness, lowering blood pressure, short-term loss of consciousness, arrhythmia, AV blockade of II and III degree, asystole, bronchospasm, ventricular disorders, sinus bradycardia and tachycardia.
Cocarboxylase: the following symptoms are reported after administration of a dose that exceeds the recommended dose by more than 100 times: headache, muscle spasm, muscle weakness, paralysis, arrhythmia.
Cyanocobalamin: after parenteral administration of a high dose, eczematous skin disorders and a benign form of acne were observed. When used in high doses, it is possible to develop hypercoagulation, violation of purine metabolism.
Nicotinamide: when applying large doses hyperpigmentation, jaundice, amblyopia, weakness, exacerbation of peptic ulcer of the stomach and duodenum were observed. With long-term use, development of steatohepatosis, increased concentration of uric acid in the blood, violation of glucose tolerance were noted.
Treatment: the drug is immediately discontinued, symptomatic therapy, including desensitizing, is prescribed.
DRUG INTERACTION
In patients who use hypoglycemic agents of the biguanide group (metformin), a decrease in the concentration of cyanocobalamin in the blood can be observed due to a violation of absorption of cyanocobalamin from the gastrointestinal tract. With other hypoglycemic agents, drug interactions are not described.
Cyanocobalamin is incompatible with ascorbic acid, heavy metal salts, thiamine, thiamine bromide, pyridoxine, riboflavin, folic acid. It is impossible to apply simultaneously cyanocobalamin with drugs that increase blood coagulability. In addition, simultaneous use of cyanocobalamin with chloramphenicol should be avoided. Aminoglycosides, salicylates, antiepileptic medicines, colchicine, potassium preparations reduce the absorption of cyanocobalamin. When the preparations containing trifosadenine are combined with dipyridamole, the action of dipyridamole is enhanced, in particular the vasodilating effect. Dimiridamol enhances the effect of trifosadenin.
There is some antagonism in the joint use of the drug with purine derivatives (caffeine, theophylline).
Do not administer simultaneously with cardiac glycosides in large doses, as the risk of developing adverse reactions from the cardiovascular system increases.
With simultaneous application of xanthinal nicotinate, the effect of the drug is reduced.
Nicotinamide potentiates the action of sedatives, tranquilizers, as well as hypotensive drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a place protected from light and inaccessible to children at a temperature of 15 to 25 В° C. Shelf life of the drug - 3 years, solvent - 4 years.
Do not use after the expiry date printed on the package.
