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(Coffeinum-natrii benzoas)
Synonyms.
Composition and release form. Powder, tablets of 0.075, 0.1 and 0.2 g; 10% and 20% solutions in ampoules of 1 and 2 ml and in syringe tubes of 1 ml.
Indications. Increased mental and physical performance; infectious and other diseases accompanied by inhibition of the functions of the central nervous system and cardiovascular system; poisoning with narcotic and other drugs that depress the central nervous system; drowsiness; hypotension; enuresis; migraine.
Pharmachologic effect. Caffeine sodium benzoate is a psychostimulant - a purine derivative. The neurochemical mechanism of action of drugs in this group is their ability to compete with adenosine for “purine” or adenosine receptors, which contributes to the development of a psychostimulating effect. Sodium caffeine benzoate in large doses inhibits phosphodiesterase, which leads to the accumulation of intracellular c-AMP, which enhances glycogenolysis, metabolic processes in muscle tissue and the central nervous system. The drug stimulates all parts of the central nervous system. Compared to amphetamine stimulants, the effect on the central nervous system is more “mild”. Sodium caffeine benzoate has a positive inotropic and chronotropic effect, causing an increase in the frequency and strength of heart contractions, and increases cardiac output.
In high doses, caffeine causes severe tachycardia, and in highly sensitive patients arrhythmias (ventricular extrasystoles) may develop. The action of caffeine has central and peripheral components regarding vascular tone. By stimulating the vasomotor center, caffeine increases vascular tone, and with a direct effect on smooth muscles, it reduces vascular tone. Caffeine increases systemic vascular resistance, which leads to increased blood pressure. These effects are associated with the drug's blockade of adenosine vasodilation and activation of the sympathetic division of the autonomic nervous system. The drug has a stimulating effect on skeletal muscles, possibly by inducing the release of acetylcholine, increasing the strength of contractions and relieving muscle fatigue. Caffeine sodium benzoate stimulates the secretion of hydrochloric acid by parietal marks and the activation of pepsin. The drug has a mild diuretic effect by increasing renal blood flow and glomerular filtration rate and reducing the reabsorption of sodium and water in the proximal renal tubules. Inhibits uterine contractility, increases the concentration of catecholamines in the blood plasma and urine, causes a short-term increase in plasma levels due to stimulation of glycogenolysis and lipolysis. The drug stimulates the respiratory center, increasing the breathing rate. In high doses, caffeine has analeptic properties.
Pharmacokinetics. The drug is easily absorbed from the gastrointestinal tract into the blood when taken orally or parenterally. Absorption of methylxanthines occurs mainly due to their lipophilicity rather than water solubility. Caffeine sodium benzoate is quickly distributed in all tissues of the body; easily penetrates the placental and blood-brain barriers; the volume of distribution in adults ranges from 0.4 to 0.6 l/kg. Binds to plasma proteins by 25-36%. The peak concentration of the drug in the blood plasma is observed 50-75 minutes after oral administration. Therapeutic concentrations in blood plasma are 5-25 mcg/ml (25.8-128.8 μmol/l). The drug is metabolized in the liver. About 80% of its dose is converted to paraxanthine (1,7-dimethylxanthine), about 10% to theobromine (3,7-dimethylxanthine), and about 4% to theophylline (1,3-dimethylxanthine). These compounds are further metabolized by demethylation to first form monomethylxanthines and ultimately methylated uric acid derivatives. T 1/2 averages 3-7 hours. The drug is excreted mainly in the form of metabolites by the kidneys, 1-2% is excreted unchanged.
Side effects. Dizziness; cardiopalmus; irritability, nervousness or severe nervous agitation; tremor; sleep disturbance; diarrhea, nausea, vomiting.
Contraindications. Increased excitability, insomnia; severe hypertension and atherosclerosis, organic diseases of the cardiovascular system; glaucoma.
Adverse reactions when interacting with other drugs. When taken concomitantly in large doses with MAO inhibitors, including procarbazine and selegiline, caffeine sodium benzoate may cause the development of dangerous cardiac arrhythmias or severe hypertension as a result of increased sympathomimetic effects of caffeine; small doses of caffeine-sodium benzoate may lead to a slight increase in blood pressure and tachycardia. With simultaneous use of the drug with other central nervous system stimulants, the development of hyperstimulation of the central nervous system, up to the development of arrhythmias and seizures, is possible. Concomitant use of barbiturates (phenobarbital) and caffeine sodium benzoate may increase caffeine metabolism due to barbiturate-induced induction of liver microsomal enzymes, leading to increased elimination of caffeine sodium benzoate. Cimetidine and OK reduce the metabolism of caffeine in the liver, which leads to an increase in its concentration in the blood and increased side effects of the latter.
Information for the patient. The drug is used orally in tablets of 0.1-0.2 g 2-3 times a day 30-40 minutes before meals. Do not take the drug immediately before bed. Extended-release capsules should be swallowed whole without breaking, crushing or chewing. It is not recommended to drink caffeine sodium benzoate with milk, as it is bound by 30% milk protein, and the release of caffeine from this binding is very slow. Smoking accelerates the metabolism of caffeine-sodium benzoate and reduces its therapeutic effects. Drinking large quantities of coffee with a high caffeine content in the drink (60 mg of caffeine per 100 g of drink), tea (50 mg per 100 g of drink), cola, cocoa and chocolate with preparations containing caffeine or caffeine-sodium benzoate may lead to tachycardia , increased breathing and dizziness. Closely monitor for signs indicating the occurrence of possible side effects, especially such as stimulation of the central nervous system and irritation of the gastrointestinal mucosa, dysfunction of the cardiovascular system.
Missed dose: Take the missed dose as soon as possible; do not take it at all if there is no time left before the next dose; do not take double doses.
Caffeine-sodium benzoate 20%/1 ml No. 10 solution d/in.amp.
Instructions for the use of the drug for specialists Caffeine-sodium benzoate (Coffeinum natrio-benzoicum) Trade name Caffeine-sodium benzoate International nonproprietary name No Dosage form Solution for injection 20% Composition 1 ml of solution contains active substances: caffeine - 0.08 g, sodium benzoate – 0.12 g, excipients: sodium hydroxide solution 0.1 M, water for injection. Description Transparent colorless or slightly yellowish liquid. Pharmacotherapeutic group Psychostimulants and nootropics. Xanthine derivatives. ATC code N06BC01 Pharmacological properties Pharmacokinetics After subcutaneous administration, absorption occurs quickly and completely. Penetrates well through all histohematic barriers, distributed throughout organs and tissues. Penetrates the BBB and the hematoplacental barrier. Concentrations in cerebrospinal fluid and amniotic fluid are comparable to caffeine concentrations in blood plasma. The concentration of caffeine in saliva is 65-85% of its concentration in plasma. After administration, it undergoes intensive metabolism in the liver with the formation of dimethyl- and monomethylxanthines, dimethyl- and monomethyluric acid, trimethyl- and dimethylallantoin, uridine derivatives. The main route of metabolism is the formation, under the influence of the cytochrome P450 CYP1A2 isoform, of dimethylxanthines (theophylline, paraxanthine), which have pharmacological activity (72-80% of the administered dose). The half-life of caffeine (T½) is 2.5-4.5 hours; in newborns, due to the low enzymatic activity of microsomal enzymes, the elimination of caffeine is slowed down, T½ is 80 ± 23 hours, at the age of 3-5 months it decreases to 14.4 hours and at 5-6 months it becomes equal to that of an adult. The total clearance of caffeine in an adult is 155 ml/kg/h, in a newborn child it is 31 ml/kg/h. In smokers, there is a decrease in the half-life of caffeine by 30-50% compared to non-smokers. Caffeine is excreted primarily in the urine in the form of metabolites. 10% of the administered dose is excreted unchanged. Pharmacodynamics It has psychostimulating and analeptic properties. The mechanism of action is associated with the ability of caffeine to act as a competitive antagonist of purine A1 and A2A receptors. As a result of receptor blockade, inhibition processes in the central nervous system are reduced, the secretion of neurotransmitters (serotonin, norepinephrine and dopamine) in the motor areas of the cerebral cortex, hypothalamus and medulla oblongata is facilitated and stabilized. In doses close to toxic, caffeine is able to block the activity of phosphodiesterases (mainly types III, IV) and slow down the breakdown of cAMP and cGMP, which stimulates the activity of neurons and accelerates metabolism in the cell. Strengthening dopaminergic transmission in the synapses of the cerebral cortex has a psychostimulating effect. Activation of adrenergic transmission in the synapses of the hypothalamus and medulla oblongata activates cortical functions, increases physical activity, causes anorexia, and has a tonic effect on the vasomotor center. Strengthening cholinergic transmission in the synapses of the cortex and medulla oblongata activates cortical functions and increases the activity of the respiratory center. Caffeine has a direct stimulating effect on the central nervous system: it stimulates mental activity, increases mental and physical performance, shortens reaction time, and activates positive conditioned reflexes. After the introduction of caffeine, vigor appears, fatigue and drowsiness are temporarily reduced or eliminated. In older people, the effect on sleep is more pronounced: sleep onset slows, total sleep time decreases, and the frequency of night awakenings increases. Against the background of depression of the respiratory center, it causes increased and deepening of breathing. Affects the cardiovascular system: increases the frequency and strength of heart contractions, and with hypotension increases blood pressure (does not affect normal blood pressure levels). In premature babies, it eliminates periodic breathing by reducing the partial pressure of carbon dioxide in the blood, increases the volume of ventilation without significantly affecting the function of the cardiovascular system. Relaxes the smooth muscles of the bronchi and bile ducts, causes dilatation of the vessels of skeletal muscles, heart and kidneys, narrows the vessels of the abdominal organs (especially with their initial dilatation). It has a weak diuretic effect due to dilation of renal vessels and inhibition of reabsorption of electrolytes in the renal tubules. Reduces platelet aggregation. Stimulates the secretion of gastric glands. Increases basal metabolism, enhances glycogenolysis, causing hyperglycemia. Indications for use - conditions associated with inhibition of the functions of the central nervous system, respiratory and cardiovascular systems: drug poisoning, severe infectious diseases, conditions after the use of general anesthetics (anesthesia) - cerebral vascular spasms - decreased mental and physical performance during the period of convalescence after suffered severe general somatic and infectious diseases - narcolepsy - breathing disorders (periodic breathing, idiopathic apnea) in newborns, incl. premature babies. Method of administration and dosage Administered subcutaneously at 200 mg (1 ml of 20% solution) for adults, 25-100 mg (0.25 - 1 ml of 10% solution or 0.1 - 0.5 ml of 20% solution) for children 2-3 once a day. To eliminate apnea in newborns, a solution of caffeine-sodium benzoate is administered intravenously or orally. Intramuscular administration of a caffeine-sodium benzoate solution is not recommended due to the possibility of developing painful spastic muscle contractions at the injection site. Side effects - anxiety, agitation, insomnia - tachycardia, arrhythmia, increased blood pressure - nausea, vomiting - development of weak psychological dependence and tolerance with long-term use in high doses - with sudden cessation of use, the development of reactive fatigue, drowsiness and depression is possible. Contraindications - arterial hypertension of the third degree - organic diseases of the cardiovascular system (including atherosclerosis) - increased excitability, sleep disorders - glaucoma - old age. Drug interactions When used simultaneously, caffeine enhances the effect of antiplatelet drugs. Reduces the effect of sleeping pills, narcotics and other central nervous system depressants. When used simultaneously, it increases the bioavailability of acetylsalicylic acid, paracetamol and ergotamine, thereby enhancing their effect. When used simultaneously with β2-adrenergic agonists in high doses (salmeterol, salbutamol, fenoterol), it increases the risk of developing hypokalemia. When used simultaneously with methylxanthines (theophylline, aminophylline), there is an increase in the concentration of theophylline in the blood plasma and an increase in the risk of its toxic effect. Anticonvulsants (carbamazepine, diphenin), barbiturates accelerate the metabolism of caffeine and reduce its concentration in plasma. Combined oral contraceptives, macrolide antibiotics (clarithromycin, erythromycin), interferon preparations and antifungals (ketoconazole, fluconazole) slow down the metabolism of caffeine and increase its concentration in plasma. When caffeine sodium benzoate is used in smokers, its plasma concentrations are lower than in non-smoking patients. Special instructions Pregnancy and lactation Since adequate and well-controlled studies have not been conducted in women during pregnancy, and also given the slow elimination of caffeine from the fetus, its use during pregnancy is possible only after assessing the benefit/risk ratio for the mother and fetus. Caffeine and its metabolites are excreted into mother's milk in small quantities. If it is necessary to use it during lactation, the benefit/risk ratio for the mother and child should be assessed. Use in neonatology Caffeine can be used during the neonatal period, as well as in premature infants. In this case, the concentration of caffeine in plasma should be monitored and maintained within therapeutic limits (3-10 mcg/ml). Use in persons with a history of gastric and duodenal ulcers Caution must be exercised when prescribing caffeine to these groups of patients, due to the increased risk of exacerbation of their peptic ulcer. Effect on the ability to perform work that requires concentration. When taken orally in high doses, caffeine makes it difficult to concentrate and increases the number of operator errors when performing work that requires concentration. Overdose Symptoms of intoxication occur when consuming caffeine in a dose of more than 300 mg/day (although cases of consuming more than 1000 mg/day of caffeine have been described). Anxiety, restlessness, tremor, headache, confusion, and tachyarrhythmia may occur. In newborns with a blood concentration of more than 50 mcg/ml of caffeine, in addition to the above-described picture, pathological strengthening of reflexes and the appearance of a convulsive syndrome are possible. There is no specific antidote. Assistance measures include discontinuation of the drug, supportive and symptomatic therapy aimed at eliminating the disorders that have arisen, monitoring blood pressure levels and stopping seizures with the administration of benzodiazepine tranquilizers (diazepam). Release form and packaging Ampoules of 1 ml. 10 ampoules with a knife for opening ampoules in a cardboard box. Storage conditions: Protected from light, at a temperature not exceeding 25 °C. Keep out of the reach of children! Shelf life: 5 years Do not use after expiration date. Conditions for dispensing from pharmacies By prescription, Republic of Belarus. Minsk region, Borisov, st. Chapaeva, 64/27
II. Pharmacological properties
9. Caffeine-sodium benzoate 20% refers to drugs that stimulate the central nervous and cardiovascular systems of animals.
10. The drug enhances and regulates excitation processes in the cerebral cortex, enhances positive conditioned reflexes and increases motor activity. The stimulating effect of caffeine leads to increased physical performance, reduced fatigue and drowsiness. The effect of the drug depends on the dose, as well as on the type of higher nervous activity of animals. Large doses of the drug can lead to depletion of nerve cells.
Under the influence of the drug, cardiac activity and diuresis increase, gas exchange increases, and water and nitrogen metabolism increases.
Caffeine-sodium benzoate 20% in terms of the degree of impact on the body is classified as a low-hazard substance (hazard class 4 according to GOST 12.1.007-76).
I. General information
1. Name of the medicinal product for veterinary use:
– trade name of the medicinal product – Caffeine-sodium benzoate 20%;
– international nonproprietary names – caffeine, sodium benzoate.
2. Dosage form: solution for injection.
1 ml of the drug contains as active ingredients: caffeine - 75 mg, sodium benzoate - 120 mg, and as excipients: sodium phosphate disubstituted 12-water, citric acid and water for injection.
3. In appearance, sodium caffeine benzoate 20% is a transparent, colorless liquid.
The shelf life of the medicinal product, subject to storage conditions in the manufacturer's closed packaging, is 3 years from the date of production, after opening the bottle - 28 days.
It is prohibited to use the medicinal product after the expiration date.
4. Sodium caffeine benzoate 20% is produced packaged in 10, 20 and 100 ml glass bottles of appropriate capacity, hermetically sealed with rubber stoppers and reinforced with aluminum caps with tamper evident clips. Each consumer package is supplied with instructions for use of the drug.
5. The medicinal product is stored in the manufacturer’s sealed packaging, separate from food and feed, in a place protected from direct sunlight at a temperature of 0°C to 25°C.
6. Sodium caffeine benzoate 20% should be kept out of the reach of children.
7. Unused medicinal product is disposed of in accordance with legal requirements.
8. Sodium caffeine benzoate 20% is available without a veterinarian's prescription.
