Caffeine sodium benzoate

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CAFFEINE SODIUM BENZOATE

Composition:

Active substance: caffeine;

1 ml of solution contains 100 mg or 200 mg of caffeine sodium benzoate;

Excipients: sodium hydroxide, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: colorless clear liquid.

Pharmacotherapeutic group. Psychostimulants, drugs used in attention deficit hyperactivity disorder and nootropic agents. Xanthine derivatives. ATC code N06BC01.

Pharmacological properties.

Pharmacodynamics. Caffeine is an alkaloid found in tea leaves and coffee beans. The pharmacological effects of the drug are classified into central and peripheral effects. The central effects, in turn, are divided into psychostimulant and analeptic actions.

The psychostimulant effect of the drug is associated with its antagonism toward adenosine in the mechanism of action on purinergic (adenosine) A1 and A2 receptors in the central nervous system (CNS). Adenosine is known to suppress CNS functions. Under the influence of the drug, mental activity, intellectual performance, and physical performance are enhanced. The psychostimulant effect is directly dose-dependent. Low doses stimulate CNS functions, while higher doses may suppress them (due to exhaustion of nerve cells).

The analeptic effect of the drug is related to its action on the respiratory and hemodynamic centers of the medulla oblongata. As a result, an increase in respiratory rate and tidal volume is observed.

The peripheral effects of the drug are variable and depend on its dose and level of influence on the vascular system and myocardium. Coronary blood flow initially increases and then decreases; renal blood flow increases; blood vessels of the abdominal cavity and skin constrict. The drug suppresses central circulation and reduces cerebrospinal fluid pressure, which explains its efficacy in migraine. The drug's effect on the heart is variable. At low doses, it produces a positive inotropic effect; at higher doses, a positive chronotropic effect. In some individuals, it may cause tachycardia and even arrhythmia.

Pharmacokinetics. The drug is rapidly distributed throughout all organs and tissues of the body. Plasma protein binding (to albumins) is 25–36%. It readily crosses the blood-brain barrier and placenta, and is excreted into breast milk. The volume of distribution is 0.4–0.6 L/kg in adults and 0.78–0.92 L/kg in infants. More than 90% of the administered dose undergoes hepatic metabolism; in infants during the first year of life, this is reduced to 10–15%. In adults, approximately 80% of the caffeine dose is metabolized to paraxanthine, about 10% to theobromine, and about 4% to theophylline. These compounds are subsequently demethylated to monomethylxanthines and then to methylated uric acids. The elimination half-life in adults is 3.9–5.3 hours (sometimes up to 10 hours), while in infants (aged 4–7 months) it ranges from 65 to 130 hours. Caffeine and its metabolites are excreted by the kidneys (1–2% unchanged in adults; up to 85% unchanged in infants).

Clinical characteristics.

Indications. Infectious and other diseases accompanied by depression of the central nervous and cardiovascular systems; respiratory depression, asphyxia; poisoning with narcotics and other substances that depress the central nervous system; asthenic syndrome; cerebral vessel spasms.

Contraindications. Hypersensitivity to xanthine derivatives and to other components of the medicinal product; increased excitability; insomnia; marked increase in arterial pressure; atherosclerosis; organic cardiovascular diseases, including acute myocardial infarction; paroxysmal tachycardia; arterial hypertension; glaucoma; age over 60 years.

Interaction with other medicinal products and other forms of interaction. Concomitant use of the drug with other medicinal products may result in:

with α- and β-adrenomimetics, analgesic-antipyretics, clozapine, xanthine derivatives, psychostimulants, cardiac glycosides, thyrotropic agents — enhancement of effects of the aforementioned medicinal products;

with anxiolytics, opioid analgesics, hypnotics and sedatives — weakening of effects of the aforementioned medicinal products;

with antiarrhythmic agents (mexiletine), hormonal oral contraceptives, disulfiram, enoxacin, erythromycin, isoniazid, methoxsalen, norfloxacin, ofloxacin, cimetidine, ciprofloxacin — enhancement of caffeine effects;

with antidepressants, barbiturates, β-adrenoblockers, primidone, anticonvulsant medicinal products (hydantoin derivatives, especially phenytoin), cholestyramine, anticholinergics — weakening of caffeine effects;

with medicinal products stimulating the central nervous system, beverages containing caffeine — excessive stimulation of the central nervous system;

with monoamine oxidase inhibitors (MAO), procarbazine, furazolidone — dangerous cardiac arrhythmias or marked increase in arterial pressure;

with ergotamine — enhanced absorption of the latter from the gastrointestinal tract;

with calcium preparations — reduced absorption of the latter from the gastrointestinal tract;

with lithium preparations — enhanced excretion of the latter in urine;

with nicotine — enhanced excretion of caffeine in urine.

The drug slightly increases the concentration of 5-hydroxyindoleacetic acid when determined in urine.

The drug slightly increases the concentration of catecholamines and vanillylmandelic acid, which may lead to false-positive test results in the diagnosis of pheochromocytoma and neuroblastoma. The drug should not be used during testing.

The drug may cause false results in determining urate concentration in blood serum by the Bittner method.

Special precautions for use.

The effect on the central nervous system depends on the type of nervous system and may manifest as either stimulation or inhibition of higher nervous activity.

Since the action of caffeine on arterial pressure involves both vascular and cardiac components, either a stimulatory effect on the heart or a mild suppression of its activity may develop.

Use with caution in patients with a history of peptic ulcer disease of the stomach and duodenum.

For apnea in newborns and infants during the postoperative period (prophylaxis), use caffeine or caffeine citrate, but not sodium caffeine benzoate.

This medicinal product contains 1.67 mmol (or 38.33 mg) of sodium per 400 mg dose of sodium caffeine benzoate. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding. The drug should not be used during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery. During treatment, caution should be exercised when driving vehicles or operating machinery. If adverse effects on the nervous system occur, patients should refrain from potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Dosage and method of administration.

For adults: administer the drug subcutaneously at a dose of 1–2 mL of 10% solution (100–200 mg). The maximum single dose is 400 mg; the maximum daily dose is 1 g.

For children aged 12 years and older: administer the drug subcutaneously at a dose of 0.25–1 mL of 10% solution (25–100 mg), depending on age.

Children. The drug is contraindicated in children under 12 years of age.

Overdose.

Symptoms: anxiety, excitement, motor restlessness, agitation, tremor or muscle twitching, epileptic seizures (in acute overdose — tonic-clonic convulsions), hyperesthesia, flickering scotoma, tinnitus, headache, insomnia, confusion, hallucinations, delirium, tachycardia, arrhythmia, hyperthermia, increased urination, dehydration, nausea, vomiting, sometimes with blood.

Treatment: maintain lung ventilation and oxygenation; maintain fluid and electrolyte balance; hemodialysis; in case of epileptic seizures — intravenous diazepam, phenobarbital, or phenytoin.

Adverse reactions.

Central nervous system effects: excitation, anxiety, tremor, restlessness, insomnia, headache, dizziness, epileptic seizures, increased reflexes, tachypnea. After abrupt discontinuation of the drug following prolonged use — enhanced effects on the central nervous system, increased fatigue, drowsiness, muscle tension, depression.

Cardiovascular system effects: palpitations, chest tightness, tachycardia, arrhythmias, increased blood pressure.

Gastrointestinal effects: nausea, vomiting, diarrhea, exacerbation of peptic ulcer disease.

Immune system, skin and subcutaneous tissue effects: hypersensitivity reactions, including rash, pruritus, urticaria, Quincke's edema, bronchospasm.

Laboratory parameters: hypo- or hyperglycemia, increased creatinine clearance, increased excretion of sodium and calcium, false elevation of plasma uric acid concentration when measured by the Bittner method, slight increase in urinary concentrations of 5-hydroxyindoleacetic acid, vanillylmandelic acid, and catecholamines.

Other effects: increased frequency of urination, nasal congestion; with prolonged use — habituation, drug dependence.

Shelf life. 5 years.

Storage conditions. Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Incompatibility. Caffeine is an adenosine antagonist.

Packaging. 1 ml in ampoules, 10 in a pack; 10, 5×2 in blister packs in a carton.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Research Plant "GNCLS".

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTIA".

Manufacturer's location and address of business activity.

8 Vorobiova Street, City of Kharkiv, Kharkiv Region, Ukraine.

(Limited Liability Company "Research Plant "GNCLS")

22 Shevchenka Street, City of Kharkiv, Kharkiv Region, 61013, Ukraine.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTIA")