Instructions Euphyllin 200 solution for injection 2% ampoule 5 ml No. 10
Composition
active ingredient: theophylline;
1 ml of solution contains 20 mg of theophylline anhydrous, calculated as 100% substance;
Excipients: sodium acetate trihydrate; sodium hydroxide; water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: clear, colorless or slightly yellowish liquid.
Pharmacotherapeutic group
Means for systemic use in obstructive airway diseases. Theophylline. ATX code R03D A04.
Pharmacological properties
Pharmacodynamics.
Euphyllin-N 200 is a bronchodilator, antispasmodic agent from the methylxanthine group (purine derivative).
The mechanism of bronchodilator action is due to the ability of theophylline to block adenosine receptors, non-selectively inhibit the phosphodiesterase enzyme and thereby increase the concentration of cyclic 3',5'-AMP (cAMP) in tissues, inhibit the transport of calcium ions through the "slow" channels of cell membranes and reduce its release from intracellular depots. Theophylline inhibits the release of inflammatory mediators from mast cells, increases mucociliary clearance, stimulates diaphragm contraction and improves the function of respiratory and intercostal muscles.
It exhibits a pronounced bronchodilator effect due to direct relaxation of bronchial smooth muscle. The severity of the bronchospasmolytic effect depends on the concentration of theophylline in the blood serum.
Normalizes respiratory function, promotes blood oxygen saturation and reduction of carbon dioxide concentration; stimulates the respiratory center. Enhances lung ventilation in conditions of hypokalemia.
Inhibits platelet aggregation (inhibits platelet activating factor and prostaglandin E2), increases the resistance of erythrocytes to deformation (improves the rheological properties of blood), reduces thrombus formation, and normalizes microcirculation.
It has a stimulating effect on the central nervous system and heart activity, increases the force and frequency of heart contractions, increases coronary blood flow and myocardial oxygen demand. It reduces the tone of blood vessels (mainly vessels of the brain, skin and kidneys). It reduces pulmonary vascular resistance, reduces pressure in the small circle of blood circulation. It increases renal blood flow, has a moderate diuretic effect. It dilates the extrahepatic bile ducts.
Therapeutic effects develop 5–15 minutes after intravenous injection.
Pharmacokinetics.
Bioavailability – 80–100%. Binding to plasma proteins – 40–60%; in newborns, as well as in adults with liver diseases, protein binding is reduced.
Penetrates through the blood-brain and placental barriers, into cerebrospinal fluid, saliva, sputum and other body secretions, into breast milk. Metabolized in the liver (90%) with the participation of several cytochrome P450 isoenzymes (the most important is CYP1A2). The main metabolites are 1,3-dimethyluric acid (has pharmacological activity that is 2–5 times inferior to theophylline) and 3-methylxanthine. Caffeine is an active metabolite and is formed in small quantities, with the exception of premature newborns and children under 6 months of age, in whom its significant accumulation in the body occurs (due to a long half-life). In children over 6 years of age and adults, the phenomenon of caffeine accumulation is absent.
It is excreted by the kidneys in the form of metabolites and unchanged (in adults - 7–13% of the administered dose, in children - 50%).
Due to significant individual differences in the rate of hepatic metabolism of theophylline, its clearance, plasma concentration, and half-life are characterized by significant variability. The rate of hepatic metabolism of theophylline depends on age, smoking habits, diet, comorbidities, and concomitant drug therapy.
The half-life (T1/2) in adult patients with bronchial asthma and practically without pathological changes in other organs and systems who do not smoke is 6–12 hours, in those who smoke – 4–5 hours. T1/2 is prolonged in patients with alcoholism, heart failure, pulmonary heart failure, “pulmonary” heart, with impaired liver and kidney function, pulmonary edema, chronic obstructive bronchitis, in elderly patients. Total clearance is reduced in children under 1 year of age, in patients with fever, severe respiratory failure, liver and heart failure, with viral infections, in patients over 55 years of age.
The optimal therapeutic concentrations of theophylline in blood plasma are: to achieve a bronchodilator effect - 10–20 μg/ml, for a stimulating effect on the respiratory center - 5–10 μg/ml. At lower concentrations, the therapeutic effect is weakly expressed, at higher concentrations - there is no significant increase in the therapeutic effect, while the risk of side effects increases significantly.
Indication
Bronchoobstructive syndrome in bronchial asthma, bronchitis, pulmonary emphysema, disorders of the respiratory center (paroxysmal nocturnal apnea), "pulmonary heart".
Contraindication
Increased individual sensitivity to the components of the drug, including other xanthine derivatives (caffeine, pentoxifylline, theobromine), pulmonary edema, severe arterial hypertension and hypotension, widespread atherosclerosis of the vessels, acute heart failure, acute myocardial infarction, decompensated chronic heart failure, angina pectoris, paroxysmal tachycardia, extrasystole, epilepsy, increased convulsive readiness, glaucoma, gastroesophageal reflux, gastric and duodenal ulcer in the acute stage, severe hepatic and/or renal failure, uncontrolled hypothyroidism, hyperthyroidism, thyrotoxicosis, sepsis, porphyria, history of bleeding, hemorrhagic stroke, retinal hemorrhage, use in children simultaneously with ephedrine.
Interaction with other medicinal products and other types of interactions
During treatment, you should not consume alcoholic beverages, large amounts of food and drinks containing methylxanthines (coffee, tea, cocoa, chocolate, Coca-Cola), drugs related to theophylline (caffeine, theobromine, pentoxifylline), because these substances can enhance the stimulating effect of theophylline on the central nervous system.
The effect of theophylline may be enhanced by concomitant use of fluconazole, methotrexate, nizatidine, allopurinol, acyclovir, carbimazole, zafirlukast, cimetidine, disulfiram, phenylbutazone, fluvoxamine, fluoroquinolones, furosemide, imipenem, isoprenaline, interferon alpha, isoniazid, calcium antagonists (verapamil, diltiazem), lincomycin, macrolides, amiodarone, mexiletine, paracetamol, pentoxifylline, oral contraceptives, probenecid, propafenone, propranolol, ranitidine, tacrine, thiabendazole, ticlopidine, viloxazine, or influenza vaccine. In patients taking one or more of the above-mentioned drugs in parallel with theophylline, the concentration of theophylline in the blood serum should be monitored and the dose reduced if necessary. The combination of theophylline and fluvoxamine should be avoided. If this combination cannot be avoided, patients should use half the dose of theophylline and carefully monitor the plasma concentrations of the latter.
When taking ciprofloxacin simultaneously, the dose of theophylline should be reduced by at least 60%, and when taking enoxacin simultaneously, by 30%.
The effect of theophylline may be reduced by concomitant administration of antiepileptic drugs (e.g. phenytoin, carbamazepine, primidone), barbiturates (especially phenobarbital and pentobarbital), aminoglutemide, isoproterenol, magnesium hydroxide, moracizin, rifampicin, ritonavir or sulfinpyrazone. The effect of theophylline may also be reduced in smokers. In patients taking one or more of the above drugs simultaneously with theophylline, the concentration of theophylline in the blood should be monitored and the dose adjusted.
The concomitant use of theophylline with herbal preparations containing St. John's wort (Hypericum perforatum) should be avoided.
Ephedrine enhances the effect of theophylline.
Theophylline may enhance the effects of β-agonists, diuretics, and reserpine. Theophylline may reduce the effectiveness of adenosine, lithium carbonate, and β-receptor antagonists. Concomitant use of theophylline and β-receptor antagonists should be avoided, as theophylline may lose its effectiveness.
Combinations of theophylline and benzodiazepines, halothane and lomustine should be used with extreme caution. Halothane anesthesia can cause serious cardiac arrhythmias in patients taking theophylline.
Concomitant use of theophylline with ketamine may reduce the seizure threshold, and with doxapram may cause stimulation of the central nervous system.
Hypokalemia may occur during treatment with theophylline, especially with combined treatment with α-receptor agonists, thiazide diuretics, furosemide, corticosteroids, and in the presence of hypoxemia; therefore, periodic monitoring of serum potassium levels is recommended.
Application features
Before parenteral administration, the solution must be warmed to body temperature.
It should be used with caution in diseases of the cardiovascular system, liver, viral infections, prolonged hyperthermia, prostatic hypertrophy, severe hypoxia, diabetes mellitus, patients over 60 years of age. The drug should be prescribed with caution only in case of acute need, in case of impaired renal function, in patients with a history of gastric and duodenal ulcers. Theophylline should be avoided in patients with a history of convulsions and alternative treatment should be used. The drug should be used with caution in patients suffering from insomnia.
Smoking and alcohol consumption may lead to increased clearance of theophylline and, consequently, to a decrease in its therapeutic effect and the need for higher doses.
Fever, regardless of its cause, may reduce the rate of theophylline excretion.
Theophylline may alter some laboratory parameters: increase the amount of fatty acids and the level of catecholamines in the urine.
This medicinal product contains 19.2 mg sodium per 5 ml vial, equivalent to 0.95% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
This medicinal product contains 38.2 mg sodium per 10 ml vial, equivalent to 1.9% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Use during pregnancy or breastfeeding
The drug is contraindicated during pregnancy. If necessary, use of the drug should be discontinued breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Considering that sensitive patients may experience adverse reactions (dizziness and others), during the period of use of the drug, one should refrain from driving vehicles and other work that requires concentration of attention.
Method of administration and doses
The dose of the drug should be selected individually, taking into account the possibility of different rates of administration.
If the patient is taking oral theophylline, the dose of parenteral theophylline should be reduced.
When administering the drug, the patient should be in a supine position; the doctor should monitor blood pressure, heart rate, respiratory rate, and the patient's general condition.
Prepare the solution immediately before use: for intravenous jet administration, dilute a single dose of the drug in 10–20 ml of 0.9% sodium chloride solution; for intravenous drip administration, dilute a single dose of the drug in 100–150 ml of 0.9% sodium chloride solution.
Administer intravenously slowly (over at least 5 minutes), intravenously drip at a rate of 30–50 drops per minute.
When administering the drug, the dose is calculated with the amount of theophylline in milligrams, taking into account that 1 ml of Euphyllin-N 200 contains 20 mg of theophylline.
Adults should be administered intravenously by jet injection at a daily dose of 10 mg/kg of body weight (on average 600–800 mg), divided into 3 injections. In case of cachexia and for people with an initial low body weight, the daily dose should be reduced to 400–500 mg, while during the first injection, no more than 200–250 mg should be administered. If palpitations, dizziness or nausea occur, the rate of administration should be reduced or an intravenous drip should be used.
Children over 14 years of age: intravenously drip at a dose of 2–3 mg/kg of body weight. The maximum daily dose for children over 14 years of age is 3 mg/kg of body weight.
Maximum daily doses that can be used without monitoring theophylline plasma concentrations: children aged 3–9 years – 24 mg/kg body weight, 9–12 years – 20 mg/kg body weight, 12–16 years – 18 mg/kg body weight, patients aged 16 and over – 13 mg/kg body weight (or 900 mg).
The highest doses for adults. Intravenously: single dose – 250 mg, daily dose – 500 mg.
Highest doses for children. Intravenously: single dose – 3 mg/kg body weight.
The duration of treatment depends on the severity and course of the disease, sensitivity to the drug and ranges from several days to two weeks (but not longer than 14 days).
Do not use in patients with severe renal and/or hepatic impairment (see Contraindications).
Children.
The drug should not be used for intravenous administration in children under 3 years of age.
For children aged 3 years and over, the drug can be used for vital indications, but not longer than 14 days.
Overdose
Rapid intravenous administration may cause convulsions, arrhythmias, severe hypotension, angina pectoris. At plasma theophylline concentrations above 20 mg/kg (110 μmol/l), nausea, vomiting (repeated vomiting, sometimes with blood, can lead to dehydration), diarrhea, agitation, tremor, hypertension, hyperventilation, supraventricular and ventricular arrhythmias, hypotension, coma, convulsions, metabolic disorders (hypokalemia, hypercalcemia, hypophosphatemia, hyperuricemia, hyperglycemia, metabolic acidosis, respiratory alkalosis). Other toxic manifestations include dementia, toxic psychosis, symptoms of acute pancreatitis, rhabdomyolysis with renal failure.
Treatment: depends on the severity of symptoms and includes drug withdrawal, correction of hemodynamics, stimulation of theophylline excretion from the body (forced diuresis, hemosorption, plasmasorption, hemodialysis, peritoneal dialysis), administration of symptomatic agents, oxygen therapy, artificial ventilation of the lungs. To stop seizures, use diazepam intravenously. The use of barbiturates is inappropriate. The use of antiarrhythmic drugs that have a proconvulsant effect, such as lidocaine, should be avoided in ventricular arrhythmias due to the risk of exacerbation of seizures.
For effectiveness and safety, the serum concentration of the drug should be maintained within 10–15 mg/kg; if it is not possible to determine the concentration of theophylline in the blood, its daily dose should not exceed 10 mg/kg.
Adverse reactions
Nervous system: dizziness, headache, restlessness, anxiety, agitation, irritability, sleep disturbances, tremor, convulsions, confusion/loss of consciousness, insomnia (especially in children), delirium, hallucinations, presyncopal state.
On the part of the gastrointestinal tract: stomach pain, nausea, vomiting, gastroesophageal reflux, heartburn, exacerbation of peptic ulcer disease, stimulation of gastric acid secretion, intestinal atony, diarrhea; with prolonged use - decreased appetite.
From the cardiovascular system: arrhythmias, palpitations, tachycardia, decreased blood pressure, shock, cardialgia, increased frequency of angina attacks, extrasystole (ventricular, supraventricular), heart failure, collapse (with rapid intravenous administration).
On the part of the urinary system: increased diuresis (due to increased glomerular filtration), in elderly patients - difficulty urinating (due to relaxation of the detrusor).
On the part of the immune system: allergic reactions, including rash, itching, urticaria, exfoliative dermatitis, angioedema, bronchospasm, anaphylactic shock.
Injection site reactions: swelling, hyperemia, pain, induration.
General disorders: increased body temperature, feeling of heat and facial flushing, increased sweating, chills, weakness, shortness of breath.
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Incompatibility.
Do not use in the same syringe with other injectable drugs, except for 0.9% sodium chloride solution, due to pharmaceutical incompatibility. The drug cannot be used with solutions of glucose, fructose (levulose).
It is necessary to take into account the pH of solutions used together with theophylline: the drug is pharmaceutically incompatible with acid solutions.
Packaging
5 ml or 10 ml in an ampoule. 5 or 10 ampoules in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
