Eufillin, 24 mg/ml 5 ml 10 pcs

Euphylline is a bronchodilator and an FDE inhibitor. It is ethylenediamine salt of theophylline (which facilitates solubility and increases absorption). It has a bronchodilator effect, apparently due to a direct relaxing effect on the smooth muscles of the airways and blood vessels of the lungs. It is believed that this effect is caused by selective inhibition of the activity of specific FDEs, which leads to an increase in the intracellular concentration of cAMP. The results of experimental studies in vitro show that the main role seems to be played by type III and type IV isoenzymes. Suppression of the activity of these isoenzymes may also cause some side effects of aminophylline (theophylline), including vomiting, arterial hypotension and tachycardia. It blocks adenosine (purine) receptors, which may be a factor of action on the bronchi.

It reduces airway hyperresponsiveness associated with the late phase of the response caused by inhaling allergens through an unknown mechanism that is not related to FDE inhibition or adenosine blockade. There are reports that aminophylline increases the number and activity of T suppressors in peripheral blood.
Increases mucociliary clearance, stimulates diaphragm contraction, improves respiratory and intercostal muscle function, stimulates the respiratory center, increases its carbon dioxide sensitivity and improves alveolar ventilation, which ultimately leads to a reduction in the severity and frequency of apnea episodes. By normalizing respiratory function, it promotes blood oxygenation and decreases carbon dioxide concentration. It enhances lung ventilation in conditions of hypokalemia.

It has a stimulating effect on heart activity, increases strength and heart rate, increases coronary blood flow and increases myocardial oxygen demand. Reduces the tone of blood vessels (mainly vessels of the brain, skin and kidneys). It has a peripheral venodilator effect, reduces pulmonary vascular resistance, lowers the pressure in the small circle of the circulation. Increases renal blood flow, has a moderate diuretic effect. Dilates extrahepatic biliary tracts. Stabilizes membranes of mast cells, inhibits release of mediators of allergic reactions. Inhibits platelet aggregation (inhibits platelet activation factor and PgE2α), increases resistance of red blood cells to deformation (improves rheological properties of blood), reduces thrombosis and normalizes microcirculation. It has a tocolytic effect and increases the acidity of gastric juice. In high doses it has epileptogenic effect.

Pharmacokinetics
In the body aminophylline is metabolized at physiological pH values with release of free theophylline. Bronchodilator properties are evident at plasma theophylline concentrations of 10-20 µg/ml. Concentrations above 20 mg/ml are toxic. The excitatory effect on the respiratory center is realized at lower concentrations of 5-10 µg/ml.
Theophylline’s binding to plasma proteins is approximately 40%; in newborns as well as in adults with disease, the binding decreases. Binding to plasma proteins is approximately 60% in adults, 36% in newborns, and 36% in cirrhotic patients. It penetrates the placental barrier (the concentration in the fetal serum is slightly higher than in the mother’s serum). It is excreted with the breast milk.

Theophylline is metabolized in the liver with the participation of several cytochrome P450 isoenzymes, the most important of which is CYP1A2. During metabolism 1,3-dimethylureic acid, 1-methylureic acid and 3-methylxanthine are formed. These metabolites are excreted in the urine. In adults, 10% is excreted unchanged. In infants a significant portion is excreted as caffeine (due to immaturity of pathways of its further metabolism), unchanged – 50%.
Significant individual differences of hepatic metabolism rate of theophylline cause marked variability of clearance values, plasma concentrations and elimination half-life. Such factors as age, tobacco smoking habits, diet, diseases, and concomitant drug therapy affect hepatic metabolism.

Theophylline’s T1/2 in non-smoking patients with bronchial asthma almost without pathological changes from other organs and systems is 6-12 hours, in smokers – 4-5 hours, in children – 1-5 hours, in newborns and premature infants – 10-45 hours.
T1/2 of theophylline is increased in elderly persons and in patients with heart failure or liver disease.
Clearance is decreased in heart failure, liver function disorders, chronic alcoholism, pulmonary edema, chronic obstructive pulmonary disease.
Ethylenediamine does not affect the pharmacokinetics of theophylline.

Indications

• asthmatic status (additional therapy),
• apnea in newborn,
• cerebral circulation disorder of the ischemic type (as part of combined therapy),
• .left ventricular insufficiency with bronchospasm and Chane-Stokes-type respiratory disorders,
• renal edema syndrome (as part of complex therapy);
• acute and chronic heart failure (as part of combination therapy).

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Active ingredient

Aminophylline

Composition

1 ml of solution for intravenous administration contains:

active ingredient:

aminophylline 24 mg.

How to take, the dosage

If necessary, the dose of the drug can be increased at intervals of 2-3 days to achieve optimal therapeutic effect.
Duration of treatment course from a few days to several months.

Intravenous administration of the drug should be carried out carefully and slowly, for at least 5 minutes. The dose of the drug is adjusted individually, taking into account the possibility of different excretion rates in different patients.

Interaction

In concomitant use with sympathomimetics mutual enhancement of action occurs; with beta-adrenoblockers and lithium preparations – action is mutually reduced. Aminophylline action intensity may decrease (due to increase of its clearance) during concomitant use with phenobarbital, rifampicin, isoniazid, carbamazepine, sulfinpyrazone, phenytoin and in smokers.
Intensity of action of aminophylline may increase (due to decrease of its clearance) in concurrent use with antibiotics from macrolide group, lincomycin, quinolones, allopurinol, beta-adrenoblockers, cimetidine, disulfiram, fluvoxamine, oral hormonal contraceptives, isoprenaline, viloxazine and during vaccination against influenza.
Xanthine derivatives may potentiate hypokalemia due to the action of β2-adrenoreceptor stimulants, corticosteroids and diuretics.
Antidiarrheals and enterosorbents decrease absorption of aminophylline.
Pharmaceutically incompatible with acid solutions.

Special Instructions

Use with caution in severe coronary artery disease (acute phase of myocardial infarction, angina pectoris), widespread atherosclerosis, hypertrophic obstructive cardiomyopathy, frequent ventricular extrasystole, increased seizure rate, hepatic and/or renal failure, gastric and duodenal ulcer (in anamnesis), recent gastrointestinal bleeding, uncontrolled hypothyroidism (possible cumulation) or thyrotoxicosis, prolonged hyperthermia, gastroesophageal reflux, prostatic hypertrophy, in elderly patients, in children (especially orally).
Aminophylline dosing regimen adjustment may be required for heart failure, liver dysfunction, chronic alcoholism, fever, ARI.
In elderly patients, dosage reduction may be required.
Clinical monitoring and control of plasma theophylline concentration is necessary during substitution of the administered aminophylline dosage form.
Aminophylline is not used simultaneously with other xanthine derivatives. During treatment, consumption of food containing xanthine derivatives (strong coffee, tea) should be avoided.

Precaution is used concomitantly with anticoagulants, with other theophylline or purine derivatives.
Concurrent use with beta-adrenoblockers should be avoided.
Aminophylline should not be used concomitantly with glucose solution.

Contraindications

• high sensitivity to aminophylline and theophylline.
• severe arterial hyper- or hypotension,
• tachyarrhythmias,
• hyperacid gastritis,
• with severe hepatic and/or renal disorderssevere hepatic and/or renal impairment,
• epilepsy,
• hemorrhagic stroke,
• retinal hemorrhage,
• simultaneous use with ephedrine in children,
• childhood (under 12 years).

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Side effects

CNS disorders: dizziness, sleep disturbances, anxiety, tremors, convulsions.

Cardiovascular system disorders: palpitations, heart rhythm disturbances; with rapid IV administration – occurrence of heart pain, decreased BP, tachycardia (including in the fetus when taken in the III trimester of pregnancy), arrhythmias, BP decrease, cardialgia, increased frequency of angina pectoris attacks.

Digestive system disorders: nausea, vomiting, gastroesophageal reflux, heartburn, aggravation of peptic ulcer disease, diarrhea; with prolonged oral administration – anorexia.

Urinary system disorders: albuminuria, hematuria.

Allergic reactions: skin rash, itching, fever.

Metabolic reactions: rarely – hypoglycemia.

Local reactions: thickening, hyperemia, pain at the injection site; in rectal administration irritation of the rectal mucosa, proctitis.

Others: chest pain, tachypnea, sensation of hot flashes in the face, albuminuria, hematuria, hypoglycemia, increased diuresis, increased sweating.

Overdose

In case of overdose facial hyperemia, insomnia, motor agitation, anxiety, photophobia, anorexia, diarrhea, nausea, vomiting, epigastric pain, gastrointestinal bleeding, tachycardia, ventricular arrhythmias, tremor, generalized convulsions, hyperventilation, a sharp decrease in blood pressure are observed. Severe poisoning may cause epileptoid seizures (especially in children without any precursors), hypoxia, metabolic acidosis, hyperglycemia, hypokalemia, skeletal muscle necrosis, confusion, renal failure with myoglobinuria.

The treatment of overdose depends on the clinical picture and includes discontinuation of the drug, stimulation of its elimination from the body (forced diuresis, hemosorption, plasma sorption, hemodialysis, peritoneal dialysis) and prescription of symptomatic measures. Diazepam (in injections) is used to relieve seizures. Barbiturates should not be used. Hemodialysis is recommended in severe intoxication (eufillin content over 50 g/l).