Eufillin, 24 mg/ml 10 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 isoenzymes of types III and IV.

The 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 action 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 sensitivity to carbon dioxide 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. It dilates extrahepatic biliary tracts. Stabilizes membranes of mast cells, inhibits the 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 a lower concentration of 5-10 µg/ml.

Theophylline’s binding to plasma proteins is approximately 40%; in neonates as well as in adults with disease, the binding decreases. Binding to plasma proteins in adults is about 60%; in newborns, 36%; in patients with cirrhosis, 36%. 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 the immaturity of its further metabolic pathways), unchanged – 50%.

Significant individual differences in the rate of hepatic metabolism of theophylline cause marked variability in values of clearance, 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 with practically no 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.

Theophylline T1/2 is increased in elderly people and in patients with heart failure or liver disease.

Clearance is decreased in heart failure, hepatic dysfunction, chronic alcoholism, pulmonary edema, and chronic obstructive pulmonary disease.
Ethylenediamine does not affect the pharmacokinetics of theophylline.

Indications

Left ventricular heart failure (as part of complex therapy).

Active ingredient

Composition

Active substance:
eufylline for injection (aminophylline) – 24.0 mg;

Excipients:
water for injection – up to 1 ml

How to take, the dosage

In adults the drug is administered slowly (within 4-6 minutes) in 5-10 ml of the drug (0.12-0.24 g) which is diluted in 10-20 ml of 0.9% sodium chloride solution beforehand.

In case of palpitation, dizziness, nausea the speed of injection is slowed down or the drug is given by drop infusion, for which 10-20 ml of the drug (0.24-0.48 g) is diluted in 100-150 ml of 0.9% sodium chloride solution; the drug is infused at the rate of 30-50 drops per minute.

Before parenteral administration the solution should be warmed to body temperature. Aminophylline is administered parenterally up to 3 times a day, not more than 14 days. The highest doses of aminophylline for adults when administered intravenously: single 0.25 g, daily -0.5 g.

In children, if necessary, aminophylline is administered intravenously by drip at a single dose of 2-3 mg/kg. The highest doses for children when administered intravenously are as follows: single dose – 3 mg/kg, daily – 0.03-0.06 g before 3 months of age, 0.06-0.09 g from 4 to 12 months, 0.09-0.12 g from 2 to 3 years, 0.12-0.24 g from 4 to 7 years, 0.25-0.5 g from 8 to 18 years.

Interaction

Increases the likelihood of side effects of glucocorticosteroids, mineralocorticosteroids (hypernatremia), drugs for general anesthesia (increases the risk of ventricular arrhythmias), drugs that excite the central nervous system (increases neurotoxicity).

The antidiarrheals and oral estrogen-containing contraceptives weaken the effects of aminophylline (they bind to the cytochrome P450 enzyme system and alter aminophylline metabolism).

Rifampicin, phenobarbital, phenytoin, isoniazid, carbamazepine and morazine, being inducers of microsomal oxidation, increase clearance of aminophylline, which may require increasing its dose.

. Concomitant use with antibiotics of the group of macrolides, lincomycin, allopurinol, cimetidine, isoprenaline, low doses of ethanol, disulfiram, fluoroquinolones, recombinant interferon alpha, methotrexate, mexiletine, propafenone, thiabendazole, ticlopidine, verapamil, and during influenza vaccination, the intensity of action of aminophylline may increase, which may require reduction of the dose.

It enhances the effect of beta-adrenergic stimulants and diuretics (including by increasing glomerular filtration), reduces the effectiveness of lithium drugs and beta-adrenoblockers.

Compatible with antispasmodics, do not use with other xanthine derivatives.

Precaution is used concomitantly with anticoagulants.

Special Instructions

The drug solution should be warmed to body temperature before use.

Elderly patients are advised to reduce the dose of the drug because of its slower elimination from the body.

In patients who smoke, it is recommended that the dose be increased because of accelerated elimination of the drug from the body.

Impact on the ability to drive vehicles, operate machinery and engage in other activities requiring concentration and quick psychomotor reactions.

When the drug is being treated it is not recommended to drive vehicles, operate machinery as well as to engage in other potentially hazardous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

Sepsis, gastric and duodenal ulcer (in anamnesis), old age (over 55 years), uncontrolled hypothyroidism (possibility of cumulation), common vascular atherosclerosis, prostatic hyperplasia, children under 14 years (because of possible side effects).

Side effects

Cardiovascular system disorders: palpitations, tachycardia (including in the fetus when taken by a pregnant woman in the III trimester), arrhythmias, decreased blood pressure, cardialgia, increased frequency of angina pectoris attacks.

Digestive system disorders: gastralgia, nausea, vomiting, gastroesophageal reflux, heartburn, aggravation of peptic ulcer disease, diarrhea; in long-term treatment – loss of appetite.

Allergic reactions: skin rash, skin itching, exfoliative dermatitis, fever.

Others: chest pain, tachypnoea, feeling of “flushes” to the face, albuminuria, hematuria, hypoglycemia, increased diuresis, increased sweating.

The side effects decrease if the dose of the drug is decreased and if the route of administration is changed (from a jet to a drip).

Local reactions: thickening, hyperemia, pain at the injection site.

Overdose

Treatment: drug withdrawal, forced diuresis, hemosorption, plasma sorption, hemodialysis (efficiency is low, peritoneal dialysis is ineffective), symptomatic therapy (including intravenous metoclopramide – for vomiting). If convulsions occur, maintain airway patency and oxygen therapy. Diazepam 0.1-0.3 mg/kg (but no more than 10 mg) should be given intravenously to relieve seizures.

Pregnancy use

Breastfeeding should be discontinued if it is necessary to use the drug during breastfeeding.