Instructions for use EUPHYLLINE solution
Aminophylline has a narrow therapeutic index. Theophylline toxicity is most likely to occur at serum concentrations greater than 20 mcg/mL and becomes increasingly severe at higher serum concentrations.
Doses greater than 3 g may be serious in adults (40 mg/kg in a child). The lethal dose may be as low as 4.5 g in adults (60 mg/kg in children), but is usually higher.
Death in adults may occur when aminophylline is administered IV in large doses in patients with renal, hepatic or cardiovascular impairment, or if the injection is given quickly.
Symptoms:
tachycardia, in the absence of hypoxia, fever, or during coadministration of sympathomimetic drugs, may be a sign of theophylline toxicity.
Gastrointestinal symptoms:
anorexia, nausea, vomiting, diarrhea, vomiting blood.
Neurological symptoms:
restlessness, insomnia, irritability, headache, agitation, hallucinations, extreme thirst, slight fever, dilated pupils and tinnitus. Seizures can occur even without previous symptoms of toxicity and often lead to death. Coma can develop in very severe cases.
Cardiovascular symptoms:
palpitations, arrhythmias, arterial hypotension, supraventricular and ventricular arrhythmias.
Metabolic symptoms:
hypokalemia can develop quickly and can be serious. Hyperglycemia, albuminuria, hyperthermia, hypomagnesemia, hypophosphatemia, hypercalcemia, respiratory alkalosis, metabolic acidosis, and rhabdomyolysis may also occur.
Treatment:
Treatment of overdose is supportive and symptomatic.
Serum theophylline and potassium levels should be checked. Repeated oral administration of activated charcoal helps eliminate theophylline from the body, even after intravenous administration. Aggressive antiemetic therapy may be required to allow oral administration of activated charcoal.
Convulsions can be stopped by intravenous administration of diazepam 0.1-0.3 mg/kg to 10 mg/kg. Restoring fluid and electrolyte balance is essential. Hypokalemia should be corrected by IV infusion of potassium chloride. Sedation with diazepam may be required in agitated patients.
Propranolol can be administered IV to reverse tachycardia, hypokalemia and hyperglycemia, provided the patient does not suffer from asthma.
In general, theophylline is metabolized quickly and hemodialysis is not warranted. In patients with congestive heart failure or liver disease, hemodialysis may increase the clearance of theophylline by 2-fold.
Hemosorption should be considered if:
- intestinal obstruction prevents the administration of several doses of activated carbon:
- plasma theophylline concentrations >80 mg/l (acute) or >60 mg/l (chronic). In the elderly, hemosorption should be considered at theophylline concentrations >40 mg/L. Clinical signs, rather than theophylline concentration, are the best guide for treatment.
Eufillin 2.4% 5 ml No. 10 amp.
Euffilin 2.4% 5ml No. 10 ampoules
Trade name Eufillin International nonproprietary name Aminophylline Dosage form Solution for intravenous administration 2.4% 5 ml Composition 5 ml of solution contains the active substance - aminophylline for injection in terms of anhydrous substance 120 mg, excipient - water for injection. Description Transparent colorless or slightly yellowish liquid
Pharmacotherapeutic group Other drugs for the treatment of obstructive airway diseases for systemic use. Xanthines. ATC code R03DA05 Pharmacological properties Pharmacokinetics After intravenous administration, it is 60% bound to blood proteins (with liver cirrhosis, the proportion of the protein-bound fraction decreases to 35%, and in newborns this figure is 36%). Penetrates well through histohematic barriers and is evenly distributed in the blood, extracellular fluid and muscle tissue. Does not accumulate in adipose tissue. Penetrates through the placental barrier and into mother's milk. The volume of distribution is 0.3-0.7 l/kg (average 0.45 l/kg). The bronchodilator effect is manifested when its concentration in the blood plasma is maintained at a level of 10-20 mcg/ml. Concentrations of aminophylline in plasma above 20 mcg/ml are toxic. Subjected to intensive metabolism in the liver (about 90%), under the influence of methylases and cytochrome P450, it is partially converted into caffeine. In children under 3 years of age, the concentration of caffeine can reach 30% of the concentration of aminophylline. In adults and children over 3 years of age, the phenomenon of caffeine accumulation is not observed. It is excreted by the kidneys, 10% in adults and about 50% in children - unchanged. The half-life of aminophylline (T1/2) in newborns and children under 6 months is >24 hours; in children over 6 months - 3.7 hours; in adults who do not suffer from bronchopulmonary pathology - 8.7 hours. In persons who smoke 20-40 cigarettes per day, T1/2 is shortened to 4-5 hours. In persons with obstructive pulmonary diseases, heart failure and cor pulmonale, the half-elimination period nation is extended to 24 hours.
Pharmacodynamics Has bronchodilating, vasodilating, antispasmodic, tocolytic and diuretic effects. The mechanism of action is associated with a blocking effect on type A2 purine receptors of smooth muscle cells. Eufillin causes relaxation of the smooth muscles of the bronchi, coronary, cerebral and pulmonary vessels, the muscles of the gastrointestinal tract and biliary tract. Eufillin reduces the hyperreactivity of the respiratory tract in response to the entry of allergens into them. Eufillin increases the contractility of skeletal muscles (including respiratory muscles - the diaphragm, intercostal muscles) and slows down the development of their fatigue. It has a stimulating effect on the heart muscle, increasing the force of its contraction (positive inotropic effect). The dilation of the vessels of the renal glomeruli is accompanied by an increase in blood filtration in the kidneys and a short-term increase in diuresis. Stimulates the respiratory center of the medulla oblongata, improves alveolar ventilation, and causes a reduction in the frequency and severity of episodes of sleep apnea. Eufillin suppresses the rhythmic contractions of the pregnant uterus, increases the secretion of hydrochloric acid in the stomach, and slightly reduces the ability of platelets to adhesion and aggregation. Indications for use - broncho-obstructive syndrome in bronchial asthma, bronchitis, emphysema, cardiac asthma (mainly for the relief of attacks) - cerebrovascular accident of the ischemic type (as part of combination therapy) - hypertension in the pulmonary circulation - left ventricular failure with bronchospasm and disorder breathing according to the Cheyne-Stokes type (as part of combination therapy) - status asthmaticus (additional therapy)
Method of administration and dosage Adults: administered intravenously slowly (over 4-6 minutes) 5-10 ml of a 24 mg/ml solution (0.12-0.24 g), which is pre-diluted in 10-20 ml of isotonic sodium chloride solution . If palpitations, dizziness, or nausea occur, the rate of administration is slowed down or switched to drip administration, for which 10-20 ml of a 24 mg/ml solution (0.24-0.48 g) is diluted in 100-150 ml of isotonic sodium chloride solution; administered at a rate of 30-50 drops per minute. Eufillin is administered parenterally up to 3 times a day, for no more than 14 days. Higher doses of aminophylline for adults: single - 0.25 g, daily - 0.5 g. In emergency conditions, adults are administered intravenously at a dose of 6 mg/kg, diluted in 10-20 ml of 0.9% NaCl solution, administered slowly over at least 5 min. For status asthmaticus, intravenous drip administration is indicated - 720-750 mg. The drug is not recommended for children under 14 years of age due to side effects. Higher doses for children intravenously: single - 3 mg/kg, daily - 0.25-0.5 g.
Side effects - dizziness, headache, anxiety, sleep disturbances, tremors, convulsions, a feeling of flushing in the face, increased sweating - chest pain, palpitations (tachypnea), cardiac arrhythmia, with rapid intravenous administration - an attack of angina, a sharp decrease in blood pressure - anorexia, nausea, vomiting, gastroesophageal reflux, heartburn, exacerbation of peptic ulcer, diarrhea - albuminuria, hematuria, increased diuresis - allergic skin reactions: urticaria, exfoliative dermatitis, fever - in some cases - hypoglycemia - phlebitis at the injection site. Side effects decrease with decreasing dosage of the drug.
Contraindications - hypersensitivity to aminophylline and other methylxanthines - acute phase of myocardial infarction - severe arterial hypotension and hypertension - severe tachyarrhythmia - hemorrhagic stroke - retinal hemorrhage - severe dysfunction of the liver and/or kidneys - epilepsy - taking ephedrine (in children) - children up to 14 years old
Drug interactions Ephedrine, β-agonists, caffeine and furosemide enhance the effect of the drug. In combination with phenobarbital, phenytoin, rifampicin, isoniazid, carbamazepine and sulfinpyrazone, acceleration of aminophylline metabolism is observed, which is accompanied by a decrease in its effect and may require an increase in the doses of the drug used. In people who smoke (20-40 cigarettes per day), an acceleration of aminophylline metabolism is also observed. When prescribed in combination with macrolide antibiotics, lincomycin, allopurinol, cimetidine, isoprenaline, combined oral contraceptives, disulfiram, fluvoxamine, viloxazine, influenza vaccines and beta-blockers, the elimination of the drug slows down, which is accompanied by an increase in its plasma concentration and may require a dose reduction. If aminophylline is used together with fluoroquinolones, the dose of aminophylline is reduced to 1/4 of the usually recommended dose. When xanthines are administered together with benzylpenicillin, its chemical inactivation occurs. Eufillin weakens the therapeutic effects of lithium salts, pyridoxine and β-blockers. In turn, the administration of β-blockers weakens the bronchodilator effect of aminophylline. When taking aminophylline together with β-adrenergic agonists, glucocorticosteroids and diuretics, the risk of developing hypoglycemia increases. Eufillin increases the likelihood of developing undesirable effects of mineralocorticosteroids (hypernatremia), fluorinated derivatives of anesthetics (ventricular arrhythmias), and drugs that excite the central nervous system (neurotoxicity). The combined administration of xanthines with cardiac glycosides is dangerous due to the development of intoxication by the latter. Compatible with antispasmodics, do not use in combination with other xanthine derivatives. When used simultaneously with macrolide antibiotics, lincomycin, allopurinol, cimetidine, isoprenaline, enoxacin, small doses of ethanol, disulfiram, fluoroquinolones, recombinant interferon alpha, methotrexate, mexiletine, propafenone, tibeabendazole, ticlopidine, verapamil and with influenza vaccination The intensity of action of aminophylline may increase, which may require a reduction in its dose. Pharmaceutically incompatible with acid solutions, glucose, fructose and levulose solutions. When preparing for infusion, the pH of the solutions used should be taken into account.
Special instructions Use in geriatrics The use of aminophylline in persons over 60 years of age should be carried out in low doses. The drug is prescribed with caution, under constant medical supervision, to patients: - with severe impairment of liver and kidney function (liver and/or renal failure) - with a recent history of bleeding from the gastrointestinal tract - with severe coronary insufficiency - with widespread vascular atherosclerosis - with frequent ventricular extrasystoles - with increased convulsive readiness - with uncontrolled hypothyroidism (possibility of cumulation) or thyrotoxicosis - with prolonged hyperthermia - with gastroesophageal reflux - with prostatic hypertrophy Use with caution, under constant medical supervision is necessary in patients with severe arterial hypertension, hyperthyroidism, tachycardia, hypertrophic obstructive cardiomyopathy, gastric and duodenal ulcers (history). In case of chronic heart failure, liver failure, viral infections or pneumonia, a reduction in aminophylline doses is required. Eufillin is not used simultaneously with other xanthine derivatives. During the treatment period, you should avoid consuming foods and drinks containing xanthine derivatives (strong tea, coffee, chocolate, cocoa, mate). Pregnancy and lactation The use of aminophylline during pregnancy can lead to the creation of potentially dangerous concentrations of theophylline and caffeine in the body of the newborn and fetus. Newborns whose mothers received aminophylline during pregnancy (especially the third trimester) require medical supervision to monitor possible symptoms of methylxanthine intoxication. Prescribing the drug during pregnancy and lactation requires an assessment of the potential risk to the child and is carried out only for extreme health conditions. Breastfeeding should be discontinued while taking the drug. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms Considering the side effects of the drug, during the treatment period you should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions
Overdose Symptoms: occur when the drug concentration in plasma is more than 20 mcg/ml. Characterized by prolonged vomiting, diarrhea, facial flushing, arrhythmia, agitation, photophobia, tremor and convulsions. When blood levels exceed 40 mcg/ml, coma develops. Treatment: assistance measures include discontinuation of the drug, forced diuresis with the use of loop diuretics: furosemide, trosemide; at levels more than 50 mcg/ml, hemosorption and plasmapheresis are indicated. Hemodialysis or peritoneal dialysis are ineffective. For convulsive syndrome - intramuscular administration of diazepam (barbiturates are contraindicated!). To relieve arrhythmias, intravenous lidocaine or verapamil is used. For vomiting, intravenous metoclopramide or ondansetron is used. The use of etaprazine or other antipsychotics as antiemetics is contraindicated! As a specific antidote for aminophylline intoxication, intravenous jet administration of riboxin (inositol) in an isotonic sodium chloride solution is used (glucose or dextrose solutions should not be used for dilution).
Release form and packaging Solution in ampoules of 5 ml. 10 ampoules each along with instructions for use in the state and Russian languages and a knife for opening ampoules in a cardboard box. It is allowed to include instructions for medical use in the state and Russian languages in a group package in a quantity corresponding to the number of boxes. 5 ampoules are placed in a liner made of polyvinyl chloride film. 2 inserts with ampoules, along with a knife for opening ampoules and with instructions for medical use in the state and Russian languages, are placed in a pack of cardboard for consumer packaging. In the case of using ampoules with a break ring or a notch and a break point, inserting a knife to open the ampoules is not provided. 10 ampoules, together with a knife for opening ampoules and with instructions for medical use in the state and Russian languages, are placed in a pack with a cardboard insert for fixing ampoules made of cardboard for consumer packaging. Storage conditions : Protected from light, at a temperature not exceeding 25°C. Keep out of the reach of children!
Shelf life: 2 years Do not use after expiration date. Conditions for dispensing from pharmacies By prescription
pharmachologic effect
Bronchodilator, methylxanthine derivative; inhibits phosphodiesterase, increases the accumulation of cyclic adenosine monophosphate (cAMP) in tissues, blocks adenosine (purine) receptors; reduces the flow of calcium ions through the channels of cell membranes, reduces the contractile activity of smooth muscles.
Relaxes the bronchial muscles, stimulates the respiratory center and improves alveolar ventilation, which ultimately leads to a reduction in the severity and frequency of apnea episodes.
It has a stimulating effect on the activity of the heart, increases the strength and frequency of heart contractions, increases coronary blood flow and myocardial oxygen demand. Reduces the tone of blood vessels (mainly those of the brain, skin and kidneys). It has a peripheral venodilating effect, reduces pulmonary vascular resistance, and lowers pressure in the pulmonary circulation. Increases renal blood flow and has a moderate diuretic effect. Expands extrahepatic bile ducts.
Stabilizes mast cell membranes, inhibits the release of mediators of allergic reactions.
Inhibits platelet aggregation (suppresses platelet activating factor and prostaglandin E2 alpha), increases the resistance of red blood cells to deformation (improves the rheological properties of blood), reduces thrombus formation and normalizes microcirculation.
It has a tocolytic effect, increases the acidity of gastric juice. When used in large doses, it has an epileptogenic effect.
special instructions
Use caution when consuming large amounts of caffeine-containing foods or drinks during treatment.
Elderly patients are recommended to reduce the dose of the drug due to its slow elimination from the body.
Smoking patients are advised to increase the dose due to the accelerated elimination of the drug from the body.
Before use, the drug solution must be warmed to body temperature.
Impact on the ability to drive vehicles and machinery.
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
