Euphyllin-ESCOM - instructions for use, dose, side effects, contraindications

Bronchodilator, purine derivative; inhibits phosphodiesterase (PDE), increases accumulation in tissues of cyclic adenosine monophosphate (cAMP), 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 muscles of the bronchi, increases mucociliary clearance, stimulates the contraction of the diaphragm, improves the function of the respiratory and intercostal muscles, 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 episodes of apnea. Normalizing the respiratory function, contributes to the saturation of blood oxygen and reduce the concentration of carbon dioxide. Strengthens lung ventilation in hypokalemia. Has a stimulating effect on the activity of the heart, increases the strength and heart rate, increases coronary blood flow and the need for myocardium in oxygen. Reduces the tone of blood vessels (mainly vessels of the brain, skin and kidneys). Has peripheral venodilating effect, reduces pulmonary vascular resistance, lowers pressure in the "small" circle of blood circulation. Increases renal blood flow, has a moderate diuretic effect. Expands extrahepatic biliary tract. Stabilizes the membranes of mast cells, inhibits the release of mediators of allergic reactions.

It inhibits platelet aggregation (suppresses the platelet activation factor and PgE2 alpha), increases the resistance of erythrocytes to deformation (improves the rheological properties of the blood), reduces thrombus formation and normalizes microcirculation.Has tocolytic effect, increases the acidity of gastric juice. When used in large doses has an epileptogenic effect.

Pharmacokinetics:

Time to reach the peak concentration in the plasma (TcmOh) with intravenous administration of 0.3 g - 15 min, the peak concentration in plasma (C_m_Oh) - 7 μg / ml. The volume of distribution is in the range 0.3-0.7 l / kg (30-70 % from the "ideal" body weight), an average of 0.45 l / kg. Communication with plasma proteins in adults - 60%, in newborns - 36%, in patients with cirrhosis of the liver - 36%. Penetrates into breast milk (10% of the dose), through the placental barrier (concentration in the fetal serum is slightly higher than in the mother's serum). Bronchodilator properties aminophylline shows in concentrations of 10-20 μg / ml. Concentration above 20 mg / ml is toxic. Exciting effect on the respiratory center is realized with a lower content of the drug in the blood - 5-10 μg / ml. Metabolized at physiological pH values with the release of free theophylline, which is further metabolized in the liver with the participation of several cytochrome P450 isoenzymes. As a result, 1,3-dimethylurea (45-55%) is formed, which has pharmacological activity, but is 1-5 times less than theophylline. Caffeine is an active metabolite and is produced in small amounts, with the exception of premature newborns and children younger than 6 months of age, who, due to extremely long T1/₂ caffeine, there is a significant accumulation in the body (up to 30 % from that for aminophylline). In children older than 3 years and in adults, the phenomenon of caffeine cumulation is absent. T1/2 in newborns and children up to 6 months - more than 24 hours; in children older than 6 months - 3.7 h; in adults, 8.7 hours; in "smokers" (20-40 cigarettes a day) - 4-5 hours (after quitting the normalization pharmacokinetics 3-4 months); in adults with chronic obstructive pulmonary disease, pulmonary heart disease and pulmonary heart disease - over 24 hours. It is excreted by the kidneys. In neonates, about 50% of theophylline is excreted unchanged in urine against 10% in adults, which is due to inadequate activity of liver enzymes.

Indications:

Bronchoobstructive syndrome in bronchial asthma, chronic obstructive pulmonary disease (mainly for relief of attacks), asthmatic status (additional therapy), apnea of newborns (a condition characterized by periods of absence of breath for 15 seconds and accompanied by cyanosis and bradycardia), cerebrovascular accident in ischemic type (as part of combination therapy),left ventricular failure with bronchospasm and respiratory depression by type of Cheyne-Stokes, edematous syndrome of renal genesis (as part of complex therapy).

Contraindications:

Hypersensitivity to aminophylline and theophylline (including other xanthine derivatives: caffeine, pentoxifylline, theobromine), epilepsy, gastritis with high acidity, peptic ulcer and duodenal ulcer, severe arterial hyper- or hypotension, severe tachyarrhythmias, hemorrhagic stroke, retinal hemorrhage, prostate adenoma, diarrhea, cystic fibrosis mastopathy, alcoholism, pulmonary heart, fever, hypoxemia, respiratory infections, edematous syndrome, hypernatremia, rectal diseases. Aminophylline Do not use simultaneously with glucose solution, simultaneously with ephedrine in children.

Carefully:

Severe coronary insufficiency (acute phase of myocardial infarction, stenocardia), widespread atherosclerosis of vessels, hypertrophic obstructive cardiomyopathy, frequent ventricular extrasystole,increased convulsive readiness, hepatic and / or renal insufficiency, peptic ulcer disease in the anamnesis, bleeding from the gastrointestinal tract in a recent history, uncontrolled hypothyroidism (the possibility of cumulation) or thyrotoxicosis, prolonged hyperthermia, gastroesophageal reflux, hypertrophy of the prostate. Because of insufficient activity of biotransformation enzymatic systems of the liver (and the possibility of cumulation) in newborns and people over 55 aminophylline appoint with caution.

Pregnancy and lactation:

Theophylline penetrates the placental barrier. The use of aminophylline during pregnancy can lead to the creation of potentially dangerous concentrations of theophylline and caffeine in the blood plasma of the newborn. Newborns, whose mothers in pregnancy received aminophylline (especially in the third trimester), medical supervision is required to control the possible symptoms of theophylline intoxication.

Theophylline excreted in breast milk. When using aminophylline in a lactating mother during lactation, irritability may develop in the child.

Thus, the use of aminophylline during pregnancy and lactation (breastfeeding) is possible in cases where the intended benefit of therapy for the mother exceeds the potential risk to the fetus or child.

Dosing and Administration:

At urgent conditions, adults are administered intravenously 6 mg / kg, diluted in 10-20 ml of 0.9% sodium chloride solution, injected slowly for at least 5 minutes. When there is a palpitations, dizziness, nausea, with asthmatic status, the rate of administration slows down or changes to intravenous drip introduction, for which 10-20 ml of 2,4 % solution of the drug (0.24-0.48 g) is diluted in 100-150 ml of isotonic sodium chloride solution and injected at a rate of 30-50 drops per minute. In the acute phase of chronic obstructive pulmonary disease in adults: the initial dose is 5-6 mg / kg (with a further increase in the dosage of the drug for every 0.5 mg / kg, the concentration of aminophylline in the blood increases by 1 μg / ml); serum concentration in blood should not exceed 20 mcg / ml; maintenance dose for "smokers" - 4 mg / kg every 6 hours; for non-smokers and patients with liver pathology - 2 mg / kg every 8 hours.

Children the initial dose is 5-6 mg / kg,Supporting (in mg / kg) - is determined by the formula: children up to 6 months - 0.07 x age in weeks + 1.7 (every 8 hours); children from 6 to 12 months - 0.05 x age in weeks + 1.25 (every 6 hours); from 1 year to 9 years - 5 mg / kg every 6 hours; from 9 to 12 years - 4 mg / kg every 6 hours; from 12 to 16 years - 3 mg / kg every 6 hours.

Outside exacerbation, adults are prescribed in an initial dose of 6-8 mg / kg / day (maximum 400 mg / day), divided into 3-4 doses; with good tolerability, a further dose increase of 25% is possible every 2-3 days - up to a maximum of 13 mg / kg / day (900 mg / day).

Children: the initial dose is 16 mg / kg / day (maximum 400 mg / day), divided into 3-4 doses; with good tolerability, an increase in the dose by 25% is possible every 2-3 days - up to a maximum daily dose, which is: for age up to 1 year - 0.3 x age in weeks + 8; from 1 year to 9 years - 22 mg / kg; from 9 to 12 years - 20 mg / kg; from 12 to 16 years - 18 mg / kg; over 16 years -13 mg / kg.

Children intravenously prescribed at the age of 3 months - 30-60 mg / day, 4-12 months - 60-90 mg / day, 2-3 years - 90-120 mg, 4-7 years - 120-240 mg, 8- 18 years - 250-500 mg / day. The duration of parenteral administration is no more than 14 days. In apnea of newborns, the initial dose (a condition characterized by periods of absence of breath for 15 seconds and accompanied by cyanosis and bradycardia) is 5 mg / kg (per nasogastric tube), maintaining a dose of 2 mg / kg in 2 divided doses.Duration of treatment is several weeks, in rare cases - months.

The maximum dose for intravenous administration for adults is a single 0.25 g, daily 0.5 g. The maximum single dose for children is 3 mg / kg.

Side effects:

From the digestive system: gastralgia, nausea, vomiting, gastroesophageal reflux, heartburn, peptic ulcer, diarrhea, with prolonged admission - a decrease in appetite.

From the central nervous system: dizziness, headache, insomnia, agitation, anxiety, irritability, tremor;

From the cardiovascular system: palpitations, tachycardia (including fetal III trimester), cardialgia, cardiac arrhythmias, an increase in the frequency of angina attacks, lowering blood pressure right up to collapse - with rapid intravenous injection.

Allergic reactions: skin rash, itchy skin, febrile reaction.

Local reactions: at the injection site - hyperemia, tenderness, denseness.

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

Overdose:

Symptoms: decreased appetite, gastralgia, diarrhea, nausea, vomiting (including blood), gastrointestinal bleeding, tachypnea, facial skin hyperemia, tachycardia, ventricular arrhythmias, insomnia, motor agitation, anxiety, photophobia, tremor, convulsions . In severe poisoning, epileptic seizures may develop (especially in children without the appearance of any precursors), hypoxia, metabolic acidosis, hyperglycemia, hypokalemia, lowering blood pressure (BP), necrosis of skeletal muscles, confusion, renal insufficiency with myoglobinuria.

Treatment: withdrawal of the drug, gastric lavage, the appointment of activated carbon, laxative drugs, washing the intestine with a combination of polyethylene glycol and electrolytes, forced diuresis, hemosorption, plasmosorption, hemodialysis (efficacy is low, peritoneal dialysis is ineffective), symptomatic therapy (incl. metoclopramide and ondansetron - when vomiting). If seizures occur, maintain airway patency and conduct oxygen therapy. For seizure seizure - in / in diazepam, 0.1-0.3 mg / kg (but not more than 10 mg).With severe nausea and vomiting - metoclopramide or ondansetron (w / w).

Interaction:

Pharmaceutically incompatible with acid solutions. It increases the likelihood of side effects of glucocorticoid funds mineralokortikosteroidnyh means (hypernatremia), funds for general anesthesia (increased risk of ventricular arrhythmias), means that excite the central nervous system (increases neurotoxicity). Rifampicin, phenobarbital, phenytoin, isoniazid, carbamazepine, sulfinpyrazone, aminoglutethimide, oral estrogen-containing contraceptives and moracisin, as inducers of microsomal oxidation, increase the clearance of aminophylline, which may require an increase in its dose. When combined with antibiotics of the macrolide group, lincomycin, allopurinol, cimetidine, isoprenaline, enoxacin, small doses of ethanol, disulfiram, fluoroquinolones, recombinant interferon alpha, methotrexate, mexiletine, propafenone, thiabendazole, ticlopidine, verapamil, and when vaccinated against influenza, the aminophylline increase, which may require a reduction in its dose.Strengthens the action of beta-adrenostimulators and diuretics (including by increasing the glomerular filtration), reduces the effectiveness of lithium and beta-blockers. Compatible with antispasmodics, do not use together with other xanthine derivatives. With caution appoint simultaneously with anticoagulants.

Special instructions:

Be careful when consuming large quantities of caffeine-containing foods or drinks during the treatment period. Before administration, the solution must be heated to body temperature.

Form release / dosage:

Solution for intravenous administration is 24 mg / ml.

Packaging:

For 5 or 10 ml of the drug in neutral glass ampoules.

For 5, 10, 30, 50 or 100 ampoules, together with the instruction for medical use of the drug and the ampoule scarifier, is placed in a cardboard box.

For 5 or 10 ampoules, together with the instruction for medical use of the drug and the ampoule scarifier, is placed in a cardboard box with cardboard partitions, or 5 or 10 ampoules are placed in a contour mesh box made of cardboard or a polyvinylchloride film.

According to 1,2, 3, 4, 5, 6, 10, 15, 20 or 30 contour mesh packages together with the instruction for medical use of the preparation and the ampoule scapegrip are placed in a pack of cardboard for consumer containers of chromium or chrome-ersatz.At 10, 15, 20, 30, 40, 50, 60 or 100 contour cell packs with 5-10 instructions for medical use of the drug and 5-10 ampoule scalers are placed in a box of corrugated cardboard [for hospitals].

When using ampoules with a notch or a fracture ring, the scarifier is not inserted.

Storage conditions:In the dark place at a temperature of no higher than 25C. Keep out of the reach of children.

Shelf life:3 years.
Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001741/09

Date of registration:10.03.2009

The owner of the registration certificate:ESKOM NPK, OAO ESKOM NPK, OAO Russia

Manufacturer: & nbsp

ESKOM NPK, OAO Russia

Information update date: & nbsp17.02.2014

Illustrated instructions

Instructions

Euphyllin-ESCOM (Euphyllini-ESKOM)