Eufillin-N 200

General characteristics. Structure:

Active ingredient: theophylline;

1 ml of solution contains theophylline anhydrous in terms of 100% substance of 20 mg;

excipients: sodium acetate trihydrate; sodium hydroxide; water for injections.

Pharmacological properties:

Pharmacodynamics. An Euphyllinum – broncholitic, an antispasmodic of group of methylxanthines (derivative purine).

The mechanism of broncholitic action is caused by ability of theophylline to block adenosine receptors, not selectively to inhibit enzyme phosphodiesterase and to increase thereby concentration of cyclic 3,5-AMF (tsAMF) in fabrics, to oppress transport of calcium ions via "slow" channels of cellular membranes and to reduce its exit from intracellular depots. Theophylline slows down release from mast cells of mediators of an inflammation, increases mukotsiliarny clearance, stimulates reduction of a diaphragm and improves function of respiratory and intercostal muscles.

Renders the expressed broncholitic effect caused by direct relaxation of smooth muscles of bronchial tubes. Expressiveness of bronkhospazmolitichesky effect depends on concentration of theophylline in serum.

Normalizes respiratory function, promotes blood saturation by oxygen and to decrease in concentration of carbonic acid; stimulates the center of breath. Strengthens ventilation of the lungs in the conditions of a hypopotassemia.

Slows down aggregation of thrombocytes (inhibits a factor of activation of thrombocytes and E2 prostaglandin), increases resistance of erythrocytes to deformation (improves rheological properties of blood), reduces a thrombogenesis and normalizes microcirculation.

Exerts the stimulating impact on the central nervous system and action of the heart, increases force and heart rate, raises a coronary blood stream and the need of a myocardium for oxygen. Reduces a tone of blood vessels (mainly, vessels of a brain, skin and kidneys). Reduces pulmonary vascular resistance, lowers pressure in a small circle of blood circulation. Increases a renal blood stream, renders moderate diuretic effect. Expands extrahepatic bilious ways.

Therapeutic effects develop in 5–15 min. after an intravenous injection.

Pharmacokinetics. Bioavailability – 80–100%. Linkng with proteins of plasma – 40–60%; at newborns, and also at adults with liver diseases linkng with proteins is reduced.

Gets through hematoencephalic and placental barriers, into cerebrospinal liquid, saliva, a phlegm and other secrets of an organism, it is found in breast milk. It is metabolized in a liver (90%) with participation of several isoenzymes of P450 cytochrome (the most important – CYP1A2). The main metabolites – 1,3-dimethyl uric acid (has the pharmacological activity conceding to theophylline by 2–5 times) and 3 methylxanthine. Caffeine is an active metabolite and is formed in small amounts, except for premature newborns and children aged up to 6 months which have its essential accumulation in an organism (because of a long elimination half-life). At children 6 years are more senior and adults the phenomenon of cumulation of caffeine is absent.

It is removed by kidneys in the form of metabolites and in not changed look (adults have 7–13% of the entered dose, children have 50%).

Owing to significant individual differences of the speed of hepatic metabolism of theophylline expressed by variability of values its clearance, concentration in plasma and an elimination half-life are characterized. Speed of metabolism of theophylline in a liver depends on age, addiction to smoking of tobacco, a diet, associated diseases, at the same time carried out medicinal therapy.

The elimination half-life (T1/2) at adult patients with bronchial asthma practically without pathological changes from other bodies and systems and non-smoking – 6–12 h, at smokers – 4–5 p. T1/2 is extended at alcoholics, heart failure, a pulmonary heart, "pulmonary" heart, at an abnormal liver function and kidneys, a fluid lungs, chronic obstructive bronchitis, at elderly patients. The general clearance is reduced at children aged till 1 year, patients with the fever expressed by respiratory insufficiency, liver and heart failure at viral infections, at patients 55 years are more senior.

Optimum therapeutic concentration of theophylline in plasma make: for achievement of broncholitic effect – 10–20 mkg/ml, for exciting effect on a respiratory center – 5–10 mkg/ml. At smaller concentration therapeutic action is expressed poorly, at big – considerable strengthening of therapeutic action while the risk of development of side effects significantly increases is not noted.

Pharmaceutical characteristics

Main physical and chemical properties: transparent, colourless or slightly yellowish liquid.

Incompatibility. Not to apply in one syringe with other injection medicines, except for isotonic solution of sodium of chloride, in connection with pharmaceutical incompatibility. Drug cannot be used with dextrose solutions, solution of glucose, fructose and levulose.

It is necessary to consider рН the solutions applied together with an Euphyllinum: pharmaceutical drug is incompatible with solutions of acids.

Indications to use:

Bronkhoobstruktivny syndrome at bronchial asthma, bronchitis, emphysema of lungs, disturbances from a respiratory center (night paroxysmal an apnoea), "pulmonary heart".

Route of administration and doses:

The dose of drug is selected individually, considering a possibility of different rate of administering. If the patient accepts theophylline drugs orally, the theophylline dose for parenteral administration is reduced.

At administration of drug the patient is in a prone position; the doctor controls the arterial pressure, heart rate, a respiration rate and the general condition of the patient.

Solution is prepared just before use – for intravenous jet administration a single dose of drug previously dissolve 0,9% of solution of sodium of chloride in 10 – 20 ml; for intravenous drop administration a single dose of drug previously dissolve 0,9% of solution of sodium of chloride in 100 – 150 ml.

Intravenously struyno enter slowly (within not less than 5 min.), intravenously kapelno – with a speed of 30-50 thaws/minute.

At administration of drug the dose is expected theophylline in milligrams, considering that 1 ml of Eufillina-N 200 contains 20 mg of theophylline.

The adult intravenously struyno enter in a daily dose 10 mg/kg of body weight (on average – 600–800 mg) divided into 3 introductions. At a cachexia and at persons with initial low body weight the daily dose is reduced to 400–500 mg, at the same time during the first introduction enter no more than 200 - 250 mg. At emergence of the accelerated heartbeat, dizzinesses or nausea reduces rate of administering or passes to introduction intravenously kapelno.

To children 14 years are more senior: intravenously kapelno in a dose of 2-3 mg/kg of body weight. The maximum daily dose for children is more senior than 14 years – 3 mg/kg of body weight.

The maximum daily doses which can be applied without control of concentration of theophylline in plasma: children at the age of 3–9 years – 24 mg/kg of body weight, 9–12 years – 20 mg/kg of body weight, 12–16 years – 18 mg/kg of body weight, patients are more senior than 16 years – 13 mg/kg of body weight (or 900 mg).

The highest doses for adults. Intravenously: one-time – 250 mg, daily – 500 mg.

The highest doses for children. Intravenously: one-time - 3 mg/kg of body weight.

Duration of treatment depends on weight and disease, sensitivity to drug and makes from several days to two weeks (but no more than 14 days).

Features of use:

With care patients should use drug 60 years at a gastroesophageal reflux, a peptic ulcer of a stomach and duodenum are more senior (in the anamnesis), adenoma of a prostate, a heavy hypoxia, a hypertension, an abnormal liver function and/or kidneys of heavy degree, a diabetes mellitus, glaucoma.

Concentration of theophylline in blood increase at patients with chronic hepatitis and cirrhosis, a hypothyroidism, at viral infections. Increase in concentration of theophylline is caused by decrease of the activity of P450 liver enzyme. In similar situations cancellation (replacement) of the specified drugs or purpose of theophylline in a smaller daily dose is recommended.

The smoking patients are recommended to increase a dose in connection with the accelerated removal of drug from an organism.

Fever, irrespective of the reason of its emergence, can reduce the speed of removal of Eufillina-N 200. The course of treatment drug should not exceed 14 days, at more long course of treatment it is necessary to compare risk and advantage for the patient.

Before parenteral administration solution needs to be heated to body temperature.

Effects of drug can amplify considerably at simultaneous use of products with the high content of caffeine or theobromine (coffee, tea, chocolate, etc.).

Ability to influence speed of response at control of motor transport or work with other mechanisms

During treatment it is necessary to abstain from occupations potentially dangerous types of activity requiring special attention and speed of psychomotor reactions.

Side effects:

From the central and peripheral nervous system: excitement, concern, sleep disorder, headache, dizziness, tremor, irritability, spasms, hallucinations, epileptiform attacks.

From cardiovascular system: a heart consciousness, a tachyarrhythmia, tachycardia, premature ventricular contraction, a lowering of arterial pressure, acute left ventricular heart failure, increase in frequency of attacks of stenocardia, a collapse (at bystry intravenous administration).

From an urinary system: increase in a diuresis (owing to increase in glomerular filtering); elderly patients have a difficulty of an urination (as a result of a detruzor relaxation).

Allergic reactions: skin rash, skin itch; the Quincke's edema is in rare instances possible.

From digestive tract: diarrhea, intestines atony.

Local reactions: reactions in an injection site (consolidation, a hyperemia, morbidity).

Another: subfebrile temperature, dermahemia.

Interaction with other medicines:

Ephedrine, beta адреностимуляторы, caffeine and furosemide strengthen action of Eufillina-N 200.

Drug increases probability of development of side effects of glucocorticosteroids, mineralokortikoid (hypernatremia), drugs for the general anesthesia (the risk of developing of ventricular arrhythmias, spasms increases).

In a combination with phenobarbital, Phenytoinum, rifampicin, an isoniazid, carbamazepine or Sulfinpyrazonum decrease in efficiency of an Euphyllinum is observed that can demand increase in a dose of drug.

Aminoglutetimid, морацизин, being inductors of a microsomal oxidation, increase clearance of an Euphyllinum that can demand increase in its dose.

The clearance of drug decreases at appointment it in a combination with antibiotics of group of macroleads, lincomycin, Allopyrinolum, Cimetidinum, izoprenaliny, beta adrenoblockers that can demand a dose decline.

Antidiarrheal drugs, intestinal sorbents weaken, and oral estragensoderzhashchy contraceptives, H2-gistaminoblokatory, blockers of slow calcium channels, мексилетин strengthen action (contact enzymatic system of P450 cytochrome and change metabolism of an Euphyllinum).

In case of use in a combination with enoksatsiny and other ftorkhinolona, small doses of ethanol, Disulfiramum, recombinant alpha interferon, a methotrexate, propafenony, thiabendazole, tiklopidiny, verapamil and at vaccination against flu intensity of action of an Euphyllinum can increase that can demand decrease in its dose.

At simultaneous use of a levofloksatsin and theophylline it is necessary to carry out monitoring of level of theophylline to blood and the corresponding dose adjustment.

Drug suppresses therapeutic effects of lithium carbonate and beta adrenoblockers. Purpose of beta adrenoblockers interferes with bronkhodilatiruyushchy action of an Euphyllinum and can cause a bronchospasm.

The Euphyllinum exponentiates effect of diuretics due to increase in glomerular filtering and reduction of a canalicular reabsorption.

With care the Euphyllinum is appointed along with anticoagulants, with other derivatives of theophylline or purine. It is not recommended to apply an Euphyllinum with the means exciting the central nervous system (increases a neurotoxicity). At use with non-selective inhibitors of the return neyronalny capture of monoamines block of psychomotor reactions is possible.

Contraindications:

The increased individual sensitivity to drug components, including to other derivatives of xanthine (caffeine, пентоксифиллин, theobromine), a fluid lungs, expressed arterial hyper - and hypotension, widespread atherosclerosis of vessels, an acute heart failure, a myocardial infarction, dekompensirovanny chronic heart failure, stenocardia, a tachyarrhythmia, epilepsy, the increased convulsive readiness, a heavy liver and/or renal failure, an uncontrollable hypothyroidism, a hyperthyroidism, a thyrotoxicosis, sepsis, bleeding in the anamnesis, a hemorrhagic stroke, an eye retinal apoplexy, the period of pregnancy and feeding by a breast.

Overdose:

At the overdose arising at concentration of theophylline in the blood plasma exceeding 20 mg/kg are observed: a dermahemia of the person, sleeplessness, motive excitement, uneasiness, a photophobia, anorexia, diarrhea, nausea, vomiting, pains in epigastric area, gastrointestinal bleeding, tachycardia, ventricular arrhythmias, a tremor, generalized spasms, a hyperventilation, a sharp lowering of arterial pressure. At a serious poisoning epileptoidny attacks (especially at children, without emergence of any harbingers), a hypoxia, a metabolic acidosis, a hyperglycemia, a hypopotassemia, a necrosis of skeletal muscles, confusion of consciousness, a renal failure with a myoglobinuria can develop. Heavy complications and symptoms of intoxication which arose owing to chronic overdose more frequent at elderly patients (60 years are more senior) at concentration of theophylline in the blood plasma exceeding 30 mg/kg. At concentration in a blood plasma higher than 40 mg/kg can develop a coma.

Treatment: depends on expressiveness of symptoms and includes drug withdrawal, correction of a hemodynamics, stimulation of removal of theophylline from an organism (an artificial diuresis, hemosorption, a plazmosorbtion, a hemodialysis, peritoneal dialysis), purpose of symptomatic means, an oxygenotherapy, artificial ventilation of the lungs. Apply diazepam to stopping of spasms intravenously. Use of barbiturates is not reasonable.

For efficiency and safety serumal concentration of drug should be maintained within 10-15 mg/kg, due to the lack of a possibility of definition of concentration of theophylline in blood its daily dose should not exceed 10 mg/kg.

Use during pregnancy or feeding by a breast

Drug is contraindicated at pregnancy. In need of use of drug in the period of a lactation it is necessary to interrupt feeding with a breast.
Children

Drug is not used for intravenous administration to children under 3 years.

To children 3 years drug use perhaps according to vital indications are more senior, but it is no more than 14 days.

Special security measures

With care use drug at a long hyperthermia, a prostatauxe and to patients of advanced age.

Storage conditions:

Period of validity. 2 years. Not to use drug after the termination of the period of validity specified on packaging. Drug should be stored in the unavailable to children, protected from light place at a temperature from 15 ºС to 25 ºС.

Issue conditions:

According to the recipe

Packaging:

On 5 ml or 10 ml in ampoules; on 5 or 10 ampoules in a pack.