Euphyllinum - Darnitsa

General characteristics. Structure:

1 ml of solution contains theophylline 20 mg;

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

Pharmacological properties:

Pharmacodynamics. Theophylline – broncholitic, spasmolytic, a vasodilator. The mechanism of action is caused preferential by blocking of adenosine receptors, oppression of phosphodiesterases, increase in maintenance of intracellular tsAMF, decrease in intracellular concentration of calcium ions owing to what smooth muscles of bronchial tubes, digestive tract, biliary tract, a uterus, coronary, cerebral and pulmonary vessels relax, peripheric vascular resistance decreases; the tone of respiratory muscles (intercostal muscles and a diaphragm) raises, resistance of pulmonary vessels decreases and blood oxygenation improves, the respiratory center of a myelencephalon is activated, its sensitivity to carbon dioxide increases, alveolar ventilation improves that leads to decrease in weight and frequency of episodes of an apnoea; eliminates a vasomotor spasm, raises a collateral blood stream and saturation of blood oxygen, reduces perifocal and general wet brain, reduces likvorny and, respectively, intracranial pressure; improves rheological properties of blood, reduces a thrombogenesis, slows down aggregation of thrombocytes (suppressing a factor of activation of thrombocytes and F2alfa prostaglandin), normalizes microcirculation; renders antiallergic effect, suppressing degranulation of mast cells and reducing the level of mediators of an allergy (serotonin, a histamine, leukotrienes); strengthens a renal blood stream, has the diuretic effect caused by decrease in a canalicular reabsorption, increases removal of water, ions of chlorine, sodium.

Pharmacokinetics. Bioavailability makes 80-100%. Communication with proteins of plasma – about 60%. Gets through a placental barrier and into breast milk. It is metabolized in a liver (90%) with participation of several enzymes of P450 cytochrome (the most important – CYP1A2). The main metabolites of drug are: 1,3-dimethyl uric acid and 3 methylxanthine. Metabolites are removed by kidneys. About 7-13% of the entered dose are removed in not changed look (children have 50%). At babies a considerable part is removed in the form of caffeine (through immaturity of ways of his further metabolism). Elimination half-life (T 1/2) at patients who do not smoke, – 6-12 hours; at people of smokers is significantly shorter – 4-5 h, children have 1-5 hours, newborn and premature children have 10-45 hours. At patients with cirrhosis, with a renal failure and at alcoholics of T1/2 it is extended. The general clearance is lowered at patients with fever, patients with the expressed respiratory, liver and heart failure, at viral infections, at patients 60 years are more senior.

 

Pharmaceutical characteristics.

Main physical and chemical properties: transparent colourless liquid.

Incompatibility. Not to apply in one syringe with other injection medicines, except for 0,9% of solution of sodium of chloride, in connection with pharmaceutical incompatibility.

Drug cannot be used with solutions of glucose, fructose and a levuloza.
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 drug is administered intravenously. The dose of drug is selected individually, considering a possibility of various speed of removal.

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 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 a minute.

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

The adult intravenously struyno enter 10 mg/kg (on average 600-800 mg of theophylline) distributed on 3 introductions in a daily dose. 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 acceleration of heartbeat, dizziness, nausea rate of administering is reduced or passed to drop administration of drug.

To children 14 years are more senior: intravenously kapelno in a dose of 2-3 mg/kg of body weight.

The maximum single 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 14-16 years – 18 mg/kg of body weight, patients are more senior than 16 years – 13 mg/kg (or 900 mg).

Duration of treatment depends on weight and the course of a disease and sensitivity to therapy, but should not exceed 14 days.

Features of use:

Use during pregnancy or feeding by a breast.

Drug is contraindicated at pregnancy. In need of drug use feeding by a breast should be stopped.

Children.
To children aged up to 14 years drug is not appointed.

Before introduction solution needs to be heated to body temperature.

With care to apply at diseases of cardiovascular system, a liver, at a viral infection, at a long hyperthermia, a prostatauxe, a heavy hypoxia, a diabetes mellitus, glaucoma, to elderly people (      60 years are more senior).

Patients who smoke are recommended to increase a dose in connection with the accelerated drug conclusion from an organism.

Fever, irrespective of the reason of its emergence, can reduce theophylline removal speed.

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

Considering that sensitive patients at use of drug can have side reactions (dizziness and others), during administration of drug it is necessary to abstain from control of vehicles and performance of other work which demands concentration of attention.

Side effects:

From the central nervous system: dizziness, headache, concern, alarm, excitement, sleep disorder, tremor, spasms, loss of consciousness, hallucinations.

From digestive tract: a stomach ache, nausea, vomiting, a gastroesophageal reflux, heartburn, an aggravation of a peptic ulcer, diarrhea, at long reception – a loss of appetite.

Metabolic disturbances: hypopotassemia, hypercalcemia, hyperuricemia, hyperglycemia, disturbance of acid-base equilibrium of blood, рабдомиолиз.

From cardiovascular system: arrhythmias, a heartbeat oshchushchuyeniye, tachycardia, a lowering of arterial pressure, shock, a cardialgia, increase in frequency of attacks of stenocardia, premature ventricular contraction (ventricular, supraventricular), heart failure, a collapse (at bystry intravenous administration).

From an urinary system: increase in a diuresis, the complicated urination.

From immune system: Quincke's disease, acute anaphylaxis.
From skin and its derivatives: skin rashes, skin itch, small tortoiseshell, exfoliative dermatitis.

Reactions in an injection site: hypostasis, hyperemia, pain, consolidations.

General disturbances: the increased body temperature, feeling of heat and a hyperemia of the person, the increased perspiration, weakness, an asthma.

Interaction with other medicines:

During treatment it is not necessary to take alcoholic beverages, a large number of food and the drinks containing methylxanthine (coffee, tea, cocoa, chocolate, Coca-Cola), drugs, related with theophylline (caffeine, theobromine, пентоксифиллин) as these substances can strengthen a promoting effect of theophylline on the central nervous system.
Effect of theophylline can amplify at simultaneous use of Allopyrinolum, Cimetidinum, Disulfiramum, phenylbutazone, a fluvoksamin, ftorkhinolon, furosemide, an imipenem, interferon an alpha, an isoniazid, antagonists of calcium, lincomycin, macroleads, Amiodaronum, mikselitin, paracetamol, a pentoksifillin, oral contraceptives, a probenetsid, a propafenon, propranolol, ranitidine, a takrin, thiabendazole, a tiklopidin, a viloksazin or a vaccine against flu. At patients who in parallel with theophylline accept one or several of the drugs stated above it is necessary to control concentration of theophylline in serum and to reduce a dose if it is necessary.

At a concomitant use of ciprofloxacin the dose of theophylline needs to be reduced at least by 60%, and at a concomitant use of an enoksatsin – for 30%.

The effect of theophylline can decrease at a concomitant use of antiepileptic means (for example, Phenytoinum, carbamazepine, Primidonum), barbiturates (especially phenobarbital and pentobarbital), Isoproterenolum, magnesium of hydroxide, a moratsizin, rifampicin, a ritonavir or Sulfinpyrazonum. Smokers can have an effect of theophylline less also. At patients who along with theophylline accept one or several of the drugs stated above it is necessary to control concentration of theophylline in serum and to adjust a dose.

Theophylline can strengthen effect of agonists of beta receptors, diuretics and Reserpinum. Theophylline can reduce efficiency of adenosine, lithium of a carbonate and antagonists of beta receptors.
It is necessary to avoid parallel use of theophylline and antagonists of beta receptors as theophylline can lose the efficiency. The anesthesia a halothane can cause serious violations of a cordial rhythm in the patients accepting theophylline.
During treatment the hypopotassemia, especially at the combined treatment by agonists of alpha receptors, thiazide diuretics, furosemide, glucocorticoids, and also at an anoxemia can arise theophylline; therefore it is recommended to check periodically potassium level in blood serum.

Contraindications:

The increased individual sensitivity to drug components, and also to other derivatives of xanthine (caffeine, пентоксифиллин, theobromine), an acute heart failure, stenocardia, an acute myocardial infarction, a Bouveret's disease, premature ventricular contraction, heavy arterial hyper - and hypotension, widespread atherosclerosis of vessels, a fluid lungs, a hemorrhagic stroke, an eye retinal apoplexy, bleeding in the anamnesis, a peptic ulcer of a stomach and duodenum (in an aggravation stage), a gastroesophageal reflux, epilepsy, the increased convulsive readiness, an uncontrollable hypothyroidism, a hyperthyroidism, a thyrotoxicosis, a heavy liver and/or renal failure, a porphyria, sepsis, pregnancy, the feeding period a breast, children's age up to 14 years.

Overdose:

At bystry intravenous administration spasms, arrhythmias, heavy hypotension, stenocardia are possible.

At concentration of theophylline in a blood plasma higher than 20 mg/ml (110 µmol/l) are observed nausea, vomiting (numerous vomiting, sometimes with blood, can lead to dehydration, diarrhea, excitement, a tremor, arterial hypertension, a hyperventilation, supraventricular and ventricular arrhythmias, arterial hypotension, spasms, metabolic disturbances (a hypopotassemia, a hypercalcemia, a hypophosphatemia, a hyperuricemia, a hyperglycemia, a metabolic acidosis, a respiratory alkalosis). Other toxic manifestations include dementia, toxic psychosis, symptoms of acute pancreatitis, рабдомиолиз with a renal failure.

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, oxygenotherapies, artificial ventilation of the lungs. Apply diazepam to stopping of spasms intravenously. Use of barbiturates is inexpedient.
For efficiency and safety serumal concentration of drug should be maintained within 10-15 mg/kg, in the absence of a possibility of definition of concentration of theophylline in blood its daily dose should not exceed 10 mg/kg.

Storage conditions:

Period of validity. 3 years. To store in the place, unavailable to children, in original packaging at a temperature not above 25 °C. Not to freeze.

Issue conditions:

According to the recipe

Packaging:

On 5 ml in an ampoule; on 10 ampoules in a box; on 5 ampoules in a blister strip packaging; on the 2nd blister strip packagings in a pack.