Ditilin-Darnitsa, solution for and 2% on 5 ml No. 10

General characteristics. Structure:

Active ingredient: suxamethoniumiodide;

1 ml rastvorasoderzhit 20 mg of Dithylinum (iodide succinylcholine) in terms of 100% dry matter;

excipients: sodium chloride, dinatrium эдетат, ascorbic acid, 0,1 M Acidum hydrochloricum solution, water for injections.

Pharmacological properties:

Pharmacodynamics. Dithylinum is the depolarizing muscle relaxant of short action. On a chemical structure Dithylinum can be considered as the doubled acetylcholine molecule. Has high affinity to a postsynaptic neuromuscular receptor, competitively blocks neuromuscular transmission, causes depolarization of a postsynaptic membrane and a short-term relaxation of skeletal muscles. Quickly collapses pseudo-cholinesterase with formation of sincaline and succinic acid because of what effect of Dithylinum short-term.

After intravenous administration effect of drug is shown in 2-3 minutes and remains in full up to 3 min. Approximately in 5 min. after the end of administration of drug the effect completely stops.

Bystry approach of effect and the subsequent bystry recovery of a tone of muscles allows to create the controlled and managed relaxation of skeletal muscles.

Pharmacokinetics. Data on pharmacokinetics of Dithylinum are significantly limited because of short time of effect of drug. At once after intravenous administration drug is affected by blood pseudo-cholinesterase. Breaks up to sincaline which in the subsequent is used for synthesis of acetylcholine, and on succinic acid which takes part in processes of tissue respiration. Drug passes through hematoencephalic and placental barriers.

Pharmaceutical characteristics.

Main physical and chemical properties: transparent colourless liquid.

Incompatibility. Ditilin-Darnits's solution pharmaceutical is incompatible with donor blood (hydrolysis is observed), blood preservatives, serumal preservatives, with blood preparations, with solutions of barbiturates, especially thiopental (the deposit is formed) and alkaline solutions.

Ditilin-Darnitsa is compatible from 0,9% chloride sodium solution, Ringer's solution, 5% solution of fructose and 6% dextran solution.

Ditilin-Darnitsa is compatible to other muscle relaxants and opioid analgetics.

Indications to use:

It is applied for the purpose of muscle relaxation at a trachea intubation, endoscopic procedures (bronkho-, esophago - laringo-, a tsistoskopiya), the short-term operations demanding muscle relaxation (reposition of dislocations, reposition of fragments of a bone) to maintenance of a mioplegiya at operative measures (gynecologic, thoracic, abdominal), elimination of spasms at tetanus.

Route of administration and doses:

Usually for bolyusny intravenous injections. Also apply in the form of intravenous infusions or intramusculary.

Ditilin-Darnits's introduction is allowed only in the presence of all conditions for carrying out artificial ventilation of the lungs.

Adults: doses establish individually, taking into account body weight, reaction of the patient, degree of a necessary muscular relaxation, a way of introduction.

For carrying out an endotracheal intubation enter intravenously in a dose 1 mg/kg of body weight. This dose usually causes a muscular relaxation in 30-60 seconds lasting from 2 to 6 minutes. High doses will cause longer muscular relaxation, but doubling of a dose not necessarily leads to doubling of duration of a relaxation. Additional doses of Dithylinum, components from 50% to 100% of an initial dose, are also entered bucketed from 5 to 10 minutes, will support a muscular relaxation during short-term surgical intervention under the general anesthesia.

For long relaxation of muscles throughout all operation Ditilin-Darnitsa it is possible to enter in the form of infusions 0,1-0,2% of the solution divorced in 5% solution of glucose or 0,9% chloride sodium solution with a speed of 2,5-4 mg/min. Speed of infusion needs to be corrected depending on reaction of the specific patient. The general dose of Ditilin-Darnits at repeated intravenous injections or continuous infusion should not exceed 500 mg/hour.

Children aged till 1 year. Patients of this age group are steadier against action of Dithylinum for comparison with adults. The recommended intravenous dose for babies makes 2 mg/kg of body weight, for the senior children – 1 mg/kg of body weight.

At Ditilin-Darnits's introduction to children by intravenous infusions the dose is defined as for adults, but the initial speed of infusion is reduced in proportion to body weight. The recommended intramuscular dose for babies makes 4-5 mg/kg of body weight, for children aged from 1 year – to 4 mg/kg of body weight. These doses cause a muscular relaxation within about 3 minutes. The total dose should not exceed 150 mg.

Use to elderly patients: Ditilin-Darnits's doses for people of advanced age are similar to doses for adults. Elderly people are more predisposed to developing of cardiac arrhythmias, especially if they accept cardiac glycosides.

Features of use:

Apply only in the conditions of specialized department of a hospital according to the decision and under careful control of the experienced anesthesiologist and in the presence of the equipment to carrying out an immediate intubation of a trachea, inhalation of oxygen and IVL.

There are data on cases of cardiac death after chloride succinylcholine use for the children and teenagers who had earlier not found neuromuscular diseases. In view of danger of by-effects are recommended to limit chloride succinylcholine use even externally healthy children and teenagers, except those cases at which the immediate intubation or release of respiratory tracts in critical situations is required.

It is necessary to consider that in high doses Dithylinum can call "the double block" when after the depolarizing action the anti-depolarizing effect develops. Therefore after the last injection of Dithylinum long time (up to 25-30 min.) does not undergo action and independent breath is not recovered.

For stopping of the last after preliminary administration of atropine enter прозерин or Galantaminum. It is necessary to remember that прозерин and other antikholinesterazny drugs, suppressing activity of cholinesterase, action of Dithylinum extend.

With care it is applied at the known hypersensitivity to other muscle relaxants or to any component of the general anesthesia.

About 0,05% of the population have hereditary reduced activity of cholinesterase of plasma. Effect of succinylcholine can be prolonged at such patients, and also at states which are followed by cholinesterase decrease of the activity: pregnancy and puerperal period; heavy course of tetanus, tuberculosis, and also other serious and/or chronic infectious diseases; massive burns; malignant new growths; chronic anemia and malnutrition; end-stages of a liver failure; acute or chronic renal failure; autoimmune diseases: myxedema, collagenic diseases; after a massive transfusion of plasma; after carrying out a plasma exchange, and also as a result of some accompanying therapy (see the section "Interaction with Other Medicines and Other Types of Interactions").

After repeated administration of succinylcholine emergence of accustoming to drug is possible.

Use of succinylcholine can be followed by the subsequent muscular pains which intensity poorly correlates with visible muscular contractions at administration of drug. Injections of not depolarizing muscle relaxants several minutes prior to Ditilin-Darnits's introduction can promote reduction of display of muscular pains. This method can demand introduction of a dose of succinylcholine, bigger, than 1 mg/kg of body weight, for achievement satisfactory conditions for an endotracheal intubation.

Patients with heavy sepsis are inclined to development of a hyperpotassemia that needs to be meant at Ditilin-Darnits's use.

Ditilin-Darnitsa to patients with a myasthenia гравис in view of high risk of development of "the double block" is not recommended to appoint. Patients with a myasthenic syndrome of Eaton-Lambert are more sensitive to effect of succinylcholine that can demand a drug dose decline.

Succinylcholine can sometimes cause bradycardia which it is possible to warn the previous intravenous administration of atropine in healthy patients (adults and children).

In the absence of a hyperpotassemia seldom, but there can be ventricular arrhythmias connected using succinylcholine. However patients who accept digitalis drugs are more inclined to development of such arrhythmias. Effect of succinylcholine on heart can lead to change of a cordial rhythm, including a cardiac standstill.

It is necessary to consider that patients with genetically caused deficit have cholinesterases, and also with a hypopotassemia Ditilin-Darnitsa can cause the prolonged respiratory depression.

With care drug should be used for treatment of patients with liver diseases, anemia, a cachexia.

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

These cautions do not belong to Ditilin-Darnits's use. Ditilin-Darnitsa always apply in the conditions of medical institution in a combination to means to the general anesthesia therefore it is necessary to observe all cautions which are inherent in use of means for the general anesthesia.

Side effects:

From sense bodys: increase in intraocular pressure.

From digestive tract: the increased salivation, increase in intragastric pressure (and, as a result, increase in risk of regurgitation and hit of gastric contents in respiratory tracts).

From a liver and biliary tract: abnormal liver function.

Metabolic disturbances: hyperglycemia, tranzitorny increase in level of potassium.

From cardiovascular system: arterial hypertension or hypotension, rushes of blood, short-term bradycardia, an asystolia, tachycardia, arrhythmia (including ventricular arrhythmias), disturbances of cordial conductivity, cardiogenic shock, a cardiac standstill, a collapse.

From a respiratory organs: the apnoea, a bronchospasm, the prolonged paralysis of respiratory muscles (connected with genetically caused disturbance of products of pseudo-cholinesterase).

From a musculoskeletal system: emergence of muscular pains in   10-12 hours after introduction of Dithylinum, a fastsikulyation of muscles, a lockjaw, рабдомиолиз with the subsequent development of a myoglobinemia and myoglobinuria.

Dermatological disturbances: erubescence.

Allergic reactions: hypersensitivity to drug, an acute anaphylaxis.

From an organism in general: hyperthermia.

Interaction with other medicines:

The listed below medicinal substances and chemical compounds reduce normal activity of cholinesterase in a blood plasma, than increase intensity and duration of myorelaxation action of Ditilin-Darnits. Treat them: organophosphorous insecticides and метрифонат; eye drops with ekhotifaty; триметафан; specific antikholinesterazny agents: неостигмин, pyridostigmine, physostigmine, эдрофониум; takrina hydrochloride; cytotoxic medicines: cyclophosphamide, мехлоретамин, триэтиленмеламин, Thiotepum; medicines which are applied in psychiatric practice: фенелзин, propazine, Chlorpromazinum; the anesthetizing medicines: ketamine, morphine, antagonists of morphine, pethidine, pankurony, Propanididum.

Promethazine, estrogen, oxytocin, glucocorticosteroids (in high doses), oral contraceptives, тербуталин, Metoclopramidum belong to other medicines which can negatively affect activity of pseudo-cholinesterase in a blood plasma Aprotininum, дифенингидрамин.

The medicinal substances and chemical compounds given below increase intensity and duration of myorelaxation action of Ditilin-Darnits in the ways which are not connected with change of activity of cholinesterase in a blood plasma. Treat them: magnesium salts; lity carbonate; Azathioprinum; quinine and chlorquinine; antibiotics of an aminoglikozidny row, clindamycin, polymyxins; antiarrhythmic drugs: quinidine, procaineamide, verapamil, beta adrenoblockers, lidocaine, Procainum; the flying and inhalation anesthetizing medicines: a halothane, энфлуран, десфлуран, изофлуран, диетилэфир and метоксифлуран – have insignificant effect on І a phase of blocking of neuromuscular transmission Ditilinom-Darnitsa, however accelerate the beginning and increase intensity ІІ phases of blocking of neuromuscular transmission by succinylcholine.

At simultaneous use with cardiac glycosides the effect of the last increases.

At simultaneous use with means for treatment of a myasthenia efficiency of the last decreases.

Galogensoderzhashchy means for the general anesthesia increase undesirable effect of Dithylinum on cardiovascular system.

Sodium thiopental, atropine reduce undesirable effect of Dithylinum on cardiovascular system.

Contraindications:

Hypersensitivity to drug components, glaucoma, a myasthenia, an acute liver failure, the expressed anemia, a malignant hyperthermia in the anamnesis, atypical activity of cholinesterase of plasma; a hyperpotassemia at extensive injuries or burns, at a long immobilization of the patient, paralysis of skeletal muscles; the hyperpotassemia connected with a renal failure; an open injury of an eye and cases when increase in intraocular pressure is undesirable; myopathy of skeletal muscles, рабдомиолиз.

Simultaneous use of the drugs increasing sensitivity to succinylcholine.

Children's age till 1 year.

Use during pregnancy or feeding by a breast.

Succinylcholine does not exert a direct impact on a uterus and other smooth muscles. In normal therapeutic doses drug does not get through a placental barrier in the quantity able to exert impact on breath of the newborn. During pregnancy drug is used only if the advantage for mother exceeds risk for a fruit.

Feeding by a breast: there are no data on ability of drug to get into breast milk.

Children.

Drug is used to children aged from 1 year. It is necessary to show care at drug use to patients of this age group because the myopathy is more often diagnosed for children, they are more inclined to development of a malignant hyperthermia and rabdomioliz and have the increased risk of development of serious side reactions after administration of succinylcholine.

Overdose:

The overdose by Dithylinum is shown by a long apnoea and paralysis of muscles.

Treatment. Artificial ventilation of the lungs, if necessary – transfusion is fresher than blood, i.e. containing pseudo-cholinesterase in the structure.

Storage conditions:

Period of validity 2 years. To store in the place, unavailable to children, in original packaging at a temperature from 2 °C to 8 °C.

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 1 or on the 2nd blister strip packagings in a pack.