Ditilin-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DITHYLIN-DARNITSA (DITHYLIN-DARNITSA)

Composition:

active substance: suxamethonium iodide;

1 ml of solution contains suxamethonium iodide (dithylin) 20 mg;

excipients: sodium chloride, disodium edetate, ascorbic acid, hydrochloric acid diluted, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Muscle relaxants. Choline derivatives. Succinylcholine.

ATC code M03A B01.

Pharmacological properties.

Pharmacodynamics.

Suxamethonium is a short-acting depolarizing neuromuscular blocker. Chemically, suxamethonium can be regarded as a doubled acetylcholine molecule. It has high affinity for the postsynaptic neuromuscular receptor, competitively blocks neuromuscular transmission, induces depolarization of the postsynaptic membrane, and causes short-term relaxation of skeletal muscles. It is rapidly hydrolyzed by plasma pseudocholinesterase into choline and succinic acid, which accounts for the short duration of suxamethonium's effect.

After intravenous administration, the drug's effect appears within 2–3 minutes and persists in full extent for up to 3 minutes. Approximately 5 minutes after completion of drug administration, the effect completely subsides.

The rapid onset of action followed by rapid recovery of muscle tone enables controlled and manageable relaxation of skeletal muscles.

Pharmacokinetics.

Data on the pharmacokinetics of suxamethonium are substantially limited due to the drug's short duration of action. Immediately after intravenous administration, the drug is metabolized by plasma pseudocholinesterase. It is broken down into choline, which is subsequently used for acetylcholine synthesis, and succinic acid, which participates in tissue respiration processes. The drug crosses the blood-brain and placental barriers.

Clinical Characteristics.

Indications.

For use as a muscle relaxant during tracheal intubation, endoscopic procedures (broncho-, eso­phago-, laryngo-, cystoscopy), short-term surgical procedures requiring muscle relaxation (reduction of dislocations, bone fragment repositioning), for maintenance of surgical paralysis during operations (gynecological, thoracic, abdominal), and for suppression of seizures in tetanus.

Contraindications.

Hypersensitivity to the components of the drug; glaucoma; myasthenia gravis; acute hepatic insufficiency; severe anemia; history of malignant hyperthermia; atypical plasma cholinesterase activity; hyperkalemia associated with extensive trauma or burns, prolonged patient immobilization, or skeletal muscle paralysis; hyperkalemia related to renal insufficiency; open eye injury and situations where increased intraocular pressure is undesirable; skeletal muscle myopathy; rhabdomyolysis.

Concomitant use of medicinal products that increase sensitivity to succinylcholine.

Interaction with other medicinal products and other forms of interactions.

The medicinal substances and chemical compounds listed below reduce plasma cholinesterase activity, thereby increasing the intensity and duration of the muscle relaxant effect of Dithyline-Darnitsya. These include: organophosphorus insecticides and metrifonate; eye drops containing echothiophate; trimethaphan; specific anticholinesterase agents: neostigmine, pyridostigmine, physostigmine, edrophonium; tacrine hydrochloride; cytotoxic medicinal products: cyclophosphamide, mechlorethamine, triethylenemelamine, thiotepa; medicinal products used in psychiatric practice: phenelzine, propanidil, chlorpromazine; anesthetic agents: ketamine, morphine, morphine antagonists, pethidine, pancuronium, propanidid.

Other medicinal products that may negatively affect plasma cholinesterase activity include: aprotinin, diphenhydramine, promethazine, estrogens, oxytocin, glucocorticoids (at high doses), oral contraceptives, terbutaline, metoclopramide.

The following medicinal substances and chemical compounds increase the intensity and duration of the muscle relaxant effect of Dithyline-Darnitsya through mechanisms unrelated to changes in plasma cholinesterase activity. These include: magnesium salts; lithium carbonate; azathioprine; quinine and chloroquine; aminoglycoside antibiotics, clindamycin, polymyxins; antiarrhythmic agents: quinidine, procainamide, verapamil, β-adrenoblockers, lidocaine, procaine; volatile and inhalational anesthetic agents: halothane, enflurane, desflurane, isoflurane, diethyl ether, and methoxyflurane – have a minor effect on Phase I neuromuscular blockade by Dithyline-Darnitsya, but accelerate the onset and enhance the intensity of Phase II neuromuscular blockade by succinylcholine.

Concomitant use with cardiac glycosides increases the effect of the latter.

Concomitant use with drugs for the treatment of myasthenia reduces the efficacy of these drugs.

Halogen-containing agents for general anesthesia enhance the adverse effects of dithyline on the cardiovascular system.

Sodium thiopental and atropine reduce the adverse cardiovascular effects of dithyline.

Special precautions for use.

Administer only in the setting of a specialized inpatient department under the decision and close supervision of an experienced anesthesiologist, with equipment available for immediate tracheal intubation, oxygen inhalation, and artificial ventilation of the lungs.

There have been reports of irreversible cardiac arrest following administration of succinylcholine chloride in children and adolescents who previously had undiagnosed neuromuscular disorders. Due to the risk of adverse effects, the use of succinylcholine chloride is recommended to be restricted to situations where immediate intubation or airway management is required in critical emergencies.

It should be noted that in high doses, suxamethonium may cause a "dual block," where, after the initial depolarizing effect, a subsequent antidepolarizing effect develops. Therefore, after the last injection of suxamethonium, the neuromuscular blockade may persist for a prolonged period (up to 25–30 minutes), and spontaneous respiration does not return.

To reverse this effect, after prior administration of atropine, administer proserin (neostigmine) or galantamine. It should be remembered that proserin and other anticholinesterase agents, by inhibiting cholinesterase activity, prolong the action of suxamethonium.

Use with caution in patients with known hypersensitivity to other muscle relaxants or to any component of general anesthesia.

Approximately 0.05% of the population has inherited reduced plasma cholinesterase activity. The effect of succinylcholine may be prolonged in these patients, as well as in conditions associated with decreased cholinesterase activity: pregnancy and the postpartum period; severe tetanus, tuberculosis, and other severe and/or chronic infectious diseases; extensive burns; malignant tumors; chronic anemia and malnutrition; terminal stages of liver failure; acute or chronic renal failure; autoimmune diseases: myxedema, collagen diseases; after massive plasma transfusion; after plasmapheresis, and as a result of certain concomitant therapies (see section "Interaction with other medicinal products and other forms of interaction").

Repeated administration of succinylcholine may lead to the development of tolerance to the drug.

Administration of succinylcholine may be associated with muscle pain, the intensity of which correlates poorly with visible muscle contractions during injection. Injection of non-depolarizing muscle relaxants a few minutes before administration of Suxamethonium-Darnitsa may help reduce the occurrence of muscle pain. This method may require administration of a succinylcholine dose exceeding 1 mg/kg body weight to achieve satisfactory conditions for endotracheal intubation.

Patients with severe sepsis are prone to hyperkalemia, which must be taken into account when using Suxamethonium-Darnitsa.

Suxamethonium-Darnitsa is not recommended for patients with myasthenia gravis due to the high risk of developing a "dual block." Patients with Eaton-Lambert myasthenic syndrome are more sensitive to the effects of succinylcholine, which may require a reduced dose of the drug.

In healthy patients (adults and children), succinylcholine may occasionally cause bradycardia, which can be prevented by prior intravenous administration of atropine.

In the absence of hyperkalemia, ventricular arrhythmias related to succinylcholine administration may rarely occur. However, patients receiving digitalis preparations are more prone to such arrhythmias. The effect of succinylcholine on the heart may lead to changes in cardiac rhythm, including cardiac arrest.

It should be noted that in patients with genetically determined cholinesterase deficiency, as well as in those with hypokalemia, Suxamethonium-Darnitsa may cause prolonged respiratory depression.

The drug should be used with caution in patients with liver disease, anemia, or cachexia.

Important information about excipients.

1 ml of the medicinal product contains less than 1 mmol of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

Succinylcholine does not exert a direct effect on the uterus or other smooth muscles. The drug crosses the placental barrier. At therapeutic doses, the drug does not affect newborn respiration.

The drug should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding: There are no data on the ability of the drug to pass into breast milk.

Ability to influence reaction rate when driving or operating machinery.

Suxamethonium-Darnitsa is intended for use in a healthcare setting in combination with general anesthetic agents; therefore, all precautions related to the use of general anesthetics must be observed.

Method of Administration and Dosage

Administer intravenously as a bolus or by infusion, or intramuscularly.

Administration of Ditiline-Darnytsia is permitted only when all conditions for artificial ventilation of the lungs are available.

Adults. The dose is determined individually by the physician, taking into account body weight, patient response, degree of required muscle relaxation, and route of administration.

For endotracheal intubation, administer intravenously at a dose of 1 mg/kg body weight. This dose usually produces muscle relaxation within 30–60 seconds, lasting from 2 to 6 minutes. Higher doses produce longer-lasting muscle relaxation, but doubling the dose does not necessarily double the duration of relaxation. Additional doses of ditiline, ranging from 50% to 100% of the initial dose, should be administered at intervals of 5 to 10 minutes to maintain muscle relaxation during short surgical procedures under general anesthesia.

For prolonged muscle relaxation throughout surgery, Ditiline-Darnytsia may be administered as an infusion of a 0.1–0.2% solution diluted in 5% glucose solution or 0.9% sodium chloride solution at a rate of 2.5–4 mg/minute. The infusion rate should be adjusted according to the individual patient's response.

The total dose of Ditiline-Darnytsia during repeated intravenous injections or continuous infusion should not exceed 500 mg/hour.

Children aged 1 year and older. Patients in this age group are more resistant to the effects of ditiline compared to adults. The recommended intravenous dose is 1 mg/kg body weight.

When administering Ditiline-Darnytsia to children by intravenous infusion, the dose should be determined as for adults, but the initial infusion rate should be reduced proportionally to body weight.

The recommended intramuscular dose for children aged 1 year and older is up to 4 mg/kg body weight. These doses produce muscle relaxation lasting approximately 3 minutes. The total dose should not exceed 150 mg.

Use in elderly patients: Ditiline-Darnytsia doses for elderly patients are similar to those for adults. Elderly patients are more prone to cardiac arrhythmias, especially if they are taking cardiac glycosides.

Children.

The medicinal product may be administered to children aged 1 year and older. Caution should be exercised when administering the drug to patients in this age group, as children have a higher incidence of myopathy, are more susceptible to developing malignant hyperthermia and rhabdomyolysis, and have an increased risk of serious adverse reactions following succinylcholine administration.

Overdose.

Symptoms: Overdose of ditiline manifests as prolonged respiratory arrest and muscle paralysis.

Treatment: Artificial ventilation of the lungs; if necessary, transfusion of fresh blood containing pseudocholinesterase.

In case of "dual block" development – administer proserin (neostigmine) and atropine (see section "Special Instructions").

Adverse reactions.

Eye disorders: increased intraocular pressure.

Respiratory, thoracic and mediastinal disorders: apnoea, bronchospasm, prolonged paralysis of respiratory muscles (associated with genetically determined deficiency of pseudocholinesterase).

Gastrointestinal disorders: increased salivation, increased intragastric pressure (and consequently increased risk of regurgitation and aspiration of gastric contents into the respiratory tract).

Hepatobiliary disorders: liver function disorders.

Metabolism and nutrition disorders: hyperglycaemia, transient increase in potassium levels.

Cardiovascular disorders: arterial hypertension or hypotension, flushing, transient bradycardia, asystole, tachycardia, arrhythmia (including ventricular arrhythmias), conduction disorders, cardiogenic shock, cardiac arrest, collapse.

Immune system disorders: hypersensitivity reactions, including urticaria, anaphylactic shock.

Skin and subcutaneous tissue disorders: skin redness, rash.

Musculoskeletal and connective tissue disorders: development of muscle pain 10–12 hours after succinylcholine administration, muscle fasciculations, trismus, rhabdomyolysis followed by myoglobinemia and myoglobinuria.

General disorders and administration site conditions: hyperthermia, injection site reactions.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature between 2 °C and 8 °C.

Keep out of reach of children.

Incompatibility.

Suxamethonium Chloride Solution (Dytelin-Darnytsia) is pharmaceutically incompatible with donor blood (hydrolysis occurs), blood preservatives, serum preservatives, blood products, barbiturate solutions (especially thiopental, resulting in precipitation), and alkaline solutions.

Dytelin-Darnytsia is compatible with 0.9% sodium chloride solution, Ringer's solution, 5% fructose solution, and 6% dextran solution.

Dytelin-Darnytsia is compatible with other muscle relaxants and opioid analgesics.

Packaging.

5 ml in an ampoule; 10 ampoules in a box; 5 ampoules in a blister pack; 1 or 2 blisters per carton.

Prescription category. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's address and location of its business activities.

13, Borispilska Street, Kyiv, 02093, Ukraine.