Dithylin-Darnitsa (Solution) Instructions for Use

Marketing Authorization Holder

Darnitsa Pharmaceutical Firm, PJSC (Ukraine)

ATC Code

M03AB01 (Suxamethonium chloride)

Active Substance

Suxamethonium iodide (PhBs Slovak Pharmacopoeia)

Dosage Form

Dithylin-Darnitsa

Solution for intravenous and intramuscular administration 100 mg/5 ml: amp. 5, 10, or 25 pcs.

Dosage Form, Packaging, and Composition

5 ml – ampoules (10) – cardboard packs.
5 ml – ampoules (5) – contour packs (1) – cardboard packs.
5 ml – ampoules (5) – contour packs (2) – cardboard packs.
5 ml – ampoules (5) – contour packs (5) – cardboard packs.

Clinical-Pharmacological Group

Peripherally acting depolarizing-type muscle relaxant

Pharmacotherapeutic Group

Peripherally acting muscle relaxant

Pharmacological Action

A short-acting depolarizing muscle relaxant. It causes a blockade of neuromuscular transmission. By interacting with H-cholinergic receptors, it causes depolarization of the end plate. The process spreads to adjacent membranes, causing generalized contraction of myofibrils (i.e., the development of blockade is preceded by muscle fasciculations – a result of a brief facilitation of neuromuscular transmission). The membranes, remaining depolarized, do not respond to additional impulses, since maintaining muscle tone requires the arrival of repeated impulses associated with repolarization of the end plate, leading to spastic paralysis.

After IV administration, muscle relaxation occurs in the following sequence: eyelid muscles, masticatory muscles, muscles of the fingers, eyes, limbs, neck, back and abdomen, vocal cords; then intercostal muscles and diaphragm.

Causes an increase in cerebral blood flow and an increase in intracranial pressure.

After IM administration, the effect develops in 2-4 minutes; after IV administration – in 54-60 seconds, within 2-3 minutes muscle relaxation reaches its maximum and remains in full for 3 minutes. The duration of action is 5-10 minutes.

The severity of the effect depends on the administered dose: 0.1 mg/kg – relaxation of skeletal muscles without significant effect on the respiratory system, 0.2-1 mg/kg – complete relaxation of the abdominal wall muscles and respiratory muscles (significant limitation or complete cessation of spontaneous breathing occurs). For prolonged muscle relaxation, repeated administration is necessary. The rapid onset of effect and subsequent rapid recovery of muscle tone allow for controlled and manageable muscle relaxation.

Pharmacokinetics

After IV administration, it is distributed in plasma and extracellular fluid. More than 90% is hydrolyzed by blood cholinesterase to succinic acid and choline. The half-life is 90 seconds with a normal level of pseudocholinesterase. It is excreted by the kidneys. Does not cross the intact blood-brain barrier. Does not accumulate.

Indications

• Cessation of spontaneous breathing (endotracheal intubation, bronchoscopy);
• Complete muscle relaxation (endoscopy, reduction of dislocations, reposition of fractures, gynecological, thoracic, abdominal surgeries);
• Prevention of convulsions during electroconvulsive therapy;
• Strychnine poisoning;
• Tetanus (symptomatic therapy).

ICD codes

Dosage Regimen

IV (bolus, drip), IM.

Adults: IV slowly, bolus or drip (for prolonged drip infusion, a 0.1% solution is used). Depending on the clinical situation, with IV administration, a single dose varies from 100 mcg/kg to 1.5-2 mg/kg.

IM is used only in children at doses up to 2.5 mg/kg, but not more than 150 mg, IV – 1-2 mg/kg.

For tracheal intubation – 0.2-0.8 mg/kg; for muscle relaxation and cessation of spontaneous breathing – 0.2-1 mg/kg; for relaxation of skeletal muscles during reduction of dislocations and reposition of bone fragments in fractures – 0.1-0.2 mg/kg, for endoscopy – 0.2 mg/kg; for prevention of complications during electroconvulsive therapy (convulsions, muscle and tendon avulsion) – 0.1-1 mg/kg IV and up to 2.5 mg/kg IM, but not more than 150 mg.

For prolonged muscle relaxation throughout the entire surgery, it can be administered fractionally, every 5-7 minutes, at 0.5-1 mg/kg. Repeated doses act for a longer duration.

Adverse Reactions

Allergic reactions (anaphylactic shock, bronchospasm); hyperkalemia, decreased BP, arrhythmias, bradycardia (more often in children, with repeated administration – in children and adults), conduction disturbances, cardiogenic shock, increased intraocular pressure, hypersalivation, fever; myalgia (in the postoperative period); prolonged paralysis of respiratory muscles (associated with genetically determined impairment of serum cholinesterase formation); rarely – rhabdomyolysis with the development of myoglobinemia and myoglobinuria.

Contraindications

• Hypersensitivity;
• Malignant hyperthermia (including in the anamnesis);
• Myasthenia gravis;
• Congenital and dystrophic myotonia;
• Duchenne muscular dystrophy;
• Closed-angle glaucoma;
• Acute hepatic failure;
• Pulmonary edema;
• Penetrating eye injuries;
• Bronchial asthma;
• Hyperkalemia;
• Infancy (up to 1 year);
• Pregnancy.

With caution decreased activity of serum pseudocholinesterase (terminal stage of hepatic failure, anemia, cachexia, prolonged starvation, chronic infections, extensive burns, trauma), postpartum period, tetanus, tuberculosis, malignant neoplasms, chronic renal failure, myxedema, systemic connective tissue diseases, conditions after plasma transfusion, plasmapheresis, artificial circulation, acute or chronic intoxication with cholinesterase inhibitor insecticides (upon ingestion) or anticholinesterase agents (neostigmine, physostigmine, distigmine, phospholine), simultaneous use of drugs competing with succinylcholine for cholinesterase (procaine IV), emergency surgery in patients with a “full stomach”.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in acute hepatic failure. With caution: decreased activity of serum pseudocholinesterase (terminal stage of hepatic failure

Use in Renal Impairment

With caution: chronic renal failure. Patients with renal failure (without signs of hyperkalemia and neuropathy) are administered the drug once in average doses, but it is not used for multiple administrations or in increased doses due to the risk of hyperkalemia.

Pediatric Use

The use of the drug is prohibited in infancy (up to 1 year).

Special Precautions

It is used only in specialized departments with equipment for artificial lung ventilation and staff proficient in this technique and against the background of general anesthesia.

Preliminary administration of 3-4 mg of d-tubocurarine or 10-15 mg of diplacin 1 minute before the infusion of suxamethonium chloride prevents muscle fasciculations and the subsequent appearance of muscle pain.

With an appropriate dose and repeated administration, it can also be used for longer operations, however, for prolonged muscle relaxation, non-depolarizing muscle relaxants are usually used, which are administered after preliminary tracheal intubation against the background of suxamethonium iodide.

Slow administration of the drug, as well as a preliminary IV injection of atropine at a dose of 1-1.5 mg, largely prevents bradycardia and increased bronchial secretion.

Patients with renal failure (without signs of hyperkalemia and neuropathy) are administered the drug once in average doses, but it is not used for multiple administrations or in increased doses due to the risk of hyperkalemia.

Prolonged muscle relaxation with possible apnea can be caused by several reasons: “atypical” serum cholinesterase, hereditary deficiency of serum cholinesterase, or a temporary decrease in its level.

If the drug is administered repeatedly and 25-30 minutes after the last injection the patient’s muscle tone does not recover, breathing remains shallow, one can suspect the transition of a depolarizing block to an anti-depolarizing block (occurrence of a “dual block”). To relieve this effect, proserin should be used according to the standard method: atropine is first administered into a vein at a dose of 0.5-0.7 mg (0.5-0.7 ml of a 0.1% solution), wait for the pulse to increase and after 1-2 minutes, proserin is administered IV at a dose of 1.5 mg (3 ml of a 0.05% solution).

In children, young patients, and women (mainly vagotonics), transient bradycardia may occur, and in some cases, asystole.

Muscle pain may occur 10-12 hours after drug administration. With repeated administration of the drug, excessively prolonged muscle relaxation and prolonged apnea may sometimes develop.

Overdose

Symptoms: respiratory arrest.

Treatment: Artificial lung ventilation, in case of decreased serum cholinesterase levels – transfusion of fresh blood.

Drug Interactions

Pharmaceutically incompatible with donor blood and blood products (hydrolysis occurs), blood and serum preservatives; with barbiturate solutions and alkaline solutions (precipitate forms). Compatible with isotonic sodium chloride solutions, Ringer’s solution, 5% fructose solution and 6% dextran solution.

Anticholinesterase agents, procaine, procainamide, lidocaine, verapamil, beta-blockers, aminoglycoside antibiotics, amphotericin B, clindamycin, cyclopropane, propanidid, organophosphorus insecticides, Mg2+ and Li+ salts, quinidine, quinine, chloroquine, pancuronium enhance and prolong the muscle relaxant effect. Compatible with other muscle relaxants, narcotic analgesics.

Enhances the cardiac effects of cardiac glycosides (bradycardia).

Reduces the effectiveness of antimyasthenic drugs.

Halogen-containing agents for general anesthesia enhance, while sodium thiopental and atropine reduce the undesirable effect on the cardiovascular system.

Drugs with the potential to reduce blood cholinesterase activity (aprotinin, diphenhydramine, promethazine, estrogens, oxytocin, glucocorticosteroids in high doses, oral contraceptives) enhance and prolong the muscle relaxant effect of suxamethonium.

Storage Conditions

List A.

The drug should be stored at a temperature not exceeding 5°C (41°F) (freezing is not allowed), in a light-protected place, out of the reach of children.

Shelf Life

Shelf life 2 years.

Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.