ARDOIN LIOF. D/PRIG. R-RA D/V/V ENTER. 4MG No. 25 COMPLETE WITH SOLVENT: SODIUM CHLORIDE SOLUTION 0.9% (AMPOULES) 2 ML-25 PCS.

Pharmacological properties of the drug Arduan

Pipecuronium bromide (2β, 16β-bis(4-dimethylpiperazine)-3α-17β-diacetoxy-5α-androstane dibromide) is a non-depolarizing muscle relaxant with a peripheral mechanism of action due to its effect on the motor end plates of striated muscles. The effect of pipecuronium bromide during intubation in the case of the use of suxamethonium chloride after the cessation of the depolarizing blockade develops after 2-3 minutes, when using only pipecuronium bromide - after 4-5 minutes. The duration of action of the drug is 40–60 minutes, depending on the dose used and the individual sensitivity of the patient. It is excreted unchanged, mainly in urine and in minimal quantities in bile. After repeated administrations of the drug, slight accumulation is possible.

Use of the drug Arduan

Adults For surgical interventions of medium and long duration, the drug is used intravenously:

for endotracheal intubation and for complete muscle relaxation during surgery, 0.06–0.08 mg/kg body weight is administered;
for patients intubated with suxamethonium chloride, Arduan is administered at an initial dose of 0.04–0.06 mg/kg;
in patients with impaired renal function, it is not recommended to exceed a dose of 0.04 mg/kg;
repeated doses of the drug are 1/4–1/3 of the initial dose. When administered at a higher dose, the effect may be prolonged.

Children and newborns When using combined anesthesia, the initial dose of Arduan is 0.08–0.09 mg/kg. For newborns, lower doses are recommended - 0.05–0.06 mg/kg. The indicated doses of the drug provide muscle relaxation during a 25-35 minute surgical intervention. If it is necessary to increase the period of muscle relaxation for the next 25–35 minutes, the drug is re-administered at a dose of 1/3 of the initial one. Reversal of effect At 80–85% blockade as measured by peripheral neuromuscular stimulator, or partial blockade as determined by clinical symptoms, the Ardoin effect in adults can be reversed by administration of neostigmine bromide at a dose of 1–3 mg in combination with atropine or galantamine at a dose of 10–30 mg. Elimination of the effect is determined using a peripheral neurostimulator or by observing characteristic clinical symptoms.

Publications in the media

(Pipecuronii bromidum) INN

Synonyms. Ardoin.

Composition and release form. Ampoules containing 4 mg of the drug, with the addition of a solvent.

Indications. For muscle relaxation during various types of surgical interventions.

Pharmachologic effect. Pipecuronium bromide is a non-depolarizing muscle relaxant. Blocks n-cholinergic receptors of skeletal muscles, reducing their sensitivity to acetylcholine, and thereby eliminates the possibility of depolarization of the end plate and excitation of the muscle fiber. The curare-like effect is associated with the presence of quaternary ammonium (onium) groups with an optical distance between them approximately equal to the distance between the onium groups in d-tubocurarine. In normal doses it does not cause significant changes in the activity of the cardiovascular system. In large doses it has a ganglion-blocking effect; does not cause histamine release. Myorelaxation occurs after 1 minute, the peak effect occurs after 3-4.5 minutes and lasts 35-45 minutes. Muscle tone stops after 60 minutes. The muscle relaxant effect of pipecuronium bromide is removed by proserin.

Pharmacokinetics. It practically does not bind to plasma proteins. Metabolized in the liver in small quantities. T1/2 is 114-116 minutes, excreted by the kidneys (80% unchanged) and 10% with bile.

Side effects. Increased blood pressure, salivation, skin rash, itching.

Contraindications. Myasthenia gravis, early pregnancy, renal dysfunction, tachycardia, hypersensitivity to the drug.

Adverse reactions when interacting with other drugs. Pipecuronium bromide enhances the inhibitory effect of narcotic analgesics on the respiratory center. Drugs that disrupt neuromuscular transmission (aminoglycoside antibiotics, clindamycin, lincomycin, polymyxin, lidocaine, novocaine, as well as novocainamide, quinidine, magnesium sulfate, etc.) enhance the muscle relaxant effect of pipecuronium bromide. Cardiac glycosides of the digitalis group against the background of the action of pipecuronium bromide can cause cardiac arrhythmias. Drugs that cause hypokalemia (thiazide diuretics, furosemide, corticosteroids, ACTH, etc.) increase the neuromuscular blockade caused by pipecuronium bromide.

Information for the patient. Pipecuronium bromide is administered intravenously. The dose for intubation is 0.04-0.08 mg/kg. For muscle relaxation during anesthesia, the drug is used in doses of 0.02 to 0.08 mg/kg. The effect of pipecuronium bromide is stopped by introducing 1-3 mg of proserine after preliminary intravenous administration of 0.25-0.5 mg of atropine. The drug is used only in a hospital.

Special instructions for the use of the drug Arduan

The use of Ardoin is possible only in a specialized hospital with equipment for endotracheal intubation, mechanical ventilation, oxygen therapy, as well as specific antidotes. Use only freshly prepared solution. It is necessary to reduce the dose of the drug in patients with neuromuscular conduction disorders, with a history of indications of poliomyelitis, as well as in obesity (due to the possibility of a relative overdose of Arduan). It should be taken into account that in patients with renal failure, the duration of action of the drug increases. Hypothermia may prolong the effect of the drug. It is recommended to reduce the initial dose of Arduan for diseases of the liver and/or bile ducts. Before starting anesthesia, water-electrolyte imbalance and blood pH disturbances should be compensated. Hypokalemia, hypocalcemia (for example after blood transfusions), hypermagnesemia, hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia, the use of cardiac glycosides, diuretics enhance the effect or increase the duration of action of the drug. The use of Ardoin during cesarean section does not affect the Apgar score, muscle tone and cardiovascular adaptation of the newborn. Only a minimal amount of the active substance penetrates the placental barrier. In pregnant women who were prescribed magnesium salts (which can potentiate neuromuscular blockade) during the treatment of toxicosis, Ardoin should be used with caution and in lower doses.

Arduan 4mg 25 pcs. lyophilisate for the preparation of solution for intravenous administration

pharmachologic effect

Non-depolarizing muscle relaxant with peripheral action.

Composition and release form Arduan 4 mg 25 pcs. lyophilisate for the preparation of solution for intravenous administration

Lyophilisate – 1 vial::

Active ingredient: pipecuronium bromide 4 mg;
Excipients: mannitol; Solvent: Sodium chloride, water for injection.

Lyophilisate for the preparation of solution for intravenous administration 4 mg / complete with solvent - sodium chloride solution 0.9%.

10 mg of lyophilisate in a clear glass bottle (Hydrolytic class 1) contains 4 mg of pipecuronium bromide; 2 ml of solvent in a colorless glass ampoule (Hydrolytic class 1).

5 bottles and 5 ampoules in a plastic tray, 5 plastic trays in a cardboard box with instructions for use.

Description of the dosage form

Lyophilisate: white or almost white lyophilisate.

Solvent: colorless and transparent solution.

Directions for use and doses

As with other non-depolarizing muscle relaxants, the dose of Arduan is selected for each patient individually, taking into account the type of anesthesia, the expected duration of surgery, possible interactions with other drugs used before or during anesthesia, concomitant diseases and the general condition of the patient.

It is recommended to use a peripheral nerve fiber stimulator to ensure control of neuromuscular block.

Use only intravenously. Immediately before administration, 4 mg of dry substance is diluted with the supplied solvent.

Recommended doses for adults and children over 14 years of age:

initial dose for intubation and subsequent surgery: 0.06-0.08 mg/kg body weight, provides good/excellent conditions for intubation for 150-180 seconds, while the duration of muscle relaxation is 60-90 minutes;
initial dose for muscle relaxation during intubation using suxamethonium: 0.05 mg/kg, provides 30-60 minutes of muscle relaxation;
maintenance dose: 0.01-0.02 mg/kg, provides 30-60 minutes of muscle relaxation during surgery;
in case of chronic renal failure, it is not recommended to use doses exceeding 0.04 mg/kg (in large doses, the duration of muscle relaxation may increase);
If you are overweight or obese, the action of Arduan may be prolonged, so you should use a dose calculated for your ideal weight.

Doses in children: from 3 to 12 months. - 0.04 mg/kg (which provides muscle relaxation lasting from 10 to 44 minutes).

From 1 year to 14 years - 0.05-0.06 mg/kg (muscle relaxation - from 18 to 52 minutes).

Termination of effect: at the moment of 80-85% blockade, measured using a peripheral nerve fiber stimulator, or at the moment of partial blockade, determined by clinical signs, the use of atropine (0.5-1.25 mg) in combination with neostigmine methyl sulfate (1- 3 mg) or galantamine (10-30 mg) stops the muscle relaxant effect of Ardoin.

Pharmacodynamics

It is a long-acting non-depolarizing muscle relaxant. Due to competitive communication with n-cholinergic receptors located on the end plate of the neuromuscular synapse of skeletal muscles, it blocks signal transmission from nerve endings to muscle fibers. Does not cause muscle fasciculation and does not have a hormonal effect.

Even in doses several times higher than its effective dose required for a 90% decrease in muscle contractility (ED90), it does not have ganglioblocking, m-anticholinergic and sympathomimetic activity.

According to studies, with balanced anesthesia, the ED50 and ED90 doses of pipecuronium bromide are 0.03 and 0.05 mg/kg body weight, respectively.

A dose equal to 0.05 mg/kg body weight provides 40-50 minutes of muscle relaxation during various operations.

The maximum effect of pipecuronium bromide depends on the dose and occurs within 1.5-5 minutes. The effect develops most rapidly at doses equal to 0.07-0.08 mg/kg. Further increase in dose reduces the time required for the development of the effect and significantly prolongs the effect of the drug.

Pharmacokinetics

When administered intravenously, the initial volume of distribution (Vdc) is 110 ml/kg body weight, the volume of distribution in the saturation phase (Vdss) reaches 300 (±78) ml/kg, plasma clearance (CI) is approximately 2.4 (±0.5) ) ml/min/kg, mean elimination half-life (T1/2β) is 121 (± 45) min, mean plasma residence time (MRT) is 140 min.

With repeated administration of maintenance doses, the cumulative effect is insignificant if doses of 0.01-0.02 mg/kg are used at the time of 25% restoration of initial muscle contractility.

It is excreted mainly by the kidneys, with 56% of the drug in the first 24 hours. One third is excreted unchanged, and the remaining amount is excreted in the form of 3-desacetyl-pipecuronium bromide.

According to preclinical studies, the liver is also involved in the elimination of pipecuronium bromide.

Penetrates through the placental barrier.

Indications for use Arduan 4 mg 25 pcs. lyophilisate for the preparation of solution for intravenous administration

Endotracheal intubation and relaxation of skeletal muscles during general anesthesia during various surgical operations requiring more than 20-30 minutes of muscle relaxation and under mechanical ventilation.

Contraindications

Hypersensitivity to pipecuronium bromide and/or bromine.

Children's age up to 3 months.

Severe liver failure.

With caution: obstruction of the biliary tract, edematous syndrome, increased circulating blood volume or dehydration, diuretics, impaired acid-base status (acidosis, hypercapnia) and water-electrolyte metabolism (hypokalemia, hypermagnesemia, hypocalcemia), hypothermia, digitalization, hypoproteinemia, cachexia, myasthenia gravis (including myasthenia gravis, Eaton-Lambert syndrome) due to the possibility in such cases of both strengthening and weakening of the effect of the drug. Small doses of Ardoin for myasthenia gravis or Eaton-Lambert syndrome can cause a strong effect. In such patients, the drug is prescribed in very low doses after a careful assessment of the potential risk, respiratory depression, renal failure (prolongs the effect of the drug and the time of post-anesthesia depression), decompensated chronic heart failure, children under 14 years of age, malignant hyperthermia, anaphylactic reaction caused by any muscle relaxant in the patient's history (due to possible cross-allergy).

Application of Arduan 4 mg 25 pcs. lyophilisate for the preparation of a solution for intravenous administration during pregnancy and lactation

There are not enough clinical studies to prove the safety of Arduan in pregnant women and the fetus. The use of the drug during pregnancy is not recommended.

There is insufficient clinical data on the safe use of Arduan during lactation. The use of the drug during breastfeeding is not recommended.

special instructions

Use exclusively in a specialized hospital with appropriate equipment for artificial respiration and in the presence of a specialist in artificial respiration due to the effect of the drug on the respiratory muscles.

Careful monitoring is necessary during surgery and in the early postoperative period to maintain vital functions until muscle contractility is fully restored.

When calculating the dose, the anesthesia technique used, possible interactions with drugs administered before or during anesthesia, the condition and sensitivity of the patient to the drug should be taken into account.

The medical literature describes cases of anaphylactic and anaphylactoid reactions when using muscle relaxants. Despite the lack of reports of a similar effect of Ardoin, the drug can only be used in conditions that allow immediate treatment of such conditions.

Increased caution should be exercised in the use of Ardoin if the patient has a history of an anaphylactic reaction caused by any muscle relaxant due to possible cross-allergy.

Doses of Ardoin that cause muscle relaxation do not have a significant cardiovascular effect and practically do not cause bradycardia.

The use and dose of m-anticholinergic agents for premedication purposes is subject to careful preliminary assessment; the stimulating effect on n should also be taken into account. vagus of other concomitantly used medications and type of surgery.

In order to avoid a relative overdose of the drug and ensure appropriate control over the restoration of muscle activity, it is recommended to use a peripheral nerve fiber stimulator.

Patients with neuromuscular transmission disorders, obesity, renal failure, diseases of the liver and biliary tract, with a history of polio, should be prescribed the drug in lower doses.

In case of liver disease, the use of Ardoin is possible only in cases where the risk is justified. In this case, the dose should be minimal.

Some conditions (hypokalemia, digitalization, hypermagnesemia, diuretics, hypocalcemia, hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia, hypothermia) may prolong or enhance the effect.

As is the case with other muscle relaxants, before using Arduan, the electrolyte balance and acid-base status should be normalized, and dehydration should be eliminated.

Like other muscle relaxants, Arduan can reduce activated partial thromboplastin and prothrombin times.

Children aged 1 to 14 years are less sensitive to pipecuronium bromide and the duration of the muscle relaxant effect is shorter than in adults and children under 1 year of age.

The effectiveness and safety of use in the neonatal period have not been studied. Muscle relaxant effect in infants from 3 months. up to 1 year is practically no different from that in adults.

Overdose

Symptoms: prolonged paralysis of skeletal muscles and apnea, marked decrease in blood pressure (BP), shock.

In case of overdose or prolonged neuromuscular block, artificial ventilation is continued until spontaneous breathing is restored. At the beginning of the restoration of spontaneous breathing, an acetylcholinesterase inhibitor (for example, neostigmine methyl sulfate, pyridostigmine bromide, edrophonium chloride) is administered as an antidote: atropine 0.5-1.25 mg in combination with neostigmine methyl sulfate (1-3 mg) or galantamine (10-30 mg). Respiratory function should be carefully monitored until satisfactory spontaneous breathing is restored.

Side effects Arduan 4 mg 25 pcs. lyophilisate for the preparation of solution for intravenous administration

From the nervous system: rarely (less than 1%): central nervous system (CNS) depression, drowsiness, hypoesthesia, skeletal muscle paralysis.

From the musculoskeletal system: rarely (less than 1%): weakness of skeletal muscles after the cessation of muscle relaxation, muscle atrophy.

From the respiratory system: rarely (less than 1%): apnea, pulmonary atelectasis, respiratory depression, laryngospasm as a result of an allergic reaction, bronchospasm, cough.

From the cardiovascular system: rarely (less than 1%): myocardial ischemia (up to myocardial infarction) and brain, arrhythmias, tachycardia, bradycardia, decrease or increase in blood pressure, atrial fibrillation, ventricular extrasystole, ventricular tachycardia.

From the hematopoietic organs and hemostatic system: rarely (less than 1%): thrombosis, decreased activated partial thromboplastin and prothrombin time.

From the urinary system: rarely (less than 1%): anuria.

Allergic reactions: rarely (less than 1%): skin rash, allergic reactions, angioedema.

Laboratory indicators: rarely (less than 1%): hypercreatininemia, hyperglycemia, hypokalemia, hypomagnesemia, hypocalcemia.

Other: blepharitis, ptosis.

Drug interactions

Inhalation anesthetics (halothane, methoxyflurane, diethyl ether, enflurane, isoflurane, cyclopropane), intravenous anesthetics (ketamine, propanidide, barbiturates, etomidate, γ-hydroxybutyric acid), depolarizing and non-depolarizing muscle relaxants, some antibiotics (aminoglycosides, nitroimidazole derivatives, including metronidazole, tetracyclines, bacitracin, capreomycin, clindamycin, polymyxins, including colistin, lincomycin, amphotericin B), nitrate anticoagulants, mineralocorticoids and glucocorticosteroids, diuretics, incl. bumetanide, carbonic anhydrase inhibitors, ethacrynic acid, corticotropin, α- and β-blockers, thiamine, monoamine oxidase (MAO) inhibitors, guanidine, protamine sulfate, phenytoin, slow calcium channel blockers, magnesium salts, procainamide, quinidine, lidocaine and procaine for intravenous administration enhances and/or prolongs the effect.

Drugs that reduce the concentration of potassium in the blood aggravate respiratory depression (even to the point of stopping it).

Opioid analgesics increase respiratory depression. High doses of sufentanil reduce the need for high initial doses of nondepolarizing muscle relaxants. Non-depolarizing muscle relaxants prevent or reduce muscle stiffness caused by high doses of opioid analgesics (including alfentanil, fentanyl, sufentanil). Does not reduce the risk of bradycardia and hypotension caused by opioid analgesics (especially against the background of vasodilators and/or beta-blockers).

During intubation with suxamethonium, Arduan is administered after the clinical signs of suxamethonium have disappeared. As with other non-depolarizing muscle relaxants, the administration of Ardoin can reduce the time required for the onset of muscle relaxation and increase the duration of the maximum effect; With long-term preliminary use of glucocorticosteroids, neostigmine methyl sulfate, edrophonium chloride, pyridostigmine bromide, norepinephrine, azathioprine, epinephrine, theophylline, potassium chloride, sodium chloride, calcium chloride, the effect may be weakened.

Depolarizing muscle relaxants can either enhance or weaken the effect of pipecuronium bromide (depending on the dose, time of use and individual sensitivity).

Doxapram temporarily masks the residual effects of muscle relaxants.

Interactions of the drug Arduan

Succinylcholine enhances the effect of Ardoin. Inhalation anesthetics (halothane, methoxyflurane, diethyl ether) and barbiturates enhance and increase the duration of action of Arduan. The use of antibiotics such as gentamicin, clindamycin, ampicillin and tetracycline during surgery in usual doses did not affect the effect of Ardoin, assessed by tetanic exhaustion. However, the absence of tetanic exhaustion does not exclude an interaction, so a prolonged effect is rarely possible in the early postoperative period. The simultaneous use of Arduan with aminoglycosides requires special caution and monitoring. Strengthening and/or increasing the duration of the action of Arduan is possible with the simultaneous use of drugs for intravenous anesthesia (ketamine, fentanyl, propanidide, barbiturates); diuretics; β-adrenergic receptor blockers; thiamine; MAO inhibitors; guanidine; protamine; phenytoin; β-adrenergic receptor blockers; calcium antagonists; lidocaine (iv injection). Weakening the effect of Ardoin is possible when using GCS, neostigmine bromide, norepinephrine, theophylline, potassium chloride, sodium chloride, calcium chloride before surgery. Changing (strengthening or weakening) the action of Ardoin is possible with the simultaneous use of depolarizing muscle relaxants (depending on their dose, period of use and individual sensitivity of the patient).