Arduan

General characteristics. Structure:

Release form: lyophilisate for preparation of solution for in/in introductions of white or almost white color; the enclosed solvent - colourless, transparent.

Active ingredient: a pipekuroniya bromide of 4 mg in each bottle.

Excipients: Mannitolum.
Solvent: Sodium chloride, water for injections.

Pharmacological properties:

Pharmacodynamics. Is not depolarizing muscle relaxant of long action. Due to competitive communication with the N-holinoretseptorami located on a trailer plate of a neuromuscular synapse of skeletal muscles blocks signal transmission from nerve terminations to muscle fibers. Does not cause a muscular fastsikulyation, has no hormonal effect.
Even in the doses several times surpassing its effective dose necessary for 90% of decrease in muscular contractility (ED90) does not render ganglioblokiruyushchy, m-holinoblokiruyushchey and sympathomimetic activity.
According to researches, at the balanced anesthesia of a dose of ED50 and ED90 a pipekuroniya of bromide make 0,03 and 0,05 mg/kg of body weight, respectively.
The dose equal to 0,05 mg/kg of body weight provides a 40-50-minute muscular relaxation during various operations.
The maximum action a pipekuroniya of bromide depends on a dose and comes in 1,5-5 min. The effect develops most quicker at the doses equal to 0,07-0,08 mg/kg. Further increase in a dose reduces time necessary for development of effect, and significantly prolongs effect of drug.

Pharmacokinetics. At intravenous administration the initial volume of distribution (Vdc) makes 110 ml/kg of body weight, distribution volume in a phase of saturation (Vdss) reaches 300 (±78) ml/kg, the plasma clearance (Cl) is approximately equal to 2,4 (±0.5) ml/min., the average elimination half-life (T1/2) makes 121 (± 45) the min. average time of stay in a blood plasma (MRT) – 140 min.
At repeated introduction of maintenance doses the cumulative effect is insignificant if at the time of 25% of recovery of initial muscular contractility doses of 0,01-0,02 mg/kg are used.
56% of drug – in the first 24 hours are removed generally by kidneys, at the same time. One third is removed in an invariable look, and other quantity – in the form of 3-dezatsetil-pipekuroniya bromides.
According to preclinical trials the liver participates in elimination a bromide pipekuroniya too.
Gets through a placental barrier.

Indications to use:

Endotracheal intubation and relaxation of skeletal muscles at the general anaesthesin during various surgeries demanding more than 20-30-minute muscle relaxation and in the conditions of IVL.

Route of administration and doses:

As well as in cases with other not depolarizing muscle relaxants, Arduan's dose is chosen for each patient individually taking into account the type of anesthesia, estimated duration of surgical intervention, possible interactions with other medicines applied to or during anesthesia, associated diseases and the general condition of the patient.
It is recommended to apply a stimulator of peripheral nerve fibrils to ensuring control of the neuromuscular block.
To apply only intravenously. Just before introduction of 4 mg of dry matter part with the enclosed solvent.

The recommended doses for adults and children are more senior than 14 years:
– an initial dose for an intubation and the subsequent surgical intervention: 0,06-0,08 mg/kg of body weight, duration of a muscular relaxation of 60-90 min. provides good/excellent conditions for an intubation during 150-180 sec., at the same time;
– an initial dose for muscle relaxation at an intubation with succinylcholine use: 0.05 mg/kg. provides 30-60-minute muscle relaxation;
– maintenance dose: 0,01-0,02 mg/kg, provide 30-60-minute muscle relaxation during surgery;
– at a chronic renal failure it is not recommended to apply the doses exceeding 0,04 mg/kg (in high doses increase in duration of muscle relaxation is possible);
– at the excess weight and obesity extension of action of Arduan therefore it is necessary to apply the dose expected ideal weight is possible.

Doses at children: from 3 to 12 months – 0,04 mg/kg (that provides a muscular relaxation lasting from 10 up to 44 min.).
From 1 year to 14 years – 0,05-0,06 mg/kg (a muscular relaxation – from 18 to 52 min.).

Termination of effect: at the time of 80-85% of the blockade measured by means of a stimulator of peripheral nerve fibrils or at the time of the partial block determined by clinical signs, from a neostigmin marked atropine use (0,5-1,25 mg) at combinations sulfate (1-3 mg) or Galantaminum (10-30 mg) stops myorelaxation action of Arduan.

Features of use:

To apply only in the conditions of a specialized hospital in the presence of the corresponding equipment to carrying out an artificial respiration and in the presence of the specialist in carrying out an artificial respiration in view of impact of drug on respiratory muscles.
Careful control is necessary during operation and in the early postoperative period for maintenance of vital signs to a complete recovery of muscular contractility.
When calculating a dose it is necessary to consider the used equipment of anesthesia, possible interactions with the medicines entered to or during anesthesia, a state and sensitivity of the patient to drug.
In medical literature cases of anaphylactic and anaphylactoid reactions at use of muscle relaxants are described. Despite the absence of messages on similar action of Arduan, drug can be used only in the conditions allowing to start immediately treatment of such states.
It is necessary to observe the increased care in Arduan's use in the presence in the anamnesis of the patient of the anaphylactic reaction caused by any muscle relaxant because of a possible cross allergy.
Arduan's doses causing muscle relaxation have no essential cardiovascular effect and practically do not cause bradycardia.
Use and dose of m-holinoblokatorov for premedication is subject to careful preliminary estimate; it is necessary to consider also stimulating influence on n. vagus of another, at the same time used medicines and like operation.
For the purpose of avoidance of relative overdose of drug and ensuring the corresponding control of recovery of muscular activity it is recommended to apply a stimulator of peripheral nerve fibrils.
Patients with disorders of neuromuscular transmission, obesity, a renal failure, diseases of a liver and bilious ways, at instructions in the anamnesis on the postponed poliomyelitis, need to appoint drug in smaller doses.
In a liver case Arduan's use is possible only in cases when the risk is justified. At the same time the dose has to be minimum.
Some states (hypopotassemia, digitalization, gipermagniyemiya, reception of diuretics, hypocalcemia, hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia, hypothermia) can promote lengthening or strengthening of effect.
As well as in a case with other muscle relaxants, before Arduan's use it is necessary to normalize electrolytic balance and an acid-base state, to eliminate dehydration.
Like other muscle relaxants Arduan can reduce the activated partial tromboplastinovy and prothrombin time.
Children aged from 1 year till 14 years are less sensitive to a pipekuroniya to bromide and duration of myorelaxation effect at them is shorter, than at adults and children aged till 1 year.
Efficiency and safety of use in the neonatal period are not studied.
The myorelaxation effect at babies from 3 months to 1 year practically does not differ from that at adults.
It is necessary to apply only freshly cooked solution.

Influence on ability of driving and worker mechanisms
In the first 24 hours after the termination of myorelaxation action of Arduan it is not recommended to drive the car and to be engaged in potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From a nervous system:
seldom (less than 1%): oppression of the central nervous system (CNS), drowsiness, hypesthesia. paralysis of skeletal muscles.
From a musculoskeletal system:
seldom (less than 1%): weakness of skeletal muscles after the muscle relaxation termination, a muscular atrophy.
From respiratory system:
seldom (less than 1%): an apnoea, a lung atelectasis, respiratory depression, a laryngospasm as a result of allergic reaction, a bronchospasm, cough.
From cardiovascular system:
seldom (less than 1%): myocardium ischemia (up to a myocardial infarction) and a brain, arrhythmias, tachycardia, bradycardia, decrease or increase in arterial pressure, fibrillation of auricles, ventricular premature ventricular contraction, ventricular tachycardia.
From bodies of a hemopoiesis and system of a hemostasis:
seldom (less than 1%): thrombosis, decrease in the activated partial tromboplastinovy and prothrombin time.
From an urinary system:
seldom (less than 1%): anury.
Allergic reactions:
seldom (less than 1%): skin rash, allergic reactions, Quincke's edema.
Laboratory indicators:
seldom (less than 1%): giperkreatininemiya, hyperglycemia, hypopotassemia, hypomagnesiemia, hypocalcemia.
Others: blepharitis, ptosis.

Interaction with other medicines:

Inhalation anesthetics (a halothane, метоксифлуран, diethyl ether, энфлуран, изофлуран, cyclopropane), anesthetics for intravenous administration (Ketaminum, Propanididum. barbiturates, этомидат, at - a hydrox and butyric acid), the depolarizing and not depolarizing muscle relaxants, some antibiotics (the aminoglycosides derivative of a nitroimidazole, including metronidazole, tetracyclines, bacitracin, капреомицин, clindamycin, polymyxins, including colistin, lincomycin, Amphotericinum In), nitrate anticoagulants, mineralokortikoida and glucocorticosteroids, diuretics, including буметанид, karboangidraza inhibitors, Acidum etacrynicum, corticotropin, α-and β-adrenoblockers, thiamin, monoamine oxidase inhibitors (MAO), guanidine, protamin strengthen sulfate, Phenytoinum, blockers of "slow" calcium channels, magnesium salts, procaineamide, quinidine, lidocaine and Procainum for intravenous administration and/or extend action.
The drugs reducing potassium concentration in blood aggravate respiratory depression (up to its stop).

Opioid analgetics strengthen respiratory depression. High doses of sufentanil reduce the need for high initial doses of not depolarizing muscle relaxants. Not depolarizing muscle relaxants warn or reduce the muscle tension caused by high doses of opiondny analgetics (including alfentanil, fentanyl, sufentanil). Does not reduce risk of bradycardia and arterial hypotension, caused by opiondny analgetics (especially against the background of vazodilatator and/or beta adrenoblockers).
During an intubation with succinylcholine Arduan enter after disappearance of clinical signs of effect of succinylcholine. As well as in a case with other not depolarizing muscle relaxants Arduan's introduction can reduce time necessary for muscle relaxation approach and increase duration of the maximum effect;
At prolonged preliminary use of glucocorticosteroids, a neostigmina of methyl sulfate, an edrofoniya of chloride, pyridostigmine bromide, Norepinephrinum, Azathioprinum, Epinephrinum, theophylline, potassium of chloride, sodium of chloride, Calcii chloridum easing of effect is possible.
The depolarizing muscle relaxants can both strengthen, and to weaken action a bromide pipekuroniya (depends on a dose, time of use and individual sensitivity).
Doksapram temporarily masks residual effects of muscle relaxants.

Contraindications:

– Hypersensitivity to a pipekuroniya to bromide and/or and to bromine.
– Children's age up to 3 months.
– Heavy liver failure.

With care:
Obstruction of biliary tract, edematous syndrome, increase in volume of the circulating blood or dehydration, reception of diuretics, disturbance of an acid-base state (acidosis, hypercapnia) and water and electrolytic exchange (a hypopotassemia. a gipermagniyemiya, a hypocalcemia), a hypothermia, a digitalization, a hypoproteinemia, a cachexia, a myasthenia (including gravis myasthenia, Eaton-Lambert's syndrome) because of possible both strengthening, and weakening of effect of drug in such cases. Small doses of Arduan at a heavy myasthenia or a syndrome Eaton-Lambert can cause strongly expressed effect. Such patient drug is appointed in very low doses after careful assessment of potential risk, by respiratory depression, a renal failure (prolongs effect of drug and time of a post-narcotic depression), dekompensirovanny chronic heart failure, children's age up to 14 years, a malignant hyperthermia, the anaphylactic reaction caused by any muscle relaxant in the anamnesis of the patient (because of a possible cross allergy).

Pregnancy and period of a lactation:
Clinical trials for the proof of safety of use of Arduan for pregnant women and a fruit are not enough. Use of drug during pregnancy is not recommended.
Clinical data on safe use of Arduan in the period of a lactation are not enough. Use of drug during breastfeeding is not recommended.

Overdose:

Symptoms: long paralysis of skeletal muscles and an apnoea, the expressed lowering of arterial pressure (ABP), shock.
In case of overdose or the prolonged neuromuscular block artificial ventilation of the lungs is continued before recovery of spontaneous breath. At the beginning of recovery of spontaneous breath as an antidote enter acetylcholinesterase inhibitor (for example, a neostigmina methyl sulfate, pyridostigmine bromide, an edrofoniya chloride): atropine of 0,5-1,25 mg in a combination from a neostigmin methyl sulfate (1-3 mg) or Galantaminum (10-30 mg). To recovery of satisfactory spontaneous breath it is necessary to carry out careful control of respiratory function.

Storage conditions:

At a temperature from 2 to 8 °C, in the place protected from light. To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for intravenous administration of 4 mg / complete with solvent – chloride sodium solution of 0,9%.
10 mg of lyophilisate from colourless glass (1 Hydrolytic class) contain 4 mg in a bottle a bromide pipekuroniya; 2 ml of solvent in a colourless glass ampoule (1 Hydrolytic class), 5 bottles and 5 ampoules in the plastic pallet, 5 plastic pallets in a cardboard pack with the application instruction.