Atracurium besilate (Solution) Instructions for Use

Instructions
Dosage forms

ATC Code

M03AC04 (Atracurium besilate)

Active Substance

Atracurium besilate (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Peripherally acting non-depolarizing competitive-type muscle relaxant

Pharmacotherapeutic Group

Muscle relaxants; peripherally acting muscle relaxants; other quaternary ammonium compounds

Pharmacological Action

A peripherally acting non-depolarizing competitive-type muscle relaxant. It blocks the n-cholinergic receptors of the end plates of skeletal muscle fibers and prevents the depolarizing action of acetylcholine, resulting in inhibition of neuromuscular transmission at the level of the postsynaptic membrane. In therapeutic doses, it has insignificant m-cholinoblocking and ganglion-blocking activity.

The effect develops rapidly, allowing for intubation within the first 90 seconds after administration of doses of 500-600 mcg/kg.

In doses of 200-600 mcg/kg, it produces a predictable, dose-proportional paralysis of skeletal muscles, which lasts 15-35 minutes.

The rate of recovery of neuromuscular transmission after administration (single and repeated) is constant, allowing for repeated doses to be administered at predictable time intervals. Recovery of normal neuromuscular transmission without the use of anticholinesterase agents occurs within 35 minutes and does not depend on the total dose or the function of the excretory and metabolic organs.

Pharmacokinetics

After IV administration, it is spontaneously metabolized by Hofmann elimination (a non-enzymatic process that occurs at physiological pH and body temperature), as well as by ester hydrolysis involving non-specific plasma esterases. This leads to the formation of laudanosine and other metabolites. The metabolites do not possess muscle relaxant activity.

The binding of atracurium besilate to plasma proteins is approximately 80%.

The T_1/2 of atracurium besilate is approximately 20 minutes, and that of laudanosine is about 3 hours. It is excreted in the urine and bile mainly in the form of metabolites.

Indications

For muscle relaxation during surgical interventions and diagnostic procedures (provided that means for endotracheal intubation and artificial ventilation are available).

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
Z51.4	Preparatory procedures for subsequent treatment or examination, not elsewhere classified

ICD-11 code	Indication
QB9A	Preparatory procedures for subsequent treatment

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Administer intravenously as a bolus, by jet injection, or by continuous infusion.

Determine the dose individually based on clinical requirements, patient factors, and the chosen method of administration.

For tracheal intubation, use a dose of 300 to 600 mcg/kg; this typically facilitates intubation within 90 seconds.

For standard neuromuscular blockade during surgery, administer an initial dose of 200 to 600 mcg/kg; this produces skeletal muscle paralysis lasting 15 to 35 minutes.

For prolonged procedures, administer maintenance doses of 100 to 200 mcg/kg as needed; the predictable recovery profile allows for repeated administration at consistent intervals.

In geriatric patients, use a reduced initial dose at the lower end of the range and administer the drug slowly.

For pediatric patients aged 1 month and older, adjust the dose according to established pediatric regimens.

In patients with hepatic or renal impairment, including end-stage failure, standard dosing regimens are applicable; no dosage adjustment is required.

Monitor neuromuscular function with a peripheral nerve stimulator to guide dosing and assess recovery.

Recovery to normal neuromuscular transmission typically occurs within 35 minutes and is independent of total cumulative dose or organ function.

Adverse Reactions

From the cardiovascular system transient arterial hypotension.

From the central nervous system in isolated cases – seizures (in predisposed patients).

Allergic reactions feeling of heat, bronchospasm (may be due to increased histamine release); rarely – anaphylactoid reactions.

Other skin hyperemia.

Contraindications

Hypersensitivity to atracurium besilate.

Use in Pregnancy and Lactation

Use during pregnancy is only possible if the intended benefit to the mother outweighs the potential risk to the fetus. Atracurium besilate and its metabolites cross the placental barrier in amounts that are not clinically significant.

It is not known whether Atracurium besilate and its metabolites are excreted in breast milk.

Use in Hepatic Impairment

Can be used in standard doses in patients with impaired liver function, including end-stage liver failure.

Use in Renal Impairment

Can be used in standard doses in patients with impaired renal function, including end-stage renal failure.

Pediatric Use

Used in children aged 1 month and older in accordance with the dosing regimen.

Geriatric Use

Can be used in standard doses in elderly patients. However, the initial dose should be lower than the lower limit of the recommended dose range; the drug should be administered slowly.

Special Precautions

Use with caution in patients with hypersensitivity to histamine.

In patients with myasthenia gravis, other neuromuscular diseases, and severe electrolyte disturbances, manifestations of increased sensitivity may occur when using non-depolarizing muscle relaxants, including atracurium besilate.

Depolarizing muscle relaxants should not be used to increase the duration of neuromuscular blockade caused by non-depolarizing muscle relaxants, including atracurium besilate.

Drug Interactions

The neuromuscular blockade caused by atracurium besilate may be enhanced by the use of halothane, isoflurane, enflurane.

It is possible to increase the intensity and duration of neuromuscular blockade caused by non-depolarizing muscle relaxants, including atracurium besilate, with the simultaneous use of certain antibiotics (aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin, clindamycin), antiarrhythmic drugs (propranolol, calcium channel blockers, lidocaine, procainamide, quinidine), diuretics (furosemide and, possibly, mannitol, thiazide diuretics, acetazolamide), magnesium sulfate, ketamine, lithium salts, ganglion blockers (trimethaphan, hexamethonium).

The administration of other non-depolarizing muscle relaxants in combination with atracurium besilate may cause a more pronounced neuromuscular blockade than would be expected with an equivalent total dose of atracurium besilate.

When using depolarizing muscle relaxants to increase the duration of neuromuscular blockade caused by non-depolarizing muscle relaxants, including atracurium besilate, prolonged and profound relaxation may develop, which is difficult to reverse with anticholinesterase agents.

With simultaneous use with drugs that can enhance the manifestations of myasthenia gravis (including latent forms) and provoke the development of myasthenic syndrome, sensitivity to atracurium besilate may increase. Such drugs include antibiotics, propranolol, oxprenolol, procainamide, quinidine, chloroquine, D-penicillamine, trimethaphan, chlorpromazine, steroids, phenytoin, and lithium.

Against the background of long-term treatment with anticonvulsant drugs, a later onset and shorter duration of neuromuscular blockade caused by atracurium besilate are possible.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Atracurium besilate [Hana Pharmaceutical, Co. Ltd. (Republic of Korea)]
Solution for intravenous administration 25 mg/2.5 mL: amp. 5, 10 or 50 pcs.

Marketing Authorization Holder

Hana Pharmaceutical, Co. Ltd. (Republic of Korea)

Dosage Form

Atracurium besilate

Solution for intravenous administration 25 mg/2.5 mL: amp. 5, 10 or 50 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration	1 ml	1 amp.
Atracurium besilate	10 mg	25 mg

2.5 ml – ampoules (5) – plastic contour packs (1) – cardboard boxes.
2.5 ml – ampoules (10) – plastic contour packs (1) – cardboard boxes.
2.5 ml – ampoules (10) – plastic contour packs (5) – cardboard boxes.

Atracurium besilate [B-PHARM, LLC (Russia)]
Solution for intravenous administration 10 mg/1 mL: amp. 2.5 mL or 5 mL 5 or 10 pcs.

Marketing Authorization Holder

B-PHARM, LLC (Russia)

Manufactured By

Kursk Biopharmaceutical Plant – Firm "Biok", FKP (Russia)

B-PHARM, LLC (Russia)

Dosage Form

Atracurium besilate

Solution for intravenous administration 10 mg/1 mL: amp. 2.5 mL or 5 mL 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration clear, from colorless to light yellow.

	1 ml
Atracurium besilate	10 mg

Excipients : 32% benzenesulfonic acid solution – to pH 3.00-3.65, water for injections – up to 1 ml.

2.5 ml – glass ampoules (5) – contour cell packs (1) – cardboard boxes.
2.5 ml – glass ampoules (5) – contour cell packs (2) – cardboard boxes.
5 ml – glass ampoules (5) – contour cell packs (1) – cardboard boxes.
5 ml – glass ampoules (5) – contour cell packs (2) – cardboard boxes.

Atracurium besilate [Promomed Rus LLC (Russia)]
Solution for intravenous administration 10 mg/1 mL: amp. 2.5 mL or 5 mL 5 or 10 pcs.

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

Dosage Form

Atracurium besilate

Solution for intravenous administration 10 mg/1 mL: amp. 2.5 mL or 5 mL 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration clear, from colorless to light yellow.

	1 ml
Atracurium besilate	10 mg

Excipients : 32% benzenesulfonic acid solution – to pH 3.00-3.65, water for injections – up to 1 ml.

2.5 ml – glass ampoules (5) – plastic contour packs (1) – cardboard boxes.
2.5 ml – glass ampoules (5) – plastic contour packs (2) – cardboard boxes.
5 ml – glass ampoules (5) – plastic contour packs (1) – cardboard boxes.
5 ml – glass ampoules (5) – plastic contour packs (2) – cardboard boxes.

Atracurium-Belmed [Belmedpreparaty RUP (Republic of Belarus)]
Solution for intravenous administration 10 mg/mL: amp. 2.5 mL or 5 mL 5 pcs.

Marketing Authorization Holder

Belmedpreparaty RUP (Republic of Belarus)

Dosage Form

Atracurium-Belmed

Solution for intravenous administration 10 mg/mL: amp. 2.5 mL or 5 mL 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration clear colorless or light yellow.

	1 ml
Atracurium besilate	10 mg

Excipients : 32% benzenesulfonic acid solution, water for injections.

2.5 ml – ampoules (1) – contour cell pack (1) – cardboard boxes.
2.5 ml – ampoules (1) – correx (1) – cardboard boxes.
5 ml – ampoules (1) – contour cell pack (1) – cardboard boxes.
5 ml – ampoules (1) – correx (1) – cardboard boxes.

Atracurium-Novo [Novopharm-Biosynthesis Firm, LLC (Ukraine)]
Solution for intravenous administration 10 mg/ml: 5 ml vial, 5 pcs.