Notrixum (Solution) Instructions for Use

Marketing Authorization Holder

PT. Novell Pharmaceutical Laboratories (Indonesia)

Manufactured By

PT. Novell Pharmaceutical Laboratories (Indonesia)

ATC Code

M03AC04 (Atracurium besilate)

Active Substance

Atracurium besilate

Dosage Form

Notrixum

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

Dosage Form, Packaging, and Composition

Solution for intravenous administration transparent, colorless.

Excipients: benzenesulfonic acid – 0.05 mg, water for injection – up to 1 ml.

2.5 ml – ampoules made of colorless glass, hydrolytic class I (5) – PVC trays (1) – cardboard packs with first-opening stickers.
5 ml – ampoules made of colorless glass, hydrolytic class I (5) – PVC trays (1) – cardboard packs with first-opening stickers.

Clinical-Pharmacological Group

Peripherally acting non-depolarizing competitive-type muscle relaxant

Pharmacotherapeutic Group

Non-depolarizing peripheral-acting muscle relaxant

Pharmacological Action

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 action develops quickly, which allows intubation within the first 90 seconds after administration in 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, which allows 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 and the function of excretory organs and metabolism.

Pharmacokinetics

After intravenous 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 nonspecific plasma esterases. This leads to the formation of laudanosine and other metabolites. The metabolites do not have muscle relaxant activity.

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

The T_1/2 of atracurium besilate is approximately 20 minutes, and that of laudanosine is about 3 hours. It is excreted in 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

Dosage Regimen

Determine the dosage regimen individually based on patient factors and clinical requirements.

Administer Notrixum intravenously only. Use either a bolus injection or a continuous infusion.

For tracheal intubation, administer an initial bolus dose of 300 to 600 mcg/kg. This typically provides adequate conditions for intubation within 90 seconds.

For provision of skeletal muscle relaxation during surgery, use an initial bolus dose of 200 to 600 mcg/kg. The resulting neuromuscular blockade generally lasts 15 to 35 minutes.

Administer maintenance doses of 100 to 200 mcg/kg to prolong muscle relaxation as required. The predictable recovery profile allows for repeated dosing at consistent intervals.

For continuous infusion, initiate only after early evidence of recovery from an initial bolus dose. Administer at a rate of 300 to 600 mcg/kg/hour (5 to 10 mcg/kg/minute). Titrate the infusion rate to maintain a 90% suppression of the twitch response.

Adjust doses for elderly patients; use a lower initial dose within the recommended range and administer slowly.

Use standard doses in patients with renal impairment or hepatic impairment, including end-stage organ failure. No dosage adjustment is required.

For pediatric patients aged 1 month and older, use the same mcg/kg dosing as for adults. Closely monitor neuromuscular function in all patients.

Adverse Reactions

From the cardiovascular system transient arterial hypotension.

From the central nervous system in isolated cases – convulsions (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 possible only 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 from 1 month 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 value 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 disorders, manifestations of increased sensitivity may occur when using non-depolarizing muscle relaxants, including atracurium besilate.

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

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).

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 deep relaxation may develop, which is difficult to reverse with anticholinesterase agents.

With simultaneous use with drugs that can enhance the manifestations of myasthenia (including latent) 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.