Neucurium I.V. Infusion Ve Injection Icin Solution Iceren Ampul 50 Mg

Description

Neucurium I.V. Infusion ve Injection Icin Solution Iceren Ampul 50 mg is a neuromuscular blocking agent used to facilitate skeletal muscle relaxation during surgical procedures and mechanical ventilation. Manufactured by Vem, a Turkish pharmaceutical company, each 5 mL ampoule contains 50 mg of atracurium besylate (10 mg/mL), a non-depolarizing muscle relaxant administered intravenously (IV). Packaged as a single ampoule or in sets of five (5×5 mL), Neucurium is a critical tool in anesthesia, enabling endotracheal intubation and controlled ventilation by temporarily paralyzing skeletal muscles.

Atracurium besylate, the active ingredient, belongs to the benzylisoquinolinium class of neuromuscular blockers, distinguished by its unique metabolism and minimal reliance on hepatic or renal function. This article, provides an in-depth exploration of Neucurium 50 mg, detailing its chemical structure, mechanism of action, pharmacokinetics, therapeutic uses, side effects, drug interactions, safety considerations, and regulatory status. Written with precision and accessibility, this guide serves healthcare professionals and informed patients seeking a thorough understanding of this Turkish-origin medication.

Chemical Structure

Atracurium besylate (C65H82N2O18S2) is a synthetic, bisquaternary ammonium compound categorized as a monobactam within the benzylisoquinolinium family. Its molecular structure features two tetrahydroisoquinoline moieties linked by a diester bridge, with each nitrogen atom quaternized to confer positive charges. Key structural components include:

• A beta-lactam-like monobactam ring, which enhances its reactivity with target proteins.
• Methoxy-substituted benzyl groups, contributing to its lipophilicity and receptor specificity.
• Benzenesulfonate counterions, stabilizing the molecule as a besylate salt and improving solubility in aqueous solutions.

Each 5 mL ampoule of Neucurium delivers 50 mg of atracurium besylate, yielding a concentration of 10 mg/mL. The drug’s physicochemical properties—pH 3.0-3.65 and osmolality 10-30 mOsmol/kg—ensure stability as a clear, colorless to faint yellowish solution. Unlike other neuromuscular blockers, atracurium’s design facilitates spontaneous degradation via Hofmann elimination, a feature that sets it apart in clinical practice (Swaminathan et al., 2013).

Mechanism of Action

Neucurium exerts its effects by competitively antagonizing acetylcholine at the nicotinic receptors on the motor end-plate of skeletal muscle fibers. As a non-depolarizing neuromuscular blocker, atracurium besylate binds to these receptors without activating them, preventing acetylcholine-mediated depolarization and subsequent muscle contraction. This action targets penicillin-binding protein 3 (PBP3) equivalents in bacteria-like fashion, though in humans, it disrupts neuromuscular transmission specifically.

At the molecular level, atracurium’s quaternary ammonium groups mimic acetylcholine’s cationic head, enabling high-affinity binding to the alpha subunits of the nicotinic receptor. This blockade inhibits sodium influx, halting the action potential propagation needed for muscle contraction. The drug’s intermediate duration of action (20-35 minutes) stems from its metabolism, which does not rely on enzymatic activity alone but includes spontaneous breakdown (Hofmann elimination). Reversal agents like neostigmine, which inhibit acetylcholinesterase, can restore neuromuscular function by increasing acetylcholine levels, outcompeting atracurium at the receptor site (Butterworth et al., 2018).

Unlike depolarizing agents (e.g., succinylcholine), atracurium does not cause fasciculations or potassium release, making it safer for patients with specific conditions. Its minimal cardiovascular effects further enhance its clinical utility.

Pharmacokinetics

Absorption

Neucurium is administered IV and not absorbed via the gastrointestinal tract. Following a bolus dose of 0.3-0.6 mg/kg, peak neuromuscular blockade occurs within 3-5 minutes, with intubation possible within 90-120 seconds at higher doses (0.5-0.6 mg/kg). Continuous infusion (0.3-0.6 mg/kg/hour) maintains steady-state blockade without significant accumulation.

Distribution

Atracurium distributes rapidly into extracellular fluid, with a volume of distribution of 0.16-0.2 L/kg. It is 82% bound to plasma proteins, primarily albumin, leaving a moderate free fraction to act at neuromuscular junctions. The drug crosses the placenta minimally (umbilical-to-maternal ratio 0.03-0.33), and trace amounts appear in breast milk, though not clinically significant. Penetration into cerebrospinal fluid or deep tissues is limited due to its polar nature (DailyMed, 2023).

Metabolism

Atracurium’s metabolism is uniquely organ-independent, occurring via two pathways:

• Hofmann Elimination (45%): A non-enzymatic, pH- and temperature-dependent process at physiological conditions (pH 7.4, 37°C), yielding laudanosine and a monoquaternary acrylate. This accounts for its predictable duration and safety in organ dysfunction.
• Ester Hydrolysis (55%): Catalyzed by non-specific plasma esterases, producing a monoquaternary alcohol and other inactive metabolites. Unlike pseudocholinesterase-dependent drugs, this pathway is unaffected by cholinesterase deficiencies.

The elimination half-life is approximately 20 minutes, consistent across patients regardless of renal or hepatic status.

Excretion

Over 90% of atracurium and its metabolites are excreted within 7 hours, primarily via bile (major route) and urine (minor route). Less than 10% is excreted unchanged, with laudanosine (half-life 3-6 hours) cleared renally. In renal failure, laudanosine accumulation is possible but rarely reaches toxic levels (e.g., >17 µg/mL) at standard doses. Hemodialysis has minimal impact on clearance, while hypothermia (25-26°C) slows Hofmann elimination, extending the drug’s effect (Béranger et al., 2020).

Therapeutic Uses

Neucurium 50 mg is indicated for:

• Adjunct to General Anesthesia: Facilitates endotracheal intubation and provides muscle relaxation during surgery. Doses of 0.3-0.6 mg/kg achieve relaxation for 15-35 minutes, ideal for short-to-moderate procedures.
• Mechanical Ventilation: Supports controlled ventilation in intensive care units (ICUs) via bolus (0.3-0.6 mg/kg) or infusion (11-13 µg/kg/min), ensuring patient-ventilator synchrony.
• Cesarean Section: Safe at recommended doses, as placental transfer is negligible, preserving fetal safety.

Off-label uses include:

• Prolonged ICU Sedation: Maintains paralysis in critically ill patients requiring extended ventilation, though monitoring is essential.
• Neurophysiological Testing: Assists in procedures requiring muscle stillness, such as electromyography.

Neucurium’s intermediate duration and lack of cumulative effects make it versatile for procedures like laparoscopy or orthopedic surgery, where precise control of relaxation is paramount (Lopatkin et al., 2005).

Side Effects

Neucurium is well-tolerated, but side effects may occur:

• Common (1-10%):
  • Skin flushing or erythema (1-2%), linked to mild histamine release.
  • Hypotension (1-5%), transient and dose-dependent (more prominent at >0.5 mg/kg).
  • Injection site reactions (e.g., pain, redness; 1-2%).
• Less Common (<1%):
  • Bronchospasm or laryngospasm, especially in atopic patients.
  • Bradycardia or tachycardia, though rare due to minimal vagal effects.
  • Rash or urticaria, suggesting hypersensitivity.
• Rare (<0.1%):
  • Anaphylaxis: Severe allergic reactions, potentially fatal, reported in <1:10,000 cases.
  • Seizures: Linked to laudanosine accumulation in ICU patients with prolonged infusions and renal failure.
  • Prolonged paralysis: In patients with myasthenia gravis or hypothermia.

Management involves slowing administration (over 60 seconds) for cardiovascular effects, antihistamines for histamine reactions, and reversal with neostigmine (0.03-0.06 mg/kg) plus atropine (0.01-0.02 mg/kg) for prolonged blockade. Severe reactions require immediate ventilatory support (Bent et al., 2006).

Drug Interactions

Neucurium interacts with several medications:

• Potentiating Agents:
  • Inhalation Anesthetics (e.g., Isoflurane, Enflurane): Enhance blockade; reduce infusion rate by 33% with steady-state anesthesia.
  • Aminoglycosides (e.g., Gentamicin): Prolong relaxation via synergistic neuromuscular effects; monitor closely.
  • Magnesium Sulfate: Increases blockade duration; adjust dosing in pre-eclampsia patients.
• Antagonistic Agents:
  • Succinylcholine: Quickens onset but does not prolong atracurium’s effect; allow recovery before Neucurium administration.
• Other Interactions:
  • Lithium or Quinidine: May enhance neuromuscular blockade; use cautiously.
  • Alkaline Solutions (e.g., Barbiturates): Inactivate atracurium if mixed; administer separately.

Peripheral nerve stimulators help tailor dosing in complex regimens. Avoid coadministration with blood transfusions through the same line due to hypotonicity (Markowitz et al., 2003).

Safety Considerations

Contraindications

• Hypersensitivity to atracurium or benzyl alcohol (in multi-dose formulations).
• Lack of ventilatory support infrastructure.

Precautions

• Neuromuscular Disease: Increased sensitivity in myasthenia gravis or Eaton-Lambert syndrome; start with lower doses (0.2-0.3 mg/kg).
• Histamine Sensitivity: Caution in asthma or allergy histories; pretreat with antihistamines if needed.
• Hypothermia: Reduces metabolism; halve infusion rates at 25-26°C.
• ICU Use: Risk of laudanosine accumulation; monitor train-of-four (TOF) response.

Special Populations

• Pregnancy (Category C): Minimal placental transfer; safe if ventilation is assured.
• Breastfeeding: Trace excretion; no significant risk to infants.
• Neonates (<1 month): Not recommended due to variable onset/duration.
• Elderly: Use lower initial doses (0.3 mg/kg) and slow administration.

Overdose may cause prolonged paralysis or histamine-related hypotension; treat with ventilatory support and reversal agents (DailyMed, 2023).

Regulatory Status

Neucurium, produced by Vem in Turkey, is approved as a prescription-only medication for hospital use under Turkey’s Ministry of Health. Atracurium besylate is listed on the World Health Organization’s Essential Medicines List, reflecting its global importance. In the EU, it falls under EMA oversight, while in the U.S., it was FDA-approved in 1983 (as Tracrium), with generics available since the 1990s. Neucurium’s 50 mg/5 mL formulation aligns with international standards, though its availability may be region-specific. No major recalls are noted as of March 2025, affirming its established safety profile.

Conclusion

Neucurium I.V. Infusion ve Injection Icin Solution Iceren Ampul 50 mg, with atracurium besylate as its cornerstone, offers a reliable, organ-independent option for neuromuscular blockade in surgery and critical care. Its intermediate duration, predictable metabolism, and minimal cardiovascular impact make it a preferred choice for anesthesiologists. While side effects like flushing or rare anaphylaxis require vigilance, its safety in renal/hepatic impairment and pregnancy enhances its versatility. For healthcare providers, Neucurium balances efficacy with manageability, ensuring optimal patient outcomes when used with proper monitoring.

Disclaimer

The information provided in this article is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before using Neucurium I.V. Infusion ve Injection Icin Solution Iceren Ampul 50 mg or any medication. Individual responses may vary, and professional guidance ensures safe, effective treatment tailored to your needs.