Atracurium
JFDA label: Tracrium Inj.
Mechanism of Action
Blocks neural transmission at the myoneural junction by binding with cholinergic receptor sites
Indications
Approved
- Adjunct to surgical anesthesia (neuromuscular blockade)
Contraindications
Source: Lexicomp
- Hypersensitivity to atracurium besylate or any component of the formulation. Multiple-dose vials contain benzyl alcohol as a preservative Absolute
- use is contraindicated in patients with a known hypersensitivity to benzyl alcohol. Documentation of allergenic cross-reactivity for neuromuscular blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute
Adverse Reactions
Other (1)
Common Cardiovascular: Flushing
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Anaphylaxis
Severe anaphylactic reactions have been reported with atracurium use; some life-threatening and fatal. Appropriate emergency treatment (including epinephrine 1 mg/mL) should be immediately available during use.
Bradycardia
May be more common with atracurium than with other neuromuscular-blocking agents since it has no clinically-significant effects on heart rate to counteract the bradycardia produced by anesthetics.
Neuromuscular cross-sensitivity
Cross-sensitivity with other neuromuscular-blocking agents may occur; use extreme caution in patients with previous anaphylactic reactions. Disease-related concerns:
Burn injury
Resistance may occur in burn patients (≥20% of total body surface area), usually several days after the injury, and may persist for several months after wound healing (Han 2009).
Conditions which may antagonize neuromuscular blockade
Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (ACCM/SCCM/ASHP [Murray 2002]; Greenberg 2013; Miller 2010; Naguib 2002).
Conditions which may potentiate neuromuscular blockade
Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, metabolic alkalosis, respiratory acidosis, Eaton-Lambert syndrome and myasthenia gravis may result in potentiation of neuromuscular blockade (Greenberg 2013; Miller 2010; Naguib 2002). Concurrent drug therapy issues:
Drug-drug interactions
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:
Elderly
Use with caution in the elderly, effects and duration are more variable.
Immobilized patients
Resistance may occur in patients who are immobilized. Dosage form specific issues:
Benzyl alcohol and derivatives
Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling. Other warnings/precautions:
Appropriate use
Maintenance of an adequate airway and respiratory support is critical. Resistance may develop with chronic treatment.
Experienced personnel
Should be administered by adequately trained individuals familiar with its use.
Histamine release
Reduce initial dosage and inject slowly (over 1 to 2 minutes) in patients in whom substantial histamine release would be potentially hazardous (eg, patients with clinically-important cardiovascular disease).
Pregnancy & Lactation
Pregnancy
Adverse events were observed in animal reproduction studies. Small amounts of atracurium have been shown to cross the placenta when given to women during cesarean section.
Lactation
It is not known if atracurium is excreted in breast milk. The manufacturer recommends that caution be exercised when administering atracurium to nursing women.
Monitoring
| Clinical pearl | Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle relaxation (via peripheral nerve stimulator and presence of spontaneous movement) In the ICU setting, prolonged paralysis and generalized myopathy, following discontinuation of agent, may be minimized by appropriately monitoring degree of blockade. |
|---|
Chemistry & Properties
| Formula | C53H72N2O12+2 |
|---|---|
| Molecular weight | 929.16 g/mol |
| IUPAC name | 5-[3-[1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-2-ium-2-yl]propanoyloxy]pentyl 3-[1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-2-ium-2-yl]propanoate |
| CAS | 64228-79-1 |
| PubChem CID | 47319 |
| InChIKey | YXSLJKQTIDHPOT-UHFFFAOYSA-N |
| logP | 8.07 (XLogP 7.9) |
| Polar surface area | 126.44 Ų |
| H-bond acceptors / donors | 12 / 0 |
| Drug-likeness (QED) | 0.04 |
| Lipinski violations | 3 |
SMILES
COc1ccc(CC2c3cc(OC)c(OC)cc3CC[N+]2(C)CCC(=O)OCCCCCOC(=O)CC[N+]2(C)CCc3cc(OC)c(OC)cc3C2Cc2ccc(OC)c(OC)c2)cc1OCBiology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 70.0% |
|---|---|
| Half-life | 1.606 h |
| Volume of distribution | 1.124 L/kg |
| Protein binding | 89.9% |
| BBB penetrant | No |
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Substrate | — |
| CYP2C19 | Inhibitor | — |
| CYP2C19 | Substrate | — |
| CYP2C8 | Inhibitor | — |
| CYP2D6 | Substrate | — |
| CYP3A4 | Inhibitor | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 1)
| Target | Action | Affinity |
|---|---|---|
| nicotinic acetylcholine receptor α1 subunit (CHRNA1) | Antagonist | pIC50 7.0 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Drug–drug interactions (43, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Amikacin | major | |
| Amikacin (liposome) | major | |
| Gentamicin | major | |
| Kanamycin | major | |
| Neomycin | major | |
| Paromomycin | major | |
| Polymyxin B | major | |
| Streptomycin | major | |
| Aminophylline | moderate | |
| Amphotericin B | moderate | |
| Amphotericin B (cholesteryl sulfate) | moderate | |
| Amphotericin B (lipid complex) | moderate | |
| Amphotericin B (liposomal) | moderate | |
| Bacitracin | moderate | |
| Chloroquine | moderate | |
| Clindamycin | moderate | |
| Clindamycin (topical) | moderate | |
| Cyclophosphamide | moderate | |
| Cyclosporine | moderate | |
| Demeclocycline | moderate | |
| Doxycycline | moderate | |
| Dyphylline | moderate | |
| Gentamicin (topical) | moderate | |
| Lidocaine | moderate | |
| Magnesium chloride | moderate | |
| Magnesium sulfate | moderate | |
| Mannitol | moderate | |
| Metoclopramide | moderate | |
| Minocycline | moderate | |
| Neomycin (topical) | moderate | |
| Oxtriphylline | moderate | |
| Oxytetracycline | moderate | |
| Oxytocin | moderate | |
| Quinine | moderate | |
| Terbutaline | moderate | |
| Tetracycline | moderate | |
| Theophylline | moderate | |
| Vancomycin | moderate | |
| Azathioprine | minor | |
| Irinotecan | minor |
Showing 40 of 43.
Registered Products (12)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Acurmil Amp. | Ampoule 50 mg/5 ml | 5 amp | AL Rahma Drug Store | — |
| Atacure Injection (2.5 mL) | Injection 25 mg/2.5 ml | 5 amp | Hikma Pharmaceuticals Co.Ltd/Jordan | — |
| Atacure Injection (5 mL) | Injection 50 mg/5 ml | 5 amp | Hikma Pharmaceuticals Co.Ltd/Jordan | — |
| Atracurium Labatec 25mg/2.5 ml Sol For Inj | Powder for Injection 25 mg/2.5 ml | 5 amp | ORIENT DRUG STORE CO | — |
| Atracurium Labatec 50mg/5ml Sol For Inj | Injection 50 mg/5 ml | 5 amp | ORIENT DRUG STORE CO | — |
| Atracurium-Hameln | Injection 10 mg/ml | 5 amp | Abu Sharef Medical Stores | — |
| Retalex 25mg/2.5ml Solution For Inj | Powder for Injection 10 mg | 1 vial pack varies | MS PHARMA/JORDAN | — |
| Retalex 25mg/2.5ml Solution For Inj | Powder for Injection 10 mg | 5 vial pack varies | MS PHARMA/JORDAN | — |
| Retalex 50mg/5ml Solution for inj | Injection 10 mg/1 ml | 1 vial pack varies | MS PHARMA/JORDAN | — |
| Retalex 50mg/5ml Solution for inj | Injection 10 mg/1 ml | 5 vial pack varies | MS PHARMA/JORDAN | — |
| Tracrium 10mg/ml Solution for injection | Injection 10 mg/ml | 5 amp pack varies | Suleiman Tannous & Sons Co. Ltd | — |
| Tracrium Inj. | Injection 10 mg/ml | 5 amp pack varies | Suleiman Tannous & Sons Co. Ltd | — |