Atracurium Besylate (atracurium besylate)

Dosage of atracurium besylate is expressed in terms of the salt. The dosage must be carefully adjusted according to individual requirements and response. The use of a peripheral nerve stimulator is recommended to accurately monitor the degree of muscle relaxation, determine the need for additional doses, determine the adequacy of spontaneous recovery or antagonism, and minimize the complications of overdosage if additional doses are administered.

Atracurium besylate is administered IV. The initial intubating dose is administered by rapid IV injection; maintenance doses may be administered by intermittent IV injection or by continuous IV infusion. Atracurium should not be administered by IM injection.

Commercially available atracurium besylate injection should be refrigerated at 2-8degreesC and protected from light; do not freeze. Once removed from refrigeration, the injection should be used within 14 days, even if the product is returned to the refrigerator.

For continuous IV infusion, atracurium besylate injection should be diluted to the desired concentration (usually 0.2 or 0.5 mg/mL) in 5% dextrose, 5% dextrose and 0.9% sodium chloride, or 0.9% sodium chloride injection. Infusion solutions may be stored under refrigeration or at room temperature, and should be used within 24 hours following dilution. Atracurium besylate should not be diluted in Lactated ringer's. Accurate dosing of continuous infusions is best achieved using a precision infusion device.

Atracurium should not be mixed in the same syringe nor administered simultaneously through the same needle as an alkaline solution (e.g., barbiturate solution).

Atracurium besylate injection and diluted solutions of the drug should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Neuromuscular Blocking Agents/General Anesthetics (INHL)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: General anesthetics enhance the pharmacologic effects of nondepolarizing muscle relaxants.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects of the nondepolarizing muscle relaxant including respiratory depression, bradycardia, hypotension, flushing, or muscle weakness.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: It may be necessary to decrease the dose of the nondepolarizing muscle relaxant. Monitor neuromuscular function and adjust the dose of the nondepolarizing muscle relaxant accordingly.

DISCUSSION: Concomitant administration of general anesthetics and nondepolarizing muscle relaxants has been shown to produce synergistic neuromuscular blocking effects of nondepolarizing muscle relaxants.

Neuromuscular Blocking Agents/Misc Antibiotics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Aminoglycosides, bacitracin, clindamycin, lincomycin, and polymyxins may enhance the pharmacologic effects of neuromuscular blocking agents.

CLINICAL EFFECTS: May see an increase in the pharmacologic effects of neuromuscular blocking agents, including prolonged respiratory depression and apnea.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly.

DISCUSSION: Concomitant administration of aminoglycosides, bacitracin, clindamycin, lincomycin, and polymixins with neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and fatal apnea. The interaction usually occurs when the antibiotic is given prior to or concurrently with the neuromuscular blocking drug, but it may also occur when given after administration. Any antibiotic dosage or route of administration may produce respiratory depression.

Neuromuscular Blocking Agents/Quinine Derivatives

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Synergistic or additive pharmacologic activity.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concurrent administration of neuromuscular blocking agents and quinine derivatives during the first several hours of postoperative period. If administered, respiratory support may be needed. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Administration of quinidine during the immediate postoperative period has been associated with respiratory paralysis and apnea.

Neuromuscular Blocking Agents/Verapamil

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Unknown.

CLINICAL EFFECTS: The neuromuscular blocking effect of nondepolarizing muscle relaxants may be extended, producing profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid administration of nondepolarizing neuromuscular blocking agents to patients receiving verapamil. When both drugs must be given, carefully monitor respiratory function to avoid prolonged neuromuscular blockade. If needed, blockade may be reversed by giving edrophonium. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Patients receiving verapamil have experienced prolonged skeletal muscle paralysis after administration of usual therapeutic doses of a nondepolarizing neuromuscular blocking agent. While muscle paralysis was unresponsive to treatment with neostigmine, reversal of blockade has been achieved by administration of edrophonium.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Anesthesia Agents/Glp-1 Receptor Agonists

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: GLP-1 receptor agonists can cause delayed gastric emptying.(1,2)

CLINICAL EFFECTS: Gastric contents may remain in the stomach after preoperative fasting, which could increase the risk of regurgitation and aspiration.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The American Society of Anesthesiologists (ASA) recommends the following for patients receiving elective procedures: - For patients on daily dosing, consider holding GLP-1 agonists on the day of the procedure. For patients on weekly dosing, consider holding GLP-1 agonists a week prior to the procedure. - Consult an endocrinologist for patients taking GLP-1 agonists for diabetes management if the GLP-1 agonist is held longer than the dosing schedule to avoid hyperglycemia. - For patients requiring urgent or emergent procedures, proceed and treat the patient as 'full stomach.'(3)

DISCUSSION: In one case report, a 31-year-old patient taking semaglutide followed preoperative fasting guidelines but food residue was discovered upon endoscopy, leading to cancellation of the surgical procedure.(4) In a case report, a semaglutide-treated patient experienced regurgitation upon induction of general anesthesia despite a 20 hour preoperative fasting period. The patient received semaglutide two days before the scheduled procedure.(5) A case report of a 42-year-old patient after fasting for 18 hours showed substantial gastric content upon endoscopy. The patient experienced intraoperative pulmonary aspiration of gastric contents which were suctioned from the trachea and bronchi using bronchoscopy.(6)

Neuromuscular Blocking Agents/Lincosamides

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Lincosamides appear to augment the neuromuscular blocking effects of nondepolarizing muscle relaxants.

CLINICAL EFFECTS: The effects of nondepolarizing neuromuscular relaxants may be prolonged leading to profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor respiratory function of the patient and provide the necessary support. In patients who have received nondepolarizing muscle relaxants, avoid use of lincosamides in the recovery room. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Lincomycin has been reported to augment the neuromuscular blocking effect of pancuronium in seven anesthetized patients. The effect was readily antagonized by neostigmine administration. In a case report, clindamycin produced prolonged neuromuscular blockade in a patient who had received pancuronium. Neostigmine was ineffective in antagonizing the blockade.

Neuromuscular Blocking Agents/Polypeptide Antibiotics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Synergistic pharmacologic activity. Polymyxin B affects neuromuscular transmission by blocking acetylcholine receptors. Its action is thus post-synaptic and the neuromuscular block has no antagonists. Polymyxin B causes neostigmine resistance to d-tubocurarine blockade and calcium resistance to the blockade evoked by aminoglycoside antibiotics (1,2,3,4). A pre-synaptic mechanism may also be involved with decreased release of acetylcholine.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Concomitant administration of polypeptide antibiotics and neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and apnea. This interaction has been documented with colistimethate, polymyxin B, bacitracin, and vancomycin.

Neuromuscular Blocking Agents/Trimethaphan

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Additive pharmacologic effects.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Available data indicate that the neuromuscular blocking effects of tubocurarine and trimethaphan may be additive.

Nondepolarizing Muscle Relaxants/Magnesium Salts, Injectable

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Magnesium may reduce postjunctional membrane neuromuscular blocking action of nondepolarizing muscle relaxants. Parenterally administered magnesium may potentiate the effects of the nondepolarizing muscle relaxants.

CLINICAL EFFECTS: Increased neuromuscular blockade with profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor respiratory function when parenteral magnesium and nondepolarizing muscle relaxants are administered concurrently. Adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: The effects of nondepolarizing muscle relaxants have been reported to be increased in laboratory animals and in humans by concomitant administration of magnesium sulfate. Respiratory depression has been reported.

Nondepolarizing Muscle Relaxants/Piperacillin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Piperacillin may prolong the neuromuscular blockade of the nondepolarizing muscle relaxants.(1,2)

CLINICAL EFFECTS: Concurrent use of nondepolarizing muscle relaxants and piperacillin may result in prolonged neuromuscular blockade including profound sedation, respiratory depression, coma, and/or death.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be monitored for increased or unexpected prolongation of neuromuscular blockade when using piperacillin with nondepolarizing muscle relaxants. Assure monitoring protocols are in place for patients receiving neuromuscular blocking agents. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Concurrent use of nondepolarizing muscle relaxants and piperacillin may result in increased or prolonged neuromuscular blockage.(1,2) If these agents are used together, patients should be monitored closely for increased neuromuscular blockage.

Select Neuromuscular Blocking Agents/Hydantoins

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: It has been suggested that phenytoin increases end-plate anticholinesterase activity, resulting in higher acetylcholine concentration at the neuromuscular junction.(1)

CLINICAL EFFECTS: A higher plasma concentration of the neuromuscular blocking agent was required to effect a given level of neuromuscular blockade in patients receiving phenytoin.(2,3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving hydantoin anticonvulsants should be monitored for a decreased response to the neuromuscular blocking agent. The dose of the neuromuscular blocking agent may need to be increased and/or given more frequently.(9)

DISCUSSION: In a study, patients receiving phenytoin were administered metocurine, attained 83% of maximum neuromuscular blockade compared with 98% in the control group.(1) In another study, patients maintained on phenytoin for more than one week had a significantly higher pancuronium requirement than those patients not receiving phenytoin.(1) In two separate case reports, patients maintained on phenytoin demonstrated a resistance to pancuronium and a decreased duration of neuromuscular blockade.(3,4) In a study, patients maintained on phenytoin and receiving vecuronium had a significantly shorter total duration and effect of neuromuscular blockade compared to those patients not receiving phenytoin.(5) In contrast, neither the effect nor duration of atracurium's neuromuscular blockade was affected by phenytoin.(5) Two in vitro studies showed that the neuromuscular blockade of curare and tubocurarine was potentiated by the use of phenytoin.(6,7) Ten children received a bolus dose of vecuronium 0.15mg/Kg while on phenytoin and showed a significantly increased clearance of vecuronium compared to the control group, 15.1 and 9.0 ml/Kg/min, respectively.(8) In a case report, a 58 year-old male previously stabilized on phenytoin (400 mg daily) was given an injection of vecuronium (8 mg) to induce muscle blockade during bowel surgery. While monitoring the effectiveness of vecuronium only 75% twitch height blockade was noted after seven minutes. The medication, due to its short duration and impaired effectiveness, had to be given more frequently throughout the surgery in order to maintain adequate muscle block.(9) A separate case report records a decreased response to pancuronium in a 15 year-old male, previously stabilized on phenytoin (350 mg daily), while undergoing surgery to remove a parietal tumor. Pancuronium (0.7 mg/kg) was given as a relaxant during the surgery and monitored using the train-of-four method. Intermittent doses of pancuronium (0.17 mg/kg) were given for the first hour of surgery without successful blockade apparent by the return of all four twitches within ten minutes of each dose. A second attempt at muscular blockade was made with continuous infusion atracurium (0.26-0.55 mg/kg/hour) for the duration of the surgery. Only 16 minutes after stopping the infusion, all four twitches were visible.(10)

*Known hypersensitivity to atracurium or any component of the formulation (e.g., benzyl alcohol in multiple dose vials).

There are no contraindication contraindications for this drug.

• Eaton-lambert syndrome
• Hypermagnesemia
• Hypocalcemia
• Hypokalemia
• Myasthenia gravis
• Systemic mastocytosis

• Hypotension
• Hypothermia

Adverse effects of atracurium observed in 5% or more of patients in clinical studies included skin flush.

Less Frequent

• Bradycardia
• Hypertension
• Hypotension
• Tachycardia

Rare or Very Rare

• Allergic dermatitis
• Anaphylaxis
• Bronchospastic pulmonary disease
• Cardiogenic shock
• Dyspnea
• Edema
• Laryngismus
• Seizure disorder

More Frequent

• Flushing

Rare or Very Rare

• Erythema
• Injection site sequelae
• Pruritus of skin
• Skin rash
• Urticaria
• Wheezing

No enhanced messaging available.

The safety and effectiveness of atracurium in pediatric patients <1 month of age have not been established.

Multiple dose vials of atracurium besylate contain benzyl alcohol, which has been associated with an increased incidence of neurological and other complications in neonates. In some cases, these complications may be fatal.

There are no adequate and well-controlled studies of atracurium in pregnant women. In animal studies, atracurium has been shown to be potentially teratogenic. When atracurium besylate was administered subcutaneously to nonventilated rabbits on days 6-18 of gestation, an increased incidence of spontaneously-occurring visceral and skeletal abnormalities was observed. Use atracurium during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Atracurium has been used in a limited number of pregnant women undergoing cesarean section. No harmful effects were attributed to atracurium in any of the neonates, although small amounts of atracurium were shown to cross the placental barrier. The potential for respiratory depression in the neonate should always be considered. In patients receiving magnesium sulfate, neuromuscular blocker reversal may be unsatisfactory and the dose of atracurium should be lowered as indicated.

It is not known whether neuromuscular blockers administered during vaginal delivery have immediate or delayed effects on the fetus or increase the likelihood that resuscitation of the newborn will be necessary. The possibility that forceps delivery will be required may increase.

It is not known whether atracurium is excreted in human milk. Use caution when administering atracurium to a breast-feeding woman.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Uncontrolled clinical experience and limited data from controlled trials have not identified differences in effectiveness, safety, or dosage requirements between healthy elderly and younger patients. As with other neuromuscular blocking agents, the use of a peripheral nerve stimulator to monitor neuromuscular function is suggested.

Elderly patients may have slightly altered pharmacokinetic parameters compared to younger patients, with a slightly decreased total plasma clearance; however, this is offset by a corresponding increase in volume of distribution. The net effect of these pharmacokinetic changes is no significant difference in clinical duration and recovery from neuromuscular blockade between elderly and younger patients.