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    Muscle Relaxants, Peripherally Acting

    BOXED WARNING

    Requires an experienced clinician, respiratory insufficiency

    Neuromuscular blocking agents cause respiratory insufficiency by paralyzing respiratory muscles. Administration requires an experienced clinician who is adequately trained and familiar with the actions, characteristics, and hazards of pancuronium. These personnel should be skilled in airway management and respiratory support. Equipment and personnel must be immediately available for intubation and support of ventilation, including administration of oxygen therapy. Adequacy of respiration must be assured through assisted or controlled ventilation. Reversal agents must be immediately available.

    DEA CLASS

    Rx

    DESCRIPTION

    Long-acting, nondepolarizing neuromuscular blocker; used as an adjunct to general anesthesia, to facilitate endotracheal intubation, or to facilitate pulmonary compliance during mechanical ventilation; associated with minimal histamine release; vagolytic properties may result in tachycardia.

    HOW SUPPLIED

    Pancuronium Bromide Intravenous Inj Sol: 1mg, 1mL, 2mg

    DOSAGE & INDICATIONS

    For neuromuscular blockade or endotracheal intubation.
    For the treatment of refractory agitation† in the intensive care unit patient.
    Intravenous dosage
    Adults

    Initial doses of 40—100 mcg/kg IV have been recommended in patients with agitation not controlled with large doses of neuroleptics, benzodiazepines, or morphine. Repeat doses should be based on clinical goals and patient response (e.g., peripheral nerve stimulation monitoring). NOTE: Nondepolarizing muscle relaxants cause paralysis without altering consciousness; liberal doses of morphine or midazolam should be used to ensure tranquility.

    For the induction of neuromuscular blockade as an adjunct to general anesthesia induction.
    Intravenous dosage
    Adults, Children, and Infants > 1 month of age

    40—100 mcg/kg IV initially followed by incremental doses of 10 mcg/kg at 25—60 minute intervals as needed to maintain muscle relaxation during prolonged surgery.

    Neonates up to 1 month

    As neonates are very sensitive to nondepolarizing neuromuscular blocking agents, give a test dose of 20 mcg/kg IV to determine response.

    As an adjunct to steady-state anesthesia with enflurane or isoflurane and/or following succinylcholine-assisted endotracheal intubation.
    Intravenous dosage
    Adults, Children, and Infants > 1 month of age

    40 mcg/kg IV initially followed by doses adjusted to patient response.

    For the facilitation of endotracheal intubation.
    Intravenous dosage
    Adults, Children, and Infants > 1 month of age

    60—100 mcg/kg IV. A satisfactory response usually occurs within 2—3 minutes.

    MAXIMUM DOSAGE

    Adults

    Specific maximum dosage information is not available.

    Elderly

    Specific maximum dosage information is not available.

    Adolescents

    Specific maximum dosage information is not available.

    Children

    Specific maximum dosage information is not available.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage should be modified depending on clinical response and degree of hepatic impairment, but no quantitative recommendations are available. Lower doses or less frequent dosing intervals may be needed.

    Renal Impairment

    Initial dosage should be modified based on clinical goals and the degree of renal impairment. Individualize further dosage based on patient response (e.g., peripheral nerve stimulation monitoring).

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Only experienced clinicians, familiar with the use of neuromuscular blocking drugs, should administer or supervise the use of pancuronium.
    To avoid distress to the patient, pancuronium should be administered only after unconsciousness has been induced.
    No dilution necessary.
    Administer by rapid IV injection. A peripheral nerve stimulator is recommended to monitor pancuronium's effects. Monitor heart rate, blood pressure, and mechanical ventilator status during administration.

    STORAGE

    Generic:
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    NOTE: Pancuronium does not cause sedation or analgesia and should be administered only after unconsciousness has been induced. Doses of pancuronium should be individualized. Use of a peripheral nerve stimulator will permit the most advantageous use of pancuronium, minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery.
     
    Long-term therapy with pancuronium should be undertaken with caution. Patients receiving long-term therapy with pancuronium may experience prolonged paralysis or skeletal muscle weakness that may not be noticed until attempts are made to wean them from the ventilator. These patients may also have contributing factors such as other drugs, electrolyte imbalance, or extreme debilitation. In addition, patients immobilized for extended periods frequently develop symptoms consistent with disuse muscle atrophy.

    Requires an experienced clinician, respiratory insufficiency

    Neuromuscular blocking agents cause respiratory insufficiency by paralyzing respiratory muscles. Administration requires an experienced clinician who is adequately trained and familiar with the actions, characteristics, and hazards of pancuronium. These personnel should be skilled in airway management and respiratory support. Equipment and personnel must be immediately available for intubation and support of ventilation, including administration of oxygen therapy. Adequacy of respiration must be assured through assisted or controlled ventilation. Reversal agents must be immediately available.

    Labor, obstetric delivery, pregnancy

    Pancuronium is classified as FDA pregnancy risk category C. It is not known if pancuronium can cause fetal harm and should only be administered to a pregnant woman if the benefit outweighs any risk to the fetus. Pancuronium may be used during labor and obstetric delivery (caesarean section); however, it is recommended that the interval between pancuronium administration and delivery be as short as possible to avoid clinically significant transfer of pancuronium to the placenta. In patients receiving magnesium sulfate, neuromuscular block reversal may be unsatisfactory, and the pancuronium dose should be lowered as indicated. It is not known whether muscle relaxants administered during labor and vaginal delivery have immediate or delayed adverse effects on the baby or increase the likelihood that resuscitation of the newborn will be necessary.

    Breast-feeding

    Information regarding breast-feeding is not available from the manufacturers of pancuronium. The elimination half-life for pancuronium is 1.5—3 hours. It is a bisquaternary ammonium compound and should pass slowly through biological membranes. If trace amounts were excreted into breast milk, quaternary ammonium muscle relaxants are poorly absorbed from the gastrointestinal tract. Based on these data, lactation could be allowed as soon as practically feasible after recovery from a surgical procedure. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Chronic obstructive pulmonary disease (COPD), pulmonary disease, respiratory depression

    Neuromuscular blocking agents can cause respiratory paralysis as a result of respiratory depression and should be used with extreme caution in patients with pulmonary disease such as chronic obstructive pulmonary disease (COPD). In addition, patients with severe obesity may be predisposed to airway or ventilatory problems which require special care before, during, and after treatment with pancuronium.

    Bromide hypersensitivity, neuromuscular blocking agent hypersensitivity

    Pancuronium is contraindicated in patients known to have hypersensitivity to pancuronium or a bromide hypersensitivity. Pancuronium should be used with caution in patients with a neuromuscular blocking agent hypersensitivity, as cross-reactivity has been reported with both depolarizing and non-depolarizing agents in this class.

    Lung cancer, myasthenia gravis, myopathy, neuromuscular disease, obesity

    Patients with conditions that impair neuromuscular function can experience prolonged or exaggerated neuromuscular block with nondepolarizing agents. These conditions include myasthenia gravis, myasthenic syndrome associated with small cell carcinomatosis (Eaton Lambert syndrome; originally associated with lung cancer), myopathy, or any other neuromuscular disease. Additionally, patients with weak muscle tone and those who suffer from severe obesity are at an increased risk for airway and ventilation complications. Use vecuronium with caution in patients with these conditions, and continue to monitor patients carefully until recovery is fully complete.

    Asthma, cardiac disease, edema

    Neuromuscular blocking agents stimulate histamine release. Compared with other neuromuscular blockers, pancuronium produces minimal stimulation, but it should be used with caution in any condition in which a significant release of histamine may be contraindicated, such as cardiac disease or asthma. In addition, use pancuronium with caution in patients with cardiac disease or other conditions that may be associated with a slower circulation time. Changes in the volume of distribution related to poor circulation or edema can delay the onset of neuromuscular blockade. Particular care is required when administering subsequent doses when it is uncertain whether maximum effect has been attained.

    Acid/base imbalance, adrenal insufficiency, dehydration, electrolyte imbalance, hypercalcemia, hypermagnesemia, hypocalcemia, hypokalemia, hypothermia, metabolic alkalosis, respiratory acidosis

    Various physiologic states can alter the expected effects of pancuronium; carefully consider each patient's clinical condition when dosing pancuronium and monitoring the patient. Electrolyte imbalance can alter a patient's sensitivity to neuromuscular blocking agents (NMBAs). Hypercalcemia can decrease sensitivity to NMBAs, while most other electrolyte disturbances increase sensitivity (e.g., hypokalemia, hypocalcemia, hypermagnesemia). Use vecuronium cautiously in patients with conditions that may lead to electrolyte imbalances, such as adrenal insufficiency. Severe acid/base imbalance may alter a patient's sensitivity to NMBAs: respiratory acidosis may enhance neuromuscular blockade and metabolic alkalosis may counteract it. Dehydration and hypothermia can also increase a patient's sensitivity to NMBAs.

    Malignant hyperthermia

    Patients with a familial history of malignant hyperthermia should be treated with extreme caution. The condition can be precipitated by the use of halogenated anesthetics because this reaction has been attributed to their use, but neuromuscular blocking agents (such as pancuronium) also may be a contributory factor.

    Tachycardia

    Pancuronium increases the heart rate, probably by a direct action on the acetylcholine receptors in the heart. Patients with tachycardia should be treated with caution, although the effect appears to be dose-related and minimal in the usual dosage range.

    Renal failure, renal impairment

    Pancuronium should be used with caution in patients with renal impairment. The elimination half-life is doubled and plasma clearance is decreased by about 60% in patients with renal failure. Neuromuscular blockade can be prolonged.

    Biliary obstruction, hepatic disease

    Pancuronium should be used with caution in patients with hepatic disease. The elimination half-life is doubled in patients with biliary obstruction or cirrhosis and plasma clearance is decreased by <50% or about 22%, respectively. In addition, patients with hepatic disease may have a 50% increase in the volume of distribution of pancuronium. This usually results in the need for a higher initial dose to achieve adequate muscle relaxation and a prolonged duration of action.

    Burns

    Patients with extensive burns can exhibit a decreased response to the effects of pancuronium. Resistance to neuromuscular blockade peaks after about 2 weeks and gradually declines as the burns heal. Increased doses of pancuronium may be required in these patients.

    Neonates, premature neonates

    Some formulations of pancuronium contain benzyl alcohol as a preservative; these formulations are contraindicated by the manufacturers for use in neonates and premature neonates. Large amounts of benzyl alcohol (> 99 mg/kg/day) have been associated with gasping syndrome in this population.

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / 0-1.0
    apnea / Delayed / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    hypotension / Rapid / 0-1.0
    edema / Delayed / 0-1.0
    erythema / Early / 0-1.0
    wheezing / Rapid / 0-1.0
    dyspnea / Early / Incidence not known
    myopathy / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known

    Mild

    flushing / Rapid / 0-1.0
    weakness / Early / Incidence not known
    hypersalivation / Early / Incidence not known
    rash (unspecified) / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Additive CNS depression may occur if dihydrocodeine is used concomitantly with other CNS depressants, including neuromuscular blockers.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of propoxyphene with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Acetazolamide: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
    Alfentanil: (Moderate) Concomitant use of alfentanil with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Aliskiren; Amlodipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Ambenonium Chloride: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Amide local anesthetics: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Aminoglycosides: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Amlodipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Atorvastatin: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Benazepril: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Olmesartan: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Telmisartan: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Valsartan: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Amphotericin B lipid complex (ABLC): (Moderate) Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Amphotericin B liposomal (LAmB): (Moderate) Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Amphotericin B: (Moderate) Amphoterecin B may cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Additive CNS depression may occur if dihydrocodeine is used concomitantly with other CNS depressants, including neuromuscular blockers.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Diphenoxylate: (Moderate) Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Edrophonium: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Bacitracin: (Moderate) Systemic bacitracin may act synergistcally to increase or prolong skeletal muscle relaxation produced by neuromuscular blocking agents and/or general anesthetics. Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, may have additive nephrotoxic potential.
    Belladonna; Opium: (Moderate) Additive CNS depression may occur if opiate agonists are used concomitantly with other CNS depressants, including neuromuscular blockers.
    Benzodiazepines: (Moderate) Concurrent use of benzodiazepines and other CNS active medications including neuromuscular blockers, can potentiate the CNS effects of either agent. Lower doses of one or both agents may be required. The severity of this interaction may be increased when additional CNS depressants are given.
    Benzonatate: (Moderate) Benzonatate may enhance the neuromuscular blocking action of nondepolarizing agents.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Botulinum Toxins: (Major) The effects of botulinum toxins can be potentiated by neuromuscular blockers, or other drugs that interfere with neuromuscular transmission. Monitor for symptoms of unintended or prolonged neuromuscular blockade, including respiratory rate and muscle movements.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Calcium Carbonate: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Calcium Carbonate; Risedronate: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Calcium Salts: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Calcium: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Calcium; Vitamin D: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Depolarizing neuromuscular blockers and non-depolarizing neuromuscular blockers could potentiate the neuromuscular blocking effect of capreomycin. If these drugs are used in combination, monitor patients for increased adverse effects.
    Carbamazepine: (Moderate) If neuromuscular blockers are administered to patients chronically receiving anticonvulsant agents such as carbamazepine, shorter durations of neuromuscular block may occur and infusion rates may be higher due to the development of resistance to muscle relaxants.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Carbonic anhydrase inhibitors: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
    Cardiac glycosides: (Moderate) Pancuronium increases the risk of developing arrhythmias and should be used with caution in patients receiving cardiac glycosides.
    Chloroquine: (Moderate) Chloroquine may affect presynaptic and postsynaptic myoneural function and potentiate the neuromuscular blocking action of neuromuscular blockers.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Additive CNS depression may occur if dihydrocodeine is used concomitantly with other CNS depressants, including neuromuscular blockers.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Additive CNS depression may occur if dihydrocodeine is used concomitantly with other CNS depressants, including neuromuscular blockers.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Cholinesterase inhibitors: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Chromium: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Cisplatin: (Moderate) Hypokalemia potentiates the neuromuscular blockade from nondepolarizing neuromuscular blockers. Cisplatin is associated with a significant risk of hypokalemia and should be monitored closely when used with neuromuscular blockers.
    Clozapine: (Moderate) Skeletal muscle relaxants should be combined cautiously with clozapine because they could cause additive depressant effects and possible respiratory depression or hypotension.
    Codeine: (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Codeine; Phenylephrine; Promethazine: (Moderate) Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants. (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Codeine; Promethazine: (Moderate) Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants. (Moderate) Concomitant use of codeine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Colistimethate, Colistin, Polymyxin E: (Moderate) Depolarizing neuromuscular blockers and non-depolarizing neuromuscular blockers can potentiate the neuromuscular blocking effect of colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
    Collagenase: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Corticosteroids: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Cyanocobalamin, Vitamin B12: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Cyclophosphamide: (Major) Cyclophosphamide treatment, which causes a marked and persistent inhibition of cholinesterase activity, potentiates the effect of depolarizing neuromuscular blockers, such as succinylcholine, and may cause prolonged apnea. If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, the anesthesiologist should be alerted.
    Cyclosporine: (Moderate) Cyclosporine may potentiate the action of nondepolarizing neuromuscular blockers. Prolonged neuromuscular blockade has been reported in patients receiving cyclosporine who receive neuromuscular blockers as part of surgical anesthesia. Monitor patients for recurrent neuromuscular blockade and respiratory depression; extended ventilatory support may be required.
    Demeclocycline: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Dextromethorphan; Promethazine: (Moderate) Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants.
    Dextromethorphan; Quinidine: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Digitoxin: (Moderate) Pancuronium increases the risk of developing arrhythmias and should be used with caution in patients receiving cardiac glycosides.
    Digoxin: (Moderate) Pancuronium increases the risk of developing arrhythmias and should be used with caution in patients receiving cardiac glycosides.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Additive CNS depression may occur if dihydrocodeine is used concomitantly with other CNS depressants, including neuromuscular blockers.
    Diltiazem: (Moderate) Prolongation of the effects of neuromuscular blockers is possible when they are given in combination with calcium-channel blockers, particularly diltiazem.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Donepezil: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Donepezil; Memantine: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Doxycycline: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Edrophonium: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Enalapril; Felodipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Entecavir: (Moderate) Both entecavir and pancuronium are secreted by active tubular secretion. In theory, coadministration of entecavir with pancuronium may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Ester local anesthetics: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Local anesthetics interfere with the release of acetylcholine and thus, can produce neuromuscular blockade. Potentiation of neuromuscular blockade by a local anesthetic can occur with either depolarizing or nondepolarizing neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Estrogens: (Minor) Estrogens have been associated in rare cases with pseudocholinesterase deficiency. Since non-depolarizing neuromuscular blockers are metabolized by cholinesterase, prolonged neuromuscular blockade may occur in individuals on concurrent therapy with estrogens.
    Felodipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Fentanyl: (Major) Although adequate sedation and analgesia must accompany the use of neuromscular blockers, coadministration of opioids such as fentanyl may enhance neuromuscular blockade and produce an increased degree of respiratory depresssion. Monitor patients for signs of respiratory depression that may be greater than otherwise expected. A dose reduction of one or both drugs may be warranted.
    Fosphenytoin: (Moderate) Chronic antiepileptic drug therapy with phenytoin may antagonize the effects of nondepolarizing neuromuscular blockers. This interaction lengthens the onset and shortens the duration of neuromuscular blockade. The exact mechanism for this interaction is unknown, but could involve neuromuscular and hepatic enzyme induction effects of phenytoin.
    Galantamine: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    General anesthetics: (Major) Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants, such as neuromuscular blockers, can potentiate CNS and respiratory depression. A dose reduction of one or both drugs may be warranted.
    Hydromorphone: (Moderate) Concomitant use of hydromorphone with other central nervous system (CNS) depressants, such as skeletal muscle relaxants, can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Furthermore, opioid analgesics such as hydromorphone may enhance the action of neuromuscular blockers and produce an excessive degree of respiratory depression. Careful monitoring of a patient's respiratory rate and oxygenation is imperative. Prior to concurrent use of hydromorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Indapamide: (Moderate) Concomitant administration of indapamide to patients receiving nondepolarizing neuromuscular blockers can cause prolonged neuromuscular blockade due to indapamide-induced hypokalemia. Serum potassium concentrations should be determined and adjusted prior to initiation of neuromuscular blockade therapy.
    Irinotecan: (Moderate) Irinotecan has anticholinesterase activity, which may antagonize the neuromuscular blockade of non-depolarizing drugs such as atracurium. Although an interaction has not been proven, use caution if these drugs are used concomitantly.
    Isradipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Ketorolac: (Moderate) Ketorolac may enhance the muscle-relaxant effect of nondepolarizing neuromuscular blockers. Caution should be exercised during concomitant administration of ketorolac with these agents.
    Levomethadyl: (Moderate) Concomitant use of levomethadyl with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Levorphanol: (Moderate) Additive CNS depression may occur if opiate agonists are used concomitantly with other CNS depressants, including neuromuscular blockers.
    Lincosamides: (Moderate) Lincosamides can potentiate the action of neuromuscular blockers, leading to skeletal muscle weakness, respiratory depression, or paralysis. Concurrent use during surgery or during the postoperative period requires close monitoring.
    Lithium: (Moderate) Lithium may potentiate the effects of nondepolarizing neuromuscular blockers. Monitor for prolonged paralysis or toxicity.
    Loop diuretics: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Magnesium: (Moderate) Parenteral magnesium salts can enhance the neuromuscular blocking effects of neuromuscular blockers. Caution should be exercised when using these agents concurrently.
    Mepenzolate: (Moderate) CNS depression can be increased when mepenzolate is combined with other CNS depressants such as neuromuscular blockers.
    Meperidine: (Moderate) Concomitant use of meperidine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Meperidine; Promethazine: (Moderate) Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants. (Moderate) Concomitant use of meperidine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Methadone: (Moderate) Concomitant use of methadone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of methadone on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Methazolamide: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
    Methohexital: (Moderate) Methohexital may enhance the neuromuscular activity of neuromuscular blocking agents, prolonging neuromuscular blockade.
    Minocycline: (Moderate) Tetracyclines, such as minocycline, may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers. Additionally, injectable minocycline contains magnesium sulfate heptahydrate, which can also enhance the neuromuscular blocking effects of neuromuscular blockers. Caution should be exercised when using these agents concurrently.
    Morphine: (Moderate) Concomitant use of morphine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of morphine on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Morphine; Naltrexone: (Moderate) Concomitant use of morphine with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of morphine on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants like neuromuscular blockers can potentiate the effects of nabilone on respiratory depression.
    Nalbuphine: (Minor) Concomitant use of nalbuphine with other CNS depressants like neuromuscular blockers can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
    Neostigmine: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Nicardipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Nimodipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Nisoldipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Oxymorphone: (Moderate) Additive CNS depression may occur if opiate agonists are used concomitantly with other CNS depressants, including neuromuscular blockers.
    Pantothenic Acid, Vitamin B5: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Perindopril; Amlodipine: (Minor) Calcium-channel blockers may prolong neuromuscular blockade.
    Phenylephrine; Promethazine: (Moderate) Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants.
    Phenytoin: (Moderate) Chronic antiepileptic drug therapy with phenytoin may antagonize the effects of nondepolarizing neuromuscular blockers. This interaction lengthens the onset and shortens the duration of neuromuscular blockade. The exact mechanism for this interaction is unknown, but could involve neuromuscular and hepatic enzyme induction effects of phenytoin.
    Physostigmine: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Piperacillin: (Moderate) Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the non-depolarizing neuromuscular blockers could be prolonged in the presence of piperacillin.
    Piperacillin; Tazobactam: (Moderate) Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the non-depolarizing neuromuscular blockers could be prolonged in the presence of piperacillin.
    Polymyxin B: (Moderate) Systemic Polymyxin B can increase the neuromuscular blockade effects of neuromuscular blockers. Polymyxin B affects both pre- and post-synaptic myoneural areas by inhibiting release of acetylcholine pre-synaptically and/or blocking acetylcholine activity post-synaptically. Thus, polymyxin B acts synergistically with these agents, increasing or prolonging the skeletal muscle relaxation of neuromuscular blockers. If polymyxin B is used postoperatively, neuromuscular blockade may recur and may cause respiratory paralysis. Concomitant use should be avoided if possible.
    Polymyxins: (Moderate) Depolarizing neuromuscular blockers and non-depolarizing neuromuscular blockers can potentiate the neuromuscular blocking effect of colistimethate sodium. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
    Procainamide: (Moderate) Patients taking procainamide who require depolarizing neuromuscular blocking agents may require less than usual doses, due to procainamide effects of reducing acetylcholine release. In addition, procainamide appears to potentiate or prolong the effects of nondepolarizing neuromuscular blockers. Patients receiving procainamide following surgery should be monitored for potential prolongation of neuromuscular blockade.
    Promethazine: (Moderate) Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants.
    Propoxyphene: (Moderate) Concomitant use of propoxyphene with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Pyridostigmine: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Pyridoxine, Vitamin B6: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Quinidine: (Major) Quinidine can potentiate the effects of neuromuscular blockers. Neostigmine will not reverse these effects. Respiratory support may be necessary if quinidine is given concomitantly or shortly after a neuromuscular blocking agent.
    Quinine: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Remifentanil: (Moderate) Concomitant use of remifentanil with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Rivastigmine: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Sedating H1-blockers: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Skeletal Muscle Relaxants: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants can result in additive CNS depression. Also, dantrolene may potentiate neuromuscular block.
    Sufentanil: (Major) High doses of neuromuscular blockers may produce increases in heart rate during sufentanil-oxygen anesthesia. Bradycardia and hypotension has also been reported with concomitant use of neuromuscular blockers during sufentanil-oxygen anesthesia; this effect may be more pronounced in the presence of beta-blockers and/or calcium-channel blockers. Additive CNS depression will also be noted with concurrent use and the doses of sufentanil and the neuromuscular blocker should be adjusted accordingly.
    Tacrine: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants including neuromuscular blockers. When such combined therapy is contemplated, a dose reduction of one or both agents should be considered.
    Tetracycline: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as neuromuscular blockers should be used cautiously due to the potential for additive bradycardia.
    Thiazide diuretics: (Moderate) Concomitant administration of hydrochlorothiazide to patients receiving nondepolarizing neuromuscular blockers (e.g., tubocurarine) can cause prolonged neuromuscular blockade due to hydrochlorothiazide-induced hypokalemia. Serum potassium concentrations should be determined and corrected (if necessary) prior to initiation of neuromuscular blockade therapy.
    Thiopental: (Moderate) Thiopental may enhance the neuromuscular activity of neuromuscular blocking agents, prolonging neuromuscular blockade.
    Trandolapril; Verapamil: (Moderate) Prolongation of the effects of neuromuscular blockers is possible when they are given in combination with calcium-channel blockers, particularly verapamil and diltiazem. It may be necessary to decrease the dosage of verapamil when it is administered to patients receiving non-depolarizing or polarizing neuromuscular blockers.
    Trospium: (Moderate) Both trospium and pancuronium are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or pancuronium due to competition for the drug elimination pathway. Careful patient monitoring is recommended and dosage adjustment of pancuronium may be necessary.
    Vancomycin: (Moderate) Vancomycin may potentiate the neuromuscular effects of neuromuscular blockers.
    Verapamil: (Moderate) Prolongation of the effects of neuromuscular blockers is possible when they are given in combination with calcium-channel blockers, particularly verapamil and diltiazem. It may be necessary to decrease the dosage of verapamil when it is administered to patients receiving non-depolarizing or polarizing neuromuscular blockers.
    Zinc Salts: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.

    PREGNANCY AND LACTATION

    Pregnancy

    Information regarding breast-feeding is not available from the manufacturers of pancuronium. The elimination half-life for pancuronium is 1.5—3 hours. It is a bisquaternary ammonium compound and should pass slowly through biological membranes. If trace amounts were excreted into breast milk, quaternary ammonium muscle relaxants are poorly absorbed from the gastrointestinal tract. Based on these data, lactation could be allowed as soon as practically feasible after recovery from a surgical procedure. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Nondepolarizing agents produce skeletal muscle paralysis by blockade at the myoneural junction. Pancuronium competes with acetylcholine for cholinergic receptor sites. Unlike depolarizing agents, pancuronium has little agonist activity, having no depolarizing effect at the motor endplate. Skeletal muscle relaxation proceeds in predictable order, starting with muscles associated with fine movements, e.g., eyes, face, and neck. These are followed by muscles of the limbs, chest, and abdomen and, finally, the diaphragm. Larger doses increase the risk of respiratory depression due to relaxation of the intercostal muscles and diaphragm. Muscle tone returns in the reverse order.In addition to its therapeutic actions, pancuronium can cause an increase in heart rate, but this is minimal at normal doses. Pancuronium produces little histamine release and no ganglion blockade, so hypotension and bronchospasm are not associated with its use. Children generally require larger mg/kg doses than adults to achieve muscle relaxation. The muscle weight-to-body weight ratio, the volume of extracellular fluid, and renal function also contribute to response.

    PHARMACOKINETICS

    Pancuronium bromide is administered intravenously. The dose required to produce 95% suppression of the muscle twitch response (ED95) is about 50 mcg/kg under balanced anesthesia and 30 mcg/kg under halothane anesthesia. Reports differ on the extent of protein binding; figures of 30—87% have been published, but it is probable that a substantial amount of the drug is bound to globulin and albumin. Small amounts of pancuronium cross the placenta. Plasma concentrations apparently fall in a triphasic manner, the last phase having a half-life of about 2 hours. Metabolism occurs via hepatic pathways to at least 3 metabolites, a 3-hydroxy metabolite, a 17-hydroxy metabolite, and a 3, 17-hydroxy metabolite. These metabolites are significantly less potent than pancuronium. Most of the drug and its metabolites are excreted in the urine. About 80% is excreted in the urine and 10% in the feces as unchanged pancuronium.

    Intravenous Route

    Intravenous administration of 60 mcg/kg produces muscle relaxation in 2—3 minutes, with peak effect occurring in about 4 minutes and lasting for 35—45 minutes. Extra doses of pancuronium can increase the intensity and duration of the neuromuscular blockade.