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  • CLASSES

    Muscle Relaxants, Peripherally Acting

    BOXED WARNING

    Accidental exposure, requires a specialized care setting, requires an experienced clinician

    Pancuronium administration requires an experienced clinician who is familiar with its actions and the possible complications that may occur after its use as well as requires a specialized care setting where facilities for intubation, artificial respiration, oxygen therapy, and reversal agents are immediately available. Accidental exposure to a neuromuscular blocking agent may be fatal in a patient for whom it is not intended. Store pancuronium with cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product. Confirm proper medication selection and clearly communicate the intended dose.[41961]

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral, long-acting, nondepolarizing, neuromuscular blocking agent
    Used for an adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation
    Minimal histamine release; associated with tachycardia and hypertension due to vagolytic properties

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For neuromuscular blockade during mechanical ventilation in intensive care patients†.
    Intermittent Intravenous dosage
    Adults

    0.05 to 0.1 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Children and Adolescents

    0.05 to 0.15 mg/kg/dose IV every 4 to 6 hours as needed; adjust dose and interval to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Infants

    0.05 to 0.1 mg/kg/dose IV every 4 to 6 hours as needed; adjust dose and interval to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Neonates

    0.05 to 0.1 mg/kg/dose IV every 4 to 6 hours as needed; adjust dose and interval to patient's twitch response. Consider a test dose of 0.02 mg/kg to measure responsiveness. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Continuous Intravenous Infusion dosage
    Adults

    0.06 to 0.1 mg/kg IV bolus, followed by 0.8 to 2 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Children and Adolescents

    0.15 mg/kg IV bolus, followed by 0.5 to 1 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Infants

    0.1 mg/kg IV bolus, followed by 0.4 to 0.6 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For neuromuscular blockade during surgery.
    Intermittent Intravenous dosage
    Adults

    0.04 to 0.1 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Later incremental doses starting at 0.01 mg/kg may be used. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Infants, Children, and Adolescents

    0.04 to 0.1 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Later incremental doses starting at 0.01 mg/kg may be used. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Neonates

    0.04 to 0.1 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Consider a test dose of 0.02 mg/kg to measure responsiveness. Later incremental doses starting at 0.01 mg/kg may be used. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For muscular relaxation during non-emergent endotracheal intubation and rapid-sequence intubation (RSI)†.
    Intravenous dosage
    Adults

    0.06 to 0.1 mg/kg/dose IV. Onset of intubating conditions is 2 to 3 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[41961]

    Infants, Children, and Adolescents

    0.06 to 0.1 mg/kg/dose IV. Usual dose: 0.1 mg/kg/dose. Onset of intubating conditions is 2 to 5 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[41961] [44771]

    Neonates

    0.05 to 0.1 mg/kg/dose IV. Consider a test dose of 0.02 mg/kg to measure responsiveness. Onset of intubating conditions is 1 to 3 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the prevention of shaking chills† induced by therapeutic hypothermia after cardiac arrest.
    Intermittent Intravenous dosage
    Adults

    Limited data; 0.1 mg/kg/dose IV every 2 hours. Guidelines suggest that neuromuscular blocking agents may be used to manage overt shivering in therapeutic hypothermia.

    Continuous Intravenous Infusion dosage
    Adults

    Limited data; 0.01 to 0.1 mg/kg/hour continuous IV infusion. Guidelines suggest that neuromuscular blocking agents may be used to manage overt shivering in therapeutic hypothermia.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Specific maximum dosage information is not available. Dosage must be individualized based on clinical response.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available. Consider the possibility of slower onset, higher total dosage, and prolongation of neuromuscular blockade when pancuronium is used in patients with hepatic disease and/or biliary tract disease.

    Renal Impairment

    Specific guidelines for dosage adjustments in adult patients with renal impairment are not available. If pancuronium is used in a patient with renal failure, consider that the rate of recovery of neuromuscular blockade is variable and sometimes very much slower than normal.[41961]
     
    Pediatric patients
    CrCl more than 50 mL/minute/1.73 m2: No initial dosage adjustment required; monitor carefully and adjust dosage to clinical effect.
    CrCl 10 to 50 mL/minute/1.73 m2: Administer 50% of normal dosage; monitor carefully and adjust dosage to clinical effect.
    CrCl less than 10 mL/minute/1.73 m2: Avoid use.[32569]

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Accidental administration of neuromuscular blocking agents can be fatal. Store pancuronium with the cap and ferrule intact, in a manner that minimizes the possibility of selecting the wrong product.

    Intravenous Administration

    Only experienced clinicians, familiar with the use of neuromuscular blocking drugs, should administer or supervise the use of pancuronium. Adequacy of respiration must be assured through assisted or controlled ventilation.
    To avoid distress to the patient, pancuronium should be administered only after unconsciousness has been induced. Adequate amnesia, sedation, and analgesia should accompany neuromuscular blockade.[41961]
     
    Intermittent IV Injection
    No further dilution necessary.
    Administer by direct IV injection over seconds.[52572]
     
    Continuous IV Infusion
    NOTE: Due to pancuronium's long duration of action, the use of shorter-acting agents is preferred when continuous infusion is the desired method of drug administration.
    Dilute to a concentration of 0.01 to 0.8 mg/mL in a compatible IV infusion solution (i.e., 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection).[41961] [52572]
    Infuse at a rate based on patient response and requirements.
    A peripheral nerve stimulator is recommended to monitor pancuronium's effects. Target response is typically 1 to 2 twitches. Incorrect electrode placement, direct stimulation of muscle due to large electrode size, acute illness, capillary leak, and edema may affect an appropriate assessment. Monitor visual and tactile stimulation on muscle movement as well as heart rate, blood pressure, and mechanical ventilator status during administration.[41961] [52441]
    Storage: Dilution is stable for 48 hours at room temperature.[41961]

    STORAGE

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

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Administer pancuronium only after unconsciousness has been induced; maintain adequate amnesia and analgesia throughout paralyzation. Neuromuscular blocking agents do not cause sedation or analgesia. Individualize pancuronium doses. 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.[41961]

    Accidental exposure, requires a specialized care setting, requires an experienced clinician

    Pancuronium administration requires an experienced clinician who is familiar with its actions and the possible complications that may occur after its use as well as requires a specialized care setting where facilities for intubation, artificial respiration, oxygen therapy, and reversal agents are immediately available. Accidental exposure to a neuromuscular blocking agent may be fatal in a patient for whom it is not intended. Store pancuronium with cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product. Confirm proper medication selection and clearly communicate the intended dose.[41961]

    Bromide hypersensitivity, neuromuscular blocking agent hypersensitivity

    Pancuronium is contraindicated in patients known to have a pancuronium bromide hypersensitivity. Use pancuronium with caution in patients with neuromuscular blocking agent hypersensitivity since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported. Severe anaphylactic reactions to neuromuscular blocking agents, including pancuronium, have been reported. These reactions have been life-threatening and fatal in some cases. Due to the potential severity of these reactions, ensure the necessary precautions, such as the immediate availability of appropriate emergency treatment.

    Burns

    Patients with burns have a decreased sensitivity to pancuronium's ability to produce neuromuscular blockade. Resistance to blockade usually develops in patients with burns more than 10% total body surface area approximately 1 week after thermal injury. Increased doses may be required in burn patients; alteration in drug effect may be seen for up to 1 year. In patients with more than 40% total body surface area burns, significant increases in dosage requirements (i.e., 2.5 to 5 times the usual dose) have been reported.[52478] [52482]

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

    Various physiologic states can alter the expected effects of pancuronium; carefully consider each patient's clinical condition when dosing pancuronium and monitoring the patient. Cachectic and debilitated patients are more sensitive to neuromuscular blocking agents (NMBAs). Electrolyte imbalance can alter a patient's sensitivity to NMBAs. Hypercalcemia can decrease sensitivity to NMBAs, while most other electrolyte disturbances increase sensitivity (e.g., hypokalemia, hypocalcemia, hypermagnesemia). Use pancuronium 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: metabolic alkalosis, metabolic acidosis, and respiratory acidosis may enhance neuromuscular blockade and/or prolong recovery time, while respiratory alkalosis reduces the potency of the drug. Dehydration and hypothermia can also increase a patient's sensitivity to NMBAs. [52486]

    Asthma, chronic lung disease (CLD), chronic obstructive pulmonary disease (COPD), pulmonary disease

    Use neuromuscular blocking agents (NMBAs), including pancuronium, with caution in patients with asthma or other pulmonary conditions. NMBAs stimulate histamine release, which could exacerbate asthma. Although histamine release is not a characteristic action of pancuronium, reactions possibly mediated by histamine release have been reported.[41961] [52452] Also, NMBAs cause respiratory muscle paralysis; residual muscle weakness and decreased respiratory function can persist even after drug discontinuation.[52480] Use NMBAs with caution in patients with pulmonary disease and conditions associated with low pulmonary function reserve, such as chronic obstructive pulmonary disease (COPD) or neonatal chronic lung disease (CLD). Carefully monitor respiratory status and adequacy of ventilation after drug recovery until the patient is clearly stabilized.

    Geriatric, myasthenia gravis, neuromuscular disease, obesity

    Use pancuronium with caution in patients with neuromuscular disease (e.g., myasthenia gravis, myasthenic syndrome [Eaton Lambert syndrome]); prolonged or exaggerated neuromuscular blockade may occur after nondepolarizing agent use. Geriatric patients may be at increased risk for residual neuromuscular block. Additionally, patients with weak muscle tone or severe obesity are at an increased risk for airway and ventilation complications. Consider the use of a small test dose and a peripheral nerve stimulator to monitor response in these patients. Monitor patients carefully until recovery is fully complete. Use ideal body weight or adjusted body weight for dosing in obese and morbidly obese adult patients (body mass index 30 kg/m2 or more).[62859] Guidelines for sustained neuromuscular blockade in critically ill children recommend calculating the dose according to IBW.

    Cardiac disease, edema

    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.

    Biliary obstruction, hepatic disease

    Use pancuronium with caution in patients with hepatic disease. Consider the possibility of slower onset, higher total dosage, and prolongation of neuromuscular blockade when pancuronium is used in patients with hepatic disease and/or biliary tract disease. The doubled elimination half-life and reduced plasma clearance determined in patients with hepatic and/or biliary tract disease, as well as limited data showing that recovery time is prolonged in patients with biliary obstruction, suggest that prolongation of neuromuscular blockade may occur. Also, these conditions are characterized by an increased volume of distribution of pancuronium, suggesting that the total initial dose to achieve adequate relaxation may, in some cases, be high.[41961]

    Renal disease, renal failure, renal impairment

    Use pancuronium with caution in patients with renal disease or renal impairment. If pancuronium is used in a patient with renal failure, consider that the rate of recovery of neuromuscular blockade is variable and sometimes very much slower than normal.[41961]

    Malignant hyperthermia

    Treat patients with a personal or familial history of malignant hyperthermia with extreme caution. Malignant hyperthermia can be precipitated by many drugs used in anesthetic practice, including halogenated anesthetics and depolarizing neuromuscular blocking agents (e.g., succinylcholine). It is unknown whether pancuronium is capable of triggering hyperthermia.

    Tachycardia

    Use pancuronium with caution in patients with preexisting tachycardia or those who cannot tolerate an increase in heart rate. Pancuronium can cause tachycardia as a result of vagolytic action and increased norepinephrine release.[52503] [62859]

    Neonates, premature neonates

    Neonates are especially sensitive to nondepolarizing neuromuscular blocking agents, such as pancuronium. A test dose is recommended to be given in neonates to measure responsiveness. The prolonged use of pancuronium for the management of neonates undergoing mechanical ventilation has been associated in rare cases with severe skeletal muscle weakness that may first be noted during attempts to wean the neonate from the ventilator; these patients usually receive other drugs, such as antibiotics, which may enhance neuromuscular blockade. Microscopic changes consistent with disuse atrophy have been noted at autopsy. Although a cause-and-effect relationship has not been established, consider the benefits-to-risk ratio when there is a need for neuromuscular blockade to facilitate long-term mechanical ventilation of neonates. Also, pancuronium products contain benzyl alcohol as a preservative. The recommended dosage range of pancuronium for preterm and term infants includes amounts of benzyl alcohol well below that associated with toxicity; however, the minimum amount of benzyl alcohol at which toxicity may occur is unknown. If the patient requires more than the recommended dosages or other medications containing this preservative, consider the daily metabolic load of benzyl alcohol from these combined sources. Excessive amounts of benzyl alcohol in neonates have been associated with hypotension, metabolic acidosis, and kernicterus. A "gasping syndrome" characterized by CNS depression, metabolic acidosis, and gasping respirations has been associated with benzyl alcohol dosages more than 99 mg/kg/day in neonates. Premature neonates and low-birth-weight neonates may be more likely to develop toxicity.[41961] [52949]

    Labor, obstetric delivery, pregnancy

    Use pancuronium during pregnancy only if the benefits outweigh the risks. It is not known whether pancuronium can cause fetal harm when administered to a pregnant woman or if it can affect reproduction capacity. Animal reproduction studies have not been performed. Pancuronium may be used in patients undergoing labor and obstetric delivery via cesarean section, but reversal of pancuronium may be unsatisfactory in patients receiving magnesium for toxemia of pregnancy. The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of toxemia in pregnancy. Reduce pancuronium dosage, as indicated, in such cases. It is also recommended that the interval between pancuronium use and labor and obstetric delivery be reasonably short to avoid clinically significant placental transfer.[41961]

    Breast-feeding

    There are limited data regarding the use of pancuronium during breast-feeding. The elimination half-life for pancuronium is 1.5 to 3 hours. It is a bisquaternary ammonium compound and should pass slowly through biological membranes. Due to poor oral absorption and poor lipid solubility, it is not likely that pancuronium would reach the infant's bloodstream. Based on these data, breast-feeding could be allowed as soon as practically feasible after surgery.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    malignant hyperthermia / Rapid / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    acute quadriplegic myopathy syndrome / Delayed / Incidence not known
    apnea / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    keratitis / Delayed / Incidence not known

    Moderate

    wheezing / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    erythema / Early / Incidence not known
    hypoxia / Early / Incidence not known
    dyspnea / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known
    myopathy / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    skin erosion / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    tolerance / Delayed / Incidence not known

    Mild

    pruritus / Rapid / Incidence not known
    rash / Early / Incidence not known
    flushing / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    weakness / Early / Incidence not known
    xerophthalmia / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    hypersalivation / Early / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    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.
    Aliskiren; Amlodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amide local anesthetics: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Aminoglycosides: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Amlodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Atorvastatin: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Benazepril: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Celecoxib: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Olmesartan: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Valsartan: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
    Amphotericin B lipid complex (ABLC): (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
    Amphotericin B liposomal (LAmB): (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
    Amphotericin B: (Moderate) Monitor serum potassium concentrations with concomitant use of neuromuscular blockers and amphotericin B. Amphotericin B-induced hypokalemia may prolong neuromuscular blockade.
    Atenolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Atenolol; Chlorthalidone: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Bacitracin: (Moderate) Concomitant use of neuromuscular blockers and systemic bacitracin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Bendroflumethiazide; Nadolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Beta-blockers: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Betaxolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Bisoprolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Botulinum Toxins: (Moderate) Use neuromuscular blockers and botulinum toxins concurrently with caution because the effect of the botulinum toxin may be potentiated. If coadministered, observe the patient closely.
    Brimonidine; Timolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Calcium Acetate: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium Carbonate: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium Carbonate; Risedronate: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium Carbonate; Simethicone: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium Chloride: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium Gluconate: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium; Vitamin D: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Calcium-channel blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Capreomycin: (Minor) Concomitant use of neuromuscular blockers and capreomycin may prolong neuromuscular blockade. A partial neuromuscular blockade was demonstrated after large intravenous doses of capreomycin.
    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.
    Carteolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Carvedilol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Chromium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Clevidipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Colistimethate, Colistin, Polymyxin E: (Moderate) Use neuromuscular blockers and polymyxins with extreme caution. Concomitant use of neuromuscular blockers and polymyxins may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Corticosteroids: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
    Cyclosporine: (Moderate) Concomitant use of neuromuscular blockers and cyclosporine may prolong neuromuscular blockade.
    Demeclocycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Desflurane: (Moderate) Concomitant use of pancuronium and desflurane may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. During maintenance of desflurane anesthesia, the pancuronium dose is likely to be reduced compared to that during nitrous oxide/opioid anesthesia. For endotracheal intubation, do not reduce the dose of pancuronium. Anesthetic concentrations of desflurane at equilibrium (administered for 15 or more minutes before testing) reduced the ED95 of pancuronium by approximately 50% compared to nitrous oxide/opioid anesthesia.
    Dextromethorphan; Quinidine: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Digoxin: (Moderate) Use pancuronium with caution in patients receiving digoxin due to an increased risk of dysrhythmia.
    Diltiazem: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Donepezil: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as donepezil.
    Donepezil; Memantine: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as donepezil.
    Dorzolamide; Timolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Doxapram: (Minor) Doxapram may temporarily mask the residual effects of neuromuscular blockers.
    Doxycycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Enalapril; Felodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Enflurane: (Major) Reduce the initial pancuronium dose if pancuronium is first administered after establishment of steady-state enflurane anesthesia. Consider the relatively long duration of action of pancuronium when the drug is selected for intubation in these circumstances. The neuromuscular blocking action of pancuronium is potentiated by enflurane anesthesia. Recommended initial doses of pancuronium may be used to facilitate tracheal intubation before administration of enflurane.
    Entecavir: (Moderate) Monitor patients receiving pancuronium and entecavir closely. Coadministration may increase serum concentrations of either drug due to competition for elimination via active tubular secretion.
    Esmolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Ester local anesthetics: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Felodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Fosphenytoin: (Moderate) Concomitant use of neuromuscular blockers and fosphenytoin may increase resistance to the neuromuscular blockade action of neuromuscular blockers, resulting in shorter durations of neuromuscular blockade and higher infusion rate requirements. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Galantamine: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as galantamine.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Indapamide: (Moderate) Concomitant use of neuromuscular blockers and indapamide may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Irinotecan Liposomal: (Moderate) Irinotecan may antagonize the neuromuscular blocking effects of pancuronium due to anticholinesterase activity.
    Irinotecan: (Moderate) Irinotecan may antagonize the neuromuscular blocking effects of pancuronium due to anticholinesterase activity.
    Isoflurane: (Major) Reduce the initial pancuronium dose if pancuronium is first administered after establishment of steady-state isoflurane anesthesia. Consider the relatively long duration of action of pancuronium when the drug is selected for intubation in these circumstances. The neuromuscular blocking action of pancuronium is potentiated by isoflurane anesthesia. Recommended initial doses of pancuronium may be used to facilitate tracheal intubation before administration of isoflurane.
    Isradipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Ketorolac: (Minor) There have been postmarketing reports of a possible interaction between ketorolac and nondepolarizing neuromuscular blockers, such as pancuronium, that resulted in apnea.
    Labetalol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Levamlodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Levobetaxolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Levobunolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Lincosamides: (Moderate) Use neuromuscular blockers and lincosamides with caution. Concomitant use of neuromuscular blockers and lincosamides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Lithium: (Moderate) Concomitant use of neuromuscular blockers and lithium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Loop diuretics: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Magnesium: (Moderate) Concomitant use of neuromuscular blockers and magnesium may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    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.
    Metoprolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Minocycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Nadolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Nebivolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Nebivolol; Valsartan: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Neostigmine: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as neostigmine. Intravenous neostigmine is indicated for reversal of the effects of nondepolarizing neuromuscular blockers, such as pancuronium.
    Nicardipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Nifedipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Nimodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Nisoldipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Omadacycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Penbutolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Perindopril; Amlodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Phenytoin: (Moderate) Concomitant use of neuromuscular blockers and phenytoin may increase resistance to the neuromuscular blockade action of neuromuscular blockers, resulting in shorter durations of neuromuscular blockade and higher infusion rate requirements. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Physostigmine: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as physostigmine.
    Pindolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Piperacillin: (Moderate) Concomitant use of pancuronium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Piperacillin; Tazobactam: (Moderate) Concomitant use of pancuronium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Polymyxin B: (Major) Avoid concomitant use of systemic polymyxin B and neuromuscular blockers due to the risk of respiratory depression. The neurotoxicity of polymyxin B may can result in neuromuscular blockade, especially when given soon after neuromuscular blockers. If signs of respiratory paralysis appear, assist respiration and discontinue drug therapy.
    Polymyxins: (Moderate) Use neuromuscular blockers and polymyxins with extreme caution. Concomitant use of neuromuscular blockers and polymyxins may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Procainamide: (Moderate) A lower neuromuscular blocker dose may be required to achieve neuromuscular block with concomitant procainamide use due to procainamide effects on reducing acetylcholine release. Concomitant use of neuromuscular blockers and procainamide may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Propranolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Pyridostigmine: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as pyridostigmine. Intravenous pyridostigmine is indicated for reversal of the effects of nondepolarizing neuromuscular blockers, such as pancuronium.
    Pyridoxine, Vitamin B6: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Quinidine: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Quinine: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
    Ranitidine: (Moderate) Ranitidine may cause resistance to pancuronium-induced neuromuscular blockade, due to pharmacodynamic alterations at the acetylcholine receptor. In vitro studies demonstrate that therapeutic serum concentrations of ranitidine inhibit acetylcholinesterase, thus increasing the amount of acetylcholine available to compete at the neuromuscular junction and reverse the neuromuscular blockade. The inhibition of acetylcholinesterase is likely dose-related. Resistance to nondepolarizing neuromuscular blockers was reported occasionally with intravenous ranitidine dosages that were slightly higher than those given clinically, but not frequently with oral therapy.
    Rivastigmine: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
    Sarecycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Sevoflurane: (Moderate) Reduce the initial pancuronium dose if pancuronium is first administered after establishment of steady-state sevoflurane anesthesia. Consider the relatively long duration of action of pancuronium when the drug is selected for intubation in these circumstances. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. The neuromuscular blocking action of pancuronium is potentiated by sevoflurane anesthesia. Recommended initial doses of pancuronium may be used to facilitate tracheal intubation before administration of sevoflurane.
    Sotalol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Succinylcholine: (Major) If succinylcholine is used before pancuronium, delay pancuronium administration until recovery from succinylcholine-induced neuromuscular blockade begins. Prior administration of succinylcholine may enhance the neuromuscular blocking effect of pancuronium and increase its duration of action. If a small dose of pancuronium is given at least 3 minutes before administration of succinylcholine, in order to reduce the incidence and intensity of succinylcholine-induced fasciculations, this dose may induce a degree of neuromuscular block sufficient to cause respiratory depression in some patients.
    Telmisartan; Amlodipine: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Tetracycline: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Tetracyclines: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Theophylline, Aminophylline: (Moderate) A higher neuromuscular blocker dose may be required to achieve neuromuscular block with concomitant aminophylline use. Aminophylline may antagonize neuromuscular blocking effects, possibly due to phosphodiesterase inhibition. (Moderate) A higher neuromuscular blocker dose may be required to achieve neuromuscular block with concomitant theophylline use. Theophylline may antagonize neuromuscular blocking effects, possibly due to phosphodiesterase inhibition.
    Thiazide diuretics: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Timolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Trandolapril; Verapamil: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Trospium: (Moderate) Monitor patients receiving pancuronium and trospium closely. Coadministration may increase serum concentrations of either drug due to competition for elimination via active tubular secretion.
    Vancomycin: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Verapamil: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.

    PREGNANCY AND LACTATION

    Pregnancy

    There are limited data regarding the use of pancuronium during breast-feeding. The elimination half-life for pancuronium is 1.5 to 3 hours. It is a bisquaternary ammonium compound and should pass slowly through biological membranes. Due to poor oral absorption and poor lipid solubility, it is not likely that pancuronium would reach the infant's bloodstream. Based on these data, breast-feeding could be allowed as soon as practically feasible after surgery.

    MECHANISM OF ACTION

    Muscle contraction is initiated by an action potential traveling from the central nervous system to the nerve terminal. At the nerve terminal, the action potential causes an influx of calcium, initiating release of acetylcholine (ACh) into the synaptic cleft. ACh binds to ACh receptors on the muscle fiber's motor end-plate causing a conformational change that briefly opens sodium ion channels. When an adequate number of ACh receptors are activated, membrane potential decreases and voltage-dependent sodium ion channels of adjacent muscle membranes activate, transmitting the action potential throughout the muscle fiber and resulting in muscle contraction.[52452] Nondepolarizing neuromuscular blocking agents (NMBAs) such as pancuronium produce skeletal muscle paralysis by competing with ACh for cholinergic receptor sites at the motor end-plate.[52486] Neuromuscular blockade progresses in a predictable order, beginning with muscles associated with fine movements (e.g., eyes, face, and neck), followed by muscles of the limbs, chest, and abdomen and, finally, the diaphragm. Larger doses increase the chance of respiratory depression associated with relaxation of the intercostal muscles and the diaphragm. Muscle tone returns in the reverse order.[52503]
     
    Pancuronium is a bisquaternary aminosteroid. In addition to its therapeutic actions, pancuronium can cause an increase in heart rate and blood pressure due to vagolytic and weak sympathomimetic properties. Pancuronium produces little histamine release and no ganglion blockade, so hypotension and bronchospasm are not associated with its use.[52503] [52565]

    PHARMACOKINETICS

    Pancuronium is administered intravenously. Protein binding is approximately 87%, primarily to gamma globulin and albumin.[41961] After administration, pancuronium distributes to the extracellular space.[52463] Vd ranges from 0.24 to 0.28 L/kg in adult patients, which is similar to that of children (0.2 L/kg).[41961] [52463] Plasma clearance is approximately 1.1 to 1.9 mL/kg/minute in both pediatric and adult patients. Metabolism occurs via hepatic pathways to at least 3 metabolites. Up to 25% of an administered pancuronium dose is recovered as the 3-hydroxy metabolite, which is approximately half as potent as the parent drug. Less than 5% of the administered dose is recovered as the 17-hydroxy and 3, 17-hydroxy metabolites, both of which are 50 times less potent than pancuronium. Of a pancuronium dose, 40% is excreted in the urine and 11% in the bile. Elimination half-life ranges from 89 to 161 minutes.[41961]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Intravenous Route

    In general, neuromuscular blockade begins within 2 to 3 minutes, peaks in approximately 4 minutes, and persists 22 to 100 minutes in adults. Intensity and duration of action are affected by the dose, age of the patient, and the use of concurrent anesthetics and other neuromuscular blocking agents.