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  • CLASSES

    Muscle Relaxants, Peripherally Acting

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral, intermediate-acting, nondepolarizing, neuromuscular blocking agent (NMBA)
    Used for an adjunct to general anesthesia to facilitate both rapid-sequence and routine tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation
    Minimal histamine release

    COMMON BRAND NAMES

    Zemuron

    HOW SUPPLIED

    Rocuronium/Rocuronium Bromide/Zemuron Intravenous Inj Sol: 1mL, 10mg

    DOSAGE & INDICATIONS

    For muscular relaxation during non-emergent endotracheal intubation.
    Intravenous dosage
    Adults

    0.45 to 1.2 mg/kg/dose IV. Onset of intubating conditions is less than 2 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. 

    Infants, Children, and Adolescents

    0.45 to 0.6 mg/kg/dose IV. Onset of intubating conditions is 60 to 75 seconds.[42031] A lower dose of 0.3 mg/kg IV has been used successfully in combination with inhalation anesthesia induction for surgery.[52549] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031]

    Neonates

    0.45 to 0.6 mg/kg/dose IV. Onset of intubating conditions is 1 to 2 minutes.[42031] [44872] [53140] [53151] The lower dose of 0.45 mg/kg results in significantly shorter recovery time compared to larger doses.[53151] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031]

    For muscular relaxation during rapid-sequence intubation (RSI).
    Intravenous dosage
    Adults

    0.6 to 1.2 mg/kg/dose IV. Onset of intubating conditions is less than 2 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Infants†, Children†, and Adolescents†

    0.6 to 1.2 mg/kg/dose IV. Usual dose: 1 mg/kg/dose. Onset of intubating conditions is 1 to 2 minutes.[44771] [52550] [64934] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031]

    Neonates†

    0.45 to 1.2 mg/kg/dose IV. Onset of intubating conditions is 1 to 2 minutes.[44872] [53140] [53151] Specific recommendations for RSI are not available; doses are extrapolated from use in non-emergent situations. The lower dose of 0.45 mg/kg results in significantly shorter recovery time compared to larger doses.[53151] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031]

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

    0.6 to 1 mg/kg IV once, followed by 0.1 to 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.

    Infants, Children, and Adolescents

    0.45 to 0.6 mg/kg IV once, followed by 0.075 to 0.6 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Children (3 to 11 years) generally have the largest dosage requirement. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.  

    Neonates

    0.45 to 0.6 mg/kg IV once, followed by 0.075 to 0.6 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Neonates generally have a lower dosage requirement. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Continuous Intravenous Infusion dosage
    Adults

    0.6 to 1 mg/kg IV bolus, followed by 8 to 12 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Usual dosage range: 4 to 16 mcg/kg/minute. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Infants, Children, and Adolescents

    0.6 mg/kg IV bolus, followed by 5 to 10 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Children (3 to 11 years) generally have the largest dosage requirement. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Neonates

    0.6 mg/kg IV bolus, followed by 5 to 10 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Neonates generally have a lower dosage requirement. 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

    0.45 to 1.2 mg/kg IV once, followed by 0.1 to 0.2 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.

    Infants, Children, and Adolescents

    0.45 to 0.6 mg/kg IV once, followed by 0.075 to 0.15 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Children (3 to 11 years) generally have the largest dosage requirement. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031]

    Neonates

    0.45 to 0.6 mg/kg IV once, followed by 0.075 to 0.15 mg/kg/dose IV as needed; adjust dose and interval to patient's twitch response. Neonates generally have a lower dosage requirement. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031]

    Continuous Intravenous Infusion dosage
    Adults

    0.45 to 1.2 mg/kg IV bolus, followed by 10 to 12 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Dosage range: 4 to 16 mcg/kg/minute. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Infants, Children, and Adolescents

    0.45 to 0.6 mg/kg IV bolus, followed by 7 to 12 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Children (3 to 11 years) generally have the largest dosage requirement. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031] 

    Neonates

    0.45 to 0.6 mg/kg IV bolus, followed by 7 to 12 mcg/kg/minute continuous IV infusion; titrate to patient's twitch response. Neonates generally have a lower dosage requirement. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[42031]

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

    Limited data; 0.6 mg/kg/dose IV as needed.[56387] Guidelines suggest that neuromuscular blocking agents may be used to manage overt shivering in therapeutic hypothermia.

    Continuous Intravenous Infusion dosage
    Adults

    Limited data; 0.25 mg/kg IV bolus, followed by 0.25 mg/kg/hour continuous IV infusion or 0.6 mg/kg IV bolus, followed by 0.15 mg/kg/hour continuous IV infusion.[56387] [65372] 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 patients with hepatic impairment are not available. Use rocuronium with caution in patients with clinically significant hepatic impairment; patients with hepatic disease may experience prolonged recovery time. In patients with ascites, an increased initial dosage may be required to achieve adequate neuromuscular blockade. Duration will be prolonged in these cases.[42031]

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available. Patients with renal failure may have a more variable duration of effect.

    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 rocuronium with the cap and ferrule intact, in a manner that minimizes the possibility of selecting the wrong product.[42031]
    Updates for coronavirus disease 2019 (COVID-19): The FDA is allowing rocuronium 50 mg/5 mL and 100 mg/10 mL to be used beyond the labeled in-use time to help ensure access during COVID-related drug shortages. This period should be as short as possible, and for a maximum of 2 hours at room temperature or 4 hours when refrigerated. In-use time is defined as the maximum amount of time allowed to elapse between penetration of a closed-container system or after reconstitution of a lyophilized drug before patient administration.[65833]

    Intravenous Administration

    Only experienced clinicians, familiar with the use of neuromuscular blocking drugs, should administer or supervise the use of rocuronium. Adequacy of respiration must be assured through assisted or controlled ventilation.
    To avoid distress to the patient, administer rocuronium only after unconsciousness has been induced. Adequate amnesia, sedation, and analgesia should accompany neuromuscular blockade.
    Do not mix rocuronium with alkaline solutions (e.g., barbiturate solutions such as thiopental) in the same syringe or administer simultaneously during IV infusion through the same needle or through the same IV line; rocuronium has an acidic pH.
    If extravasation occurs, stop the injection or infusion and restart in another vein.[42031]
     
    Intermittent IV Injection
    No dilution necessary.
    Administer by direct IV injection over 5 to 10 seconds.[42031]
    Continuous IV Infusion
    Dilute with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringer's Injection, or Sterile Water for Injection to a concentration up to 5 mg/mL.[42031]
    ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 10 mg/mL (undiluted).[64020]
    Infuse at a rate based on patient response and requirements.
    A peripheral nerve stimulator is recommended to monitor rocuronium'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.[42031] [52441]
    Storage: Diluted solutions may be stored at room temperature for up to 24 hours in plastic bags, glass bottles, and plastic syringe pumps.[42031]

    Intramuscular Administration

    NOTE: Rocuronium is not FDA-approved for intramuscular administration.
    Not recommended. In children 3 months to 5 years, a rapid single bolus into the deltoid muscle has been studied; adequate intubating conditions were not consistently obtained in studies.

    STORAGE

    Zemuron:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Product must be used within 60 days after removal from refrigeration to room temperature (77 degrees F)
    - Product should be used within 30 days after opening
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Administer rocuronium only after unconsciousness has been induced; maintain adequate amnesia and analgesia throughout paralyzation. Neuromuscular blocking agents do not cause sedation or analgesia. Individualize rocuronium doses. Use of a peripheral nerve stimulator will permit the most advantageous use of rocuronium, minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery.

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

    Rocuronium 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 rocuronium 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.[42031]

    Bromide hypersensitivity, neuromuscular blocking agent hypersensitivity

    Rocuronium is contraindicated in patients known to have a rocuronium bromide hypersensitivity or other neuromuscular blocking agent hypersensitivity. Cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported. Severe anaphylactic reactions to neuromuscular blocking agents, including rocuronium, 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 rocuronium'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.[42031] [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 rocuronium; carefully consider each patient's clinical condition when dosing rocuronium 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 rocuronium 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.

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

    Use neuromuscular blocking agents (NMBAs) with caution in patients with asthma or other pulmonary conditions. NMBAs stimulate histamine release, which could exacerbate asthma. Compared with other NMBAs, rocuronium produces little or no histamine release.[52452] While some experts consider rocuronium to be an NMBA of choice in asthmatic patients, it should be used with caution in those with any condition in which a release of histamine may be contraindicated.[52565] 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 rocuronium 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.[42031] 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 rocuronium 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 in administering subsequent doses when it is uncertain whether maximum effect has been attained.

    Ascites, hepatic disease

    Use rocuronium with caution in patients with clinically significant hepatic impairment; patients with hepatic disease may experience prolonged recovery time. In patients with ascites, an increased initial dosage may be required to achieve adequate neuromuscular blockade. Duration will be prolonged in these cases.[42031]

    Renal failure

    Patients with renal failure may have a more variable duration of effect.

    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 rocuronium is capable of triggering hyperthermia.

    Pulmonary hypertension, valvular heart disease

    Use rocuronium with caution in patients with pulmonary hypertension or valvular heart disease because it has been associated with transient increases pulmonary vascular resistance.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypomagnesemia, hypothyroidism, inflammation, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Analysis of ECG data in pediatric patients suggests concomitant use of rocuronium with general anesthesia (i.e., halothane, sevoflurane, isoflurane, and nitrous oxide) may cause QT prolongation.[42031] Use rocuronium in combination with general anesthetics with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving other medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457] [42031] [56592] [65180]

    Infants, neonates

    Neonates and infants are more sensitive to the effects of rocuronium compared to older patients; they may take longer to recover from neuromuscular blockade. Monitor young patients carefully during and after administration.

    Labor, obstetric delivery, pregnancy

    Use rocuronium during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies with rocuronium in pregnant women. Animal data reveal no teratogenic effects of rocuronium. Rocuronium has been used in a limited number of patients undergoing labor and obstetric delivery via cesarean section. Rocuronium is not recommended for rapid sequence induction in cesarean section patients. When used with thiopental for rapid sequence induction of anesthesia for cesarean section, no neonate had APGAR scores more than 7 at 5 minutes. Umbilical venous plasma concentrations were 18% of maternal concentrations at delivery. The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of toxemia in pregnancy.[42031]

    Breast-feeding

    There are limited data regarding the use of rocuronium during breast-feeding. Due to poor oral absorption, poor lipid solubility, and short duration of action, it is not likely that rocuronium would reach the infant's bloodstream. No adverse effects, including dizziness and drowsiness, occurred in 4 infants of breast-feeding mothers who underwent various urgent surgeries during which rocuronium was used to facilitate intubation. Breast-feeding resumed 90 minutes to 5 hours after anesthesia.[46961] [63111] [63112]

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / 0-1.0
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    malignant hyperthermia / Rapid / Incidence not known
    apnea / Delayed / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    acute quadriplegic myopathy syndrome / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    keratitis / Delayed / Incidence not known
    pulmonary hypertension / Delayed / Incidence not known

    Moderate

    hypertension / Early / 0.1-2.0
    hypotension / Rapid / 0.1-2.0
    sinus tachycardia / Rapid / 0-1.4
    wheezing / Rapid / 0-1.0
    edema / Delayed / 0-1.0
    QT prolongation / Rapid / Incidence not known
    erythema / Early / Incidence not known
    dyspnea / Early / Incidence not known
    hypoxia / Early / Incidence not known
    myopathy / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    skin erosion / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    tolerance / Delayed / Incidence not known

    Mild

    hiccups / Early / 0-1.0
    pruritus / Rapid / 0-1.0
    rash / Early / 0-1.0
    nausea / Early / 0-1.0
    vomiting / Early / 0-1.0
    injection site reaction / Rapid / 0-1.0
    urticaria / Rapid / Incidence not known
    flushing / Rapid / Incidence not known
    weakness / Early / Incidence not known
    xerophthalmia / Early / Incidence not known
    anxiety / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    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; Magnesium Hydroxide; 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 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.
    Colistin: (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.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor clinical effect and decrease the rocuronium dosage, if needed, if rocuronium is used concomitantly with ritonavir. Ritonavir may potentially decrease biliary excretion of rocuronium.
    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 rocuronium 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 rocuronium dose is likely to be reduced compared to that during nitrous oxide/opioid anesthesia. For endotracheal intubation, do not reduce the dose of rocuronium.
    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.
    Diltiazem: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Donepezil: (Moderate) A higher rocuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as donepezil.
    Donepezil; Memantine: (Moderate) A higher rocuronium 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 rocuronium dose if rocuronium is first administered after establishment of steady-state enflurane anesthesia. Enflurane may prolong the duration of action of initial and maintenance doses of rocuronium and decrease the average rocuronium infusion requirement by 40% compared to opioid/nitrous oxide/oxygen anesthesia. Use of enflurane in 10 patients resulted in a 20% increase in mean clinical duration of the initial intubating dose, and a 37% increase in the duration of subsequent maintenance doses, when compared in the same study to 10 patients under opioid/nitrous oxide/oxygen anesthesia. The clinical duration of initial doses of rocuronium 0.57 to 0.85 mg/kg under enflurane anesthesia was increased by 11%. The duration of maintenance doses was affected to a greater extent, increasing by 30% to 50% under either enflurane anesthesia. Under enflurane anesthesia, the infusion rates are decreased by approximately 40% compared to opioid/nitrous oxide/oxygen anesthesia. The median spontaneous recovery time (from 25% to 75% of control T1, defined as 3 twitches of train-of-four) is prolonged by enflurane (15% longer).
    Ephedrine: (Minor) Ephedrine may reduce the onset time of neuromuscular blockade when used for intubation with rocuronium if given simultaneously with anesthetic induction.
    Ephedrine; Guaifenesin: (Minor) Ephedrine may reduce the onset time of neuromuscular blockade when used for intubation with rocuronium if given simultaneously with anesthetic induction.
    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 rocuronium 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 rocuronium due to anticholinesterase activity.
    Irinotecan: (Moderate) Irinotecan may antagonize the neuromuscular blocking effects of rocuronium due to anticholinesterase activity.
    Isoflurane: (Major) Reduce the initial rocuronium dose if rocuronium is first administered after establishment of steady-state isoflurane anesthesia. Isoflurane may prolong the duration of action of initial and maintenance doses of rocuronium and decrease the average rocuronium infusion requirement by 40% compared to opioid/nitrous oxide/oxygen anesthesia. The clinical duration of initial doses of rocuronium 0.57 to 0.85 mg/kg under isoflurane anesthesia was increased by 23%. The duration of maintenance doses was affected to a greater extent, increasing by 30% to 50% under either isoflurane anesthesia. Under isoflurane anesthesia, the infusion rates are decreased by approximately 40% compared to opioid/nitrous oxide/oxygen anesthesia. The median spontaneous recovery time (from 25% to 75% of control T1, defined as 3 twitches of train-of-four) is prolonged by isoflurane (62% longer).
    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 rocuronium, 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.
    Lopinavir; Ritonavir: (Moderate) Monitor clinical effect and decrease the rocuronium dosage, if needed, if rocuronium is used concomitantly with ritonavir. Ritonavir may potentially decrease biliary excretion of rocuronium.
    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.
    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 rocuronium 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 rocuronium.
    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.
    Nirmatrelvir; Ritonavir: (Moderate) Monitor clinical effect and decrease the rocuronium dosage, if needed, if rocuronium is used concomitantly with ritonavir. Ritonavir may potentially decrease biliary excretion of rocuronium.
    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.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor clinical effect and decrease the rocuronium dosage, if needed, if rocuronium is used concomitantly with ritonavir. Ritonavir may potentially decrease biliary excretion of rocuronium.
    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 rocuronium 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 rocuronium 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 rocuronium 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.
    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 rocuronium 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 rocuronium.
    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 rocuronium-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.
    Ritonavir: (Moderate) Monitor clinical effect and decrease the rocuronium dosage, if needed, if rocuronium is used concomitantly with ritonavir. Ritonavir may potentially decrease biliary excretion of rocuronium.
    Rivastigmine: (Moderate) A higher rocuronium 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) Concomitant use of rocuronium and sevoflurane 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 sevoflurane anesthesia, the rocuronium dose is likely to be reduced compared to that during nitrous oxide/opioid anesthesia. For endotracheal intubation, do not reduce the dose of rocuronium.
    Sotalol: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
    Succinylcholine: (Major) If succinylcholine is used before rocuronium, delay rocuronium administration until recovery from succinylcholine-induced neuromuscular blockade begins. The median duration of action of rocuronium 0.6 mg/kg administered after succinylcholine 1 mg/kg when T1 (defined as 3 twitches of train-of-four) returned to 75% of control was 36 minutes (range: 14 to 57, n = 12) vs. 28 minutes (range: 17 to 51, n = 12) without succinylcholine.
    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.
    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 rocuronium during breast-feeding. Due to poor oral absorption, poor lipid solubility, and short duration of action, it is not likely that rocuronium would reach the infant's bloodstream. No adverse effects, including dizziness and drowsiness, occurred in 4 infants of breast-feeding mothers who underwent various urgent surgeries during which rocuronium was used to facilitate intubation. Breast-feeding resumed 90 minutes to 5 hours after anesthesia.[46961] [63111] [63112]

    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 the 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 rocuronium 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]
     
    Rocuronium is a monoquaternary aminosteroid. It is an analog of vecuronium and was developed in an attempt to provide an agent with a more rapid onset of action to rival the polarizing agent succinylcholine. It is 10% to 15% as potent as its parent compound. NMBAs do not have the same effects on every muscle group and the onset of laryngeal adductor paralysis is slower with rocuronium compared to succinylcholine.[52557] In addition to its therapeutic actions, rocuronium can cause an increase in heart rate, but this is minimal even at large doses. Rocuronium produces little histamine release and no ganglion blockade; therefore, hypotension and bronchospasm are not associated with its use.[52452] [52557]

    PHARMACOKINETICS

    Rocuronium is administered intravenously; although not FDA-approved, the intramuscular route has been studied in pediatric patients. Rocuronium is distributed into the extracellular space and not into fat reserves. Protein binding is about 30%. Tissue redistribution accounts for about 80% of the initial dose administered. As tissue compartments fill with continued dosing (4 to 8 hours), less drug is redistributed away from the site of action, and the infusion rate to maintain neuromuscular blockade falls to about 20% of the initial infusion rate. The use of a loading dose and a smaller infusion rate reduces the need for dosage adjustment. Metabolism of rocuronium occurs in the liver. Rarely, the metabolite 17-desacetyl-rocuronium has been detected in human plasma or urine. In animal models, this metabolite is one-twentieth as potent as the parent compound. Data suggest pharmacokinetic parameters are linearly proportional to body weight. The terminal half-life decreases with increasing age from 1.1 hours in neonates to 0.7 to 0.8 hours in older children and adolescents. In comparison, the terminal half-life in healthy adults is approximately 1.4 to 2.4 hours.[42031] [52452]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
    Based on in vitro data, rocuronium is primarily metabolized by CYP3A4.[65228] [65229]

    Intravenous Route

    Onset time and clinical duration vary with dose, age, and anesthetic technique. After IV administration, plasma concentrations follow a 3-compartment open model; the half-life is 1 to 2 minutes during the rapid distribution phase and 14 to 18 minutes during the slower distribution phase. Larger doses decrease time to maximum effect and prolong the duration of action. In general, maximum neuromuscular effect is seen within 1 to 3 minutes in adults. Clinical duration is 22 to 67 minutes after a single bolus dose. In general, spontaneous recovery and reversal of neuromuscular blockade after rocuronium infusion discontinuation can be expected to be comparable to that after similar total exposure to single bolus doses.[42031]

    Intramuscular Route

    Reported bioavailability after IM administration (deltoid muscle) of 14 infants and children (3 months to 5 years) was 82.6% Time to adequate tracheal intubation has varied among studies but is consistently longer than after IV rocuronium and IM succinylcholine administration. In a pilot study of infants and children (n = 29) anesthetized with nitrous oxide and halothane, rocuronium 1 mg/kg IM in infants and 1.8 mg/kg IM in children permitted tracheal intubation at 2.5 to 3 minutes and produced complete paralysis (100% twitch depression) in 7.4 minutes in infants and 6.3 minutes in children. A multicenter, randomized study of infants and children (n = 38, 3 months to 12 years) specifically designed to confirm those results reported inadequate intubating conditions at 3.5 to 4 minutes, with complete paralysis (at least 98% twitch depression) in 7.4 minutes in infants and 8.9 minutes in children. Simulations based on pharmacokinetic parameters suggest a median Tmax of 13 minutes (range: 9 to 19.8 minutes). In infants and children, 25% recovery occurred in 79 minutes and 86 minutes, respectively.