Rocuronium Bromide

Rocuronium Bromide Injection is indicated for inpatients and outpatients as 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.

To be administered only by experienced clinicians or adequately trained individuals supervised by an experienced clinician familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents. (

• Individualize the dose for each patient. (
  2.1 Important Dosing and Administration Information

  Rocuronium bromide injection is for intravenous use only.

  This drug should only be administered by experienced clinicians or trained individuals supervised by an experienced clinician familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents. Doses of rocuronium bromide injection should be individualized and a peripheral nerve stimulator should be used to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered.

  The dosage information which follows is derived from studies based upon units of drug per unit of body weight. It is intended to serve as an initial guide to clinicians familiar with other neuromuscular blocking agents to acquire experience with rocuronium bromide injection.

  In patients in whom potentiation of, or resistance to, neuromuscular block is anticipated, a dose adjustment should be considered

  [see Dosage and Administration , Warnings and Precautions , Drug Interactions , and Use in Specific Populations ]

  .

  Risk of Medication Errors

  Accidental administration of neuromuscular blocking agents may be fatal. Store rocuronium bromide injection with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product

  [see Warnings and Precautions ]

  .
  )
• Peripheral nerve stimulator recommended for determination of drug response and need for additional doses, and to evaluate recovery. (
  2.1 Important Dosing and Administration Information

  Rocuronium bromide injection is for intravenous use only.

  This drug should only be administered by experienced clinicians or trained individuals supervised by an experienced clinician familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents. Doses of rocuronium bromide injection should be individualized and a peripheral nerve stimulator should be used to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered.

  The dosage information which follows is derived from studies based upon units of drug per unit of body weight. It is intended to serve as an initial guide to clinicians familiar with other neuromuscular blocking agents to acquire experience with rocuronium bromide injection.

  In patients in whom potentiation of, or resistance to, neuromuscular block is anticipated, a dose adjustment should be considered

  [see Dosage and Administration , Warnings and Precautions , Drug Interactions , and Use in Specific Populations ]

  .

  Risk of Medication Errors

  Accidental administration of neuromuscular blocking agents may be fatal. Store rocuronium bromide injection with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product

  [see Warnings and Precautions ]

  .
  )
• Store rocuronium bromide injection with cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product. (
  2.1 Important Dosing and Administration Information

  Rocuronium bromide injection is for intravenous use only.

  This drug should only be administered by experienced clinicians or trained individuals supervised by an experienced clinician familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents. Doses of rocuronium bromide injection should be individualized and a peripheral nerve stimulator should be used to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered.

  The dosage information which follows is derived from studies based upon units of drug per unit of body weight. It is intended to serve as an initial guide to clinicians familiar with other neuromuscular blocking agents to acquire experience with rocuronium bromide injection.

  In patients in whom potentiation of, or resistance to, neuromuscular block is anticipated, a dose adjustment should be considered

  [see Dosage and Administration , Warnings and Precautions , Drug Interactions , and Use in Specific Populations ]

  .

  Risk of Medication Errors

  Accidental administration of neuromuscular blocking agents may be fatal. Store rocuronium bromide injection with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product

  [see Warnings and Precautions ]

  .
  )
• Tracheal intubation
  : Recommended initial dose is 0.6 mg/kg. (
  2.2 Dose for Tracheal Intubation

  The recommended initial dose of rocuronium bromide injection, regardless of anesthetic technique, is 0.6 mg/kg. Neuromuscular block sufficient for intubation (80% block or greater) is attained in a median (range) time of 1 (0.4-6) minute(s) and most patients have intubation completed within 2 minutes. Maximum blockade is achieved in most patients in less than 3 minutes. This dose may be expected to provide 31 (15-85) minutes of clinical relaxation under opioid/nitrous oxide/oxygen anesthesia. Under halothane, isoflurane, and enflurane anesthesia, some extension of the period of clinical relaxation should be expected

  [see Drug Interactions ]

  .

  A lower dose of rocuronium bromide injection (0.45 mg/kg) may be used. Neuromuscular block sufficient for intubation (80% block or greater) is attained in a median (range) time of 1.3 (0.8-6.2) minute(s), and most patients have intubation completed within 2 minutes. Maximum blockade is achieved in most patients in less than 4 minutes. This dose may be expected to provide 22 (12-31) minutes of clinical relaxation under opioid/nitrous oxide/oxygen anesthesia. Patients receiving this low dose of 0.45 mg/kg who achieve less than 90% block (about 16% of these patients) may have a more rapid time to 25% recovery, 12 to 15 minutes.

  A large bolus dose of 0.9 or 1.2 mg/kg can be administered under opioid/nitrous oxide/oxygen anesthesia without adverse effects to the cardiovascular system

  [see Clinical Pharmacology ]

  .
  )
• Rapid sequence intubation
  : 0.6 to 1.2 mg/kg. (
  2.3 Rapid Sequence Intubation

  In appropriately premedicated and adequately anesthetized patients, rocuronium bromide injection 0.6 to 1.2 mg/kg will provide excellent or good intubating conditions in most patients in less than 2 minutes

  [see Clinical Studies ]

  .
  )
• Maintenance doses
  : Guided by response to prior dose, not administered until recovery is evident. (
  2.4 Maintenance Dosing

  Maintenance doses of 0.1, 0.15, and 0.2 mg/kg rocuronium bromide injection, administered at 25% recovery of control T₁(defined as 3 twitches of train-of-four), provide a median (range) of 12 (2-31), 17 (6-50), and 24 (7-69) minutes of clinical duration under opioid/nitrous oxide/oxygen anesthesia

  [see Clinical Pharmacology ]

  . In all cases, dosing should be guided based on the clinical duration following initial dose or prior maintenance dose and not administered until recovery of neuromuscular function is evident. A clinically insignificant cumulation of effect with repetitive maintenance dosing has been observed

  [see Clinical Pharmacology ]

  .
  )
• Continuous infusion
  : Initial rate of 10 to 12 mcg/kg/min. Start only after early evidence of spontaneous recovery from an intubating dose. (
  2.5 Use by Continuous Infusion

  Infusion at an initial rate of 10 to 12 mcg/kg/min of rocuronium bromide injection should be initiated only after early evidence of spontaneous recovery from an intubating dose. Due to rapid redistribution

  [see Clinical Pharmacology ]

  and the associated rapid spontaneous recovery, initiation of the infusion after substantial return of neuromuscular function (more than 10% of control T₁) may necessitate additional bolus doses to maintain adequate block for surgery.

  Upon reaching the desired level of neuromuscular block, the infusion of rocuronium bromide injection must be individualized for each patient. The rate of administration should be adjusted according to the patient's twitch response as monitored with the use of a peripheral nerve stimulator. In clinical trials, infusion rates have ranged from 4 to 16 mcg/kg/min.

  Inhalation anesthetics, particularly enflurane and isoflurane, may enhance the neuromuscular blocking action of nondepolarizing muscle relaxants. In the presence of steady-state concentrations of enflurane or isoflurane, it may be necessary to reduce the rate of infusion by 30% to 50%, at 45 to 60 minutes after the intubating dose.

  Spontaneous recovery and reversal of neuromuscular blockade following discontinuation of rocuronium bromide injection infusion may be expected to proceed at rates comparable to that following comparable total doses administered by repetitive bolus injections

  [see Clinical Pharmacology ]

  .

  Infusion solutions of rocuronium bromide injection can be prepared by mixing rocuronium bromide injection with an appropriate infusion solution such as 5% glucose in water or lactated Ringers

  [see Dosage and Administration ].

  These infusion solutions should be used within 24 hours of mixing. Unused portions of infusion solutions should be discarded.

  Infusion rates of rocuronium bromide injection can be individualized for each patient using the following tables for 3 different concentrations of rocuronium bromide injection solution as guidelines:

  Table 1: Infusion Rates Using Rocuronium Bromide Injection (0.5 mg per mL)*

  * 50 mg rocuronium bromide in 100 mL solution.
  Patient Weight		Drug Delivery Rate (mcg/kg/min)
  (kg)	(lbs)	4	5	6	7	8	9	10	12	14	16
  		Infusion Delivery Rate (mL/hr)
  10	22	4.8	6	7.2	8.4	9.6	10.8	12	14.4	16.8	19.2
  15	33	7.2	9	10.8	12.6	14.4	16.2	18	21.6	25.2	28.8
  20	44	9.6	12	14.4	16.8	19.2	21.6	24	28.8	33.6	38.4
  25	55	12	15	18	21	24	27	30	36	42	48
  35	77	16.8	21	25.2	29.4	33.6	37.8	42	50.4	58.8	67.2
  50	110	24	30	36	42	48	54	60	72	84	96
  60	132	28.8	36	43.2	50.4	57.6	64.8	72	86.4	100.8	115.2
  70	154	33.6	42	50.4	58.8	67.2	75.6	84	100.8	117.6	134.4
  80	176	38.4	48	57.6	67.2	76.8	86.4	96	115.2	134.4	153.6
  90	198	43.2	54	64.8	75.6	86.4	97.2	108	129.6	151.2	172.8
  100	220	48	60	72	84	96	108	120	144	168	192

  Table 2: Infusion Rates Using Rocuronium Bromide Injection (1 mg per mL)*

  * 100 mg rocuronium bromide in 100 mL solution.
  Patient Weight		Drug Delivery Rate (mcg/kg/min)
  (kg)	(lbs)	4	5	6	7	8	9	10	12	14	16
  		Infusion Delivery Rate (mL/hr)
  10	22	2.4	3	3.6	4.2	4.8	5.4	6	7.2	8.4	9.6
  15	33	3.6	4.5	5.4	6.3	7.2	8.1	9	10.8	12.6	14.4
  20	44	4.8	6	7.2	8.4	9.6	10.8	12	14.4	16.8	19.2
  25	55	6	7.5	9	10.5	12	13.5	15	18	21	24
  35	77	8.4	10.5	12.6	14.7	16.8	18.9	21	25.2	29.4	33.6
  50	110	12	15	18	21	24	27	30	36	42	48
  60	132	14.4	18	21.6	25.2	28.8	32.4	36	43.2	50.4	57.6
  70	154	16.8	21	25.2	29.4	33.6	37.8	42	50.4	58.8	67.2
  80	176	19.2	24	28.8	33.6	38.4	43.2	48	57.6	67.2	76.8
  90	198	21.6	27	32.4	37.8	43.2	48.6	54	64.8	75.6	86.4
  100	220	24	30	36	42	48	54	60	72	84	96

  Table 3: Infusion Rates Using Rocuronium Bromide Injection (5 mg per mL)*

  * 500 mg rocuronium bromide in 100 mL solution.
  Patient Weight		Drug Delivery Rate (mcg/kg/min)
  (kg)	(lbs)	4	5	6	7	8	9	10	12	14	16
  		Infusion Delivery Rate (mL/hr)
  10	22	0.5	0.6	0.7	0.8	1	1.1	1.2	1.4	1.7	1.9
  15	33	0.7	0.9	1.1	1.3	1.4	1.6	1.8	2.2	2.5	2.9
  20	44	1	1.2	1.4	1.7	1.9	2.2	2.4	2.9	3.4	3.8
  25	55	1.2	1.5	1.8	2.1	2.4	2.7	3	3.6	4.2	4.8
  35	77	1.7	2.1	2.5	2.9	3.4	3.8	4.2	5	5.9	6.7
  50	110	2.4	3	3.6	4.2	4.8	5.4	6	7.2	8.4	9.6
  60	132	2.9	3.6	4.3	5	5.8	6.5	7.2	8.6	10.1	11.5
  70	154	3.4	4.2	5	5.9	6.7	7.6	8.4	10.1	11.8	13.4
  80	176	3.8	4.8	5.8	6.7	7.7	8.6	9.6	11.5	13.4	15.4
  90	198	4.3	5.4	6.5	7.6	8.6	9.7	10.8	13	15.1	17.3
  100	220	4.8	6	7.2	8.4	9.6	10.8	12	14.4	16.8	19.2
  )

Rocuronium Bromide Injection is available as

• 5 mL multi-dose vials containing 50 mg rocuronium bromide injection (10 mg per mL)
• 10 mL multi-dose vials containing 100 mg rocuronium bromide injection (10 mg per mL)

• Labor and Delivery
  : Not recommended for rapid sequence induction in patients undergoing Caesarean section. (
  8.2 Labor and Delivery

  The use of rocuronium bromide in Caesarean section has been studied in a limited number of patients

  [see Clinical Studies ]

  . Rocuronium bromide is not recommended for rapid sequence induction in Caesarean section patients.
  )
• Pediatric Use
  : Onset time and duration will vary with dose, age, and anesthetic technique. Not recommended for rapid sequence intubation in pediatric patients. (
  8.4 Pediatric Use

  The use of rocuronium bromide has been studied in pediatric patients 3 months to 14 years of age under halothane anesthesia. Of the pediatric patients anesthetized with halothane who did not receive atropine for induction, about 80% experienced a transient increase (30% or greater) in heart rate after intubation. One of the 19 infants anesthetized with halothane and fentanyl who received atropine for induction experienced this magnitude of change

  [see Dosage and Administration and Clinical Studies ]

  .

  Rocuronium bromide was also studied in pediatric patients up to 17 years of age, including neonates, under sevoflurane (induction) and isoflurane/nitrous oxide (maintenance) anesthesia. Onset time and clinical duration varied with dose, the age of the patient, and anesthetic technique. The overall analysis of ECG data in pediatric patients indicates that the concomitant use of rocuronium bromide with general anesthetic agents can prolong the QTc interval. The data also suggest that rocuronium bromide may increase heart rate. However, it was not possible to conclusively identify an effect of rocuronium bromide independent of that of anesthesia and other factors. Additionally, when examining plasma levels of rocuronium bromide in correlation to QTc interval prolongation, no relationship was observed

  [see Dosage and Administration , Warnings and Precautions , and Clinical Studies ]

  .

  Rocuronium bromide is not recommended for rapid sequence intubation in pediatric patients. Recommendations for use in pediatric patients are discussed in other sections

  [see Dosage and Administration and Clinical Pharmacology ]

  .
  )

• Appropriate Administration and Monitoring
  : Use only if facilities for intubation, mechanical ventilation, oxygen therapy, and an antagonist are immediately available. (
  5.1 Appropriate Administration and Monitoring

  Rocuronium bromide should be administered in carefully adjusted dosages by or under the supervision of experienced clinicians who are familiar with the drug's actions and the possible complications of its use. The drug should not be administered unless facilities for intubation, mechanical ventilation, oxygen therapy, and an antagonist are immediately available. It is recommended that clinicians administering neuromuscular blocking agents such as rocuronium bromide employ a peripheral nerve stimulator to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered.
  )
• Anaphylaxis
  : Severe anaphylaxis has been reported. Consider cross-reactivity among neuromuscular blocking agents. (
  5.2 Anaphylaxis

  Severe anaphylactic reactions to neuromuscular blocking agents, including rocuronium bromide, have been reported. These reactions have, in some cases (including cases with rocuronium bromide), been life threatening and fatal. Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken. Precautions should also be taken in those patients who have had previous anaphylactic reactions to other neuromuscular blocking agents, since cross-reactivity between neuromuscular blocking agents, both depolarizing and nondepolarizing, has been reported.
  )
• Risk of Death due to Medication Errors
  : Accidental administration can cause death. (
  5.3 Risk of Death due to Medication Errors

  Administration of rocuronium bromide results in paralysis, which may lead to respiratory arrest and death, a progression that may be more likely to occur in a patient for whom it is not intended. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings. If another healthcare provider is administering the product, ensure that the intended dose is clearly labeled and communicated.
  )
• Need for Adequate Anesthesia:
  Must be accompanied by adequate anesthesia or sedation. (
  5.4 Need for Adequate Anesthesia

  Rocuronium bromide has no known effect on consciousness, pain threshold, or cerebration. Therefore, its administration must be accompanied by adequate anesthesia or sedation.
  )
• Residual Paralysis
  : Consider using a reversal agent in cases where residual paralysis is more likely to occur. (
  5.5 Residual Paralysis

  In order to prevent complications resulting from residual paralysis, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Geriatric patients (65 years or older) may be at increased risk for residual neuromuscular block. Other factors which could cause residual paralysis after extubation in the post-operative phase (such as drug interactions or patient condition) should also be considered. If not used as part of standard clinical practice the use of a reversal agent should be considered, especially in those cases where residual paralysis is more likely to occur.
  )