Rocuronium Bromide

ROCURONIUM BROMIDE- rocuronium bromide injection
Sagent Pharmaceuticals

1 INDICATIONS AND USAGE

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.

2 DOSAGE AND ADMINISTRATION

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.

In patients in whom potentiation of, or resistance to, neuromuscular block is anticipated, a dose adjustment should be considered [see Dosage and Administration (2.6), Warnings and Precautions (5.10, 5.13), Drug Interactions (7.2, 7.3, 7.4, 7.5, 7.6, 7.8, 7.10), and Use in Specific Populations (8.6)].

Risk of Medication Errors

Accidental administration of neuromuscular blocking agents may be fatal. Store rocuronium bromide with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product [see Warnings and Precautions (5.3)].

2.2 Dose for Tracheal Intubation

The recommended initial dose of rocuronium bromide, 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 to 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 to 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 (7.3)].

A lower dose of rocuronium bromide (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 to 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 to 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 (12.2)].

2.3 Rapid Sequence Intubation

In appropriately premedicated and adequately anesthetized patients, rocuronium bromide 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 (14.1)].

2.4 Maintenance Dosing

Maintenance doses of 0.1, 0.15, and 0.2 mg/kg rocuronium bromide, administered at 25% recovery of control T₁ (defined as 3 twitches of train-of-four), provide a median (range) of 12 (2 to 31), 17 (6 to 50) and 24 (7 to 69) minutes of clinical duration under opioid/nitrous oxide/oxygen anesthesia [see Clinical Pharmacology (12.2)]. 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 (12.2)].

2.5 Use by Continuous Infusion

Infusion at an initial rate of 10 to 12 mcg/kg/min of rocuronium bromide should be initiated only after early evidence of spontaneous recovery from an intubating dose. Due to rapid redistribution [see Clinical Pharmacology (12.3)] 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 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 infusion may be expected to proceed at rates comparable to that following comparable total doses administered by repetitive bolus injections [see Clinical Pharmacology (12.2)].

Infusion solutions of rocuronium bromide can be prepared by mixing rocuronium bromide with an appropriate infusion solution such as 5% glucose in water or lactated Ringers [see Dosage and Administration (2.7)]. These infusion solutions should be used within 24 hours of mixing. Unused portions of infusion solutions should be discarded.

Infusion rates of rocuronium bromide can be individualized for each patient using the following tables for 3 different concentrations of rocuronium bromide 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