Zemuron Information
Zemuron (Rocuronium bromide) Indications And Usage
Zemuron (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.
Zemuron (Rocuronium bromide) Dosage And Administration
Zemuron (Rocuronium bromide) is for intravenous use only.
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 Zemuron (Rocuronium bromide) .
In patients in whom potentiation of, or resistance to, neuromuscular block is anticipated, a dose adjustment should be considered .
Zemuron (Rocuronium bromide) Dosage Forms And Strengths
Zemuron (Rocuronium bromide) injection is available as
Zemuron (Rocuronium bromide) Contraindications
Zemuron (Rocuronium bromide) is contraindicated in patients known to have hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents .
Zemuron (Rocuronium bromide) Warnings And Precautions
Severe anaphylactic reactions to neuromuscular blocking agents, including Zemuron (Rocuronium bromide) , have been reported. These reactions have, in some cases (including cases with Zemuron (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 non depolarizing, has been reported.
Zemuron (Rocuronium bromide) has not been studied for long-term use in the intensive care unit (ICU). As with other nondepolarizing neuromuscular blocking drugs, apparent tolerance to Zemuron (Rocuronium bromide) may develop during chronic administration in the ICU. While the mechanism for development of this resistance is not known, receptor up-regulation may be a contributing factor. Prolonged paralysis and/or skeletal muscle weakness may be noted during initial attempts to wean from the ventilator patients who have chronically received neuromuscular blocking drugs in the ICU.
Myopathy after long-term administration of other nondepolarizing neuromuscular blocking agents in the ICU alone or in combination with corticosteroid therapy has been reported. Therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible and only used in the setting where in the opinion of the prescribing physician, the specific advantages of the drug outweigh the risk.
Zemuron (Rocuronium bromide) has not been studied in MH-susceptible patients. Because Zemuron (Rocuronium bromide) is always used with other agents, and the occurrence of malignant hyperthermia during anesthesia is possible even in the absence of known triggering agents, clinicians should be familiar with early signs, confirmatory diagnosis, and treatment of malignant hyperthermia prior to the start of any anesthetic.
In an animal study in MH-susceptible swine, the administration of Zemuron (Rocuronium bromide) Injection did not appear to trigger malignant hyperthermia.
Zemuron (Rocuronium bromide) Adverse Reactions
In clinical trials, the most common adverse reactions (2%) are transient hypotension and hypertension.
The following adverse reactions are described, or described in greater detail, in other sections:
Zemuron (Rocuronium bromide) Drug Interactions
Use of inhalation anesthetics has been shown to enhance the activity of other neuromuscular blocking agents (enflurane > isoflurane > halothane).
Isoflurane and enflurane may also prolong the duration of action of initial and maintenance doses of Zemuron (Rocuronium bromide) and decrease the average infusion requirement of Zemuron (Rocuronium bromide) by 40% compared to opioid/nitrous oxide/oxygen anesthesia. No definite interaction between Zemuron (Rocuronium bromide) and halothane has been demonstrated. In one study, 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 Zemuron (Rocuronium bromide) of 0.57 to 0.85 mg/kg under enflurane or isoflurane anesthesia, as used clinically, was increased by 11% and 23%, respectively. The duration of maintenance doses was affected to a greater extent, increasing by 30% to 50% under either enflurane or isoflurane anesthesia.
Potentiation by these agents is also observed with respect to the infusion rates of Zemuron (Rocuronium bromide) required to maintain approximately 95% neuromuscular block. Under isoflurane and 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 T) is not affected by halothane, but is prolonged by enflurane (15% longer) and isoflurane (62% longer). Reversal-induced recovery of Zemuron (Rocuronium bromide) neuromuscular block is minimally affected by anesthetic technique .
The use of Zemuron (Rocuronium bromide) before succinylcholine, for the purpose of attenuating some of the side effects of succinylcholine, has not been studied.
If Zemuron (Rocuronium bromide) is administered following administration of succinylcholine, it should not be given until recovery from succinylcholine has been observed. The median duration of action of Zemuron (Rocuronium bromide) 0.6 mg/kg administered after a 1 mg/kg dose of succinylcholine when T returned to 75% of control was 36 minutes (range: 14–57, n=12) vs. 28 minutes (range: 17–51, n=12) without succinylcholine.
Zemuron (Rocuronium bromide) Use In Specific Populations
The use of Zemuron (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 .
Zemuron (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 Zemuron (Rocuronium bromide) with general anesthetic agents can prolong the QTc interval. The data also suggest that Zemuron (Rocuronium bromide) may increase heart rate. However, it was not possible to conclusively identify an effect of Zemuron (Rocuronium bromide) independent of that of anesthesia and other factors. Additionally, when examining plasma levels of Zemuron (Rocuronium bromide) in correlation to QTc interval prolongation, no relationship was observed .
Zemuron (Rocuronium bromide) is not recommended for rapid sequence intubation in pediatric patients. Recommendations for use in pediatric patients are discussed in other sections .
Zemuron (Rocuronium bromide) Overdosage
Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia. The primary treatment is maintenance of a patent airway, controlled ventilation, and adequate sedation until recovery of normal neuromuscular function is assured. Once evidence of recovery from neuromuscular block is observed, further recovery may be facilitated by administration of an anticholinesterase agent in conjunction with an appropriate anticholinergic agent.
Zemuron (Rocuronium bromide) Description
Zemuron (Rocuronium bromide) injection is a nondepolarizing neuromuscular blocking agent with a rapid to intermediate onset depending on dose and intermediate duration. Rocuronium bromide is chemically designated as 1-[17β-(acetyloxy)-3α-hydroxy-2β-(4-morpholinyl)-5α-androstan-16β-yl]-1-(2-propenyl)pyrrolidinium bromide.
The structural formula is:
The chemical formula is CHBrNO with a molecular weight of 609.70. The partition coefficient of rocuronium bromide in n-octanol/water is 0.5 at 20°C.
Zemuron (Rocuronium bromide) is supplied as a sterile, nonpyrogenic, isotonic solution that is clear, colorless to yellow/orange, for intravenous injection only. Each mL contains 10 mg rocuronium bromide and 2 mg sodium acetate. The aqueous solution is adjusted to isotonicity with sodium chloride and to a pH of 4 with acetic acid and/or sodium hydroxide.
Zemuron (Rocuronium bromide) Clinical Pharmacology
The ED (dose required to produce 95% suppression of the first [T] mechanomyographic [MMG] response of the adductor pollicis muscle [thumb] to indirect supramaximal train-of-four stimulation of the ulnar nerve) during opioid/nitrous oxide/oxygen anesthesia is approximately 0.3 mg/kg. Patient variability around the ED dose suggests that 50% of patients will exhibit T depression of 91% to 97%.
Table 4
Table 5
Table 6
The time to 80% or greater block and clinical duration as a function of dose are presented in and .
The clinical durations for the first 5 maintenance doses, in patients receiving 5 or more maintenance doses are represented in .
Once spontaneous recovery has reached 25% of control T, the neuromuscular block produced by Zemuron (Rocuronium bromide) is readily reversed with anticholinesterase agents, e.g., edrophonium or neostigmine.
The median spontaneous recovery from 25% to 75% T was 13 minutes in adult patients. When neuromuscular block was reversed in 36 adults at a T of 22% to 27%, recovery to a T of 89 (50–132)% and T/T of 69 (38–92)% was achieved within 5 minutes. Only 5 of 320 adults reversed received an additional dose of reversal agent. The median (range) dose of neostigmine was 0.04 (0.01–0.09) mg/kg and the median (range) dose of edrophonium was 0.5 (0.3–1.0) mg/kg.
In geriatric patients (n=51) reversed with neostigmine, the median T/T increased from 40% to 88% in 5 minutes.
In clinical trials with halothane, pediatric patients (n=27) who received 0.5 mg/kg edrophonium had increases in the median T/T from 37% at reversal to 93% after 2 minutes. Pediatric patients (n=58) who received 1 mg/kg edrophonium had increases in the median T/T from 72% at reversal to 100% after 2 minutes. Infants (n=10) who were reversed with 0.03 mg/kg neostigmine recovered from 25% to 75% T within 4 minutes.
There were no reports of less than satisfactory clinical recovery of neuromuscular function.
The neuromuscular blocking action of Zemuron (Rocuronium bromide) may be enhanced in the presence of potent inhalation anesthetics .
Zemuron (Rocuronium bromide) Clinical Studies
In US clinical studies, a total of 1137 patients received Zemuron (Rocuronium bromide) , including 176 pediatric, 140 geriatric, 55 obstetric, and 766 other adults. Most patients (90%) were ASA physical status I or II, about 9% were ASA III, and 10 patients (undergoing coronary artery bypass grafting or valvular surgery) were ASA IV. In European clinical studies, a total of 1394 patients received Zemuron (Rocuronium bromide) , including 52 pediatric, 128 geriatric (65 years or greater), and 1214 other adults.
Zemuron (Rocuronium bromide) 0.45, 0.6, or 1 mg/kg was evaluated under sevoflurane (induction) and isoflurane/nitrous oxide (maintenance) anesthesia for intubation in 326 patients in 2 studies. In 1 of these studies maintenance bolus and infusion requirements were evaluated in 137 patients. In all age groups, doses of 0.6 mg/kg provided time to maximum block in about 1 minute. Across all age groups, median (range) time to reappearance of T for doses of 0.6 mg/kg was shortest in the children [36.7 (20.1–65.9) minutes] and longest in infants [59.8 (32.3–87.8) minutes]. For pediatric patients older than 3 months, the time to recovery was shorter after stopping infusion maintenance when compared with bolus maintenance .
Zemuron (Rocuronium bromide) 0.6 or 0.8 mg/kg was evaluated for intubation in 75 pediatric patients (n=28; age 3–12 months, n=47; age 1–12 years) in 3 studies using halothane (1%–5%) and nitrous oxide (60%–70%) in oxygen. Doses of 0.6 mg/kg provided a median (range) time to maximum block of 1 (0.5–3.3) minute(s). This dose provided a median (range) time of clinical relaxation of 41 (24–68) minutes in 3-month to 1-year-old infants and 26 (17–39) minutes in 1- to 12-year-old pediatric patients .
Zemuron (Rocuronium bromide) How Supplied/storage And Handling
Zemuron (Rocuronium bromide) injection is available in the following:
The packaging of this product contains natural rubber (latex).
Zemuron (Rocuronium bromide) should be stored in a refrigerator, 2°–8°C (36°–46°F). DO NOT FREEZE. Upon removal from refrigeration to room temperature storage conditions (25°C/77°F), use Zemuron (Rocuronium bromide) within 60 days. Use opened vials of Zemuron (Rocuronium bromide) within 30 days.
Zemuron (Rocuronium bromide) Patient Counseling Information
Obtain information about your patient's medical history, current medications, any history of hypersensitivity to rocuronium bromide or other neuromuscular blocking agents. If applicable, inform your patients that certain medical conditions and medications might influence how Zemuron (Rocuronium bromide) works.
In addition, inform your patient that severe anaphylactic reactions to neuromuscular blocking agents, including Zemuron (Rocuronium bromide) , have been reported. Since allergic cross-reactivity has been reported in this class, request information from your patients about previous anaphylactic reactions to other neuromuscular blocking agents.
Zemuron (Rocuronium bromide)
Zemuron (Rocuronium bromide)
