Nimbex Injection 2 mg/ml

INJECTION, SOLUTION

**Dosage and Administration** As with other neuromuscular blocking agents, monitoring of neuromuscular function is recommended during the use of _NIMBEX_ in order to individualise dosage requirements. - **Use by I.V. bolus injection in adults** **Tracheal intubation**: The recommended intubation dose of _NIMBEX_ for adults is 0.15 mg/kg administered rapidly over 5 to 10 seconds. This dose produces good to excellent conditions for tracheal intubation 120 seconds following injection. Higher doses will shorten the time to onset of neuromuscular block. Table 1 summarises mean pharmacodynamic data when _NIMBEX_ injection was administered at doses of 0.1 to 0.4 mg/kg to healthy adult patients during opioid (thiopentone/fentanyl/midazolam) or propofol anaesthesia.  Enflurane or isoflurane anaesthesia may extend the clinically effective duration of an initial dose of _NIMBEX_ by as much as 15%. **Maintenance**: Neuromuscular block can be extended with maintenance doses of _NIMBEX_. A dose of 0.03 mg/kg provides approximately 20 minutes of additional clinically effective neuromuscular block during opioid or propofol anaesthesia. Consecutive maintenance doses do not result in progressive prolongation of effect. **Spontaneous recovery**: Once spontaneous recovery from neuromuscular block is underway, the rate is independent of the _NIMBEX_ dose administered. During opioid or propofol anaesthesia, the median times from 25 to 75% and from 5 to 95% recovery are approximately 13 and 30 minutes, respectively. **Reversal**: Neuromuscular block following _NIMBEX_ administration is readily reversible with standard doses of anticholinesterase agents. The mean times from 25 to 75% recovery and to full clinical recovery (T4:T1 ratio more than or equal to 0.7) are approximately 2 and 5 minutes, respectively, following administration of the reversal agent at an average of 13% T1 recovery. - **Use by I.V. bolus injection in children (1 month to 12 years of age)** _NIMBEX_ has not been studied for intubation in ASA Class III–IV paediatric patients. There are limited data on the use of _NIMBEX_ in paediatric patients under 2 years of age undergoing prolonged or major surgery. **Tracheal intubation**: As in adults, the recommended initial intubation dose of _NIMBEX_ is 0.15 mg/kg administered rapidly over 5 to 10 seconds. This dose produces good to excellent conditions for tracheal intubation 120 seconds following injection of _NIMBEX_. Pharmacodynamic data for this dose are presented in the tables 2 and 3. If a shorter clinical duration is required, pharmacodynamic data suggest that a dose of 0.1 mg/kg may produce similar intubation conditions at 120 to 150 seconds. In paediatric patients aged 1 month to 12 years, _NIMBEX_ has a shorter clinically effective duration and a faster spontaneous recovery profile than those observed in adults under similar anaesthetic conditions. Small differences in the pharmacodynamic profile were observed between the age ranges 1 to 11 months and 1 to 12 years which are summarised in Tables 2 and 3 below.   Halothane may be expected to extend the clinically effective duration of _NIMBEX_ by up to 20%. No information is available on the use of _NIMBEX_ in children during isoflurane or enflurane anaesthesia but these agents may also be expected to extend the clinically effective duration of a dose of _NIMBEX_ by up to 20%. **Maintenance (paediatric patients aged 2–12 years)**: Neuromuscular block can be extended with maintenance doses of _NIMBEX_ injection. A dose of 0.02 mg/kg provides approximately 9 minutes of additional clinically effective neuromuscular block during halothane anaesthesia. Consecutive maintenance doses do not result in progressive prolongation of effect. There are insufficient data to make a specific recommendation for maintenance dosing in paediatric patients under 2 years of age. However, very limited data from clinical studies in paediatric patients under 2 years age suggest that a maintenance dose of 0.03 mg/kg may extend clinically effective neuromuscular block for a period of up to 25 minutes during opioid anaesthesia. **Spontaneous recovery**: Once recovery from neuromuscular block is underway, the rate is independent of the _NIMBEX_ dose administered. During opioid or halothane anaesthesia, the median times from 25 to 75% and from 5 to 95% recovery are approximately 11 and 28 minutes, respectively. **Reversal**: Neuromuscular block following _NIMBEX_ administration is readily reversible with standard doses of anticholinesterase agents. The mean times from 25 to 75% recovery and to full clinical recovery (T4:T1 ratio more than or equal to 0.7) are approximately 2 and 5 minutes, respectively, following administration of the reversal agent at an average of 13% T1 recovery. - **Use by I.V. infusion in adults and children (2 to 12 years of age)** Maintenance of neuromuscular block may be achieved by infusion of _NIMBEX_. An initial infusion rate of 3 micrograms/kg/min (0.18 mg/kg/h) is recommended to restore 89 to 99% T1 suppression following evidence of spontaneous recovery. After an initial period of stabilisation of neuromuscular block, a rate of 1 to 2 micrograms/kg/min (0.06 to 0.12 mg/kg/h) should be adequate to maintain block in this range in most patients. Reduction of the infusion rate by up to 40% may be required when _NIMBEX_ is administered during isoflurane or enflurane anaesthesia. ( _see Interactions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). The infusion rate will depend upon the concentration of _NIMBEX_ in the infusion solution, the desired degree of neuromuscular block, and the patient's weight. Table 4 provides guidelines for delivery of undiluted _NIMBEX_.  Steady rate continuous infusion of _NIMBEX_ is not associated with a progressive increase or decrease in neuromuscular blocking effect. Following discontinuation of infusion of _NIMBEX_, spontaneous recovery from neuromuscular block proceeds at a rate comparable to that following administration of a single bolus. - **Neonates aged less than 1 month** No dosage recommendation for neonates can be made as administration of _NIMBEX_ has not been studied in this patient population. - **Elderly** No dosing alterations are required in elderly patients. In these patients _NIMBEX_ has a similar pharmacodynamic profile to that observed in young adult patients but, as with other neuromuscular blocking agents, it may have a slightly slower onset. - **Patients with renal impairment** No dosing alterations are required in patients with renal failure. In these patients _NIMBEX_ has a similar pharmacodynamic profile to that observed in patients with normal renal function but it may have a slightly slower onset. - **Patients with hepatic impairment** No dosing alterations are required in patients with end-stage liver disease. In these patients _NIMBEX_ has a similar pharmacodynamic profile to that observed in patients with normal hepatic function but it may have a slightly faster onset. - **Patients with cardiovascular disease** When administered by rapid bolus injection (over 5 to 10 seconds) to patients with serious cardiovascular disease _NIMBEX_ has not been associated with clinically significant cardiovascular effects at any dose studied (up to and including 0.4 mg/kg (8 x ED95)). However, there are limited data for doses above 0.3 mg/kg in this patient population. _NIMBEX_ has not been studied in children undergoing cardiac surgery. - **ICU patients** _NIMBEX_ may be administered by bolus dose and/or infusion to adult patients in the ICU. An initial infusion rate of _NIMBEX_ of 3 micrograms/kg/min (0.18 mg/kg/h) is recommended for adult ICU patients. There may be wide inter-patient variation in dosage requirements and these may increase or decrease with time. In clinical studies the average infusion rate was 3 micrograms/kg/min \[range 0.5 to 10.2 micrograms/kg/min (0.03 to 0.6 mg/kg/h)\]. Table 5 provides guidelines for delivery of undiluted _NIMBEX_. The median time to full spontaneous recovery following long-term (up to 6 days) infusion of _NIMBEX_ in ICU patients was approximately 50 minutes.  The recovery profile after infusions of _NIMBEX_ to ICU patients is independent of duration of infusion. - **Patients undergoing hypothermic cardiac surgery** There have been no studies of _NIMBEX_ in patients undergoing surgery with induced hypothermia (25°C to 28°C). As with other neuromuscular blocking agents, the rate of infusion required to maintain adequate surgical relaxation under these conditions may be expected to be significantly reduced.