Esmeron has a shelf life of 3 years, provided it is stored under the prescribed conditions (see Special precautions for storage). The date mentioned on the carton and on the label of the vial is the expiry date; this is the date up to which Esmeron may be used. Since Esmeron does not contain a preservative, the solution should be used immediately after opening the vial.
After dilution with infusion fluids , chemical and physical in-use stability has been demonstated for 72 hours at 30°C. From a microbiological point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user/administrator and would normally not be longer than 24 hours at 2 to 8oC, unless dilution has taken place in controlled and validated aseptic conditions.
Physical incompatibility has been documented for Esmeron when added to solutions containing the following drugs: amphotericin, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin, intralipid, methohexital, methylprednisolone, prednisolone sodium succinate, thiopental, trimethoprim and vancomycin.
If Esmeron is administered via the same infusion line that is also used for other drugs, it is important that this infusion line is adequately flushed (e.g. with 0.9% NaCl) between administration of Esmeron and drugs for which incompatibility with Esmeron has been demonstrated or for which compatibility with Esmeron has not been established.
Esmeron contains the following excipients:
- Sodium acetate (E262) (for pH adjustment)
- Sodium chloride
- Acetic acid (E260) (for pH adjustment)
- Water
No preservative has been added
Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
There is no proper animal model to mimic the usually extremely complex clinical situation of the ICU patient. Therefore the safety of Esmeron when used to facilitate mechanical ventilation in the Intensive Care Unit is mainly based on results obtained in clinical studies.
After intravenous administration of a single bolus dose of rocuronium bromide the plasma concentration time course runs in three exponential phases. In normal adults, the mean (95% CI) elimination half-life is 73 (66-80) minutes, the (apparent) volume of distribution at steady state conditions is 203 (193-214) ml/kg and plasma clearance is 3.7 (3.5-3.9) ml/kg/min.
Rocuronium is excreted in urine and bile. Excretion in urine approaches 40% within 12-24 hours. After injection of a radiolabeled dose of rocuronium bromide, excretion of the radiolabel is on average 47% in urine and 43% in faeces after 9 days. Approximately 50% is recovered as the parent compound. No metabolites are detected in plasma.
Paediatric population
Pharmacokinetics of rocuronium bromide in paediatric patients (n=146) with ages ranging from 0 to 17 years were evaluated using a population analysis of the pooled pharmacokinetic datasets from two clinical trials under sevoflurane (induction) and isoflurane/nitrous oxide (maintenance) anesthesia. All pharmacokinetic parameters were found to be linearly proportional to body weight illustrated by a similar clearance (l.hr-1.kg-1). The volume of distribution (l.kg-1) and elimination half-life (h) decrease with age (years). The pharmacokinetic parameters of typical paediatrics within each age group are summarized below:
Estimated PK parameters (Mean [SD]) of rocuronium bromide in typical paediatric patients during sevoflurane and nitrous oxide (induction) and isoflurane/nitrous oxide (maintenance anaesthesia)
|
PK Parameters |
Patient age range | ||||
|
Term newborn infants (0-27 days) |
Infants (28 days to 2 months) |
Toddlers (3-23 months) |
Children (2-11 years) |
Adolescents (12-17 years) | |
|
CL (L/kg/hr) |
0.31 (0.07) |
0.30 (0.08) |
0.33 (0.10) |
0.35 (0.09) |
0.29 (0.14) |
|
Volume of distribution (L/kg) |
0.42 (0.06) |
0.31 (0.03) |
0.23 (0.03) |
0.18 (0.02) |
0.18 (0.01) |
|
t ½ β (hr) |
1.1 (0.2) |
0.9 (0.3) |
0.8 (0.2) |
0.7 (0.2) |
0.8 (0.3) |
Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure
In controlled studies the plasma clearance in geriatric patients and in patients with renal dysfunction was reduced, in most studies however without reaching the level of statistical significance. In patients with hepatic disease, the mean elimination half-life is prolonged by 30 minutes and the mean plasma clearance is reduced by 1 ml/kg/min. ()
Intensive Care unit
When administered as a continuous infusion to facilitate mechanical ventilation for 20 hours or more, the mean elimination half-life and the mean (apparent) volume of distribution at steady state are increased. A large between patient variability is found in controlled clinical studies, related to nature and extent of (multiple) organ failure and individual patient characteristics. In patients with multiple organ failure a mean (± SD) elimination half-life of 21.5 (± 3.3) hours, a (apparent) volume of distribution at steady state of 1.5 (± 0.8) l/kg and a plasma clearance of 2.1 (± 0.8) ml/kg/min were found.
23 November 2017
NV Organon, Kloosterstraat 6, PO Box 20, 5340 BH Oss, The Netherlands
Storage in the Refrigerator
Esmeron should be stored at 2°-8°C in the dark and used within the expiry date given on the pack.
Storage out of the refrigerator
Esmeron may also be stored outside of the refrigerator at a temperature of up to 30°C for a maximum 12 weeks, after which it should be discarded. The product should not be placed back into the refrigerator, once it has been kept outside. The storage period must not exceed the shelf-life.
Esmeron 25 mg in 2.5 ml (10mg/ml)
Packaging of 10 vials each containing 25 mg rocuronium bromide.
Esmeron 50 mg in 5 ml (10mg/ml)
Packaging of 10 vials each containing 50 mg rocuronium bromide.
Esmeron 100 mg in 10 ml (10mg/ml)
Packaging of 10 vials each containing 100 mg rocuronium bromide.
Not all pack sizes may be marketed.
Type 1 Ph.Eur., clear, colourless, glass vial with a rubber closure and flip off cap. The rubber stopper of the vial does not contain latex.
In correspondence please quote lot number.
PL 05003/0041
Compatibility studies with the following infusion fluids have been performed: In nominal concentrations of 0.5 mg/ml and 2.0 mg/ml Esmeron has been shown to be compatible with: 0.9% NaCl, 5% dextrose, 5% dextrose in saline, sterile water for injections, Lactated Ringers and Haemaccel. Administration should be begun immediately after mixing, and should be completed within 24 hours. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Date of first authorisation: 15th July 1996
Date of latest renewal: 7th May 2002
