Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Merck Sharp & Dohme (UK) Limited, 120 Moorgate, London, EC2M 6UR, UK
Hypersensitivity to rocuronium or to the bromide ion or to any of the excipients.
Since Esmeron causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this drug until adequate spontaneous respiration is restored. As with all neuromuscular blocking agents, it is important to anticipate intubation difficulties, particularly when used as part of a rapid sequence induction technique.
As with other neuromuscular blocking agents, residual neuromuscular blockade has been reported for Esmeron. In order to prevent complications resulting from residual neuromuscular blockade, 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 neuromuscular blockade 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 (such as sugammadex or acetylcholinesterase inhibitors) should be considered, especially in those cases where residual neuromuscular blockade is more likely to occur.
High rates of cross-sensitivity between neuromuscular blocking agents have been reported. Therefore, where possible, before administering Esmeron, hypersensitivity to other neuromuscular blocking agents should be excluded. Esmeron should only be used when absolutely essential in susceptible patients. Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers.
Rocuronium may increase the heart rate.
In general, following long-term use of neuromuscular blocking agents in the ICU, prolonged paralysis and/or skeletal muscle weakness has been noted. In order to help preclude possible prolongation of neuromuscular block and/or overdosage it is strongly recommended that neuromuscular transmission is monitored throughout the use of neuromuscular blocking agents. In addition, patients should receive adequate analgesia and sedation. Furthermore, neuromuscular blocking agents should be titrated to effect in the individual patients by or under supervision of experienced clinicians who are familiar with their actions and with appropriate neuromuscular monitoring techniques.
Myopathy after long-term administration of other non-depolarising neuromuscular blocking agents in the ICU in combination with corticosteroid therapy has been reported regularly. 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.
If suxamethonium is used for intubation, the administration of Esmeron should be delayed until the patient has clinically recovered from the neuromuscular block induced by suxamethonium.
Because rocuronium bromide is always used with other drugs and because of the risk of malignant hyperthermia during anesthesia, even in the absence of known triggering factors, physicians should be aware of the early symptoms, confirmatory diagnosis and treatment of malignant hyperthermia prior to the start of anesthesia. Animal studies have shown that rocuronium bromide is not a triggering factor for malignant hyperthermia. Rare cases of malignant hyperthermia with ESMERON have been observed thru post-marketing surveillance; however, the causal association has not been proven.
The following conditions may influence the pharmacokinetics and/or pharmacodynamics of Esmeron
Because rocuronium is excreted in urine and bile, it should be used with caution in patients with clinically significant hepatic and/or biliary diseases and/or renal failure. In these patient groups prolongation of action has been observed with doses of 0.6 mg/kg rocuronium bromide.
Conditions associated with prolonged circulation time such as cardiovascular disease, old age and oedematous state resulting in an increased volume of distribution, may contribute to a slower onset of action. The duration of action may also be prolonged due to a reduced plasma clearance.
Like other neuromuscular blocking agents, Esmeron should be used with extreme caution in patients with a neuromuscular disease or after poliomyelitis since the response to neuromuscular blocking agents may be considerably altered in these cases. The magnitude and direction of this alteration may vary widely. In patients with myasthenia gravis or with the myasthenic (Eaton-Lambert) syndrome, small doses of Esmeron may have profound effects and Esmeron should be titrated to the response.
In surgery under hypothermic conditions, the neuromuscular blocking effect of Esmeron is increased and the duration prolonged.
Like other neuromuscular blocking agents, Esmeron may exhibit a prolonged duration and a prolonged spontaneous recovery in obese patients when the administered doses are calculated on actual body weight.
Patients with burns are known to develop resistance to non-depolarising neuromuscular blocking agents. It is recommended that the dose is titrated to response.
Hypokalaemia (e.g. after severe vomiting, diarrhoea and diuretic therapy), hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, dehydration, acidosis, hypercapnia, cachexia.
Severe electrolyte disturbances, altered blood pH or dehydration should therefore be corrected when possible.
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.
The following drugs have been shown to influence the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents.
Increased effect:
Other drugs:
Recurarisation has been reported after post-operative administration of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine, quinine and magnesium salts (see section 4.4).
Decreased effect:
Variable effect:
Esmeron combined with lidocaine may result in a quicker onset of action of lidocaine.
No formal interaction studies have been performed. The above mentioned interactions for adults and their special warnings and precautions for use (see section 4.4) should be taken into account for paediatric patients.
For rocuronium bromide, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Caution should be exercised when prescribing Esmeron to pregnant women.
In patients undergoing Caesarean section, Esmeron can be used as part of a rapid sequence induction technique, provided no intubation difficulties are anticipated and a sufficient dose of anaesthetic agent is administered or following suxamethonium facilitated intubation. However, Esmeron, administered in doses of 0.6 mg/kg may not produce adequate conditions for intubation until 90 seconds after administration. This dose has been shown to be safe in parturients undergoing Caesarean section. Esmeron does not affect Apgar score, foetal muscle tone or cardiorespiratory adaptation. From umbilical cord blood sampling it is apparent that only limited placental transfer of rocuronium bromide occurs which does not lead to the observation of clinical adverse effects in the newborn.
Note 1: doses of 1.0 mg/kg have been investigated during rapid sequence induction of anaesthesia, but not in Caesarean section patients. Therefore, only a dose of 0.6 mg/kg is recommended in this patient group.
Note 2: Reversal of neuromuscular block induced by neuromuscular blocking agents may be inhibited or unsatisfactory in patients receiving magnesium salts for toxemia of pregnancy because magnesium salts enhance neuromuscular blockade. Therefore, in these patients the dosage of Esmeron should be reduced and be titrated to twitch response.
It is unknown whether rocuronium bromide is excreted in human breast milk. Animal studies have shown insignificant levels of rocuronium bromide in breast milk.
Insignificant levels of rocuronium bromide were found in the milk of lactating rats. There are no human data on the use of Esmeron during lactation. Esmeron should be given to lactating women only when the attending physician decides that the benefits outweigh the risks. After the administration of a single dose, it is recommended to abstain from next breastfeeding for five elimination half-lives of rocuronium, i.e. for about 6 hours.
Since Esmeron is used as an adjunct to general anaesthesia, the usual precautionary measures after a general anaesthesia should be taken for ambulatory patients.
The most commonly occurring adverse drug reactions include injection site pain/reaction, changes in vital signs and prolonged neuromuscular block. The most frequently reported serious adverse drug reactions during post-marketing surveillance is ‘anaphylactic and anaphylactoid reactions’ and associated symptoms. See also the explanations below the table.
| MedDRA SOC | Preferred term1 | ||
|---|---|---|---|
| Uncommon/rare2 (<1/100, >1/10 000) | Very rare (<1/10 000) | Not Known | |
| Immune system disorders | Hypersensitivity Anaphylactic reaction Anaphylactoid reaction Anaphylactic shock Anaphylactoid shock | ||
| Nervous system disorders | Flaccid paralysis | ||
| Cardiac disorders | Tachycardia | Kounis syndrome | |
| Vascular disorders | Hypotension | Circulatory collapse and shock Flushing | |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm | ||
| Skin and subcutaneous tissue disorders | Angioneurotic oedema Urticaria Rash Erythematous rash | ||
| Musculoskeletal and connective tissue disorders | Muscular weakness3 Steroid myopathy3 | ||
| General disorders and administration site conditions | Drug ineffective Drug effect/therapeutic response decreased Drug effect/therapeutic response increased Injection site pain Injection site reaction | Face oedema | |
| Injury, poisoning and procedural complications | Prolonged neuromuscular block Delayed recovery from anaesthesia | Airway complication of anaesthesia | |
MedDRA version 8.1
1 Frequencies are estimates derived from post-marketing surveillance reports and data from the general literature.
2 Post-marketing surveillance data cannot give precise incidence figures. For that reason, the reporting frequency was divided over two rather than five categories.
3 after long-term use in the ICU
Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including Esmeron, have been reported. Anaphylactic/anaphylactoid reactions are: bronchospasm, cardiovascular changes (e.g. hypotension, tachycardia, circulatory collapse – shock), and cutaneous changes (e.g. angioedema, urticaria). These reactions have, in some cases, been fatal. Due to the possible severity of these reactions, one should always assume they may occur and take the necessary precautions.
Since neuromuscular blocking agents are known to be capable of inducing histamine release both locally at the site of injection and systemically, the possible occurrence of itching and erythematous reaction at the site of injection and/or generalised histaminoid (anaphylactoid) reactions (see also under anaphylactic reactions above) should always be taken into consideration when administering these drugs.
In clinical studies only a slight increase in mean plasma histamine levels has been observed following rapid bolus administration of 0.3-0.9 mg/kg rocuronium bromide.
The most frequent adverse reaction to non-depolarising blocking agents as a class consists of an extension of the drug’s pharmacological action beyond the time period needed. This may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or apnea.
Myopathy has been reported after the use of various neuromuscular blocking agents in the ICU in combination with corticosteroids (see section 4.4).
During rapid sequence induction of anaesthesia, pain on injection has been reported, especially when the patient has not yet completely lost consciousness and particularly when propofol is used as the induction agent. In clinical studies, pain on injection has been noted in 16% of the patients who underwent rapid sequence induction of anaesthesia with propofol and in less than 0.5% of the patients who underwent rapid sequence induction of anaesthesia with fentanyl and thiopental.
A meta-analysis of 11 clinical studies in paediatric patients (n=704) with rocuronium bromide (up to 1 mg/kg) showed that tachycardia was identified as adverse drug reaction with a frequency of 1.4%.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
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.
Esmeron must not be mixed with other medicinal products except those mentioned in section 6.6.
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.
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