Sugammadex

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Bridion (Schering Plough)
vials containing 100 mg/mL solution for injection
Approved indication: reversal of neuromuscular blockade by rocuronium or vecuronium
Australian Medicines Handbook section 2.4.4

Drugs that reverse neuromuscular blockade are used by anaesthetists at the end of surgery to accelerate recovery from drug-induced muscle relaxation. Sugammadex is a modified gamma cyclodextrin designed to selectively reverse the effects of the neuromuscular blockers rocuronium and vecuronium. It works by forming a complex with these drugs, reducing their availability to bind to nicotinic receptors in the neuromuscular junction. There are no safety and efficacy data to support the use of sugammadex for reversing other neuromuscular blockers including suxamethonium, and benzylisoquinolium compounds such as atracurium and cisatracurium. Similarly, sugammadex should not be used to reverse pancuronium-induced blockade.

Until now, cholinesterase inhibitors such as neostigmine and edrophonium have been used to reverse neuromuscular blockade after surgery. However, these drugs have a relatively slow onset and have adverse effects associated with stimulation of muscarinic receptors. In addition, neostigmine cannot be used to reverse profound blockade.

The dose of sugammadex depends on the degree of neuromuscular blockade required. In a comparative trial of 182 randomised patients, sugammadex (4 mg/kg) was more effective than neostigmine (70 microgram/kg) at reversing profound neuromuscular blockade induced by rocuronium or vecuronium. The mean time to recovery of muscle function (measured using an acceleromyograph) was three minutes after the sugammadex injection compared to 50 minutes after neostigmine.^1,2 Sugammadex (2 mg/kg) was also quicker than neostigmine (50 microgram/kg) at reversing moderate neuromuscular blockade (mean recovery times of 1-2 mins vs 16-18 mins) in a trial of 189 patients.

In situations where immediate reversal of rocuronium-induced blockade is required, the recommended dose is 16 mg/kg of sugammadex three minutes after rocuronium administration. This recommendation is based on a trial comparing sugammadex for immediate reversal of rocuronium-induced blockade with spontaneous recovery of 110 patients given the short-duration muscle relaxant suxamethonium. Mean recovery times were quicker with sugammadex than with the comparator (4 mins vs 7 mins). There are no clinical data to recommend sugammadex for immediate reversal of vecuronium-induced blockade.³

Following intravenous administration, sugammadex has an elimination half-life of 2.2 hours. This is increased in elderly patients and decreased in children. After injection, most of the sugammadex dose is excreted unchanged in the urine, so its use in people with severe renal impairment is not recommended. Longer recovery times may be observed in older patients as well as people with cardiovascular disease, oedema or severe hepatic impairment.³

If re-administration of rocuronium or vecuronium is required after reversal with sugammadex, a waiting period is recommended. The duration depends on the dose of sugammadex, the dose of rocuronium or vecuronium, and the patient's renal function.

The most common adverse effect of sugammadex is a disturbance in taste (metallic or bitter taste), which was reported by 12% of patients in a dose escalation trial (mainly after a higher dose of 32 mg/kg). Recurrent blockade has occurred with sugammadex (2% of patients), however this was mostly associated with a suboptimal dose of sugammadex (less than 2 mg/kg). Anaesthetic complications such as body movement, coughing or grimacing during the anaesthetic (which are signs of restoration of neuromuscular function) were thought to be related to sugammadex treatment in about 1% of patients. Allergic reactions, such as flushing or erythematous rash, have been observed with sugammadex.

Sugammadex should not be used in children less than two years. In older children and adolescents, there are limited efficacy and safety data to support its routine use. Immediate reversal in children has not been assessed.

Although no direct drug interactions are expected with sugammadex, drugs interacting with vecuronium or rocuronium could potentially affect the efficacy of sugammadex. Toremifene, fusidic acid and flucloxacillin can displace vecuronium or rocuronium from the complex with sugammadex. This would potentially delay recovery time. High doses of flucloxacillin (500 mg or more) should be avoided in the postoperative period.

Prescribers need to be aware that sugammadex may decrease progestogen concentrations, similar to the decrease observed after missing a daily dose of an oral contraceptive. Women on the pill should refer to the missed dose advice for their contraceptive. Likewise, women using non-oral hormonal contraceptives, such as depot formulations, should be advised to use additional contraception for the next seven days.

Sugammadex may affect haemostasis by interfering with the coagulation cascade. Patients with pre-existing coagulation abnormalities should therefore be monitored for activated partial thromboplastin time, prothrombin time and INR after receiving sugammadex.

Prolongation of the QT_c interval has been noted in some patients receiving sugammadex, however torsades des pointes has not occurred. QT_c prolongation is a concern in situations where sugammadex is given with other drugs that affect the QT_c interval such as the anaesthetics sevoflurane and propofol.

Sugammadex is the first selective relaxant binding agent. It rapidly reverses neuromuscular block induced by rocuronium or vecuronium regardless of the depth of the block. However, recurrence of neuromuscular blockade has been reported with this drug so close monitoring of respiratory function remains vital during the recovery period. This drug has not been assessed in intensive care units.

manufacturer provided only the product information

The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).

At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).