Sugammadex: The First Selective Relaxant Binding Agent

Sugammadex (Bridion; Merck & Co., Inc.) is the first of a new class of drugs: selective relaxant binding agents. The drug reverses the neuromuscular blocking effects of rocuronium and vecuronium, two steroidal neuromuscular blocking agents (NMBAs) used to facilitate endotracheal intubation in patients undergoing surgery. Sugammadex forms complexes with and reduces the free concentration of NMBA available to bind nicotinic receptors of the neuromuscular junction, which reverses their effects.

Efficacy

Approval of sugammadex was based on three multicenter randomized blinded studies with parallel groups and active controls. Train-of-four (TOF) monitoring of muscle response to impulses along a nerve was used to assess for spontaneous recovery. A TOF response ratio of 0.9 or greater correlates to recovery and the patient’s ability to maintain spontaneous breathing.

In two studies, sugammadex rapidly resulted in a TOF ratio of at least 0.9 within minutes (median times to TOF>/= 0.9 for sugammadex versus neostigmine; 1.4 minutes versus 21.5 minutes, and 2.1 minutes and 29.0 minutes, respectively).

A third study assessed the use of 16 mg/kg of sugammadex to reverse rocuronium 1.2 mg/kg in 110 participants undergoing similar surgical procedures that required intubation, compared to spontaneous recovery from 1 mg/kg of succinylcholine. Sugammadex was given 3 minutes after the administration of rocuronium. The time of recovery of the first twitch of the TOF to 10% of baseline was assessed for all participants. Recovery was faster among participants receiving sugammadex (median time: 4.2 minutes versus 7.1 minutes).

Safety

The most common adverse effects associated with sugammadex use are nausea, pruritis, and urticaria. Rare but serious adverse effects include hypersensitivity reactions (which may occur with first exposure), significant bradycardia including cardiac arrest, and prolonged neuromuscular blockade. A clinically significant displacement reaction leading to recurrence of neuromuscular blockade can occur with concomitant use of toremifene. Concomitant, post-operative use of other medications that increase the effects of vecuronium or rocuronium can also increase risk of neuromuscular blockade recurrence.

Dosage

Dosing of sugammadex is either 2 mg/kg or 4 mg/kg, based on the spontaneous return to twitch response via TOF monitoring. When a single dose of rocuronium 1.2 mg/kg has been administered and rapid reversal of neuromuscular blockade is required, 16 mg/kg of sugammadex is indicated. Sugammadex is not for use in patients with severe renal dysfunction or on dialysis. Use of sugammadex at lower than recommended doses can lead to recurrence of neuromuscular blockade. Patients who are using hormonal contraceptives should  use a back-up method of contraception for 7 days after sugammadex.

Anticholinesterases have commonly been used to reverse the effects of NMBAs. These drugs breakdown acetylcholine in the neuromuscular junction to reverse the NMBA effect. However, they are also associated with significant parasympathetic adverse effects. Antimuscarinic drugs are used to combat these effects but may also add to undesirable clinical effects. Sugammadex offers an alternative and a quick return to spontaneous respiration with fewer adverse effects.