Dr.Proxy

Final clinical trials are currently underway in the United States and Europe testing sugammadex, a member of a new class of reversal drugs, which may dramatically alter the practice of anesthesiology. Su refers to sugar and gammadex refers to the structural molecule, a modified cyclodextrin.

Mechanism of Action

The three-dimensional structure of sugammadex resembles a doughnut with a hydrophobic cavity and a hydrophilic exterior. Hydrophobic interactions trap the drug into the cyclodextrin cavity (the doughnut hole) forming a very tight complex at a 1:1 ratio with steroidal neuromuscular blocking drugs (rocuronium > vecuronium >> pancuronium) causing a rapid and long-acting reversal of neuromuscular blockade.

Dose

The usual dose is 2 - 4 mg per kg body weight. A higher dose may be given if the doctor wants you to recover faster.

Side Effects

Sugammadex is biologically inactive, does not bind to plasma proteins, and appears to be safe and well tolerated..

Effects on Other Drugs

Steroids

Sugammadex does form complexes with naturally occurring steroidal molecules but at a much lower affinity.

Neuromuscular Blocking Agents

This drug cannot be used to reverse neuromuscular blockade induced by succinylcholine and benzylisoquinolinium neuromuscular blockers.

Speed of Recovery

Reversal of neuromuscular blockade is exceedingly rapid.  Sugammadex (8 mg/kg IV) administered 3 minutes after rocuronium (0.6 mg/kg) returned the TOF ration to 0.9 within 2 minutes.  The speed of recovery from neuromuscular blockade induced by rocuronium (1.2 mg/kg IV) followed by 3 min later by sugammadex (16 mg/kg IV) is shorter than the spontaneous recovery of neuromuscular function than from succinylcholine.

Impact on the Practice of Anesthesiology

• Would the use of sugammadex prevent anesthesiologists from encountering a patient whose neuromuscular blockade is hard to reverse at the end of surgery?
• Would anesthesiologists still need to use neuromuscular function monitoring with sugammadex?

• If the rocuronium induction followed by sugammadex reversal achieves or exceeds the reliability of succinylcholine, will this mark the end of years of effort searching for the Holy Grail of Neuromuscular Blocking Agents?
• Will succinylcholine and the benzylisoquinolinium drugs (cis-atracurium and atracurium) remain on the hospital formulary?

Economic Considerations

If sugammadex is to replace neostigmine as an antagonist for rocuronium-induced neuromuscular blockade, then this clinical decision will depend in part on the cost of the drug and the improvement in patient outcomes that occurs with its use.

Release Date

In August 2008 Schering-Plough announced that the FDA issued a "not-approvable" letter for sugammadex for the reversal of rocuronium- or vecuronium.  The company will work with the agency to address the issues noted in the letter.