Sugammadex

Sugammadex is an agent for reversal of neuromuscular blockade by the rocuronium. It is the first selective relaxant binding agent 

Mechanism of action:

Sugammadex is a modified γ-cyclodextrin, with a lipophilic core and a hydrophilic periphery. Their three-dimensional structure resembles a hollow truncated cone. The structure has a hydrophobic cavity and a hydrophilic exterior. Hydrophobic interactions trap the drug in the cyclodextrin cavity (the “doughnut hole”), thereby resulting in the formation of a water-soluble guesthost complex. 

unmodified γ-cyclodextrin possesses a larger lipophilic cavity (7.5 to 8.3 Å) than any other cyclodextrin does, it is still not deep enough to accommodate the larger rigid structure of the rocuronium molecule. Therefore, the cavity was modified by adding eight side chains to enlarge the cavity for better accommodation of rocuronium and by adding negatively charged carboxyl groups to enhance electrostatic binding to quaternary nitrogen of rocuronium.

The stability of the rocuronium-sugammadex complex is the end result of an interplay of van der Waals forces, hydrogen bonds and hydrophobic interactions.

Sugammadex exerts its effect by forming very tight complexes in a 1 : 1 ratio with steroidal neuromuscular blocking agents (rocuronium > vecuronium >> pancuronium).

Pharmacokinetics:

Because of the soluble nature of the rocuronium-cyclodextrin complex, urinary excretion becomes the major route of elimination of rocuronium.

Pharmacodynamics:

Sugammadex produces rapid and effective reversal of even more profound rocuronium-induced neuromuscular blockade.

Sugammadex is ineffective against succinylcholine and benzylisoquinolinium neuromuscular blockers such as mivacurium, atracurium, and cisatracurium because it cannot form inclusion complexes with these drugs.

Side effects:

hypotension, coughing, movement, nausea, vomiting, dry mouth, parosmia (an abnormal sense of smell), a sensation of a changed temperature, and abnormal levels of N-acetyl-glucosaminidase in urine

Use: Reversal of rocuronium (ROC) or vecuronium (VEC) induced neuromuscular (NM) block in adults. For routine reversal of ROC-induced block in children and adolescents.

Dose:

Adults:

Routine reversal following ROC- or VEC-induced block:

• 4 mg/kg if recovery has reached at least 1-2 post-tetanic counts (PTC). Median recovery time (T4/T1 = 0.9) ≅ 3 minutes
• 2 mg/kg if recovery has occurred up to at least T2. Median recovery time (T4/T1 =0.9) ≅ 2 minutes
• Immediate reversal of ROC-induced block -16 mg/kg. Median recovery time (T4/T1 = 0.9) ≅ 1.5

Not recommended for immediate reversal of VEC-induced block.

Re-administration of ROC or VEC after sugammadex: A waiting time of 24 hours should be taken into account.