Sugammadex CCC

Reviewed and revised 27 January 2014

CLASS

• modified cyclodextrin

MECHANISM OF ACTION

• selective relaxant binding agent for reversal of the aminosteroid NMBDs rocuronium, vecuronium and pancuronium
• gamma-cyclodextrin component has a hydrophilic exterior and hydrophobic core that traps the aminosteroid ring
• complex is pH- and temperature-independent and very stable
• Two phase reversal: encapsulation in bloodstream followed by elimination of the complexes renally

PHARMACEUTICS

• 200mg in 2 mL or 500mg in 5 mL
• clear colourless solution
• photosensitive and must be stored protected from ambient light at <30C
• shelf life of 3 years
• 200 mg costs Aus$170

DOSE

• guided by degree of neuromuscular blockade and NMBD to be reversed
• no published dose recommendations for pancuronium
• onset is slower for vecuronium than for rocuronium
• Shallow block (TOF = 2): 2 mg/kg
• Deep block  (PTC = 1 to 2) 4 mg/kg
• Immediate rescue reversal: 16 mg/kg (dose not known for vecuronium) — recovery of first TOF to 90% takes mean 4.4 min following 1.2 mg/kg rocuronium (despite a 3 minute delay in administration!)

INDICATIONS

1. selective reversal of neuromuscular blockade by the aminosteroid NMBD rocuronium; vecuronium and pancuronium

CONTRA-INDICATIONS

• not recommended if severe renal dysfunction or dialysis (although efficacy is maintained and can be removed by hemodialysis)

ADVERSE EVENTS

<1%, well tolerated

• hypotension
• cough
• altered taste
• hypersensitivity reactions

PHARMACOKINETICS

• Absorption – IV
• Distribution – Protein binding < 1%, Volume of distribution at steady state 18 L
• Metabolism – nil
• Elimination – renal, t1/2 = 100 minutes, Plasma clearance 120 mL/minute

INTERACTIONS

• none known to be clinically significant
• theoretical risk of displacement interactions (e.g. flucloxacillin) leading to release of bound aminosteroid NMBDs or capture interactions (e.g. oral contraceptives, cortisone, atropine, verapamil) leading to decreased efficacy of another drug
• potential role in treatment of hypersensitivity reactions due to aminosteroids (but may also bind steroids given as therapy!)

OTHER INFORMATION

• reversal is independent of the intensity of neuromuscular blockade prior to sugammadex administration — even deep neuromuscular blockade can be predictably and reliably reversed
• sourcing the drug, dose calculation and preparation may lead to substantial delays in administration in the ‘can’t intubate, can’t ventilate’ scenario
• rocuronium reversal (1.2 mg/kg) with sugammadex (16 mg/kg) is faster than suxamethonium (1.5mg/kg) reversal by approximately 2 minutes

References and Links

LITFL

• Tox Library – Sugammadex

Journal articles

• Karalapillai D, Kaufman M, Weinberg L. Sugammadex. Crit Care Resusc. 2013 Mar;15(1):57-62. PMID: 23432503.