- Cyclodextrins are a family of compounds with a wide range of clinical uses
- They are ring structures made up of sugars, and can be classified by the number of sugars:
- ɑ-cyclodextrins have 6 sugars
- β-cyclodextrins have 7 sugars
- ɣ-cyclodextrins have 8 sugars
- The inside of the ring is hydrophobic, while the outside is hydrophilic, enabling the cyclodextrin to form complexes with hydrophobic drugs
- This increases hydrophobic drug solubility, which may be used for better drug delivery, drug elimination or to eliminate odors (i.e. how Febreeze works)
Sugammadex
Sugammadex
- Sugammadex is a modified ɣ-cyclodextrin 'selective relaxant binding agent'
Uses
- Reversal of rocuronium (and vecuronium) induced neuromuscular blockade
- Despite some affinity for pancuronium, not used for its reversal
- Putative role in rocuronium anaphylaxis
Presentation
- Presents as a colourless solution stored in glass vials at room temperature with a 3yr shelf life
- Concentration 100mg/ml
Dose
- Dosing is based on actual body weight
- For routine reversal:
- 2mg/kg for moderate block as identified by 2 twitches on ToF (effect in 1 - 1.5mins)
- 4mg/kg for deep block e.g. 1-2 post-tetanic count (effect in 2 - 3mins)
- Immediate reversal of RSI dose rocuronium: 16mg/kg (effect in 3.5 - 5mins)
- Selectively encapsulates the aminosteroid NMBAs
- The active site of these drugs is thus bound to carboxyl groups within the cyclodextrin, so cannot interact with nAChR at the NMJ
- Binding the agent effectively removes it from the plasma and the NMJ
- Encapsulation in the plasma generates a concentration gradient and causes diffusion of the agent away from the NMJ to plasma
Adverse reactions
- Can cause hypersensitivity reactions
- Bradycardia ± asystolic arrest reported (rare)
- Does not appear to affect blood sugar despite dextrin component
Drug interactions
- Aminosteroid NMBA should not be used for 24hrs following sugammadex administration as may take a very long time for onset of paralysis e.g. 4mins with rocuronium
- There is the potential for sugammadex to release the encapsulated aminosteroid NMBA in the presence of:
- Toremifene (a selective oestrogen receptor modulator)
- Fusidic acid via IV infusion
- Sugammadex reduces the progesterone available from contraceptives
- For the OCP a bolus dose equates to missing one day
- For non-oral hormonal contraception, a bolus equates to 7 days missed
Effect on clotting
- Seems to cause dose-dependent, temporary (≤30min) increases in APTT and PT of up to 22% (Cureus, 2021)
- Also manifests as a prolonged K time on a TEG (Int J Med Sci, 2021)
- The effect is not clinically relevant with respect to the incidence of peri-operative bleeding complications, including interaction with prophylactic dose anticoagulants (European Medicines Agency)
- Non-biologically active, non-protein bound molecule
- Volume of distribution 11-14L
- Demonstrates linear kinetics at therapeutic doses
- T1/2 2hrs
- It is not metabolised and excreted solely via the kidneys
- Caution advised once CrCl ≤30ml/min