History
Discovered by pharmaceutical company, Organon international, Netherlands in March 1999. First batch marketed as Org 25969 by Dr Bom and colleagues. Initial human trials in 2005. Approved for clinical use in Europe and Australia in 2008.
FDA approved the drug in the year 2015 after denying approval multiple times citing hypersensitivity concerns.
Chemical Structure
Modified gamma cyclodextrin. It has hollow truncated cone structure with a lipophillic cavity and hydrophilic exterior because of the presence of polar hydroxyl groups.
Formula : C72H112O48S8
Mechanism of Action
Sugammadex exerts its effect by forming very tight complexes at 1:1 ratio with steriodal neuromuscular blocking agents (Rocuronium > Vecuronium > Pancuronium ). On entering the plasma, this drug encapsulates the circulating amino-steroid forming a complex in plasma and renders it inactive. Thereby, it reduces the amount of neuromuscular blocking agent available to bind to nicotinic cholinergic receptors in the neuromuscular junction. This results in the reversal of neuromuscular blockade induced by Rocuronium and Vecuronium
Pharmacokinetics
- Linear – in the dose range of O.lmg/kg -8mg/kg
- Protein binding- Doesn’t bind to protein/RBC
- Volume of distribution-18L
- Metabolism- No metabolite of sugammadex observed
- Clearance 120mL/min
- Elimination Half-life -100 mins
- Excretion- 98% in urine
Rocuronium-Sugammadex Complex
Rocuronium is eliminated primarily by biliary excretion > 75% and to a lesser degree by renal excretion (10-25%). When sugammadex is administered, the plasma clearance of rocuronium is decreased by a factor > 2. This is because the biliary route of excretion becomes unavailable.
Dosing
Due to one-to-one binding capacity with rocuronium, Sugammadex has the ability to reverse any depth of rocuronium induced neuromuscular blockade.
| Type of block | Dose of Sugammadex | Time to TOF>0.9 |
| Routine- TOF count 2 | 2mg/kg | 2mins |
| Moderate PTC 1-2 | 4mg/kg | 3mins |
| Profound 3-5 mins post NMBD | 16mg/kg | 1.5 mins |
Adverse Effects
- Hypersensitivity- most concerning side effect of this drug.
- Other common side effects- dysgeusia, headache, fatigue, nausea, vomiting, dizziness, urticaria, pain abdomen.
Sugammadex Vs Neostigmine for reversing Amino steroid induced neuromuscular blockade
| Sugammadex | Neostigmine |
|---|---|
| Complete reversal of aminosteroidal neuromuscular blockade | Variable degree of blockade |
| 17 times faster than neostigmine | Can not reverse the profound depth of block |
Specific Populations
- Elderly- Dose remains the same. However, the onset of action may be slower, attributed to reduced cardiac output in elderly population.
- Paediatrics- Routine reversal of TOF count 2 with sugammadex 2mg/kg in children aged 2 to 17 years is recommended. However, its use is not much endorsed in neonates & infants.
- Pregnancy- No documented cases of sugammadex being used during pregnancy.
- Renal Disease- CrCI < 30ml/min- Sugammadex is not recommended.
- Sugammadex is significantly slower in achieving TOF>0.9 in renally impaired patients compared to normal population.
- In renal disease patients, using a high flux filter haemodialysis can be used to remove sugammadex.
- Liver Disease- No dose reduction is necessary in patients with mild to moderate hepatic dysfunction.