sugammadex

Action and Spectrum

Actions and Spectrum: 

The mechanism of action of sugammadex involves a unique process called “selective encapsulation.” Host-guest interaction forms a complex with aminosteroid-based NMBAs, such as rocuronium and vecuronium.

This interaction involves binding the NMBA molecule’s steroidal ring into the sugammadex molecule’s hydrophobic cavity. This encapsulation process rapidly reduces the concentration of free NMBA molecules in the bloodstream, quickly reversing neuromuscular blockade. 

sugammadex has a high affinity for aminosteroid NMBAs, making it very effective in reversing their effects. It has a relatively low affinity for non-aminosteroid NMBAs and is ineffective against depolarizing NMBAs like succinylcholine. 

The spectrum of activity of sugammadex is limited to the reversal of neuromuscular blockade induced by aminosteroid NMBAs, such as rocuronium and vecuronium. It does not affect other aspects of anesthesia, pain management, or other drug classes. It is important to note that sugammadex is not a general anesthetic, analgesic, or muscle relaxant; its function focuses solely on reversing the effects of a specific class of NMBAs. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Pediatrics 

Procedural pain  

Adults 

Nausea  

Hypotension  

Pain  

Vomiting 

1-10% 

Adults 

Pyrexia (5-9%) 

Airway complication of anesthesia (1-9%) 

Procedural complication (1-8%) 

Headache (5-10%) 

Anesthetic complication (1-9%) 

Hypertension (5-9%) 

Cough (1-8%) 

Chills (3-7%) 

Abdominal pain (4-6%) 

Dizziness (3-6%) 

Incision site pain (4-6%) 

Tachycardia (2-5%) 

Pruritus (2-3%) 

Insomnia (2-5%) 

Bradycardia (1-5%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Known Allergies: Individuals with known allergies or hypersensitivity to sugammadex or its components should not receive the medication. 
• Hypersensitivity Reactions: sugammadex can rarely cause hypersensitivity reactions, including anaphylaxis. In patients with a history of severe allergic reactions, caution is advised. 
• Non-Steroidal Neuromuscular Blockers: sugammadex is designed to reverse steroidal NMBAs like rocuronium and vecuronium. It is not effective against non-steroidal NMBAs like succinylcholine. Using sugammadex to reverse non-steroidal NMBAs can reduce efficacy and potential harm. 

Caution: 

• Dosage and Timing: Dosage should be based on the patient’s weight and the degree of neuromuscular blockade. Administering an incorrect dose or administering sugammadex too early or too late can affect its efficacy. 
• Risk of Recurarization: In some cases, rapid administration of sugammadex can lead to a partial reversal of neuromuscular blockade followed by a recurrence of muscle relaxation. This risk is significant in patients with significant cardiovascular conditions, as the sudden increase in muscle function can lead to hemodynamic changes. 
• Allergic Reactions: Although rare, allergic reactions, including anaphylaxis, have been reported with sugammadex use. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

sugammadex is a cyclodextrin-based molecule specifically designed to reverse the effects of neuromuscular blocking agents (NMBAs), such as rocuronium and vecuronium. It works through a unique mechanism of action called “selective encapsulation,” which involves forming a complex with the NMBAs and effectively neutralizing their effects.  

• Selective Encapsulation: sugammadex belongs to a class of compounds known as modified γ-cyclodextrins. It has a hydrophobic central cavity that can encapsulate and trap lipophilic molecules, such as aminosteroid NMBAs (rocuronium and vecuronium). The lipophilic part of the NMBA molecule, which includes the steroidal ring structure, fits into the cavity of sugammadex. 
• Reversal of Neuromuscular Blockade: NMBAs like rocuronium and vecuronium work by binding to nicotinic acetylcholine receptors at the neuromuscular junction, preventing the binding of acetylcholine and leading to muscle relaxation. sugammadex binds to these NMBAs with high affinity, effectively removing them from circulation and reversing their effects. This allows acetylcholine to bind to receptors once again, restoring normal neuromuscular function.

Pharmacokinetics: 

Absorption 

sugammadex is administered intravenously since it’s delivered directly into the vascular system; there’s no absorption phase from the gastrointestinal tract as there would be for orally administered medications. 

Distribution  

The Vd of sugammadex is estimated to be between 11-14 L. This value represents the apparent space where the drug is distributed in the body.  

Metabolism 

sugammadex is not metabolized in the body to a significant extent. It maintains its chemical structure without extensive breakdown or transformation into other compounds. 

Elimination and Excretion 

The clearance of sugammadex is approximately 88 mL/min. It is predominantly eliminated through the kidneys, with approximately 96% of the drug excreted in the urine—only a negligible amount (<0.02%) is excreted through feces or expired air. 

The half-life of sugammadex: 

• Normal renal function: Approximately 2 hours. 
• Mild renal impairment: Extended to around 4 hours. 
• Moderate renal impairment: Further extended to approximately 6 hours. 
• Severe renal impairment: Significantly prolonged to about 19 hours. 

Adminstartion

Administration: 

Intravenous administration 

Administer via IV bolus into an existing intravenous line.  

Ensure the infusion line has been thoroughly flushed (e.g., with 0.9% NaCl) between sugammadex sodium and other medications. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sugammadex 

Why do we use sugammadex? 

sugammadex is a medication primarily used in anesthesia to reverse the effects of specific neuromuscular blocking agents (NMBAs), specifically rocuronium and vecuronium. These NMBAs are commonly used during surgeries to induce muscle relaxation and facilitate procedures that require intubation. sugammadex’s primary use is to accelerate the recovery of muscle function after surgery and anesthesia. Here are the primary uses of sugammadex: 

• Reversal of Neuromuscular Blockade: sugammadex rapidly reverses the effects of aminosteroid NMBAs like rocuronium and vecuronium. These drugs cause temporary muscle paralysis, which is essential for procedures like surgery and intubation. However, restoring normal muscle function quickly after these procedures is crucial to ensure safe and comfortable patient recovery. sugammadex effectively binds to these NMBAs and removes them from circulation, allowing the muscles to regain their normal function. 
• Preventing Residual Paralysis: One of the risks associated with using NMBAs is residual paralysis, where the effects of the NMBAs persist after the surgery. This can lead to impaired breathing, decreased oxygen saturation, and other complications. sugammadex helps prevent this by reversing the neuromuscular blockade rapidly, reducing the risk of residual paralysis and its associated complications. 
• Improving Patient Safety: By accelerating the reversal of neuromuscular blockade, sugammadex contributes to patient safety during the recovery phase after surgery. Patients can regain control of their muscles more quickly, allowing them to breathe spontaneously, cough effectively, and protect their airways. 
• Minimizing Postoperative Complications: Delayed recovery from neuromuscular blockade can contribute to various postoperative complications, including respiratory issues and longer stays in the post-anesthesia care unit (PACU). sugammadex’s rapid action helps minimize these complications and supports smoother postoperative recovery.