Sugammadex

Sugammadex is a modified gamma cyclodextrin that rapidly reverses rocuronium- and vecuronium-induced neuromuscular block, including deep block, by forming a tight complex with the drug in plasma. It does not inhibit cholinesterase, so no antimuscarinic drug is needed. It can reverse a profound block within minutes. It is much more costly than neostigmine, and has important interactions with hormonal contraceptives and a rare risk of anaphylaxis.

Class. Selective relaxant binding agent (modified gamma cyclodextrin).

Mechanism. Encapsulates aminosteroid neuromuscular blocking drugs (rocuronium, then vecuronium) in a one-to-one complex, so that free drug falls in plasma and diffuses away from the neuromuscular junction. The complex is stable and excreted by the kidney.

Pharmacokinetics. Onset within 1 to 3 minutes. The elimination half-life is about 2 hours. The complex is excreted almost entirely unchanged in urine within 24 hours. Little is metabolised. Clearance falls with kidney impairment, and the complex stays in the plasma for longer.

Indications are reversal of rocuronium or vecuronium block after surgery, and immediate reversal after a rapid sequence induction dose of rocuronium when intubation fails.

Adults

• Moderate block (train-of-four count of 2 or more, or return of T2): 2 mg/kg intravenously.
• Deep block (post-tetanic count of 1 to 2, no response to train-of-four): 4 mg/kg intravenously.
• Immediate reversal 3 minutes after rocuronium 1 to 1.2 mg/kg: 16 mg/kg intravenously.
• If the train-of-four ratio has not reached 0.9 after the first dose, repeat 4 mg/kg once.
• The dose is calculated from actual body weight (use is contested in severe obesity).
• Maximum: 16 mg/kg; repeat doses are given only as needed.

Children

• Aged 2 to 17 years: 2 mg/kg at moderate block and 4 mg/kg at deep block, given as a rapid intravenous bolus over 10 seconds.
• Under 2 years: not licensed in most markets; use only with specialist advice.

Further relaxation after reversal. If a relaxant is needed again within 24 hours, use a benzylisoquinolinium drug (atracurium or cisatracurium), because rocuronium or vecuronium may be bound and ineffective.

Contraindications. Hypersensitivity to sugammadex. Severe kidney impairment with a creatinine clearance under 30 mL/minute (use is not advised outside specialist care).

Boxed-warning-level risks. Anaphylaxis (rare but may be severe); marked bradycardia and asystole within minutes of administration; reduced effect of hormonal contraceptives.

Adverse effects. Common: nausea, vomiting, taste disturbance, headache, pain on injection. Serious: anaphylaxis, bradycardia, cardiac arrest, recurrence of neuromuscular block if the dose is too low, bronchospasm, transient prolongation of clotting tests for up to 1 hour.

Interactions. Binds progestogens: a dose is equivalent to missing one dose of an oral contraceptive; the patient should use a non-hormonal method for 7 days. Toremifene, fusidic acid and flucloxacillin may displace rocuronium from the complex and delay recovery. Anticoagulants: a transient rise in activated partial thromboplastin time and prothrombin time.

Common prescribing errors. Using too low a dose at deep block; extubating without checking the train-of-four ratio; giving it to reverse a benzylisoquinolinium relaxant; forgetting to warn patients using hormonal contraception; repeating rocuronium too soon after sugammadex.

Special groups

• Pregnancy: limited data; used when needed. Rapid reversal may help in obstetric airway emergencies.
• Breastfeeding: limited data; likely compatible after a single dose.
• Older adults: usual dose; recovery may be slower.
• Kidney impairment: avoid with a creatinine clearance under 30 mL/minute; the complex is cleared slowly.
• Liver impairment: usual dose.
• Regional: cost and supply limit its use; keep it for the failed intubation, deep block and patients with high aspiration or airway risk; neostigmine with glycopyrronium remains the usual reversal drug where sugammadex is not available.

Formulations. Injection 100 mg/mL (200 mg in 2 mL and 500 mg in 5 mL).

Administration. Give as a single rapid intravenous bolus over 10 seconds into a running fast-flowing line. Flush the line before and after, because it is incompatible with verapamil, ondansetron and ranitidine.

Baseline. Time and dose of rocuronium or vecuronium, train-of-four count and post-tetanic count, kidney function, use of hormonal contraceptives.

Monitoring. Continuous electrocardiogram, heart rate, oxygen saturation and capnography. Train-of-four ratio to 0.9 or more before extubation. Observe for 1 to 2 hours for recurrence of block.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Do not repeat doses unless the train-of-four ratio remains under 0.9. Stop and treat for bradycardia or hypersensitivity.

Referral and escalation. Anaphylaxis needs intramuscular adrenaline, fluids and airway support. Bradycardia needs atropine 0.5 to 1 mg intravenously. Recurrent block needs a repeat dose of 4 mg/kg and ventilation until recovery.