Sugammadex

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Bridion, Sugammadex Juno

ICU INDICATIONS:

1. Reversal of aminosteroid neuromuscular blockade (from rocuronium or vecuronium)

PRESENTATION AND ADMINISTRATION:

IV:

100 mg/mL solution of sugammadex sodium. Supplied as 200 mg in 2 mL vial or 500 mg in 5 mL vial. Clear and colourless or slightly yellow solution for injection as an undiluted bolus. Store at room temperature. Discard remaining solution after use.

Give as rapid bolus (over 10 seconds) & flush line after administration.

Compatible with the following IV fluids: 5% dextrose, Normal saline, Glucose and sodium chloride

DOSAGE:

The dose of sugammadex depends on the level of neuromuscular blockade to be reversed and duration since administration of paralysing agent. The former is determined by the number of muscle twitches observed on train-of-four monitoring.

For obese patients, dosing should be based on actual body weight. Recovery time (measured as a T4/T1 ratio of 0.9) is stated below.

Two twitches:

2 mg/kg

Median recovery time 2 mins

No twitches but 1-2 post-tetanic counts:

4 mg/kg

Median recovery time 3 mins

Immediate reversal of rocuronium (given at dose up to 1.2 mg/kg):

16 mg/kg

Median recovery time 1.5 mins

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose in renal impairment

DOSAGE IN PAEDIATRICS:

Do not use sugammadex in children under 2 years old.

The dose of sugammadex depends on the level of neuromuscular blockade to be reversed. This is determined by the number of muscle twitches observed on train-of-four monitoring.

For more accurate dosing, sugammadex can be diluted with 0.9% sodium chloride to a concentration of 10 mg/mL.

Two twitches:

2 mg/kg

No twitches, 1-2 post-tetanic counts:

4 mg/kg

Higher doses (e.g. for immediate reversal) have not been investigated in children.

CLINICAL PHARMACOLOGY:

Sugammadex is a modified gamma cyclodextrin which forms a complex with rocuronium and vecuronium, reducing the amount of neuromuscular blocking agent available to bind to nicotinic receptors at the neuromuscular junction. Complex-bound and unchanged sugammadex are renally excreted.

CONTRAINDICATIONS:

1. Hypersensitivity to sugammadex
2. Severe renal impairment (see DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY above)

WARNINGS:

Hypersensitivity reactions, including anaphylaxis, may occur in patients with no prior history of exposure to sugammadex.

Rare cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes of administration. Monitor for haemodynamic changes and administer atropine if clinically significant bradycardia observed.

Recurrence of neuromuscular blockade has been described in 0.2% of patients receiving sugammadex at doses appropriate for their prior depth of blockade.

Recovery times may be longer in patients with significant oedema (such as in severe hepatic impairment) or prolonged circulation time due to cardiovascular disease or old age.

PRECAUTIONS:

General:

Sugammadex should not be used for the reversal of non-steroidal neuromuscular blocking agents (e.g. atracurium) nor suxamethonium.

Risk of recurrence of neuromuscular blockade when recommended doses are used is low (observed incidence 0.2%).

Respiratory function must be monitored with ongoing ventilatory support as required until neuromuscular function has fully returned. Anaesthesia must be maintained until paralysis has resolved to reduce the risk of awareness.

Drug/Laboratory Test Interactions:

Small and transient increases in the aPTT and PT have been observed with doses of sugammadex of 4 mg/kg, with no increase in observed clinical bleeding risk. Use with caution in patient with pre-existing coagulopathy. Sugammadex is physically incompatible with verapamil, ondansetron & ranitidine.

Pregnancy, Lactation and Contraception:

No data to inform risks in pregnant women. Avoid sugammadex if possible in early pregnancy, as it binds to and encapsulates progesterone.

It is unknown if sugammadex is excreted in human breastmilk; the likelihood of significant oral absorption by an infant is low.

As sugammadex encapsulates progesterone, it may reduce the efficacy of oral hormonal contraceptives, equivalent to missing one dose. Patients should be advised of this to allow them to make choices around non-hormonal contraception for the next 7 days.

IMPORTANT DRUG INTERACTIONS IN ICU:

Readministration of neuromuscular blocking agent after sugammadex:

If readministration of rocuronium is required in a patient with normal renal function after administration of sugammadex up to 4 mg/kg, wait at least 4 hours (rocuronium dose 0.6 mg/kg) or 5 minutes (rocuronium dose 1.2 mg/kg). In a patient with mild to moderate renal impairment, wait at least 24 hours. If muscle relaxation is required sooner than this, a non-steroidal agent (e.g. atracurium) should be used. Onset of a depolarising muscle relaxant (e.g. suxamethonium) given after sugammadex may be slower than expected.

High doses of fusidic acid and flucloxacillin could theoretically displace sugammadex from rocuronium/vecuronium and lead to delay in reversal. However significant delay has not been clinically observed.

ADVERSE REACTIONS:

General:

Hypersensitivity reactions including anaphylaxis

Cardiovascular:

Bradycardia (rare) but can be severe, leading to cardiac arrest (very rare). Hypotension

Respiratory:

Bronchospasm, cough

Dermatological:

Flushing, rash, urticaria