Data on Dosing for Rocuronium-induced Moderate NMB in Cardiac Patients

Indication

BRIDION is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery.

In a clinical study, BRIDION provided reversal of rocuronium-induced moderate neuromuscular blockade (NMB) (reappearance of T₂) to recovery of the train-of-four (TOF) ratio to 0.9 in patients diagnosed with or having a history of cardiac disease.

Study Design: Multicenter, randomized, parallel-group, placebo-controlled, safety-assessor–blinded study compared the safety and efficacy of 2 mg/kg and 4 mg/kg of BRIDION for reversal of rocuronium-induced moderate NMB (reappearance of T₂) in 76 patients who were diagnosed with or have a history of cardiac disease (eg, patients with ischemic disease, chronic heart failure, or arrhythmia), primarily New York Heart Association (NYHA) Class II. The primary end point was to evaluate the safety of BRIDION 2 mg/kg and 4 mg/kg, with the time from start of BRIDION administration to a TOF ratio of 0.9 as a secondary end point.¹

Vecuronium: Median time from vecuronium-induced moderate NMB to a TOF ratio of 0.9 was 2.1 minutes following administration of 2 mg/kg of BRIDION (Quartiles [Q1, Q3]: 1.8, 3.4 minutes; n=48) vs a median time of 29.0 minutes (Quartiles [Q1, Q3]: 12.2, 76.2 minutes; n=45) following administration of 50 µg/kg of neostigmine and 10 µg/kg of glycopyrrolate.³

Study Design: Multicenter, randomized, parallel-group, active-controlled, safety-assessor–blinded study compared the efficacy of 2 mg/kg of BRIDION vs 50 μg/kg of neostigmine and 10 μg/kg of glycopyrrolate for reversal of rocuronium- or vecuronium-induced moderate NMB (reappearance of T₂) in 189 patients (87 women and 102 men, American Society of Anesthesiologists majority class 1,2).^2,3 Patients underwent elective procedures that were mainly endocrine, ocular, ear, nose, and throat, abdominal (gynecological, colorectal, urological), orthopedic, vascular, or dermatological in nature. An objective monitoring device (TOF-Watch^® SX) was used to evaluate neuromuscular function, to measure the depth of block based on responses to TOF stimulation (TOF count or twitches), and to calculate the degree of recovery using TOF ratio (which cannot be calculated without an objective monitoring device).^4,5 The primary end point was the time from start of BRIDION or neostigmine administration to a TOF ratio of 0.9, which generally correlates with recovery from NMB.

BRIDION is contraindicated in patients with known hypersensitivity to sugammadex or any of its components. Hypersensitivity reactions that occurred varied from isolated skin reactions to serious systemic reactions (i.e., anaphylaxis, anaphylactic shock) and have occurred in patients with no prior exposure to sugammadex.

Side Effects

Potentially serious hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with BRIDION. In a clinical study, anaphylaxis occurred in 0.3% (n=1/299) of healthy volunteers treated with BRIDION. The most common hypersensitivity adverse reactions reported were nausea, pruritus and urticaria and showed a dose response relationship, occurring more frequently in the 16 mg/kg group compared to the 4 mg/kg and placebo groups. Observe patients for an appropriate period of time after administration and take the necessary precautions. Anaphylaxis has also been reported in the post-marketing setting. Clinical features in anaphylaxis reports have included dermatologic symptoms; hypotension often requiring the use of vasopressors; and prolonged hospitalization and/or the use of additional respiratory support until full recovery.

Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after the administration of BRIDION. Monitor for hemodynamic changes and treat with anticholinergic agents, such as atropine, if clinically significant bradycardia is observed.

Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored and the ability to maintain a patent airway is assured.

In clinical trials, a small number of patients experienced a delayed or minimal response to BRIDION. Monitor ventilation until recovery occurs.

A minimum waiting time is necessary before re-administration of a steroidal neuromuscular blocking agent after administration of BRIDION.

Re-administration of Rocuronium or 
Vecuronium after Reversal (up to 4 mg/kg BRIDION^® [sugammadex] Injection)

If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocking agent.

Due to the administration of BRIDION, certain drugs, including hormonal contraceptives, could become less effective due to a lowering of the (free) plasma concentrations. If an oral contraceptive is taken on the same day that BRIDION is administered, the patient must use an additional, nonhormonal contraceptive method or back-up method of contraception (such as condoms and spermicides) for the next 7 days. In the case of non-oral hormonal contraceptives, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception (such as condoms and spermicides) for the next 7 days.

Recurrence of neuromuscular blockade may occur due to displacement of rocuronium or vecuronium from BRIDION by other drugs. Mechanical ventilation may be required. Stop the administration of the drug which caused displacement, if being administered by infusion.

The use of lower than recommended doses of BRIDION may lead to an increased risk of recurrence of neuromuscular blockade and is not recommended.

BRIDION doses of up to 16 mg/kg were associated with increases in activated partial thromboplastin time and prothrombin time/international normalized ratio. Carefully monitor coagulation parameters in patients with known coagulopathies; being treated with therapeutic anticoagulation; receiving thromboprophylaxis drugs other than heparin and low molecular weight heparin; or receiving thromboprophylaxis drugs and who then receive a dose of 16 mg/kg sugammadex.

BRIDION is not recommended for use in patients with severe renal impairment, including those requiring dialysis.

The most common adverse reactions (reported in ≥ 10% of patients at a 2, 4, or 16 mg/kg BRIDION dose and higher than placebo rate) were vomiting (11%, 12%, or 15% versus placebo at 10%), pain (48%, 52%, or 36% versus placebo at 38%), nausea (23%, 26%, or 23% versus placebo at 23%), hypotension (4%, 5%, or 13% versus placebo at 4%), and headache (7%, 5%, or 10% versus placebo at 8%).

References

1. Amao R, Zornow MH, Cowan RM, et al. Use of sugammadex in patients with a history of pulmonary disease.  J Clin Anesth. 2012;24(4):289‑297.
2. Blobner M, Eriksson LI, Scholz J, et al. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial.  Eur J Anaesthesiol. 2010;27(10):874–881.
3. Khuenl-Brady KS, Wattwil M, Vanacker BF, et al. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial.  Anesth Analg. 2010;110(1):64–73.
4. Data available on request from Merck & Co., Inc., Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package ANES-1143289-0001.
5. Viby-Mogensen J. Neuromuscular monitoring. In: Miller RD, ed.  Miller’s Anesthesia. 8th ed. Philadelphia, PA: Elsevier Saunders; 2010:1604–1621.e4.