BRIDION SIDE EFFECTS
- Generic Name: sugammadex injection
- Brand Name: Bridion
SIDE EFFECTS
The following serious adverse reactions are described elsewhere in the labeling:
- Anaphylaxis and Hypersensitivity
- Marked Bradycardia
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect 2914 subjects exposed to 2, 4, or 16 mg/kg BRIDION and 544 to placebo in pooled Phase 1-3 studies. The population was 18 to 92 years old, 47% male and 53% female, 34% ASA (American Society of Anesthesiologists) Class 1, 51% ASA Class 2, and 14% ASA Class 3, and 82% Caucasian. Most subjects received a single dose of BRIDION 2 mg/kg or 4 mg/kg.
Adverse reactions reported in ≥10% of patients at a 2, 4, or 16 mg/kg BRIDION dose with a rate higher than the placebo rate are: vomiting, pain, nausea, hypotension, and headache.
All adverse reactions occurring in ≥2% of subjects treated with BRIDION and more often than placebo for adult subjects who received anesthesia and/or neuromuscular blocking agent in pooled Phase 1 to 3 studies are presented in Table 1.
Table 1: Percent of Subject Exposures in Pooled Phase 1 to 3 Studies with Adverse Reactions Incidence ≥2%
| Body System Preferred Term | Sugammadex | Placebo (N=544) n (%) |
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| 2 mg/kg (N=895) n (%) |
4 mg/kg (N=1921) n (%) |
16 mg/kg (N=98) n (%) |
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| Injury, poisoning and procedural complications | ||||
| Incision site pain | 58 (6) | 106 (6) | 4 (4) | 6 (1) |
| Procedural complication | 13 (1) | 27 (1) | 8 (8) | 3 (1) |
| Airway complication of anesthesia | 11 (1) | 13 (1) | 9 (9) | 0 |
| Anesthetic complication | 8 (1) | 14 (1) | 9 (9) | 1 (<1) |
| Wound hemorrhage | 5 (1) | 38 (2) | 0 | 8 (1) |
| Recurrence of neuromuscular blockade | 0 | 1 (<1) | 2 (2) | 0 |
| Gastrointestinal disorders | ||||
| Nausea* | 208 (23) | 503 (26) | 23 (23) | 127 (23) |
| Vomiting* | 98 (11) | 236 (12) | 15 (15) | 57 (10) |
| Abdominal pain* | 48 (5) | 68 (4) | 6 (6) | 17 (3) |
| Flatulence | 17 (2) | 51 (3) | 1 (1) | 10 (2) |
| Dry mouth | 9 (1) | 5 (<1) | 2 (2) | 0 |
| General disorders and administration site conditions | ||||
| Pain* | 434 (48) | 993 (52) | 35 (36) | 207 (38) |
| Pyrexia | 77 (9) | 109 (6) | 5 (5) | 17 (3) |
| Chills | 30 (3) | 61 (3) | 7 (7) | 27 (5) |
| Nervous system disorders | ||||
| Headache | 61 (7) | 99 (5) | 10 (10) | 42 (8) |
| Dizziness | 44 (5) | 67 (3) | 6 (6) | 13 (2) |
| Hypoesthesia | 12 (1) | 24 (1) | 3 (3) | 9 (2) |
| Respiratory, thoracic and mediastinal disorders | ||||
| Oropharyngeal pain | 42 (5) | 66 (3) | 5 (5) | 27 (5) |
| Cough | 13 (1) | 49 (3) | 8 (8) | 11 (2) |
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 13 (1) | 35 (2) | 6 (6) | 15 (3) |
| Musculoskeletal pain | 16 (2) | 33 (2) | 1 (1) | 6 (1) |
| Myalgia | 5 (1) | 17 (1) | 2 (2) | 3 (1) |
| Psychiatric disorders | ||||
| Insomnia | 20 (2) | 103 (5) | 5 (5) | 22 (4) |
| Anxiety | 14 (2) | 19 (1) | 3 (3) | 1 (<1) |
| Restlessness | 3 (<1) | 17 (1) | 2 (2) | 2 (<1) |
| Depression | 2 (<1) | 5 (<1) | 2 (2) | 0 |
| Investigations | ||||
| Red blood cell count decreased* | 13 (1) | 34 (2) | 1 (1) | 2 (<1) |
| Electrocardiogram QT interval abnormal* | 13 (1) | 7 (<1) | 6 (6) | 4 (1) |
| Blood creatine phosphokinase increased | 9 (1) | 14 (1) | 2 (2) | 1 (<1) |
| Vascular disorders | ||||
| Hypertension* | 48 (5) | 96 (5) | 9 (9) | 38 (7) |
| Hypotension* | 33 (4) | 102 (5) | 13 (13) | 20 (4) |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 17 (2) | 50 (3) | 2 (2) | 9 (2) |
| Erythema | 5 (1) | 31 (2) | 0 | 6 (1) |
| Metabolism and nutrition disorders | ||||
| Hypocalcemia | 15 (2) | 12 (1) | 0 | 4 (1) |
| Cardiac disorders | ||||
| Tachycardia* | 17 (2) | 29 (2) | 5 (5) | 4 (1) |
| Bradycardia* | 9 (1) | 21 (1) | 5 (5) | 6 (1) |
| Surgical and medical procedures | ||||
| Hysterectomy | 0 | 0 | 2 (2) | 0 |
| * Combinations of preferred terms are as follows: Nausea includes preferred terms nausea and procedural nausea Vomiting includes preferred terms vomiting and procedural vomiting Abdominal pain includes preferred terms abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, and epigastric discomfort Pain includes preferred terms pain and procedural pain |
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Anaphylaxis And Hypersensitivity
Hypersensitivity reactions, including anaphylaxis, have occurred in both premarketing clinical trials and in post-marketing spontaneous reports. In a dedicated hypersensitivity study in healthy volunteers, the frequency of anaphylaxis was 0.3%. These reactions 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.
Symptoms associated with these reactions can include: flushing, urticaria, erythematous rash, (severe) hypotension, tachycardia, swelling of tongue, swelling of pharynx, bronchospasm and pulmonary obstructive events. Severe hypersensitivity reactions can be fatal.
A randomized, double-blind study examined the incidence of drug hypersensitivity reactions in healthy volunteers given up to 3 doses of placebo (N=76), sugammadex 4 mg/kg (N=151) or sugammadex 16 mg/kg (N=148). Reports of suspected hypersensitivity were adjudicated by a blinded committee. The incidence of adjudicated hypersensitivity was 1%, 7% and 9% in the placebo, sugammadex 4 mg/kg and sugammadex 16 mg/kg groups, respectively. There were no reports of anaphylaxis after placebo or sugammadex 4 mg/kg. There was a single case of adjudicated anaphylaxis after the first dose of sugammadex 16 mg/kg. The frequency of anaphylaxis for the 299 healthy volunteers treated with intravenous sugammadex was 0.3%. There was no evidence of increased frequency or severity of hypersensitivity with repeat dosing.
In a previous study of similar design, there were three adjudicated cases of anaphylaxis, all after sugammadex 16 mg/kg (incidence 1% in the 298 healthy volunteers treated with sugammadex).
Recurrence Of Neuromuscular Blockade
In clinical studies with subjects treated with rocuronium or vecuronium, where BRIDION was administered using a dose labeled for the depth of neuromuscular blockade (N=2022), an incidence of <1% was observed for recurrence of neuromuscular blockade as based on neuromuscular monitoring or clinical evidence.
Bronchospasm
In one dedicated clinical trial and in post-marketing data, in patients with a history of pulmonary complications, bronchospasm was reported as a possibly related adverse event.
Post-Marketing Experience
The following adverse reactions have been identified during post-approval use of BRIDION. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac Disorders
Cases of marked bradycardia and bradycardia with cardiac arrest have been observed within minutes after administration of sugammadex. Other cardiac rhythm abnormalities have included atrial fibrillation, atrioventricular block, cardiac/cardiorespiratory arrest, electrocardiographic (ECG) ST segment changes, supraventricular tachycardia/extrasystoles, tachycardia, ventricular fibrillation, and ventricular tachycardia. Anaphylaxis associated with ECG ST segment changes (elevation or depression) consistent with myocardial ischemia or coronary spasm has also been reported.
General Disorders And Administration Site Conditions
Cases of BRIDION not having the intended effect.
Immune System Disorders
Hypersensitivity events including anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, and Type 1 hypersensitivity have been reported.
Respiratory, Thoracic, And Mediastinal Disorders
Events of laryngospasm, dyspnea, wheezing, pulmonary edema, and respiratory arrest have been reported.
SRC: NLM .