Sugammadex

5 WARNINGS AND PRECAUTIONS Anaphylaxis : Be prepared for hypersensitivity reactions (including anaphylactic reactions) and take necessary precautions. ( 5.1 ) Marked Bradycardia : Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after administration. Monitor for hemodynamic changes and administer anticholinergic agents such as atropine if clinically significant bradycardia is observed. ( 5.2 ) Respiratory Function Monitoring : Ventilatory support is mandatory until adequate spontaneous respiration is restored and the ability to maintain a patent airway is assured. Provide adequate ventilation if neuromuscular blockade persists after sugammadex injection or recurs following extubation. ( 5.3 , 5.4 ) Waiting Times for Re-Administration of Neuromuscular Blocking Agents : If re-administration of a neuromuscular blocking agent is required after reversal with sugammadex injection, waiting times should be based on the dose of sugammadex injection and the renal function of the patient. Consider use of a nonsteroidal neuromuscular blocking agent. ( 5.5 ) 5.1 Anaphylaxis and Hypersensitivity Clinicians should be prepared for the possibility of drug hypersensitivity reactions (including anaphylactic reactions) and take the necessary precautions [see Contraindications ( 4 ), Adverse Reactions ( 6.1 )] . Potentially serious hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with sugammadex injection. The nature and frequency of anaphylaxis and hypersensitivity associated with sugammadex injection administration were evaluated in a randomized, double-blind, placebo-controlled, parallel-group, repeat-dose study in which 375 subjects were randomized to receive 3 doses of sugammadex injection IV with a 5-week washout period: 151 subjects received 4 mg/kg, 148 received 16 mg/kg and 76 received placebo. The frequency of anaphylaxis for the 299 healthy volunteers treated with intravenous sugammadex injection was 0.3% (n=1 in the sugammadex injection 16 mg/kg group on the first dose). Signs and symptoms included conjunctival edema, urticaria, erythema, swelling of the uvula and reduction in peak expiratory flow within 5 minutes of dose administration. 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. Anaphylaxis has also been reported in the post-marketing setting, including at doses less than 16 mg/kg. The most commonly described clinical features in reports of anaphylaxis were dermatologic symptoms (including urticaria, rash, erythema, flushing and skin eruption); and clinically important hypotension often requiring the use of vasopressors for circulatory support. In addition, prolonged hospitalization and/or the use of additional respiratory support until full recovery (re-intubation, prolonged intubation, manual or mechanical ventilation) have been noted in a number of the anaphylaxis reports. 5.2 Marked Bradycardia Cases of marked bradycardia, some of which have resulted in cardiac arrest, have been observed within minutes after the administration of sugammadex injection [see Adverse Reactions ( 6.2 )] . Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade. Treatment with anticholinergic agents, such as atropine, should be administered if clinically significant bradycardia is observed. 5.3 Respiratory Function Monitoring During Recovery Ventilatory support is mandatory for patients until adequate spontaneous respiration is restored and the ability to maintain a patent airway is assured. Even if recovery from neuromuscular blockade is complete, other drugs used in the peri- and post-operative period could depress respiratory function and therefore ventilatory support might still be required. Should neuromuscular blockade persist after sugammadex injection administration or recur following extubation, take appropriate steps to provide adequate ventilation. 5.4 Risk of Prolonged Neuromuscular Blockade In clinical trials, a small number of patients experienced a delayed or minimal response to the administration of sugammadex injection [see Clinical Studies ( 14.1 )] . Thus, it is important to monitor ventilation until recovery occurs. 5.5 Waiting Times for Re-Administration of Neuromuscular Blocking Agents for Intubation Following Reversal with Sugammadex Injection A minimum waiting time is necessary before administration of a steroidal neuromuscular blocking agent after administration of sugammadex injection. Table 1: Re-administration of Rocuronium or Vecuronium after Reversal (up to 4 mg/kg Sugammadex Injection) Minimum Waiting Time NMBA and Dose to be Administered 5 minutes 1.2 mg/kg rocuronium 4 hours 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium When rocuronium 1.2 mg/kg is administered within 30 minutes after reversal with sugammadex injection, the onset of neuromuscular blockade may be delayed up to approximately 4 minutes and the duration of neuromuscular blockade may be shortened up to approximately 15 minutes. The recommended waiting time in patients with mild or moderate renal impairment for re-use of 0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium after reversal with up to 4 mg/kg sugammadex injection should be 24 hours. If a shorter waiting time is required, the rocuronium dose for a new neuromuscular blockade should be 1.2 mg/kg. For re-administration of rocuronium or administration of vecuronium after reversal of rocuronium with 16 mg/kg sugammadex injection, a waiting time of 24 hours is suggested. If neuromuscular blockade is required before the recommended waiting time has elapsed, use a nonsteroidal neuromuscular blocking agent . The onset of a depolarizing neuromuscular blocking agent might be slower than expected, because a substantial fraction of postjunctional nicotinic receptors can still be occupied by the neuromuscular blocking agent. 5.6 Interactions Potentially Affecting the Efficacy of Other Drugs Due to the administration of sugammadex injection, certain drugs, including hormonal contraceptives, could become less effective due to a lowering of the (free) plasma concentrations. In this situation, consider the re-administration of the other drug, the administration of a therapeutically equivalent drug (preferably from a different chemical class), and/or non-pharmacological interventions as appropriate [see Drug Interactions ( 7.3 )] . 5.7 Risk of Recurrence of Neuromuscular Blockade Due to Displacement Interactions Recurrence of neuromuscular blockade may occur due to displacement of rocuronium or vecuronium from sugammadex injection by other drugs [see Drug Interactions ( 7.2 )] . In this situation the patient may require mechanical ventilation. Administration of the drug which caused displacement should be stopped in case of an infusion. The risk of displacement reactions will be the highest in the time period equivalent to 3 times the half-life of sugammadex injection [see Clinical Pharmacology ( 12.3 )] . 5.8 Risk of Recurrence of Neuromuscular Blockade with Lower Than Recommended Dosing The use of lower than recommended doses of sugammadex injection may lead to an increased risk of recurrence of neuromuscular blockade after initial reversal and is not recommended [see Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 )] . 5.9 Risk of Recurrence of Neuromuscular Blockade Due to the Administration of Drugs that Potentiate Neuromuscular Blockade When drugs which potentiate neuromuscular blockade are used in the post-operative phase, special attention should be paid to the possibility of recurrence of neuromuscular blockade. Refer to the package insert for rocuronium or vecuronium for a list of the specific drugs which potentiate neuromuscular blockade. In case recurrence of neuromuscular blockade is observed, the patient may require mechanical ventilation. 5.10 Risk of Coagulopathy and Bleeding Sugammadex injection doses up to 16 mg/kg were associated with increases in the coagulation parameters activated partial thromboplastin time (aPTT) and prothrombin time/international normalized ratio [PT(INR)] of up to 25% for up to 1 hour in healthy volunteers. In patients undergoing major orthopedic surgery of the lower extremity who were concomitantly treated with heparin or low molecular weight heparin for thromboprophylaxis, increases in aPTT and PT(INR) of 5.5% and 3.0%, respectively, were observed in the hour following sugammadex injection 4 mg/kg administration. This clinical trial did not demonstrate an increased blood loss or anemia incidence with sugammadex injection compared with usual treatment. The rate of adjudicated bleeding events within 24 hours was 2.9% for sugammadex and 4.1% for usual care. The rate of post-operative anemia was 21% for sugammadex and 22% for usual care. The mean 24-hour drainage volume was 0.46 L for sugammadex and 0.48 L for usual care. The need for any post-operative transfusion was 37% for sugammadex and 39% for usual care. In vitro experiments demonstrated additional aPTT and PT(INR) prolongations for sugammadex in combination with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban, and dabigatran up to ~25% and ~50% at C max levels of sugammadex corresponding to 4 mg/kg and 16 mg/kg doses, respectively. Since bleeding risk has been studied systematically with only heparin and low molecular weight heparin thromboprophylaxis and 4 mg/kg doses of sugammadex coagulation parameters should be carefully monitored 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. 5.11 Renal Impairment Sugammadex injection is not recommended for use in patients with severe renal impairment, including those requiring dialysis [see Use in Specific Populations ( 8.6 )] . With regard to the recommended waiting time for re-administration in patients with mild or moderate renal impairment, see Waiting Times for Re-Administration of Neuromuscular Blocking Agents for Intubation Following Reversal with Sugammadex Injection [see Warnings and Precautions ( 5.5 )] . 5.12 Light Anesthesia When neuromuscular blockade was reversed intentionally in the middle of anesthesia in clinical trials, e.g., when investigating urgent reversal, signs of light anesthesia were noted occasionally (movement, coughing, grimacing and suckling of the tracheal tube). 5.13 Reversal after Rocuronium or Vecuronium Administration in the ICU Sugammadex injection has not been studied for reversal following rocuronium or vecuronium administration in the ICU. 5.14 Reversal of Neuromuscular Blocking Agents Other Than Rocuronium or Vecuronium Do not use sugammadex injection to reverse blockade induced by nonsteroidal neuromuscular blocking agents such as succinylcholine or benzylisoquinolinium compounds. Do not use sugammadex injection to reverse neuromuscular blockade induced by steroidal neuromuscular blocking agents other than rocuronium or vecuronium.

<table ID="t1" width="100%"><caption>Table 1: Re-administration of Rocuronium or Vecuronium after Reversal (up to 4 mg/kg Sugammadex Injection) </caption><col width="33.150%" align="left"/><col width="66.850%" align="left"/><tbody><tr><td align="center" valign="top" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Minimum Waiting Time</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">NMBA and Dose to be Administered</content></td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule">5 minutes </td><td align="center" valign="top" styleCode="Botrule Rrule">1.2 mg/kg rocuronium </td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule">4 hours </td><td align="center" valign="top" styleCode="Botrule Rrule">0.6 mg/kg rocuronium or 0.1 mg/kg vecuronium </td></tr></tbody></table>

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Anaphylaxis and Hypersensitivity [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] Marked Bradycardia [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (reported in ≥10% of adult patients at a 2, 4, or 16 mg/kg sugammadex injection dose and higher than the placebo rate): vomiting, pain, nausea, hypotension, and headache. ( 6.1 ) Most common adverse reactions (reported in ≥10% of pediatric patients 2 to <17 years of age at sugammadex injection doses of 2 or 4 mg/kg) were pain, vomiting, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. Adult Patients The data described below reflect 2,914 subjects exposed to 2, 4, or 16 mg/kg sugammadex injection and 544 to placebo in pooled Phase 1 to 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 sugammadex injection 2 mg/kg or 4 mg/kg. Adverse reactions reported in ≥10% of patients at a 2, 4, or 16 mg/kg sugammadex injection 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 sugammadex injection 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 2 . Table 2: Percent of Subject Exposures in Pooled Phase 1 to 3 Studies with Adverse Reactions Incidence ≥2% Sugammadex Placebo Body System Preferred Term 2 mg/kg (N=895) n (%) 4 mg/kg (N=1,921) n (%) 16 mg/kg (N=98) n (%) (N=544) n (%) * 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 Red blood cell count decreased includes preferred terms red blood cell count decreased, hemoglobin decreased, and hematocrit decreased Electrocardiogram QT interval abnormal includes preferred terms electrocardiogram QT interval abnormal and electrocardiogram QT interval prolonged Hypertension includes preferred terms hypertension, procedural hypertension, and blood pressure increased Hypotension includes preferred terms hypotension, procedural hypotension, and blood pressure decreased Tachycardia includes preferred terms tachycardia and heart rate increased Bradycardia includes preferred terms bradycardia and heart rate decreased 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 Pediatric Patients 2 to <17 years of age The safety of sugammadex injection has been assessed in a randomized, active-controlled study of pediatric patients 2 to <17 years of age, with 242 receiving treatment with sugammadex injection. Adverse events occurring in ≥5% of pediatric patients are presented in Table 3 . The safety profile was generally consistent with that observed in adults. Table 3: Pediatric Patients (2 to <17 years of age) with Adverse Events Incidence ≥5% in One or More Treatment Groups Up to 7 Days Post-Treatment * Combines preferred terms of bradycardia and sinus bradycardia Every subject is counted a single time for each applicable row and column. A system organ class or specific adverse event appears in this table only if its incidence in one or more of the columns meets the incidence criterion in the table title, after rounding. Sugammadex 2 mg/kg Sugammadex 4 mg/kg n (%) n (%) Subjects in population 51 191 with one or more specific adverse events 40 (78) 143 (75) with no specific adverse events 11 (22) 48 (25) Cardiac disorders 5 (10) 16 (8) Bradycardia * 5 (10) 13 (7) Eye disorders 3 (6) 1 (1) Gastrointestinal disorders 8 (16) 35 (18) Nausea 1 (2) 12 (6) Vomiting 4 (8) 20 (10) Injury, poisoning and procedural complications 34 (67) 121 (63) Incision site pain 3 (6) 6 (3) Procedural nausea 4 (8) 9 (5) Procedural pain 30 (59) 111 (58) Procedural vomiting 3 (6) 5 (3) 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% [see Warnings and Precautions ( 5.1 )] . 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 sugammadex injection was administered using a dose labeled for the depth of neuromuscular blockade (N=2,022), an incidence of <1% was observed for recurrence of neuromuscular blockade as based on neuromuscular monitoring or clinical evidence [see Warnings and Precautions ( 5.8 )] . Bronchospasm In one dedicated clinical trial and in post-marketing data, in patients with a history of pulmonary complications [see Use in Specific Populations ( 8.9 )] , bronchospasm was reported as a possibly related adverse event. Additional pediatric use information is approved for Merck Sharp & Dohme LLC's BRIDION ® (sugammadex) injection. However, due to Merck Sharp & Dohme LLC's marketing exclusivity rights, this drug product is not labeled with that information. 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of sugammadex injection. 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 [see Warnings and Precautions ( 5.2 )] . 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 sugammadex injection not having the intended effect. Immune System Disorders : Hypersensitivity events including anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, and Type 1 hypersensitivity have been reported [see Warnings and Precautions ( 5.1 )] . Respiratory, Thoracic, and Mediastinal Disorders : Events of laryngospasm, dyspnea, wheezing, pulmonary edema, and respiratory arrest have been reported.

<table ID="t2" width="100%"><caption>Table 2: Percent of Subject Exposures in Pooled Phase 1 to 3 Studies with Adverse Reactions Incidence &#x2265;2% </caption><col width="57.349%" align="left"/><col width="9.738%" align="left"/><col width="10.978%" align="left"/><col width="10.958%" align="left"/><col width="10.978%" align="left"/><thead><tr><th align="justify" valign="top" styleCode="Toprule Botrule Lrule Rrule"/><th colspan="3" align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Sugammadex</content></th><th align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Placebo</content></th></tr><tr><th align="justify" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Body System</content> <content styleCode="bold"> Preferred Term</content></th><th align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">2 mg/kg (N=895)</content> <content styleCode="bold">n (%)</content></th><th align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">4 mg/kg (N=1,921)</content> <content styleCode="bold">n (%)</content></th><th align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">16 mg/kg</content> <content styleCode="bold">(N=98)</content> <content styleCode="bold">n (%)</content></th><th align="center" valign="middle" styleCode="Botrule Rrule"><content styleCode="bold">(N=544)</content> <content styleCode="bold">n (%)</content></th></tr></thead><tfoot><tr><td colspan="5" align="left" valign="top"><paragraph styleCode="footnote">* 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 Red blood cell count decreased includes preferred terms red blood cell count decreased, hemoglobin decreased, and hematocrit decreased Electrocardiogram QT interval abnormal includes preferred terms electrocardiogram QT interval abnormal and electrocardiogram QT interval prolonged Hypertension includes preferred terms hypertension, procedural hypertension, and blood pressure increased Hypotension includes preferred terms hypotension, procedural hypotension, and blood pressure decreased Tachycardia includes preferred terms tachycardia and heart rate increased Bradycardia includes preferred terms bradycardia and heart rate decreased </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Injury, poisoning and procedural complications</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Incision site pain </td><td align="center" valign="top" styleCode="Botrule Rrule">58 (6) </td><td align="center" valign="top" styleCode="Botrule Rrule">106 (6) </td><td align="center" valign="top" styleCode="Botrule Rrule">4 (4) </td><td align="center" valign="top" styleCode="Botrule Rrule">6 (1) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Procedural complication </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">27 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (8) </td><td align="center" valign="top" styleCode="Botrule Rrule">3 (1) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Airway complication of anesthesia </td><td align="center" valign="top" styleCode="Botrule Rrule">11 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (9) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Anesthetic complication </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">14 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (9) </td><td align="center" valign="top" styleCode="Botrule Rrule">1 (&lt;1) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Wound hemorrhage </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">38 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (1) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Recurrence of neuromuscular blockade </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td><td align="center" valign="top" styleCode="Botrule Rrule">1 (&lt;1) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Nausea* </td><td align="center" valign="top" styleCode="Botrule Rrule">208 (23) </td><td align="center" valign="top" styleCode="Botrule Rrule">503 (26) </td><td align="center" valign="top" styleCode="Botrule Rrule">23 (23) </td><td align="center" valign="top" styleCode="Botrule Rrule">127 (23) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Vomiting* </td><td align="center" valign="top" styleCode="Botrule Rrule">98 (11) </td><td align="center" valign="top" styleCode="Botrule Rrule">236 (12) </td><td align="center" valign="top" styleCode="Botrule Rrule">15 (15) </td><td align="center" valign="top" styleCode="Botrule Rrule">57 (10) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Abdominal pain* </td><td align="center" valign="top" styleCode="Botrule Rrule">48 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">68 (4) </td><td align="center" valign="top" styleCode="Botrule Rrule">6 (6) </td><td align="center" valign="top" styleCode="Botrule Rrule">17 (3) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Flatulence </td><td align="center" valign="top" styleCode="Botrule Rrule">17 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">51 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">1 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">10 (2) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Dry mouth </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (&lt;1) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">General disorders and administration site conditions</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Pain* </td><td align="center" valign="top" styleCode="Botrule Rrule">434 (48) </td><td align="center" valign="top" styleCode="Botrule Rrule">993 (52) </td><td align="center" valign="top" styleCode="Botrule Rrule">35 (36) </td><td align="center" valign="top" styleCode="Botrule Rrule">207 (38) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Pyrexia </td><td align="center" valign="top" styleCode="Botrule Rrule">77 (9) </td><td align="center" valign="top" styleCode="Botrule Rrule">109 (6) </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">17 (3) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Chills </td><td align="center" valign="top" styleCode="Botrule Rrule">30 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">61 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">7 (7) </td><td align="center" valign="top" styleCode="Botrule Rrule">27 (5) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Nervous system disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Headache </td><td align="center" valign="top" styleCode="Botrule Rrule">61 (7) </td><td align="center" valign="top" styleCode="Botrule Rrule">99 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">10 (10) </td><td align="center" valign="top" styleCode="Botrule Rrule">42 (8) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Dizziness </td><td align="center" valign="top" styleCode="Botrule Rrule">44 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">67 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">6 (6) </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (2) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Hypoesthesia </td><td align="center" valign="top" styleCode="Botrule Rrule">12 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">24 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">3 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (2) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Oropharyngeal pain </td><td align="center" valign="top" styleCode="Botrule Rrule">42 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">66 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">27 (5) </td></tr><tr><td align="justify" valign="top" styleCode="Botrule Lrule Rrule"> Cough </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">49 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">8 (8) </td><td align="center" valign="top" styleCode="Botrule Rrule">11 (2) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Pain in extremity </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">35 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">6 (6) </td><td align="center" valign="top" styleCode="Botrule Rrule">15 (3) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Musculoskeletal pain </td><td align="center" valign="top" styleCode="Botrule Rrule">16 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">33 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">1 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">6 (1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Myalgia </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">17 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">3 (1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Psychiatric disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Insomnia </td><td align="center" valign="top" styleCode="Botrule Rrule">20 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">103 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">22 (4) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Anxiety </td><td align="center" valign="top" styleCode="Botrule Rrule">14 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">19 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">3 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">1 (&lt;1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Restlessness </td><td align="center" valign="top" styleCode="Botrule Rrule">3 (&lt;1) </td><td align="center" valign="top" styleCode="Botrule Rrule">17 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (&lt;1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Depression </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (&lt;1) </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (&lt;1) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Investigations</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Red blood cell count decreased* </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">34 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">1 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (&lt;1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Electrocardiogram QT interval abnormal* </td><td align="center" valign="middle" styleCode="Botrule Rrule">13 (1) </td><td align="center" valign="middle" styleCode="Botrule Rrule">7 (&lt;1) </td><td align="center" valign="middle" styleCode="Botrule Rrule">6 (6) </td><td align="center" valign="middle" styleCode="Botrule Rrule">4 (1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Blood creatine phosphokinase increased </td><td align="center" valign="middle" styleCode="Botrule Rrule">9 (1) </td><td align="center" valign="middle" styleCode="Botrule Rrule">14 (1) </td><td align="center" valign="middle" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="middle" styleCode="Botrule Rrule">1 (&lt;1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Vascular disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Hypertension* </td><td align="center" valign="top" styleCode="Botrule Rrule">48 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">96 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (9) </td><td align="center" valign="top" styleCode="Botrule Rrule">38 (7) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Hypotension* </td><td align="center" valign="top" styleCode="Botrule Rrule">33 (4) </td><td align="center" valign="top" styleCode="Botrule Rrule">102 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">13 (13) </td><td align="center" valign="top" styleCode="Botrule Rrule">20 (4) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Pruritus </td><td align="center" valign="top" styleCode="Botrule Rrule">17 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">50 (3) </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (2) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Erythema </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">31 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td><td align="center" valign="top" styleCode="Botrule Rrule">6 (1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Metabolism and nutrition disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Hypocalcemia </td><td align="center" valign="top" styleCode="Botrule Rrule">15 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">12 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td><td align="center" valign="top" styleCode="Botrule Rrule">4 (1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Cardiac disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Tachycardia* </td><td align="center" valign="top" styleCode="Botrule Rrule">17 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">29 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">4 (1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Bradycardia* </td><td align="center" valign="top" styleCode="Botrule Rrule">9 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">21 (1) </td><td align="center" valign="top" styleCode="Botrule Rrule">5 (5) </td><td align="center" valign="top" styleCode="Botrule Rrule">6 (1) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Surgical and medical procedures</content></td><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Hysterectomy </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td><td align="center" valign="top" styleCode="Botrule Rrule">2 (2) </td><td align="center" valign="top" styleCode="Botrule Rrule">0 </td></tr></tbody></table>

<table ID="t3" width="100%"><caption>Table 3: Pediatric Patients (2 to &lt;17 years of age) with Adverse Events Incidence &#x2265;5% in One or More Treatment Groups Up to 7 Days Post-Treatment </caption><col width="50.000%" align="left"/><col width="9.180%" align="left"/><col width="15.820%" align="left"/><col width="9.760%" align="left"/><col width="15.240%" align="left"/><tfoot><tr><td colspan="5" align="left" valign="top"><paragraph styleCode="footnote">* Combines preferred terms of bradycardia and sinus bradycardia Every subject is counted a single time for each applicable row and column. A system organ class or specific adverse event appears in this table only if its incidence in one or more of the columns meets the incidence criterion in the table title, after rounding. </paragraph></td></tr></tfoot><tbody><tr><td rowspan="2" align="left" valign="top" styleCode="Toprule Botrule Lrule Rrule"/><td colspan="2" align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Sugammadex 2 mg/kg</content></td><td colspan="2" align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Sugammadex 4 mg/kg</content></td></tr><tr><td align="center" valign="top" styleCode="Botrule"><content styleCode="bold">n</content></td><td align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">(%)</content></td><td align="center" valign="top" styleCode="Botrule"><content styleCode="bold">n</content></td><td align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">(%)</content></td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule">Subjects in population </td><td align="center" valign="top">51 </td><td align="left" valign="top" styleCode="Rrule"/><td align="center" valign="top">191 </td><td align="left" valign="top" styleCode="Rrule"/></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> with one or more specific adverse events </td><td align="center" valign="top">40 </td><td align="center" valign="top" styleCode="Rrule">(78) </td><td align="center" valign="top">143 </td><td align="center" valign="top" styleCode="Rrule">(75) </td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> with no specific adverse events </td><td align="center" valign="top">11 </td><td align="center" valign="top" styleCode="Rrule">(22) </td><td align="center" valign="top">48 </td><td align="center" valign="top" styleCode="Rrule">(25) </td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> <content styleCode="bold">Cardiac disorders</content></td><td align="center" valign="top"> <content styleCode="bold">5</content></td><td align="center" valign="top" styleCode="Rrule"> <content styleCode="bold">(10)</content></td><td align="center" valign="top"> <content styleCode="bold">16</content></td><td align="center" valign="top" styleCode="Rrule"> <content styleCode="bold">(8)</content></td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Bradycardia^*</td><td align="center" valign="top">5 </td><td align="center" valign="top" styleCode="Rrule">(10) </td><td align="center" valign="top">13 </td><td align="center" valign="top" styleCode="Rrule">(7) </td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">Eye disorders</content></td><td align="center" valign="top"><content styleCode="bold">3</content></td><td align="center" valign="top" styleCode="Rrule"><content styleCode="bold">(6)</content></td><td align="center" valign="top"><content styleCode="bold">1</content></td><td align="center" valign="top" styleCode="Rrule"><content styleCode="bold">(1)</content></td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td align="center" valign="top"><content styleCode="bold">8</content></td><td align="center" valign="top" styleCode="Rrule"><content styleCode="bold">(16)</content></td><td align="center" valign="top"><content styleCode="bold">35</content></td><td align="center" valign="top" styleCode="Rrule"><content styleCode="bold">(18)</content></td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Nausea </td><td align="center" valign="top">1 </td><td align="center" valign="top" styleCode="Rrule">(2) </td><td align="center" valign="top">12 </td><td align="center" valign="top" styleCode="Rrule">(6) </td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Vomiting </td><td align="center" valign="top">4 </td><td align="center" valign="top" styleCode="Rrule">(8) </td><td align="center" valign="top">20 </td><td align="center" valign="top" styleCode="Rrule">(10) </td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">Injury, poisoning and procedural complications</content></td><td align="center" valign="top"><content styleCode="bold">34</content></td><td align="center" valign="top" styleCode="Rrule"><content styleCode="bold">(67)</content></td><td align="center" valign="top"><content styleCode="bold">121</content></td><td align="center" valign="top" styleCode="Rrule"><content styleCode="bold">(63)</content></td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Incision site pain </td><td align="center" valign="top">3 </td><td align="center" valign="top" styleCode="Rrule">(6) </td><td align="center" valign="top">6 </td><td align="center" valign="top" styleCode="Rrule">(3) </td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Procedural nausea </td><td align="center" valign="top">4 </td><td align="center" valign="top" styleCode="Rrule">(8) </td><td align="center" valign="top">9 </td><td align="center" valign="top" styleCode="Rrule">(5) </td></tr><tr><td align="left" valign="top" styleCode="Lrule Rrule"> Procedural pain </td><td align="center" valign="top">30 </td><td align="center" valign="top" styleCode="Rrule">(59) </td><td align="center" valign="top">111 </td><td align="center" valign="top" styleCode="Rrule">(58) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Procedural vomiting </td><td align="center" valign="top" styleCode="Botrule">3 </td><td align="center" valign="top" styleCode="Botrule Rrule">(6) </td><td align="center" valign="top" styleCode="Botrule">5 </td><td align="center" valign="top" styleCode="Botrule Rrule">(3) </td></tr></tbody></table>