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. 2022 Apr 18;42(5):403–416. doi: 10.1007/s40261-022-01139-5

Table 2.

Adverse events (by system organ class/preferred term)

MedDRA/J term Open-label period Double-blind perioda
Tramadol Placebo
N = 248 N = 78 N = 81
Any 200 (80.6) 30 (38.5) 11 (13.6)
Infections and infestations 5 (2.0) 4 (5.1) 4 (4.9)
 Cellulitis 0 1 (1.3) 0
 Cystitis 1 (0.4) 1 (1.3) 0
 Gastroenteritis 0 1 (1.3) 0
 Nasopharyngitis 3 (1.2) 2 (2.6) 3 (3.7)
 Otitis media 1 (0.4) 0 0
 Paronychia 0 0 1 (1.2)
Metabolism and nutrition disorders 13 (5.2) 2 (2.6) 0
 Dehydration 2 (0.8) 0 0
 Decreased appetite 12 (4.8) 2 (2.6) 0
Psychiatric disorders 2 (0.8) 0 0
 Insomnia 2 (0.8) 0 0
Nervous system disorders 77 (31.0) 2 (2.6) 1 (1.2)
 Dizziness 21 (8.5) 0 0
 Dysgeusia 2 (0.8) 0 0
 Headache 11 (4.4) 1 (1.3) 1 (1.2)
 Hypoesthesia 3 (1.2) 0 0
 Migraine 1 (0.4) 0 0
 Somnolence 53 (21.4) 1 (1.3) 0
 Tremor 2 (0.8) 0 0
Ear and labyrinth disorders 4 (1.6) 0 0
 Vertigo 4 (1.6) 0 0
Cardiac disorders 2 (0.8) 1 (1.3) 0
 Palpitations 2 (0.8) 1 (1.3) 0
 Supraventricular extrasystoles 1 (0.4) 0 0
Vascular disorders 3 (1.2) 1 (1.3) 0
 Hypertension 3 (1.2) 1 (1.3) 0
Respiratory, thoracic and mediastinal disorders 1 (0.4) 0 1 (1.2)
 Cough 0 0 1 (1.2)
 Hyperventilation 1 (0.4) 0 0
Gastrointestinal disorders 175 (70.6) 19 (24.4) 2 (2.5)
 Abdominal discomfort 9 (3.6) 4 (5.1) 0
 Abdominal distension 1 (0.4) 0 0
 Abdominal pain upper 1 (0.4) 0 0
 Cheilitis 0 1 (1.3) 0
 Constipation 101 (40.7) 2 (2.6) 0
 Diarrhea 1 (0.4) 0 0
 Dyspepsia 6 (2.4) 0 1 (1.2)
 Feces hard 1 (0.4) 0 0
 Feces soft 1 (0.4) 0 0
 Nausea 110 (44.4) 8 (10.3) 1 (1.2)
 Stomatitis 0 1 (1.3) 0
 Vomiting 44 (17.7) 5 (6.4) 0
 Esophageal discomfort 0 0 1 (1.2)
Hepatobiliary disorders 1 (0.4) 0 0
 Liver disorder 1 (0.4) 0 0
Skin and subcutaneous tissue disorders 18 (7.3) 2 (2.6) 1 (1.2)
 Cold sweat 2 (0.8) 0 0
 Dermatitis contact 0 1 (1.3) 0
 Hemorrhage subcutaneous 1 (0.4) 0 0
 Hyperhidrosis 2 (0.8) 0 0
 Palmoplantar keratoderma 1 (0.4) 0 0
 Pruritus 11 (4.4) 1 (1.3) 0
 Pruritus generalized 1 (0.4) 0 1 (1.2)
 Rash 2 (0.8) 0 0
Musculoskeletal and connective tissue disorders 2 (0.8) 4 (5.1) 1 (1.2)
 Arthralgia 0 1 (1.3) 0
 Back pain 0 1 (1.3) 0
 Neck pain 1 (0.4) 0 0
 Muscle rigidity 0 1 (1.3) 0
 Musculoskeletal pain 1 (0.4) 0 0
 Musculoskeletal chest pain 1 (0.4) 0 0
 Musculoskeletal stiffness 1 (0.4) 0 0
 Rotator cuff syndrome 0 0 1 (1.2)
 Spinal osteoarthritis 0 1 (1.3) 0
Renal and urinary disorders 4 (1.6) 0 0
 Dysuria 1 (0.4) 0 0
 Pollakiuria 1 (0.4) 0 0
 Proteinuria 1 (0.4) 0 0
 Urinary retention 1 (0.4) 0 0
 Renal impairment 1 (0.4) 0 0
General disorders and administration site conditions 13 (5.2) 1 (1.3) 0
 Feeling abnormal 1 (0.4) 0 0
 Malaise 0 1 (1.3) 0
 Thirst 12 (4.8) 0 0
Laboratory tests 7 (2.8) 3 (3.8) 3 (3.7)
 Alanine aminotransferase increased 0 0 1 (1.2)
 Blood creatine phosphokinase increased 3 (1.2) 1 (1.3) 0
 Blood creatinine increased 0 1 (1.3) 0
 Blood pressure increased 0 0 1 (1.2)
 Blood urine present 1 (0.4) 0 0
 Gamma-glutamyltransferase increased 1 (0.4) 0 0
 Glucose urine present 1 (0.4) 0 1 (1.2)
 Occult blood positive 0 1 (1.3) 0
 Urine output decreased 1 (0.4) 0 0
Injury, poisoning and procedural complications 2 (0.8) 2 (2.6) 0
 Animal bite 1 (0.4) 0 0
 Contusion 1 (0.4) 0 0
 Foot fracture 0 1 (1.3) 0
 Nail avulsion 0 1 (1.3) 0

Safety analysis set (open-label and double-blind periods)

MedDRA/J Version 17.1

Values are number (percent) of patients

aAdverse events that newly occurred in the double-blind period; adverse events that occurred in both periods are shown only in the open-label period