TABLE 1.
Meta-analysis of safety outcomes in different systems.
| System | Group | Study | n/N | Heterogeneity | Incidence rate (95% CI) | P |
|---|---|---|---|---|---|---|
| Nervous system | Sedation | 8 | 190/1,317 | P = 0.000, I 2 = 95.1% | 0.158 (0.088, 0.228) | <0.001 |
| — | Dizziness | 59 | 1849/9,334 | P = 0.000, I 2 = 95.8% | 0.157 (0.127, 0.187) | 0.0125 |
| — | Fatigue | 21 | 384/3,462 | P = 0.000, I 2 = 88.2% | 0.094 (0.067, 0.121) | <0.001 |
| — | Somnolence/drowsiness | 41 | 502/6,421 | P = 0.000, I 2 = 91.1 | 0.079 (0.063, 0.094) | <0.001 |
| — | Headache | 37 | 613/7,258 | P = 0.000, I 2 = 89.8% | 0.066 (0.051, 0.082) | <0.001 |
| — | Vertigo | 6 | 77/1,405 | P = 0.000, I 2 = 89.1% | 0.060 (0.025, 0.095) | 0.001 |
| — | Diplopia/double version | 28 | 404/5,521 | P = 0.000, I 2 = 86.6% | 0.057 (0.042, 0.072) | <0.001 |
| — | Ataxia | 17 | 201/2,978 | P = 0.000, I 2 = 83.7% | 0.056 (0.037, 0.074) | <0.001 |
| — | Vision blurred | 10 | 145/2,276 | P = 0.000, I 2 = 85.6% | 0.051 (0.028, 0.074) | <0.001 |
| — | Nystagmus | 6 | 85/1,331 | P = 0.000, I 2 = 91.4% | 0.050 (0.016, 0.084) | 0.004 |
| — | Gait disturbance | 6 | 68/1,467 | P = 0.000, I 2 = 81.9% | 0.045 (0.020, 0.069) | <0.001 |
| — | Anxiety | 9 | 60/1,368 | P = 0.021, I 2 = 55.8% | 0.040 (0.023, 0.057) | <0.001 |
| — | Depression | 9 | 72/1952 | P = 0.000, I 2 = 85.5% | 0.033 (0.014, 0.051) | <0.001 |
| — | Insomnia | 7 | 33/874 | P = 0.009, I 2 = 64.9% | 0.027 (0.007, 0.046) | 0.007 |
| — | Memory impairment | 3 | 6/309 | P = 0.913, I 2 = 0.0% | 0.019 (0.004, 0.034) | 0.015 |
| — | Asthenia | 3 | 6/248 | P = 0.496, I 2 = 0.0% | 0.019 (0.002, 0.036) | 0.028 |
| — | Paresthesia/cognitive side effect | 5 | 15/1,052 | P = 0.053, I 2 = 57.3% | 0.011 (0.000, 0.021) | 0.047 |
| Digestive system | Nausea/vomiting | 41 | 751/6,540 | P = 0.000, I 2 = 93.1% | 0.093 (0.072, 0.115) | <0.001 |
| — | Dyspepsia | 1 | 4/59 | Not applicable | 0.068 (0.004, 0.132) | 0.038 |
| — | Gastrointestinal distress/diarrhoea | 12 | 93/2,204 | P = 0.000, I 2 = 76.8% | 0.036 (0.021, 0.051) | <0.001 |
| Respiratory system | Nasopharyngitis | 7 | 231/1948 | P = 0.000, I 2 = 86.2% | 0.115 (0.077, 0.154) | <0.001 |
| — | Upper respiratory tract infection | 5 | 160/1,458 | P = 0.000, I 2 = 87.9% | 0.097 (0.055, 0.140) | <0.001 |
| — | Influenza | 1 | 9/456 | Not applicable | 0.020 (0.007, 0.033) | 0.002 |
| Circulatory system | Atrioventricular block | 1 | 1/98 | Not applicable | 0.059 (0.008, 0.442) | 0.006 |
| — | ECG PR interval prolongation | 1 | 1/98 | Not applicable | 0.059 (0.008, 0.442) | 0.006 |
| — | Bradycardia | 2 | 2/169 | P = 0.58, I 2 = 72.2% | 0.025 (0.002, 0.369) | 0.007 |
| — | Palpitation | 3 | 7/500 | P = 1.000, I 2 = 0.0% | 0.014 (0.004, 0.024) | 0.008 |
| Locomotor system | Falls | 3 | 54/498 | P = 0.000, I 2 = 87.4% | 0.055 (0.011, 0.265) | 0.097 |
| — | Tremor | 19 | 180/4,045 | P = 0.000, I 2 = 75.9% | 0.038 (0.025, 0.051) | <0.001 |
| — | Behavior disorders | 5 | 32/708 | P = 0.000, I 2 = 83.9% | 0.030 (0.006, 0.054) | 0.013 |
| Skin system | Irritability | 13 | 54/1,601 | P = 0.001, I 2 = 65.2% | 0.027 (0.013, 0.041) | <0.001 |
| — | Rash | 20 | 74/3,158 | P = 0.566, I 2 = 0.0% | 0.018 (0.014, 0.023) | <0.001 |
| — | Pruritus | 1 | 1/66 | Not applicable | 0.015 (0.002, 0.111) | 0.314 |
| Others | Dry mouth | 1 | 6/100 | Not applicable | 0.060 (0.013, 0.107) | 0.012 |
| — | Back pain | 1 | 2/64 | Not applicable | 0.032 (0.008, 0.123) | 0.151 |
| — | Chest pain | 2 | 5/170 | P = 0.957, I 2 = 0.0% | 0.029 (0.004, 0.055) | 0.023 |
| — | Weight gain | 1 | 7/322 | Not applicable | 0.022 (0.006, 0.038) | 0.007 |
| — | Abdominal pain | 4 | 8/293 | P = 0.070, I 2 = 57.5% | 0.027 (0.008, 0.095) | <0.001 |
| — | Weight loss | 5 | 6/888 | P = 0.040, I 2 = 60.0% | 0.012 (0.003, 0.046) | <0.001 |
| Any adverse event | — | 75 | 4,581/9,839 | P = 0.000, I 2 = 98.8% | 0.387 (0.315, 0.458) | <0.001 |
| Any adverse event (studies only including children) | — | 17 | 355/1,051 | P = 0.000, I 2 = 93.3% | 0.349 (0.244, 0.454) | <0.001 |