Table 7.
Frequency of adverse effects of CQ or HCQ alone when treating COVID-19 reported in observational and randomised studies.
| First Author, Year | Type of Study, Drug and Sample Size | Cardiac | Gastrointestinal Disorders | Hepatobiliary | Neurological | Sense Organs | Dermatological | Other | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| QT Prolongation | Prolonged QTc ≥ 500 ms | Prolongued QTc ≥ 60 ms | Ventricular Arrythmia | Torsade Depointes | Arrhythmogenic Death | Diarrhea | Nausea/Vomiting | Abdominal Pain/Dyspepsia | Bilirubin/GGT Increase | Transaminase Increase | Headache/Dizziness | |||||
| Seyhan AU, 2020 [241] | OBS HCQ n = 51 |
NA | 1.96% | 1.96% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Abella BS, 2021 [270] |
RAN HCQ n = 132 |
NA | NA | NA | NA | NA | NA | 32% | 9% | 6% | NA | NA | Headache 0% Dizziness 2% |
NA | Rash 5% | Paraesthesia 2% |
| Bernardini A, 2021 [246] | OBS HCQ n = 40 |
40% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Furtado RHM, 2020 [247] | RAN HCQ n = 183 |
21% | NA | NA | CRVA 3% | NA | 0% | NA | NA | 24% | 3% | NA | NA | NA | NA | NA |
| Satlin MJ, 2020 [250] | OBS HCQ n = 153 |
NA | NA | NA | Monomorphic VT 0.6% | 0% | NA | NA | NA | NA | NA | Grade 3 11% Grade 4 9% |
NA | NA | NA | NA |
| Hsia BC, 2020 [253] | OBS HCQ n = 40 |
NA | NA | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| OBS CQ n = 5 |
NA | NA | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| Skipper CP, 2020 [252] |
RAN HCQ n = 212 |
NA | NA | NA | NA | NA | NA | 23.6% | 31.1% | NA | NA | NA | Headache 0.9% Dizziness 9.4% |
Ringing in ears 3.8% Changes in vision 1.9 Taste, dry mouth 0% |
Rash 2.8 | NA |
| Boulware DR, 2020 [271] | RAN HCQ n = 414 |
NA | NA | NA | NA | NA | NA | NA | 22.9% | 23.2% | NA | NA | 3.7% | Tinnitus 2.3% Visual changes 0.9% Taste change or dry mouth 0.9% |
Skin reaction 1.1% | NA |
| Falcão F, 2020 [239] | OBS HCQ n = 20 |
10% | NA | NA | NA | NA | NA | 5% | Nausea 10% Vomiting 5% |
0% | Liver cholestasis 0% | 10% | NA | Ocular disorders 0% | Skin and subcutaneous disorders 10% | NA |
| Sogut O, 2021 [240] | OBS HCQ n = 152 |
64.5% | 0% | 0% | NA | NA | 0% | 22.3% | NA | NA | 16.4% | NA | Itching and redness 2.6% | NA | ||
| Mitjà O, 2021 [268] | RAN HCQ n = 1116 |
NA | NA | NA | NA | NA | NA | 42.6% | NA | NA | 21.7% | NA | NA | General disorder: myalgia, fatigue, malaise 8.6% | ||
| Barnabas RV, 2021 [269] | RAN HCQ n = 407 |
NA | NA | NA | NA | NA | NA | NA | 3.4% | 6.1% | NA | NA | Headache 1.2% Dizziness 1.5% |
Taste change or dry mouth 0.2% Visual changes 1% Tinnitus 0% |
Rash 2.7% | Fatigue 1% |
| Nagaraja BS, 2020 [272] | OBS HCQ n = 156 |
NA | NA | NA | NA | NA | NA | 7.22% | Nausea 10.24% Vomiting 1.20% |
7.22% | NA | NA | Headache 6% Dizziness 3.6% |
Tinnitus 0.6% Transient visual blurring 2.4% |
Hair fall 1.8% Oral ulcer 1.2% Itching 0.6% |
Psychiatric 4.8% Nightmare 0.6% Nervousness 1.20% Fatigue, lethargyWeakness 7.2% |
| Özdemir IH, 2020 [256] | OBS HCQ n = 45 |
NA | NA | NA | NSVT 0% SVT 0% VF 0% |
0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Cavalcanti AB, 2021 [257] | RAN HCQ n = 221 |
14.6% | NA | NA | VT 0% | NA | NA | NA | Nausea 4.5% Vomiting 0% |
NA | 2.5% | 8.5% | NA | Hypoacusia 0% | Itching 0.5% | Hypoglycaemia 0.5% |
| Çap M, 2020 [258] | OBS HCQ n = 66 |
6% | NA | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Lauriola M, 2020 [259] |
OBS HCQ n = 17 |
NA | NA | NA | NA | NA | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Ramireddy A, 2020 [264] | OBS HCQ n = 10 |
NA | NA | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Tanriverdİ E, 2021 [260] | OBS HCQ n = 30 |
NA | NA | NA | 0% | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Arshad S, 2020 [261] |
OBS HCQ n = 1202 |
NA | NA | NA | NA | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Pereira MR, 2020 [265] | OBS HCQ n = NA |
0% | NA | NA | 0% | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Jain S, 2020 [230] | OBS HCQ n = 415 |
23.6% | NA | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Hor CP, 2020 [228] | OBS HCQ n = 2 |
100% | NA | NA | 0% | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Paccoud O, 2020 [227] |
OBS HCQ n = 38 |
5.3% | NA | NA | NA | NA | NA | 2.6% | NA | NA | NA | NA | Headache 2.6% | NA | NA | NA |
| Lagier JC, 2020 [226] |
OBS HCQ n = 101 |
NA | NA | 2% | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Reis G, 2021 [233] | RAN HCQ n = 207 |
NA | NA | NA | NA | NA | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Faruqui AR, 2021 [267] | OBS HCQ n = 1303 (HCQ + AZ: 0.8%; CQ: 0.5%) |
NA | NA | NA | NA | NA | NA | NA | Nausea 8.7% Vomiting 1.4% |
7.0% | NA | NA | NA | Photosensitivity 0.5% | NA | NA |
| Eftekhar SP, 2021 [236] |
OBS HCQ n = 29 |
10.3% | NA | NA | 0% | 3.4% | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Mazzanti A, 2020 [229] |
OBS HCQ n = 50 |
NA | NA | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Karolyi M, 2021 [231] |
OBS CQ n = 20 |
NA | NA | NA | NA | NA | NA | 0% | 5% | NA | NA | 10% | NA | NA | NA | NA |
| Mitjà O, 2020 [232] | RAN HCQ n = 136 |
NA | NA | NA | NA | NA | 0% | 88.1% | NA | NA | 37.5% | Ear and labyrinth disorders 3% Eye disorders 3% |
6.5% | Psychiatric disorders 1.2% | ||
| Lofgren SM, 2020 [266] | RAN HCQ once-daily n = 576 |
NA | NA | NA | NA | NA | 0% | Upset stomach or nausea 25.3% Diarrhea, vomiting, or abdominal pain 22.7% |
NA | NA | Headache 2.6% Irritability, dizziness, vertigo 6.8% |
Tinnitus 2.8% Visual changes 1.2% Taste change or dry mouth 0.5% |
Skin reaction 1.7% | Panic 0% | ||
| RAN HCQ once-weekly n = 473 |
NA | NA | NA | NA | NA | 0% | Upset stomach or nausea 17.5% Diarrhea, vomiting, or abdominal pain 12.9% |
NA | NA | Irritability, dizziness, vertigo 5.7% | Tinnitus 2.1% Visual changes 1.5% |
Skin reaction 2.7% | Sleep disturbance 2.1% | |||
| RAN HCQ twice-weekly n = 463 |
NA | NA | NA | NA | NA | 0% | Upset stomach or nausea 19.4% Diarrhea, vomiting, or abdominal pain 17.1% |
NA | NA | Irritability, dizziness, vertigo 5.2% | Tinnitus 1.5% Visual changes 0.9% |
Skin reaction 5.0% | Sleep disturbance 1.5% | |||
| Bessière F, 2020 [207] |
OBS HCQ n = 22 |
NA | 5% | NA | NA | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Mercuro NJ, 2020 [215] |
OBS HCQ n = 37 |
NA | 19% | 8% | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Rosenberg ES, 2020 [218] | OBS HCQ n = 271 |
14.4% | NA | NA | NA | NA | NA | 17.0% | NA | NA | NA | NA | NA | NA | NA | NA |
| Saleh M, 2020 [219] | OBS HCQ or CQ n = 82 |
NA | 8.5% | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Van den Broek MPH 2020 [220] | RAN CQ n = 95 |
NA | 23% | NA | NA | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Chen Z, 2020 [222] | RAN HCQ n = 31 |
NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Headache 3.2% | NA | 3.2% | NA |
| Huang M, 2020 [223] |
RAN CQ n = 10 |
NA | NA | NA | NA | NA | NA | 50.0% | Nausea 40% Vomiting 50% |
10% | NA | NA | Headache 0% Dizziness 0% |
NA | 10% | Psychosis 0% |
| Fernández-Ruiz M, 2020 [212] |
OBS HCQ n = 4 |
NA | 25% | NA | NA | 0% | 0% | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Chen J, 2020 [224] | OBS HCQ n = 15 |
NA | NA | NA | NA | NA | NA | 13.3% | NA | NA | 6.66% | NA | NA | NA | NA | Weakness 6.6% |
AEs: adverse effects, AF: atrial fibrillation, BBB: bundle branch block, CRVA: clinically rellevant ventricular arryhtmia, COVID-19: coronavirus disease 2019, CQ: chloroquine, ECG: electrocardiograph, HCQ: hydroxychloroquine, ms: milliseconds, NA: not available/not applicable, NSVT: non-sustained ventricular tachycardia, OBS: observational, QTc: corrected QT interval, RAN: randomised, SVT: sustained ventricular tachycardia, SVT: supraventricular tachycardia, VF: ventricula fibrillation, VT: ventricular tachycardia.