Table 2.
Descriptive characteristics of fatal QTc prolongation-related case reports listing use of hydroxychloroquine/chloroquine monotherapy and hydroxychloroquine/chloroquine + azithromycin combination therapy in COVID-19 cases reported to FAERS from January 1, 2020, to December 31, 2020
| Characteristics | HCQ/CQ + azithromycin (N = 74) | HCQ/CQ monotherapy (N = 48) | Total (N = 122) |
|---|---|---|---|
| Age, years | 39 reported | 26 reported | 65 reported |
| Median (IQR) | 66 (43–69) | 70 (47–75) | 67 (44–74) |
| Sex | 38 reported | 28 reported | 66 reported |
| Female | 12 (31.6) | 9 (32.1) | 21 (31.8) |
| Precipitating factorsa | |||
| Hypertension | 5 (6.8) | 5 (10.4) | 10 (8.2) |
| Heart failure | 1 (1.4) | 3 (6.3) | 4 (3.3) |
| Diabetes | 1 (1.4) | 3 (6.3) | 4 (3.3) |
| Sepsis | 0 (0) | 1 (2.1) | 1 (0.8) |
| Female sex | 12/38 (31.6) | 9/28 (32.1) | 21/66 (31.8) |
| Advanced age >65 years | 22/39 (56.4) | 16/26 (61.5) | 38/65 (58.5) |
| Concurrent QTc-prolonging medications may induce QTsb | |||
| Lopinavir/ritonavir | 2 (2.7) | 3 (6.3) | 5 (4.1) |
| Loop diuretics | 4 (5.4) | 6 (12.5) | 10 (8.2) |
| Quinolones | 1 (1.4) | 0 | 1 (0.8) |
| Azole antifungals | 0 | 4 (8.3) | 4 (3.3) |
| Macrolide | 0 | 1 (0.8) | 1 (0.8) |
| HCQ/CQ alone | NA | 35 (72.9) | 35 (28.7) |
| Two QTc-prolonging agents | 67 (90.5) | 12 (25.0) | 79 (64.8) |
| Three QTc-prolonging agents | 7 (9.5) | 1 (2.1) | 8 (6.6) |
| Serious outcomes | 74 reported | 46 reported | 120 reported |
| Hospitalization | 29 (39.2) | 25 (52.08) | 54 (44.3) |
| Life threatening | 25 (33.8) | 9 (18.8) | 34 (27.9) |
| Death | 22 (29.7) | 18 (37.5) | 40 (32.8) |
| Other serious events | 54 (73.0) | 32 (66.7) | 86 (70.5) |
| Dosing of HCQ/CQ | 23 reported | 25 reported | 48 reported |
| 400 mg qd, with or without a loading dose | 9 | 5 | 14 |
| 600 mg bid | 0 | 1 | 1 |
| 800 mg qd | 0 | 3 | 3 |
| 600 mg qd | 7 | 1 | 8 |
| 400 mg bid | 4 | 2 | 6 |
| 200 mg bid | 3 | 6 | 9 |
| 1000 mg qd or 500 mg bid (CQ) | 0 | 4 | 4 |
| 500 mg qd (CQ) | 1 | 1 | 2 |
| 200 mg tid | 0 | 1 | 1 |
| Duration, days | 24 reported | 24 reported | 48 reported |
| Median (IQR) | 4 (2–5) | 4 (1–9.5) | 4 (2–5) |
Data are presented as n (%) of events unless otherwise noted
bid twice daily, COVID-19 coronavirus disease 2019, CQ chloroquine, HCQ hydroxychloroquine, IQR interquartile range, NA not applicable, qd once daily, SCAE serious cardiovascular adverse event, tid three times daily
aPrecipitating factors included heart failure, hypertension, hyperlipidemia, left ventricular hypertrophy, severe renal disease, diabetes, female sex, advanced age >65 years, sepsis, hypokalemia, hypomagnesemia, hypocalcemia, and obesity. Those with zero or missing values were not listed
bThe individual drugs for each group are shown in Table S5 in the electronic supplementary material