Adverse drug reactions to chloroquine/hydroxychloroquine in combination with azithromycin in COVID-19 in-patients: data from intensive pharmacovigilance in Morocco, 2020.

In Morocco, chloroquine/hydroxychloroquine + azithromycin have been used off-label for COVID-19 treatment. This study aimed to describe the distribution, nature and seriousness of the adverse drug reactions (ADRs) associated with the two drug combinations in COVID-19 in-patients. We conducted a prospective observational study based on intensive pharmacovigilance in national COVID-19 patients' management facilities from April 1 to June 12, 2020. Hospitalized patients treated with chloroquine/hydroxychloroquine + azithromycin and who experienced ADRs during their hospital stay were included in the study. The causality and seriousness of the ADRs were assessed using the World Health Organization-Uppsala Monitoring Centre method and the agreed criteria in the ICH guideline (E2A) respectively. A total of 237 (51.7%) and 221 (48.3%) COVID-19 in-patients treated respectively with chloroquine + azithromycin and hydroxychloroquine + azithromycin experienced 946 ADRs. Serious ADRs occurred in 54 patients (11.8%). Gastrointestinal system was most affected both in patients taking chloroquine + azithromycin (49.8%) or hydroxychloroquine + azithromycin (54.2%), followed by nervous system and psychiatric. Eye disorders were more frequent in patients receiving chloroquine + azithromycin (10.3%) than those receiving hydroxychloroquine + azithromycin (1.2%). Cardiac ADRs accounted for 6.4% and 5.1% respectively. Chloroquine + azithromycin caused more ADRs by patients than hydroxychloroquine + azithromycin (2.6 versus 1.5 ADRs/patient). Causality assessment was possible for 75.7% of the ADRs. Diabetes was identified as a risk factor for serious ADRs (ORa 3.56; IC: 95% 1.5-8.6). The off-label use of the two drug combinations in COVID-19 in-patients according to the national therapeutic protocol seems to be safe and tolerable. ADRs were mainly expected. However, precaution should be taken in using the drugs in diabetic patients to prevent the risk of serious ADRs.