Analysis of spontaneous reports of adverse reaction cases associated with the use of medicinal products in the treatment of COVID19 received by VigiBase during March 2020 (first interim results)

During March 2020, the WHO Global Database – VigiBase received 26 reports of cases of adverse reactions that occurred after the use of medicinal products included in the WHO SOLIDARITY program, as well as relevant antiviral medicines currently being studied in clinical trials reported in the WHO International Clinical Trials Registry Platform.

Reports were received from 6 European countries: Italy (17 cases), France (3 cases), Spain (3 cases), Austria (1 case), Switzerland (1 case), and Germany (1 case).

The report included data on the following patients: 7 women with a mean age of 60,5 years and 17 men with a mean age of 70,5 years. In two cases, the sex of the patients was not indicated. The age range of patients in the reports was 41 – 83 years. Overall, adverse reactions were noted in 72,7% of men and 27,3% of women. Only one case of an adverse reaction was recorded in a patient older than 80 years. The highest percentage (36,7%) of adverse reactions was noted in patients of the 46 – 60 years age group.

10 cases of adverse reactions were associated with monotherapy, i.e., a single medicinal product was used in the treatment of the patient with coronavirus infection. Of these, by seriousness, 5 cases of adverse reactions were serious and 5 were non-serious.

Of 4 cases of adverse reactions that occurred after the use of Lopinavir/ritonavir – the medicinal products (MPs) were discontinued in 3 patients, of whom 2 cases ended in recovery and 1 in no change. In 1 case, neither the discontinuation of the MP nor the outcome of the adverse reaction was indicated.

Of 5 cases associated with the use of Remdesivir – 1 case ended in the patient's death. In 1 case, discontinuation of the medicinal product and the outcomes were not specified. In 1 case, the medicinal product was discontinued, the outcome is unknown. In 2 cases, the medicinal product was not discontinued, the outcome is unknown.

In the case of an adverse reaction after the use of Hydroxychloroquine the medicinal product was discontinued without recovery.

Distribution by systemic manifestations that occurred after the use of monotherapy with Lopinavir/ritonavir, Remdesivir, and Hydroxychloroquine

Table 1.

11 cases were recorded following the use of combination therapy with Lopinavir/ritonavir + Hydroxychloroquine. Of these, by seriousness, 1 case of adverse reaction was serious and 10 were non-serious. In 5 cases, discontinuation of the medicinal product and the outcome of the adverse reaction were not specified. In 1 case, the entire combination therapy was discontinued and recovery was noted as the outcome. In 3 cases, only Lopinavir/ritonavir was discontinued and recovery was noted. In 2 cases, recovery was recorded without discontinuation of the combination therapy.

Distribution by systemic manifestations that occurred after the use of the specified combination therapy

Table 2.

5 cases of adverse reactions were reported following the use of combination therapy Lopinavir/ritonavir + Oseltamivir; Lopinavir/ritonavir + Hydroxychloroquine + Interferon β + Tocilizumab; Lopinavir/ritonavir + Remdesivir; Lopinavir/ritonavir + Interferon β; Remdesivir + Hydroxychloroquine. By seriousness, 2 of them were serious and 3 were non-serious adverse reactions.

Distribution by system manifestations that occurred after the use of the specified combinations

Table 3.

Discontinuation of the medicinal product and Outcome are not marked if no such information is available.