Table 3.

Known adverse events of marketed anti-infective and anti-inflammatory drugs mostly provided as off-label treatments in the first phase of the COVID-19 pandemic

Drug	Adverse events
Lopinavir/ritonavir	•Hypercholesterolaemia and increased serum triglycerides (3–39%)
	•Increased γ-glutamyl transferase (10–29%)
	•Diarrhoea (7–28%; greater with once-daily dosing)
	•Increased serum ALT (grade 3/4: 1–11%)
	•Nausea (5–16%)
	•Upper respiratory tract infection (14%)
	•Abdominal pain (1–11%)
	•Vomiting (2–7%)
	•Fatigue (8%)
	•Increased serum amylase and/or lipase (3–8%)
	•Headache (2–6%)
	•Skin rash (≤5%)
	•Neutropenia (grade 3/4: 1–5%)
	•Anxiety (4%)
	•Insomnia (≤4%)
Chloroquine/hydroxychloroquine	•Retinopathy (4% of treated patients)a
	•Other adverse effects with unknown frequency included Stevens-Johnson syndrome, abdominal pain, diarrhoea, nausea, vomiting, agranulocytosis, leukopenia, thrombocytopenia, abnormal hepatic function tests, acute hepatic ailure, myopathy, bronchospasm
	•Risk of prolonged QT interval, further increased when administered with fluoroquinolones or azithromycin
Tocilizumab	•Increased serum ALT (≤36%) and AST (≤22%)
	•Increased LDL cholesterol (9–10%)
	•Injection site reaction (4–10%)
	•Neutropenia (grade 3: 2–7% of all adult patients)
	•Headache (1–7%)
	•Hypertension (1–6%)
	•Dizziness (3%)
	•Hypothyroidism (<2%)
	•Abdominal pain (2%)
	•Oral mucosa or gastric ulcers (2%)
	•Infections due to Pneumocystis, Mycobacterium tuberculosis and varicella zoster have been reported after tocilizumab, but their prevalence has not been clearly established
Anakinra	•Injection site reactionb (24–71%)
	•Antibody development (up to 50% of the patients but no correlation of antibody development and adverse effects)
	•Headache and vomiting (12–14%)
	•Arthralgia (10–12%)
	•Fever (10–12%)
	•Haematologic disorder including eosinophilia, leukopenia and change in platelet count (2–9%)
	•Nausea and diarrhoea (7–8%)
	•Serious infectionc (2–3%)

Off-label drugs mostly provided in Italy during the first phase of the COVID-19 pandemic according to the authors' direct experience.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; LDL, low-density lipoprotein.

^aSerum concentration dependent adverse effect; early changes are generally reversible but may progress despite discontinuation if advanced.

^bInjection site reactions were considered serious in 2–3% of cases.

^cSerious infections included cellulitis, pneumonia, and bone and joint infections.