Table 1.

Summary of published literature describing anti-COVID-19 drugs-associated adverse events

Study design	Drug	Number of cases/participants	Age (years)/sex	Dose of therapy	Concomitant therapy/ies	Adverse event(s)	Treatment and outcome	References
Randomized controlled trial	Dexamethasone	2104 patients assigned to dexamethasone	66.9#/766 female 1338 male	6 mg once a day	NR	Hyperglycemia, gastrointestinalhemorrhage, and psychosis	NR	[11]
Case report	Hydroxychloroquine	Case 1	37/female	200 mg once	Ciprofloxacin 500 mg	QT interval prolongation	Metoprolol tartrate 25 mg twice a day, discharged with cardiac rhythm holter to monitor her cardiac electrical activity	[12]
		Case 2	58/male	200 mg twice a day	Azithromycin 500 mg once a day and oseltamivir 75 mg twice a day		Drug discontinuation, stable cardiac condition
		Case 3	24/NR	NR	NR		Drug discontinuation, improvement of the condition
Case series	Hydroxychloroquine	Case 1	75/male	NR	Azithromycin and cefepime	Multiple episodes of non-sustained ventricular tachycardia	Drug discontinuation, resolution of the adverse event	[13]
		Case 2	56/female	NR	Azithromycin and cefepime	Nausea, vomiting, severe abdominal cramps, and unbearable watery diarrhea	Drug discontinuation and supportive care, improvement of symptoms
Case report	Hydroxychloroquine		29/female	400 mg twice a day	Azithromycin and piperacillin–tazobactam	Tenfold increase in transaminases level	Drug discontinuation, level of transaminases returned to near-normal values within 5 days	[14]
Case report	Hydroxychloroquine		84/female	200 mg twice a day	Oral nifedipine 30 mg twice a day and irbesartan 75 mg twice a day	Sinus bradycardia with QTc prolongation	Drug discontinuation, isoproterenol IV at a maximal dose of 10 mcg/min and epinephrine at a maximal dose of 1 mcg/kg/min, QTc interval was normalized	[15]
Case report	Hydroxychloroquine		42/female	200 mg twice a day	Acetaminophen 500 mg every 6 h	Stevens–Johnson syndrome (SJS)	Drug discontinued and therapy changed to lopinavir/ritonavir 400 mg twice a day, loratadine 10 mg twice a day and diphenhydramine 50 mg thrice a day, discharge after 5 days with nonpruritic scalded skin on the distal of upper extremities	[16]
Case report	Hydroxychloroquine		38/male	200 mg twice a day	Ceftriaxone 2 g intravenously every 12 h and lopinavir + ritonavir 400/100 mg tablet twice a day	Involuntary movements involving bilateral, asynchronous, irregular myoclonus of the limbs	Drug discontinuation, discharge with complete resolution of all involuntary movements	[17]
Case report	Hydroxychloroquine		37/female	200 mg twice a day	Lopinavir-ritonavir 200/50 mg/12 h and azithromycin 250 mg/day	DRESS syndrome	NR	[18]
Case report	Hydroxychloroquine		60/female	400 mg starting dose followed by 200 mg twice a day	Amoxicillin–clavulanic acid 1.2 g thrice a day, oseltamivir 75 mg twice a day, lopinavir 400 mg/ritonavir 100 mg twice a day, meropenem 1,000 mg thrice a day, and amoxicillin–clavulanic acid was replaced by meropenem	Right bundle branch block (RBBB) and critically prolonged QTc	Drug discontinuation, normalization of QTc	[19]
Case series	Hydroxychloroquine	Case 1	74/female	NR	Ondansetron, oseltamivir, and azithromycin	QTc prolongation, and several premature ventricular contractions with R-on-T waves	Hydroxychloroquine, ondansetron, and azithromycin discontinuation, improvement of symptoms and eventual discharge from the hospital	[20]
		Case 2	40/female	NR	NR	Nausea, vomiting, diarrhea, and marked sinus bradycardia	Drug discontinuation, improvement of symptoms, and eventual discharge from the hospital
Case report	Hydroxychloroquine		68/male	600 mg, single dose	Piperacillin/tazobactam	Worsening of hemolysis in a patient with G6PD deficiency	NR	[21]
Case report	Hydroxychloroquine		76/male	200 mg thrice a day	Azithromycin, ceftriaxone	Acute general pustular erythema eruption	Death of patient due to pulmonary embolism	[22]
Randomized controlled trial	Hydroxychloroquine	491 participants Assigned to hydroxychloroquine (n = 244) Contributed data to the primary endpoint (n = 212)	41*/123 female 89 male	800 mg (4 tablets) once, then 600 mg (3 tablets) 6 to 8 h later, then 600 mg (3 tablets) once a day for 4 more days (5 days in total)	NR	Upset stomach, nausea, abdominal pain, diarrhea, or vomiting	NR	[23]
Randomized controlled trial	Hydroxychloroquine	150 patients, 75 patients assigned to hydroxychloroquine plus standard of care 70 received	46#/82 male	Loading dose of 1200 mg daily for 3 days followed by a maintenance dose of 800 mg once a day	Antiviral agents, antibiotics, and systemic glucocorticoid therapy	Diarrhea, nausea	NR	[24]
Case report	Hydroxychloroquine		Early 70 s/male	200 mg twice a day	NR	Phospholipidosis, acute kidney injury	Drug discontinuation, death	[25]
Case report	Chloroquine		84/female	500 mg twice a day	Bisoprolol, letrozole, memantine, and apixaban	Extremely prolonged QT interval, torsades de pointes (TdP)	Chloroquine, memantine, letrozole, and bisoprolol discontinuation, treated with intravenous magnesium, potassium, lidocaine, and isoproterenol, resolution of arrhythmias and normalization of QT interval followed by discharge	[26]
Case report	Chloroquine	Case 1	46/male	NR	Vortioxetine, azithromycin	Psychotic symptoms such as visual hallucinations and incoherent speech, with an outburst of odd behavior and repeated attempts to run away from the hospital	COVID-19 medication and vortioxetine discontinuation, amisulpride 100 mg once a day, disappearance of psychotic symptoms	[27]
		Case 2	35/female	NR	Azithromycin	Insomnia, panic attacks, anxiety, a sensation of death and fear, uncontrollable thoughts and distress	Lorazepam 2.5 mg, azithromycin, chloroquine discontinuation, disappearance of anxiety symptoms
Case report	Chloroquine		66/female	Loading dose of 600 mg orally and a maintenance dose of 300 mg twice a day	NR	QTc prolongation, TdP	Drug discontinuation, erythromycin 250 mg twice a day for gastrointestinal motility started and later discontinued, intravenous Mg 2 g, normalization of QTc interval	[28]
Case report	Remdesivir		59/male	Loading dose of 200 mg intravenously followed by 100 mg IV	Convalescent plasma	Sinus bradycardia, elevated ALT	Drug discontinuation, increase in heart rate and discharge	[29]
Case report	Remdesivir	Case 1	26/female	NR	Ceftriaxone, azithromycin, methylprednisolone, and convalescent plasma	Sinus bradycardia, QTc interval prolongation, and T wave abnormality	Drug discontinuation, stable condition	[30]
		Case 2	77/female	NR	Ceftriaxone, azithromycin, and methylprednisolone	Sinus bradycardia	Drug discontinuation, normalization of heart rate
Case report	Remdesivir		64/male	NR	Amiodarone 700 mg	Acute increase in ALT and AST	Drug discontinuation, rapid decrease in ALT and AST levels to normal	[31]
Case report	Remdesivir		54/female	Loading dose of 200 mg and proceeding with 100 mg once a day	NR	Sinus bradycardia	Drug discontinuation, atropine, condition improved	[32]
Case report	Remdesivir		36/male	Loading dose 200 mg on day 1 followed by 100 mg once a day	Ceftriaxone 2 g once a day, vibramycin 100 mg twice a day, dexamethasone 6 mg once a day, and enoxaparin 60 mg twice a day	Sinus bradycardia	Drug discontinuation, atropine, condition improved	[33]
Case series	Remdesivir	Case 1	68/female	Loading dose of 200 mg IV and a maintenance of 100 mg IV every 24 h	Amiodarone	Increase in AST and ALT levels, acute liver failure	Remdesivir and amiodarone discontinuation, continuous infusion of acetylcysteine, decrease in AST and ALT levels and return to stable values	[34]
		Case 2	80/female	200 mg IV loading dose followed by 100 mg IV once day	Dexamethasone 6 mg orally once a day	Acute liver failure	Continuous infusion of acetylcysteine, restoring of normal values, death due to cardiac arrest
Randomized controlled trial	Remdesivir	193 (10-day remdesivir) 191 (5-day remdesivir)	56*/118 male 75 female, 58*/114 male 77 female	200 mg on day 1, followed by 100 mg once a day	Steroids. hydroxychloroquine/chloroquine, lopinavir-ritonavir, tocilizumab, azithromycin	Nausea, diarrhea, hypokalemia, headache	Drug discontinuation	[35]
Case report	Favipiravir		42/male	1,800 mg twice a day on administration day 1 and 800 mg twice a day after	NR	Hyperuricemia, acute gouty arthritis	Nonsteroidal anti-inflammatory drugs (NSAIDs), improvement of pain and swelling and complete recovery	[36]
Case report	Favipiravir		82/male	1,600 mg twice the first day and 800 mg twice the second day	Ceftriaxone	Fever	Drug discontinuation, improvement of fever	[37]
Case report	Favipiravir		73/male	6000 mg on day 1 and 2400 mg/day from day 2	Meropenem, vancomycin, antithrombin III agents, steroids, trimethoprim-sulfamethoxazole, and micafungin	Acute cholestatic liver injury	NR	[38]
Case report	Favipiravir	Case 1	38/male	1600 mg twice a day followed by 600 mg twice a day for 5 days	Hydroxychloroquine 400 mg twice a day followed by 200 mg	Increase in serum creatinine levels	Drug discontinuation, Improvement of renal functions	[39]
		Case 2	51/male	1600 mg twice a day followed by 600 mg twice a day for 5 days	Hydroxychloroquine 400 mg twice a day followed by 200 mg, methylprednisolone 40 mg twice a day, enoxaparin 40 mg once a day	Increase in serum creatinine levels with non-oliguria	Drug discontinuation, improvement of renal functions
Randomized clinical trial	Favipiravir	40 patients	NR	1600 mg twice a day on day 1 followed by 600 mg twice a day or 1800 mg twice a day on day 1 followed by 800 mg twice a day	Antibiotics, anticoagulants, and/or immunosuppressants and symptomatic treatment	Diarrhea, nausea, vomiting, chest pain, and an increase in liver transaminase levels	Drug discontinuation	[40]
Randomized clinical trial	Favipiravir	73 patients	44.5*/21 female 51 male	1800 mg twice a dayloading dose on day 1; 800 mg twice a daymaintenance dose thereafter	NR	Increased blood uric acid, abnormal liver function tests	NR	[41]
Case report	Lopinavir/ritonavir	Case 1	56/female	400/100 mg twice a day	Arbidol, pantoprazole, methylprednisolone, and chloroquine	QTc interval prolongation	Drug discontinuation, potassium chloride 1 g thrice a day, QTc interval decreased and patient discharged	[42]
		Case 2	56/female	400/100 mg twice a day	Arbidol, pantoprazole, and chloroquine	QTc interval prolongation	Drug discontinuation, potassium chloride 1 g thrice a day, QTc interval decreased and patient discharged
Case report	Lopinavir–ritonavir		67/male	400 mg/100 mg twice a day	Intravenous piperacillin–tazobactam 4 g/0.5 g every 8 h	Sick sinus syndrome	Drug discontinuation, resolution of bradycardic episodes	[43]
Case report	Lopinavir–ritonavir		67/male	Lopinavir 4 mg/kg/ritonavir 1 mg/kg 12-hourly was initiated	Propofol IV, fentanyl	Severe bradycardia and hypotension	Drug discontinuation, ephedrine IV 20 mg, atropine 1200 mcg, dopamine IV 5 mcg/kg/min, transcutaneous pacing pads introduced, bradyarrhythmia episodes disappeared, patient recovered	[44]
Case report	Lopinavir–ritonavir (LPV/r)	Case 1	66/male	400 mg/100 mg twice a day	Hydroxychloroquine 200 mg twice a day, lithium 800 mg once a day, duloxetine 120 mg once a day, haloperidol 1 mg twice a day	Serotonin syndrome (SS)	Duloxetine, lithium, haloperidol, and LPV/r discontinuation, improvement of symptoms	[45]
		Case 2	78/male	400 mg/100 mg twice a day	Hydroxychloroquine 200 mg twice a day, interferon beta-1b, tocilizumab, risperidone 1 mg twice a day, morphine 3 mg	Serotonin syndrome (SS)	LPV/r and risperidone discontinuation. Fluid therapy, active cooling. Clonazepam 0.25 mg every 6 h, improvement of symptoms
Randomized controlled trial	Lopinavir/ritonavir	21 patients	52.2#/11 male 10 female	Oral, q12h, 500 mg each time	Methylprednisolone 40 mg once a day and gamma globulin 10 g once a day	Diarrhea, loss of appetite, elevation of ALT	NR	[46]
Randomized controlled trial	Ivermectin	94 patients assessed, 12 treated with ivermectin	26*/5 female 7 male	Oral, 400 mcg/kg, single dose	NR	Dizziness, blurred vision	NR	[47]
Randomized clinical trial	Ivermectin	476 patients enrolled, 275 assigned to ivermectin	38*/163 female 112 male	Oral, 300 μg/kg	NR	Headache, dizziness, diarrhea, nausea, abdominal pain, visual disturbance	Drug discontinuation in 15 patients	[48]
Case report	Tocilizumab (TCZ)		45/male	8 mg/kg	Favipiravir, nafamostat, propofol, and methylprednisolone 1 g once a day	Hypertriglyceridemia	Fenofibrate, stable triglyceride levels	[49]
Case report	Tocilizumab (TCZ)	Case 1	65/male	NR	Lopinavir/ritonavir, ribavirin, hydroxychloroquine, propofol	Hypertriglyceridemia	NR	[50]
		Case 2	43/male	NR	Lopinavir/ritonavir, ribavirin, hydroxychloroquine, propofol	Hypertriglyceridemia	NR
Case report	Tocilizumab		52/male	Two doses of 400 mg (8 mg/kg), with a 12-h break between doses	Ceftriaxone, azithromycin, and methylprednisolone	Acute liver injury	NR	[51]
Case report	Tocilizumab		65/male	Two doses of tocilizumab IV 8 mg/kg administered 12 h apart	Piperacillin-tazobactam	Neutropenia	NR	[52]
Randomized controlled trial	Tocilizumab	34 patients	63.5*/18 male 16 female	First dose 400 mg IV for more than 1 h, second dose given when patient remained febrile for 24 h after first dose	NR	Hepatic function abnormality, leukopenia, and neutropenia	Symptomatic treatment	[53]

Drug discontinuation refers to the withdrawal of the primary anti-COVID-19 drug being reviewed, unless stated otherwise.

ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; IV, intravenous; NR, not reported.

*Median

#Mean