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OFF-X COVID-19 REPORT:

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    DRUGS & BIOLOGICS
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The COVID-19 outbreak is posing a tremendous challenge for the global biomedical community to find potential treatments, vaccination strategies and supportive medications. To complement the efforts being made in developing the most appropriate efficacy-oriented projects, Bioinfogate is providing, on a complimentary basis, all the relevant safety and toxicity information detected by our editorial team.

This report provides a compilation of safety alerts derived from recent publications related to COVID-19 as well as previous OFF-X content that may be of interest. Content can be sorted by target or by drug of interest. Click on any alert to jump to OFF-X and retrieve the full alert details.

Access to the COVID-19 report is granted under the following Terms & Conditions

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OFF-X COVID-19 REPORT
5-HT1A receptor
5-HT2A receptor
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 03, 2020
Case series of 16 Caucasian men with COVID-19 receiving intramuscular aripiprazole (5-HT1A receptor agonist, 5-HT2A/D2 receptor antagonist; 9.75 mg/1.3 ml) to treat delirium and psychomotor agitation. Mild sedation was reported in 5 patients. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 04, 2020
Article reporting that viral infections, including COVID-19, may have contributed to the high incidence of clozapine myocarditis observed in a meta-analysis. [Journal]
Jul 12, 2020
Literature review evaluating psychiatric aspects of chloroquine and hydroxychloroquine treatment in patients with COVID-19. Chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications. These drugs may also prolong the QT interval. Neuropsychiatric side effects are listed. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
Apr 19, 2020
Review of the rational use of clozapine for treatment-resistant schizophrenia. Clozapine has been associated with fatal adverse events (AEs) such as agranulocytosis, pneumonia and myocarditis. Clozapine may increase the risk of pneumonia in COVID-19 patients. Other AEs are listed. [Journal]
5-HT2C receptor
5-HT3 receptor
5-HT4 receptor
5-HT7 receptor
5-LOX
50S ribosomal protein
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 09, 2020
Review of azithromycin (50S ribosomal protein inhibitor), as monotherapy or in combination, for the treatment of COVID-19. The most common adverse effects (AEs) of azithromycin are gastrointestinal, but it has also been associated with an increased risk of cardiac events such as QTc prolongation, torsade de pointes, ventricular tachycardia and sudden cardiac death. Other AEs of azithromycin, hydroxychloroquine and the combination of both drugs are listed. [Journal]
Sep 03, 2020
Review on remdesivir (viral RNA polymerase inhibitor) for COVID-19 in pediatric patients. Remdesivir is not recommended in pediatric patients with hepatic impairment or hepatotoxicity at baseline as it increases liver aminotransferase levels (11.7%). Increased ALT was observed in a 5-year-old child with acute lymphoblastic leukemia receiving remdesivir for concomitant SARS-CoV-2 infection. Drug-drug interactions have also been reported with remdesivir in combination with P-glycoprotein inhibitors such as hydroxychloroquine, azithromycin, cyclosporine, tacrolimus and amiodarone, which may have caused the hepatocellular toxicity. [Journal]
Sep 02, 2020
Review evaluating the cardiovascular risk associated with the use of chloroquine or hydroxychloroquine for COVID-19 treatment. Both drugs have been associated with QTc interval prolongation, ventricular arrhythmias, polymorphic ventricular tachycardia and torsades de pointes. When combined with azithromycin, mortality was increased and the rate of QTc prolongation was higher than that observed with either drug as monotherapy. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Jul 30, 2020
Clinical trial of hydroxychloroquine with or without azithromycin in 667 patients with mild-to-moderate COVID-19. Prolongation of the QTc interval was observed in the combination group (14.7% patients) and the hydroxychloroquine group (14.6%). Other adverse events (AEs) included increased ALT/AST (10.9% and 8.5% in the combination and hydroxychloroquine groups, respectively), anemia (9.6% and 7%) and low lymphocyte levels (12.1% and 8.5%). Other AEs are listed. [Journal]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jul 14, 2020
Retrospective study of hydroxychloroquine (HCQ; 200 mg tid) and azithromycin (AZ; 250 mg qd), alone or in combination, in patients with COVID-19. Common adverse events (AEs) considered possibly related to HCQ/AZ included diarrhea (1.6%), nausea, vomiting (0.8% each), abdominal pain (0.7%) and prolonged QTc interval (0.6%). AEs considered related to HCQ monotherapy included skin disorders, abdominal pain/digestive disorders (3% each), prolonged QTc interval and headache (2% each). AEs considered possibly related to AZ included prolonged QTc (2.2%) and neuropsychiatric signs (0.7%). Other AEs considered treatment-related are listed. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
Jun 02, 2020
Study of 6 patients with COVID-19 receiving ibrutinib for Waldenström’s macroglobulinemia. 1 patient discontinued azithromycin after 3 days due to wide QRS complex tachyarrhythmia. [Journal]
May 31, 2020
Article stating that azithromycin (50S ribosomal protein inhibitor) should not be used to treat COVID-19 patients. Compared to hydroxychloroquine alone, the combination of azithromycin with hydroxychloroquine has been associated with an increased risk of cardiovascular mortality, chest pain/angina and heart failure. Both drugs can cause QT prolongation, torsade de pointes and sudden cardiac death. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 27, 2020
Review of clinical trials of potential treatments for COVID-19. Side effects of chloroquine, azithromycin, lopinavir/ritonavir and tocilizumab are listed. [Journal]
May 27, 2020
Study of hydroxychloroquine and azithromycin, as monotherapies or in combination, in patients with COVID-19 in New York State. Cardiac arrest and abnormal electrocardiogram findings were more common in the hydroxychloroquine + azithromycin group (15.5% and 27.1%, respectively) and hydroxychloroquine alone group (13.7% and 27.3) than in the azithromycin alone group (6.2% and 16.1%) or in patients not treated with either drug (6.8% and 14.0%). Other side effects are listed. [Journal]
May 27, 2020
Swissmedic, together with Sanofi and Helvepharm, have issued a Direct Healthcare Professional Communication warning about the risk of QT prolongation and subsequent arrhythmias (such as torsades de pointes) associated with hydroxychloroquine (TLR7/9 antagonist). The risk of QT prolongation and other hydroxychloroquine-related serious and life-threatening adverse events (including torsade de pointes, syncope, cardiac arrest and sudden death) was increased in patients receiving hydroxychloroquine combined with other drugs known to prolong QT interval, such as azithromycin. Therefore, doctors must be cautious when using hydroxychloroquine to treat Covid-19. [Regulatory Agency Communication]
May 26, 2020
Analysis of VigiBase assessing the risk of cardiovascular adverse drug reactions of proposed treatments for COVID-19 (hydroxychloroquine and azithromycin). QT prolongation and/or ventricular tachycardia including Torsades-de-Pointes were more frequently reported with each drug than with any other drug in the database (IC025 = 1.04 for hydroxychloroquine; 1.67 for azithromycin). Hydroxychloroquine was also associated with conduction disorders (1.04; including atrioventricular and bundle branch blocks) and heart failure (0.06; including fatal cases). QT prolongation and/or ventricular tachycardia including Torsades-de-Pointes were reported significantly more frequently with the combination of both drugs than with either monotherapy (ROR = 2.48 [1.28-4.79]). Whilst lethal cases of ventricular tachycardia and Torsades-de-Pointes were seen with both drugs, lethal cases of prolonged QT were only seen with azithromycin. [Journal]
May 23, 2020
Review on the cardiovascular safety of potential drugs for the treatment of COVID-19, including chloroquine, hydroxychloroquine, azithromycin, remdesivir, lopinavir in combination with ritonavir, and interferon alpha-2b. Safety data is listed. [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 08, 2020
Case series of 490 patients confirmed or suspected to have COVID-19 who were treated with azithromycin (28%), hydroxychloroquine (10%) or a combination of both (62%). QTc prolongation rates were higher in the combination group than in the azithromycin group. 12% of patients suffered critical QTc prolongation. [Journal]
Apr 21, 2020
Review of azithromycin (50S ribosomal protein inhibitor) and its application for COVID-19. Side effects of azithromycin used as monotherapy or in combination with chloroquine are listed. [Journal]
Apr 10, 2020
Review of the safety considerations regarding the use of chloroquine, hydroxychloroquine and azithromycin for SARS-CoV2 infection. Common adverse events (AEs) of chloroquine and hydroxychloroquine include pruritus, nausea and headache. Both drugs have been linked with life-threatening arrhythmias, serious hypoglycemia, hypersensitivity reactions and serious cutaneous toxicities, and are extremely toxic in overdose. Other AEs are listed. [Journal]
ABCA4
ABL1
ACE
Sep 16, 2020
Study evaluating the association between angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARBs) and risk of SARS-CoV-2 infection. No significant increase in risk was noted with ACEIs (adjusted OR 0.95; 95% CI 0.86-1.05) or ARBs (aOR 1.05; 95% CI 0.97-1.14). However, ARBs increased the risk of SARS-CoV-2 infection in subjects aged <60 years. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
May 28, 2020
Systematic review and meta-analysis evaluating the risk and severity of COVID-19 in patients taking ACE inhibitors (ACEI) or AT1/2 receptor antagonists (ATRA). ACEI/ATRA exposure was not associated with higher risk of infection (OR = 0.99 [0-1.04]). ACEI/ATRA users with infections did not have a higher risk of severe infection (0.98 [0.87-1.09] or mortality (0.73 [0.5-1.07]). [Journal]
May 27, 2020
The AEMPS is reporting that no unfavorable effect of ACE inhibitors and AT1/AT2 receptor antagonists was seen in patients with COVID-19. No differences were seen in hospitalizations or risk of infection among subjects taking ACE inhibitors and AT1/AT2 receptor antagonists with respect to subjects on other antihypertensives. [Regulatory Agency Communication]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 07, 2020
Case-control study assessing the link between AT1/AT2 receptor antagonists and ACE inhibitors and COVID-19. Neither drug class was associated with COVID-19 among overall patients (aOR = 0.95 [0.86-1.05] for AT1/AT2 receptor antagonists; 0.96 [0.87-1.07] for ACE inhibitors) or among patients with severe/fatal course of the disease (0.83 [0.63-1.1]; 0.91 [0.69-1.21]). Other drug classes not associated with COVID-19 are listed. [Journal]
May 07, 2020
Study assessing the risk of COVID-19 infection among patients receiving renin-angiotensin-aldosterone system inhibitors. Neither drug class was associated with an increased likelihood of a positive test nor a substantial increase in the risk of severe illness among patients who tested positive. [Journal]
May 06, 2020
Retrospective study of 1,178 patients hospitalized with COVID-19. No evidence of a higher severity or mortality risk was found in patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. [Journal]
Apr 23, 2020
Review discussing the role of the renin-angiotensin-aldosterone system in Covid-19. Preclinical studies suggested that ACE inhibitors and AT1/2 receptor antagonists can increase ACE2 expression, which may increase susceptibility to SARS-CoV-2 infection. There is insufficient data to evaluate whether these observations can be translated to humans. [Journal]
Mar 30, 2020
The EMA is currently evaluating the potential association between the use of ACE inhibitors and angiotensin receptor blockers (ARBs) and the worsening of COVID-19. These drugs can increase the expression of ACE2, which is the entry point of the virus to human cells. Currently, there is no clinical or epidemiological evidence establishing a link between ACE inhibitors/ARBs and the severity of COVID-19. [Regulatory Agency Communication]
Mar 27, 2020
Article suggesting that patients with COVID-19 taking ACE inhibitors or angiotensin receptor blockers may have an increased risk of severe or fatal disease outcomes. These drugs increase the expression of ACE2 in the lungs, the receptor that serves as binding site for coronaviruses to enter the lungs. [Journal]
Mar 18, 2020
Study reporting that increased expression of ACE2 could facilitate infection with SARS-CoV-2. ACE2 can be increased by thiazolidinediones, ibuprofen, ACE inhibitors and angiotensin receptor blockers, suggesting an increased risk of Covid-19 in patients with cardiac diseases, hypertension, or diabetes taking these drugs. [Journal]
ACE2
Jun 08, 2020
Article discussing the possible role of interferons on the pathogenesis of SARS-CoV-2. Interferons may affect the pathogenesis as they enhance ACE2 expression, the protein required for viral entry. [Journal]
Apr 23, 2020
Review discussing the role of the renin-angiotensin-aldosterone system in Covid-19. Preclinical studies suggested that ACE inhibitors and AT1/2 receptor antagonists can increase ACE2 expression, which may increase susceptibility to SARS-CoV-2 infection. There is insufficient data to evaluate whether these observations can be translated to humans. [Journal]
Mar 30, 2020
The EMA is currently evaluating the potential association between the use of ACE inhibitors and angiotensin receptor blockers (ARBs) and the worsening of COVID-19. These drugs can increase the expression of ACE2, which is the entry point of the virus to human cells. Currently, there is no clinical or epidemiological evidence establishing a link between ACE inhibitors/ARBs and the severity of COVID-19. [Regulatory Agency Communication]
Mar 27, 2020
Article suggesting that patients with COVID-19 taking ACE inhibitors or angiotensin receptor blockers may have an increased risk of severe or fatal disease outcomes. These drugs increase the expression of ACE2 in the lungs, the receptor that serves as binding site for coronaviruses to enter the lungs. [Journal]
Mar 18, 2020
Study reporting that increased expression of ACE2 could facilitate infection with SARS-CoV-2. ACE2 can be increased by thiazolidinediones, ibuprofen, ACE inhibitors and angiotensin receptor blockers, suggesting an increased risk of Covid-19 in patients with cardiac diseases, hypertension, or diabetes taking these drugs. [Journal]
AChE
AhR
alpha1-Adrenoceptor
Antithrombin-III
AT1 receptor
Sep 16, 2020
Study evaluating the association between angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARBs) and risk of SARS-CoV-2 infection. No significant increase in risk was noted with ACEIs (adjusted OR 0.95; 95% CI 0.86-1.05) or ARBs (aOR 1.05; 95% CI 0.97-1.14). However, ARBs increased the risk of SARS-CoV-2 infection in subjects aged <60 years. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
May 28, 2020
Systematic review and meta-analysis evaluating the risk and severity of COVID-19 in patients taking ACE inhibitors (ACEI) or AT1/2 receptor antagonists (ATRA). ACEI/ATRA exposure was not associated with higher risk of infection (OR = 0.99 [0-1.04]). ACEI/ATRA users with infections did not have a higher risk of severe infection (0.98 [0.87-1.09] or mortality (0.73 [0.5-1.07]). [Journal]
May 27, 2020
The AEMPS is reporting that no unfavorable effect of ACE inhibitors and AT1/AT2 receptor antagonists was seen in patients with COVID-19. No differences were seen in hospitalizations or risk of infection among subjects taking ACE inhibitors and AT1/AT2 receptor antagonists with respect to subjects on other antihypertensives. [Regulatory Agency Communication]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 07, 2020
Case-control study assessing the link between AT1/AT2 receptor antagonists and ACE inhibitors and COVID-19. Neither drug class was associated with COVID-19 among overall patients (aOR = 0.95 [0.86-1.05] for AT1/AT2 receptor antagonists; 0.96 [0.87-1.07] for ACE inhibitors) or among patients with severe/fatal course of the disease (0.83 [0.63-1.1]; 0.91 [0.69-1.21]). Other drug classes not associated with COVID-19 are listed. [Journal]
May 07, 2020
Study assessing the risk of COVID-19 infection among patients receiving renin-angiotensin-aldosterone system inhibitors. Neither drug class was associated with an increased likelihood of a positive test nor a substantial increase in the risk of severe illness among patients who tested positive. [Journal]
May 06, 2020
Retrospective study of 1,178 patients hospitalized with COVID-19. No evidence of a higher severity or mortality risk was found in patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. [Journal]
Apr 23, 2020
Review discussing the role of the renin-angiotensin-aldosterone system in Covid-19. Preclinical studies suggested that ACE inhibitors and AT1/2 receptor antagonists can increase ACE2 expression, which may increase susceptibility to SARS-CoV-2 infection. There is insufficient data to evaluate whether these observations can be translated to humans. [Journal]
Mar 30, 2020
The EMA is currently evaluating the potential association between the use of ACE inhibitors and angiotensin receptor blockers (ARBs) and the worsening of COVID-19. These drugs can increase the expression of ACE2, which is the entry point of the virus to human cells. Currently, there is no clinical or epidemiological evidence establishing a link between ACE inhibitors/ARBs and the severity of COVID-19. [Regulatory Agency Communication]
Mar 27, 2020
Article suggesting that patients with COVID-19 taking ACE inhibitors or angiotensin receptor blockers may have an increased risk of severe or fatal disease outcomes. These drugs increase the expression of ACE2 in the lungs, the receptor that serves as binding site for coronaviruses to enter the lungs. [Journal]
Mar 18, 2020
Study reporting that increased expression of ACE2 could facilitate infection with SARS-CoV-2. ACE2 can be increased by thiazolidinediones, ibuprofen, ACE inhibitors and angiotensin receptor blockers, suggesting an increased risk of Covid-19 in patients with cardiac diseases, hypertension, or diabetes taking these drugs. [Journal]
AT2 receptor
Sep 16, 2020
Study evaluating the association between angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARBs) and risk of SARS-CoV-2 infection. No significant increase in risk was noted with ACEIs (adjusted OR 0.95; 95% CI 0.86-1.05) or ARBs (aOR 1.05; 95% CI 0.97-1.14). However, ARBs increased the risk of SARS-CoV-2 infection in subjects aged <60 years. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
May 28, 2020
Systematic review and meta-analysis evaluating the risk and severity of COVID-19 in patients taking ACE inhibitors (ACEI) or AT1/2 receptor antagonists (ATRA). ACEI/ATRA exposure was not associated with higher risk of infection (OR = 0.99 [0-1.04]). ACEI/ATRA users with infections did not have a higher risk of severe infection (0.98 [0.87-1.09] or mortality (0.73 [0.5-1.07]). [Journal]
May 27, 2020
The AEMPS is reporting that no unfavorable effect of ACE inhibitors and AT1/AT2 receptor antagonists was seen in patients with COVID-19. No differences were seen in hospitalizations or risk of infection among subjects taking ACE inhibitors and AT1/AT2 receptor antagonists with respect to subjects on other antihypertensives. [Regulatory Agency Communication]
May 07, 2020
Case-control study assessing the link between AT1/AT2 receptor antagonists and ACE inhibitors and COVID-19. Neither drug class was associated with COVID-19 among overall patients (aOR = 0.95 [0.86-1.05] for AT1/AT2 receptor antagonists; 0.96 [0.87-1.07] for ACE inhibitors) or among patients with severe/fatal course of the disease (0.83 [0.63-1.1]; 0.91 [0.69-1.21]). Other drug classes not associated with COVID-19 are listed. [Journal]
May 07, 2020
Study assessing the risk of COVID-19 infection among patients receiving renin-angiotensin-aldosterone system inhibitors. Neither drug class was associated with an increased likelihood of a positive test nor a substantial increase in the risk of severe illness among patients who tested positive. [Journal]
May 06, 2020
Retrospective study of 1,178 patients hospitalized with COVID-19. No evidence of a higher severity or mortality risk was found in patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. [Journal]
Apr 23, 2020
Review discussing the role of the renin-angiotensin-aldosterone system in Covid-19. Preclinical studies suggested that ACE inhibitors and AT1/2 receptor antagonists can increase ACE2 expression, which may increase susceptibility to SARS-CoV-2 infection. There is insufficient data to evaluate whether these observations can be translated to humans. [Journal]
Mar 30, 2020
The EMA is currently evaluating the potential association between the use of ACE inhibitors and angiotensin receptor blockers (ARBs) and the worsening of COVID-19. These drugs can increase the expression of ACE2, which is the entry point of the virus to human cells. Currently, there is no clinical or epidemiological evidence establishing a link between ACE inhibitors/ARBs and the severity of COVID-19. [Regulatory Agency Communication]
Mar 27, 2020
Article suggesting that patients with COVID-19 taking ACE inhibitors or angiotensin receptor blockers may have an increased risk of severe or fatal disease outcomes. These drugs increase the expression of ACE2 in the lungs, the receptor that serves as binding site for coronaviruses to enter the lungs. [Journal]
Mar 18, 2020
Study reporting that increased expression of ACE2 could facilitate infection with SARS-CoV-2. ACE2 can be increased by thiazolidinediones, ibuprofen, ACE inhibitors and angiotensin receptor blockers, suggesting an increased risk of Covid-19 in patients with cardiac diseases, hypertension, or diabetes taking these drugs. [Journal]
Bacterial penicillin-binding protein
BChE
Bcl-2
BCR/ABL
beta-Adrenoceptor
beta2-Adrenoceptor
C5a1 receptor
Calcineurin
Calcium channel
Carcinoembryonic antigen
Carcinoembryonic antigen-related cell adhesion molecule 5
CD20
CD52
CD6
CFTR
Coagulation factor Xa
Complement C5
COX-1
Sep 02, 2020
Systematic review of 8 studies evaluating cardiovascular and respiratory complications with non-steroidal anti-inflammatory drugs in patients with acute lower respiratory tract infections. No cardiovascular complications were reported in these studies. A significant increase in pleuro-pulmonary complications was reported in 4 studies, all of which were observational studies and had a high risk of publication bias due to lack of adjustment for confounding variables. [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
May 27, 2020
Study of patients with inflammatory bowel disease to identify risk factors associated with severe COVID-19. A significant association was found for systemic corticosteroids (adjusted odds ratio [aOR] 6.9; 95% CI 2.3-20.5) and sulfasalazine or 5-aminosalicylate (aOR 3.1; 95% CI 1.3-7.7). TNF-alpha inhibitors were not associated with severe COVID-19 (aOR 0.9; 95% CI 0.4-2.2). [Journal]
May 07, 2020
Case-control study assessing the link between AT1/AT2 receptor antagonists and ACE inhibitors and COVID-19. Neither drug class was associated with COVID-19 among overall patients (aOR = 0.95 [0.86-1.05] for AT1/AT2 receptor antagonists; 0.96 [0.87-1.07] for ACE inhibitors) or among patients with severe/fatal course of the disease (0.83 [0.63-1.1]; 0.91 [0.69-1.21]). Other drug classes not associated with COVID-19 are listed. [Journal]
Apr 01, 2020
Article discussing the contradictory evidence regarding the role of non-steroidal antiinflammatory drugs and corticosteroids in the treatment of COVID-19. Currently, there is no evidence for or against the use of ibuprofen for COVID-19. Corticosteroids have shown positive results in the treatment of viral infections, but prolonged administration could cause viral rebound and adverse events including acute respiratory distress syndrome. Preclinical studies in pigs suggested that prolonged administration of dexamethasone could enhance viral replication. [Journal]
Mar 23, 2020
The Australian Therapeutic Goods Administration (TGA) is monitoring the possible link between ibuprofen (COX-1/2 inhibitor) and Covid‑19 worsening. There is currently no published peer-reviewed scientific evidence to support a direct link. The TGA recommends patients to not stop taking ibuprofen without first talking to a doctor. [Regulatory Agency Communication]
Mar 23, 2020
The FDA is investigating the possible link between ibuprofen (COX-1/2 inhibitor) and Covid‑19 worsening. No scientific evidence supporting the link is available. [Regulatory Agency Communication]
Mar 18, 2020
Study reporting that increased expression of ACE2 could facilitate infection with SARS-CoV-2. ACE2 can be increased by thiazolidinediones, ibuprofen, ACE inhibitors and angiotensin receptor blockers, suggesting an increased risk of Covid-19 in patients with cardiac diseases, hypertension, or diabetes taking these drugs. [Journal]
Mar 18, 2020
The EMA is monitoring the concern about ibuprofen and Covid‑19 worsening. There is currently no scientific evidence establishing a link between ibuprofen and worsening of Covid‑19. Current advice recommends using the lowest effective dose for the shortest possible period. [Regulatory Agency Communication]
COX-2
Sep 02, 2020
Systematic review of 8 studies evaluating cardiovascular and respiratory complications with non-steroidal anti-inflammatory drugs in patients with acute lower respiratory tract infections. No cardiovascular complications were reported in these studies. A significant increase in pleuro-pulmonary complications was reported in 4 studies, all of which were observational studies and had a high risk of publication bias due to lack of adjustment for confounding variables. [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
May 27, 2020
Study of patients with inflammatory bowel disease to identify risk factors associated with severe COVID-19. A significant association was found for systemic corticosteroids (adjusted odds ratio [aOR] 6.9; 95% CI 2.3-20.5) and sulfasalazine or 5-aminosalicylate (aOR 3.1; 95% CI 1.3-7.7). TNF-alpha inhibitors were not associated with severe COVID-19 (aOR 0.9; 95% CI 0.4-2.2). [Journal]
May 07, 2020
Case-control study assessing the link between AT1/AT2 receptor antagonists and ACE inhibitors and COVID-19. Neither drug class was associated with COVID-19 among overall patients (aOR = 0.95 [0.86-1.05] for AT1/AT2 receptor antagonists; 0.96 [0.87-1.07] for ACE inhibitors) or among patients with severe/fatal course of the disease (0.83 [0.63-1.1]; 0.91 [0.69-1.21]). Other drug classes not associated with COVID-19 are listed. [Journal]
Apr 01, 2020
Article discussing the contradictory evidence regarding the role of non-steroidal antiinflammatory drugs and corticosteroids in the treatment of COVID-19. Currently, there is no evidence for or against the use of ibuprofen for COVID-19. Corticosteroids have shown positive results in the treatment of viral infections, but prolonged administration could cause viral rebound and adverse events including acute respiratory distress syndrome. Preclinical studies in pigs suggested that prolonged administration of dexamethasone could enhance viral replication. [Journal]
Mar 23, 2020
The Australian Therapeutic Goods Administration (TGA) is monitoring the possible link between ibuprofen (COX-1/2 inhibitor) and Covid‑19 worsening. There is currently no published peer-reviewed scientific evidence to support a direct link. The TGA recommends patients to not stop taking ibuprofen without first talking to a doctor. [Regulatory Agency Communication]
Mar 23, 2020
The FDA is investigating the possible link between ibuprofen (COX-1/2 inhibitor) and Covid‑19 worsening. No scientific evidence supporting the link is available. [Regulatory Agency Communication]
Mar 18, 2020
Study reporting that increased expression of ACE2 could facilitate infection with SARS-CoV-2. ACE2 can be increased by thiazolidinediones, ibuprofen, ACE inhibitors and angiotensin receptor blockers, suggesting an increased risk of Covid-19 in patients with cardiac diseases, hypertension, or diabetes taking these drugs. [Journal]
Mar 18, 2020
The EMA is monitoring the concern about ibuprofen and Covid‑19 worsening. There is currently no scientific evidence establishing a link between ibuprofen and worsening of Covid‑19. Current advice recommends using the lowest effective dose for the shortest possible period. [Regulatory Agency Communication]
CRAC
CXCR6
Cyclophilin A
CYP2D6
CYP3A4
D2 receptor
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 03, 2020
Case series of 16 Caucasian men with COVID-19 receiving intramuscular aripiprazole (5-HT1A receptor agonist, 5-HT2A/D2 receptor antagonist; 9.75 mg/1.3 ml) to treat delirium and psychomotor agitation. Mild sedation was reported in 5 patients. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 04, 2020
Article reporting that viral infections, including COVID-19, may have contributed to the high incidence of clozapine myocarditis observed in a meta-analysis. [Journal]
Jul 12, 2020
Literature review evaluating psychiatric aspects of chloroquine and hydroxychloroquine treatment in patients with COVID-19. Chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications. These drugs may also prolong the QT interval. Neuropsychiatric side effects are listed. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
Apr 19, 2020
Review of the rational use of clozapine for treatment-resistant schizophrenia. Clozapine has been associated with fatal adverse events (AEs) such as agranulocytosis, pneumonia and myocarditis. Clozapine may increase the risk of pneumonia in COVID-19 patients. Other AEs are listed. [Journal]
D3 receptor
D4 receptor
DAT
DHODH
Dihydropteroate synthase
DNA
DNA topoisomerase 1
DNA topoisomerase 2
Dopamine receptor
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 03, 2020
Case series of 16 Caucasian men with COVID-19 receiving intramuscular aripiprazole (5-HT1A receptor agonist, 5-HT2A/D2 receptor antagonist; 9.75 mg/1.3 ml) to treat delirium and psychomotor agitation. Mild sedation was reported in 5 patients. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 04, 2020
Article reporting that viral infections, including COVID-19, may have contributed to the high incidence of clozapine myocarditis observed in a meta-analysis. [Journal]
Jul 12, 2020
Literature review evaluating psychiatric aspects of chloroquine and hydroxychloroquine treatment in patients with COVID-19. Chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications. These drugs may also prolong the QT interval. Neuropsychiatric side effects are listed. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
Apr 19, 2020
Review of the rational use of clozapine for treatment-resistant schizophrenia. Clozapine has been associated with fatal adverse events (AEs) such as agranulocytosis, pneumonia and myocarditis. Clozapine may increase the risk of pneumonia in COVID-19 patients. Other AEs are listed. [Journal]
EGFR
Estrogen receptor
Ferriprotoporphyrin IX
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 02, 2020
Review evaluating the cardiovascular risk associated with the use of chloroquine or hydroxychloroquine for COVID-19 treatment. Both drugs have been associated with QTc interval prolongation, ventricular arrhythmias, polymorphic ventricular tachycardia and torsades de pointes. When combined with azithromycin, mortality was increased and the rate of QTc prolongation was higher than that observed with either drug as monotherapy. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 19, 2020
Review evaluating the possibility of ocular toxicity due to chloroquine/hydroxychloroquine therapy for COVID-19. [Journal]
Aug 17, 2020
Review of cutaneous adverse reactions of drugs under investigation for the management of COVID-19. Safety issues are listed. [Journal]
Jul 25, 2020
Safety data from clinical trials of chloroquine and hydroxychloroquine. Gastrointestinal discomfort is the most common side effect of both drugs, manifesting as nausea, vomiting, diarrhea, loss of appetite and stomach pain. Other toxicities included hypoglycemia, rash, itching and hemolytic anemia (serious). Retinal toxicity is a well-described adverse effect of hydroxychloroquine. Chloroquine and hydroxychloroquine are associated with QT prolongation. [Journal]
Jul 17, 2020
Retrospective observational study assessing the risk of QTc interval prolongation in 397 patients with COVID-19 receiving chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor). The mean prolongation in QT interval during treatment with chloroquine was 33 ms. 19 patients discontinued or required dose adjustments due to QT prolongation. [Journal]
Jul 12, 2020
Literature review evaluating psychiatric aspects of chloroquine and hydroxychloroquine treatment in patients with COVID-19. Chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications. These drugs may also prolong the QT interval. Neuropsychiatric side effects are listed. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jul 07, 2020
Case report of a patient with COVID-19 who suffered drug-induced liver injury due to a potential interaction between remdesivir and P-glycoprotein inhibitors (amiodarone and chloroquine). He suffered elevations in ALT and AST. Amiodarone was given to treat the new-onset atrial fibrillation which appeared after starting remdesivir. [Journal]
Jun 24, 2020
Review of antiviral therapy for treating COVID-19. The FDA has warned of the risk of heart rhythm problems associated with chloroquine and hydroxychloroquine. Side effects observed in trials of hydroxychloroquine and lopinavir/ritonavir are listed. [Congress Alert]
Jun 18, 2020
Article discussing the importance of screening for G6PD deficiency before treatment with hydroxychloroquine (HC) for COVID-19. The FDA has issued a warning about the risk of hemolysis in G6PD-deficient patients receiving HC. A case of HC-induced serious hemolysis has been reported. Other AEs of HC include neutropenia, pancytopenia, hypoglycemia, delirium, epithelial keratopathy, renal failure and long QT syndrome. Other drugs linked to hemolysis in patients with G6PD deficiency are listed. [Journal]
Jun 16, 2020
The FDA has issued a warning about a potential drug interaction between remdesivir and chloroquine or hydroxychloroquine, that could result in reduced antiviral activity of remdesivir. Data from the clinical setting is being evaluated as no instances of this drug interaction have been identified. The FDA has also updated the fact sheet of remdesivir to include additional information about possible allergic reactions. [Regulatory Agency Communication]
Jun 16, 2020
The FDA has revoked the emergency use authorization for chloroquine phosphate and hydroxychloroquine sulfate in patients with COVID-19. This follows recent data showing that these drugs are unlikely to be effective and may lead to serious cardiac adverse events and other potential serious side effects. The known and potential benefits no longer outweigh the known and potential risks for the authorized use. [Regulatory Agency Communication]
Jun 05, 2020
Case report of a 57-year-old woman receiving escitalopram for subsyndromal anxiety and self-medicated with chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor) for COVID-19. She experienced a first episode of psychosis induced by chloroquine. [Journal]
Jun 03, 2020
The EMA reminds healthcare professionals to closely monitor patients with COVID-19 who are receiving hydroxychloroquine or chloroquine considering the serious adverse events that can result from these medications. An increased risk of heart problems (including cardiac arrhythmias and cardiac arrest) has been reported with these drugs (alone and combined with azithromycin). Neuropsychiatric disorders may also appear, including agitation, insomnia, confusion, psychosis and suicidal ideation. These medications are also known to affect the liver, cause neuronal damage (leading to seizures) and lower blood sugar. Some EU countries have suspended or stopped clinical trials investigating these drugs for COVID-19. [Regulatory Agency Communication]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 27, 2020
Review of clinical trials of potential treatments for COVID-19. Side effects of chloroquine, azithromycin, lopinavir/ritonavir and tocilizumab are listed. [Journal]
May 27, 2020
Review on chloroquine and hydroxychloroquine for the treatment of COVID-19. In a pilot study assessing the efficacy and safety of chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor; 500 mg) in 10 in-patients with COVID-19, adverse events included vomiting, abdominal pain, nausea, diarrhea, rash/itch, cough and shortness of breath. [Journal]
May 27, 2020
The WHO has announced that it will stop a global study of hydroxychloroquine in patients with COVID-19 due to recent discouraging findings. Results from a study in 96,000 patients receiving hydroxychloroquine or chloroquine with or without an antibiotic showed a higher risk of deaths and heart problems than those who did not receive this medication. The death rate was 1/6 in patients taking hydroxychloroquine or chloroquine alone, 1/5 in patients taking chloroquine and an antibiotic, 1/4 in patients taking hydroxychloroquine and an antibiotic, and 1/11 in patients not taking any investigational drug. Serious cardiac arrythmias were increased in all treatment groups. [Website Reference]
May 26, 2020
Multinational registry analysis of 96,032 patients with COVID-19 treated with chloroquine or hydroxychloroquine, alone or in combination with a macrolide. Compared to the control group, the risk of death and de-novo ventricular arrhythmia was significantly increased in patients receiving hydroxychloroquine, hydroxychloroquine with a macrolide, chloroquine or chloroquine with a macrolide. [Journal]
May 23, 2020
Review on the cardiovascular safety of potential drugs for the treatment of COVID-19, including chloroquine, hydroxychloroquine, azithromycin, remdesivir, lopinavir in combination with ritonavir, and interferon alpha-2b. Safety data is listed. [Journal]
May 22, 2020
Article alerting of a possible synergistic retinal toxicity in COVID-19 patients treated with combinations of drugs known to cause macular toxicity, including ritonavir, chloroquine, hydroxychloroquine and tamoxifen. Ritonavir is known to cause hypertrophy of the retinal pigmented epithelium. [Journal]
May 22, 2020
The AEMPS has warned of neuropsychiatric disorders related to chloroquine and hydroxychloroquine, including psychosis and attempted and completed suicide. A literature search found reports of other psychiatric disorders with these drugs, including agitation, insomnia, confusion, mania, hallucinations, paranoia, depression, catatonia, psychosis and suicidal ideation. These events have been observed in COVID-19 patients receiving hydroxychloroquine (800 mg first dose followed by 400 mg/day), including serious cases. A review is ongoing. [Data from an update of an AEMPS communication on possible adverse events in patients with COVID-19] [Regulatory Agency Communication]
May 20, 2020
Case report of an 84-year-old woman who developed torsade de pointes after 5 days on chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor; 500 mg twice daily) for COVID-19. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 18, 2020
Study of the effects of chloroquine/hydroxychloroquine with or without azithromycin on the QTc interval in 201 patients with SARS-CoV-2 infection. 7 patients (3.5%) discontinued treatment due to QTc prolongation. The maximum QTc was significantly longer in patients who received azithromycin than in those receiving chloroquine or hydroxychloroquine alone (470.4 ± 45.0 ms vs 453.3 ± 37.0 ms; p = 0.004). [Journal]
May 18, 2020
Systematic review of 14 studies assessing the risk of QT prolongation, torsades de pointes, ventricular arrhythmia and sudden death related to chloroquine or hydroxychloroquine in patients with COVID-19. Approximately 10% hospitalized COVD-19 patients taking chloroquine or hydroxychloroquine developed severe QT prolongation. In other studies, QTc prolongation was observed in 12% of 84 patients treated with hydroxychloroquine plus azithromycin and in healthy volunteers treated with chloroquine phosphate and/or azithromycin. 2 patients treated with chloroquine developed ventricular arrhythmia, while atrioventricular block and left bundle branch block was reported in 2 patients on hydroxychloroquine. No sudden deaths were reported with chloroquine in malaria. [Journal]
May 11, 2020
Pharmacovigilance study assessing the cardiac safety of hydroxychloroquine, azithromycin, lopinavir/ritonavir and chloroquine when used off-label for COVID-19. 120 reports of cardiac adverse drug reactions were identified by the French Pharmacovigilance Network, including 103 cases associated with hydroxychloroquine (alone or combined with azithromycin). 17 events were caused by lopinavir/ritonavir. Chloroquine was involved in 3 cases. Hydroxychloroquine-related reactions are listed. [Journal]
May 11, 2020
Phase IIb study of high-dose vs low-dose chloroquine for SARS-CoV-2 infection in patients taking azithromycin and ceftriaxone. 1 patient suffered severe rhabdomyolysis, which could be attributed to chloroquine or to the virus. Other adverse events included hemoglobin decrease, increased creatinine, increased creatine phosphokinase, increased creatine phosphokinase-MB and prolongation of the QTcF interval. 2 patients suffered ventricular tachycardia. [Journal]
May 11, 2020
Retrospective study of QTc prolongation in patients with COVID-19 treated with chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor). Chloroquine was linked to a mean QTc prolongation of 35 ms (95% CI 28-43 ms) using computerized interpretation and 34 ms (95% CI 25-43 ms) on manual interpretation. 23% patients had a QTc interval >500 ms during treatment. [Journal]
Apr 28, 2020
Editorial article discussing the use of chloroquine for COVID-19 infection. The adverse effects of chloroquine and hydroxychloroquine are well known and can be severe, including psychiatric effects, arrhythmia and sudden death. [Journal]
Apr 27, 2020
Health Canada has issued a communication warning against self-medication with chloroquine or hydroxychloroquine for COVID-19. These drugs can cause serious heart rhythm problems, which can be exacerbated when they are combined with azithromycin. [Regulatory Agency Communication]
Apr 27, 2020
The FDA has issued a drug safety communication warning against the use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting and clinical trials. This warning is based on the known serious heart rhythm problems that can be caused by intake of these drugs, including QT interval prolongation, ventricular tachycardia and ventricular fibrillation (including fatal cases). Combination with azithromycin can increase the risk of heart rhythm problems. [Regulatory Agency Communication]
Apr 24, 2020
The EMA has issued a communication reminding the risk of serious side effects associated with chloroquine and hydroxychloroquine, as their use may be increased due to its potential efficacy for Covid-19. Both drugs can cause serious or fatal heart rhythm problems (including QT prolongation), which may be exacerbated at high doses or when combined with azithromycin. Other adverse events of chloroquine and hydroxychloroquine include liver and kidney problems, nerve cell damage leading to seizures and hypoglycemia. [Regulatory Agency Communication]
Apr 23, 2020
In vitro and in vivo data assessing the efficacy and safety of hydroxychloroquine (TLR7/9 antagonist) for treating COVID-19. Adverse events associated with hydroxychloroquine included QTc prolongation (by hERG blockage), retinopathy and gastrointestinal toxicity. Chloroquine was used as a model to predict the risk of QT prolongation. [Journal]
Apr 22, 2020
The NIH recommends monitoring the QTc interval in patients with COVID-19 treated with chloroquine or hydroxychloroquine. Hydroxychloroquine is better tolerated but both drugs have a similar safety profile, including QTc prolongation, torsade de pointes, ventricular arrhythmia, cardiac death, hypoglycemia, rash, nausea, retinopathy and bone marrow suppression. Other safety considerations and adverse events observed in clinical trials of COVID-19 are listed. [Data from the NIH COVID-19 Treatment Guidelines] [Website Reference]
Apr 15, 2020
Article discussing the use of chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor) as a prophylactic agent against COVID-19. High dosage chloroquine may have severe side effects including cardiac toxicity. The most frequent side effects with chloroquine/proguanil are epigastralgia, diarrhea and nausea. [Journal]
Apr 14, 2020
Phase IIb clinical study of chloroquine diphosphate (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor; 600 mg twice daily for 10 days or 450 mg twice the first day, once daily for 4 days) in 81 patients with severe respiratory syndrome due to SARS-CoV-2 infection. Adverse events were decreased hemoglobin (7/20 patients [35%]), increased creatinine (13/18 [72.2%]), prolonged QTc (10/56 [17.9%]), ventricular tachycardia (2/56 [3.5%]) and severe rhabdomyolysis (1 case). [Journal]
Apr 10, 2020
Review of the safety considerations regarding the use of chloroquine, hydroxychloroquine and azithromycin for SARS-CoV2 infection. Common adverse events (AEs) of chloroquine and hydroxychloroquine include pruritus, nausea and headache. Both drugs have been linked with life-threatening arrhythmias, serious hypoglycemia, hypersensitivity reactions and serious cutaneous toxicities, and are extremely toxic in overdose. Other AEs are listed. [Journal]
Apr 06, 2020
Study comparing chloroquine with lopinavir/ritonavir for treating COVID-19. Adverse events (AEs) with chloroquine included vomiting, diarrhea (5/10 patients [50%] each) and nausea (4/10 [40%]). With lopinavir/ritonavir, AEs included diarrhea (8/12 [66.67%]), cough (6/12 [50%]) and nausea (5/12 [41.67%]). Other AEs are listed. [Journal]
Mar 30, 2020
Review of the literature regarding chloroquine and hydroxychloroquine for the treatment of COVID-19. Both drugs have shown potential to prolong the QTc interval, a risk that is increased when azithromycin is added to hydroxychloroquine. Concurrent use of chloroquine/hydroxychloroquine and lopinavir/ritonavir can increase the risk of hypoglycemia. There have been reports of cardiomyopathy and reversible heart failure in patients treated with chloroquine. [Journal]
Mar 28, 2020
Article discussing possible harmful effects of chloroquine/hydroxychloroquine for COVID-19. In nonhuman primate models, chloroquine enhanced Chikungunya virus infection, while in a clinical study it increased the risk of chronic complications of Chikungunya virus infection. [Journal]
Mar 26, 2020
Article discussing the importance of QTc monitoring during treatment for COVID-19. Some drugs being tested for COVID-19, such as chloroquine, hydroxychloroquine, lopinavir and ritonavir, carry a known risk for drug-induced ventricular arrhythmias and sudden cardiac death. Hydroxychloroquine has the potential to cause prolongation of the QT interval. [Website Reference]
Mar 17, 2020
Systematic review of chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor) for the treatment of patients infected with COVID-19. Patients administered chloroquine should be monitored for the development of anemia, thrombocytopenia, leukopenia, electrolyte disturbances, hepatic/renal dysfunction, QT interval prolongation, bradycardia and visual/mental impairment. [Journal]
FKBP prolyl isomerase 1A
GABAA
GABAA (benzodiazepine receptor)
Glucocorticoid receptor
Sep 15, 2020
Meta-analysis evaluating serious adverse events associated with corticosteroids (dexamethasone, hydrocortisone and methylprednisolone) in patients with COVID-19 infection. Safety data is listed. [Journal]
Sep 10, 2020
Phase IV study of fixed-dose and shock-dependent hydrocortisone (glucocorticoid receptor modulator) in 384 patients with severe COVID-19. 2 events considered possibly related to treatment were reported in the fixed-dose hydrocortisone group: severe neuromyopathy and fungemia. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 17, 2020
Review of cutaneous adverse reactions of drugs under investigation for the management of COVID-19. Safety issues are listed. [Journal]
Aug 03, 2020
Article discussing potential strategies to prevent the development of Strongyloides hyperinfection in COVID-19 patients treated with dexamethasone (glucocorticoid receptor modulator). [Journal]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jul 13, 2020
Review discussing the use of dexamethasone antiemetic prophylaxis in patients with COVID-19. Dexamethasone administration should be minimized due to the risk of immunosuppression associated with glucocorticoids, which may increase the susceptibility to viral and respiratory infections. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 28, 2020
Systematic review and meta-analysis of published studies of COVID-19. Treatment with corticosteroids was significantly associated with an increased rate of acute respiratory distress syndrome (p = 0.0003). [Journal]
May 27, 2020
Study of patients with inflammatory bowel disease to identify risk factors associated with severe COVID-19. A significant association was found for systemic corticosteroids (adjusted odds ratio [aOR] 6.9; 95% CI 2.3-20.5) and sulfasalazine or 5-aminosalicylate (aOR 3.1; 95% CI 1.3-7.7). TNF-alpha inhibitors were not associated with severe COVID-19 (aOR 0.9; 95% CI 0.4-2.2). [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
Apr 30, 2020
Retrospective study of methylprednisolone (glucocorticoid receptor modulator; 1-2 mg/kg/day) in 26 patients with COVID-19. The most common treatment-induced complication was secondary infection. [Journal]
Apr 01, 2020
Article discussing the contradictory evidence regarding the role of non-steroidal antiinflammatory drugs and corticosteroids in the treatment of COVID-19. Currently, there is no evidence for or against the use of ibuprofen for COVID-19. Corticosteroids have shown positive results in the treatment of viral infections, but prolonged administration could cause viral rebound and adverse events including acute respiratory distress syndrome. Preclinical studies in pigs suggested that prolonged administration of dexamethasone could enhance viral replication. [Journal]
Glutamate-gated chloride channel
GM-CSF receptor, alpha subunit
Granulocyte macrophage colony-stimulating factor receptor
H+/K+ ATPase
H1 receptor
H2 receptor
HCV NS5A protein
HDAC
HER
HER2
HIV protease
Aug 17, 2020
Review of cutaneous adverse reactions of drugs under investigation for the management of COVID-19. Safety issues are listed. [Journal]
Aug 05, 2020
Prospective study of lopinavir/ritonavir in patients with COVID-19. 9/41 (22%) patients suffered bradycardia (8 cases of sinus bradycardia and 1 of third-degree atrioventricular block). Bradycardia occurred at least 48 hours after initiation of treatment and resolved after drug discontinuation or dose reduction. Ritonavir plasma overdose in elderly critical ill patients may increase the risk of bradycardia. [Journal]
Aug 04, 2020
Review on the adverse drug reactions associated with emerging treatments for COVID-19. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jul 06, 2020
Case report of a 58-year-old kidney transplant recipient who was diagnosed with COVID-19 and started antiviral therapy. Significant interaction between protease inhibitors (darunavir/ritonavir) and tacrolimus led to an increased exposure of tacrolimus, which caused acute kidney injury. [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 22, 2020
Article alerting of a possible synergistic retinal toxicity in COVID-19 patients treated with combinations of drugs known to cause macular toxicity, including ritonavir, chloroquine, hydroxychloroquine and tamoxifen. Ritonavir is known to cause hypertrophy of the retinal pigmented epithelium. [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
Mar 26, 2020
Article discussing the importance of QTc monitoring during treatment for COVID-19. Some drugs being tested for COVID-19, such as chloroquine, hydroxychloroquine, lopinavir and ritonavir, carry a known risk for drug-induced ventricular arrhythmias and sudden cardiac death. Hydroxychloroquine has the potential to cause prolongation of the QT interval. [Website Reference]
IL-1beta
IL-6
IMPDH
Integrin, alpha 4 subunit
Interferon alpha/beta receptor
Sep 10, 2020
Phase II/III trial comparing interferon beta1b (interferon-alpha/beta receptor agonist) to controls (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine) in 97 patients with severe COVID-19. Adverse events reported only in the interferon beta1b group included injection site reactions and flu-like syndrome. Other AEs are listed. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Jul 20, 2020
Clinical study of interferon beta-1a (interferon alpha/beta receptor agonist) in 42 patients with severe COVID-19. 8 patients (19.04%) had drug-related injection reactions (fever, chills, myalgia, headache and fatigue). 4 patients had neuropsychiatric problems, including severe agitation and mood swings in 2 patients each. Other adverse events are listed. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jun 28, 2020
Study of interferon alpha 2b plus darunavir/cobicistat compared to interferon alpha 2b alone in patients with COVID-19. Adverse events included diarrhea (3/30 patients in the combination group vs 2/30 in the control group), elevated transaminase levels (2 vs 4), renal dysfunction (2 vs 1) and anemia (1 vs 0). [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
Jun 18, 2020
Systematic review and meta-analysis of the safety and efficacy of antivirals for COVID-19. Safety issues potentially associated with the different treatments are listed. [Journal]
Jun 08, 2020
Article discussing the possible role of interferons on the pathogenesis of SARS-CoV-2. Interferons may affect the pathogenesis as they enhance ACE2 expression, the protein required for viral entry. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 23, 2020
Review on the cardiovascular safety of potential drugs for the treatment of COVID-19, including chloroquine, hydroxychloroquine, azithromycin, remdesivir, lopinavir in combination with ritonavir, and interferon alpha-2b. Safety data is listed. [Journal]
May 21, 2020
Review on alisporivir (cyclophilin A inhibitor) as a possible antiviral treatment for COVID-19. In clinical trials in patients infected with hepatitis C virus, the most common adverse events with the highest dose were headache, nausea, fatigue and a few cases of reversible hyperbilirubinemia. The phase III program of alisporivir for chronic hepatitis C was interrupted in 2012 due to 3 cases of acute pancreatitis, including 1 fatal case. The frequency of acute pancreatitis during the clinical development program of alisporivir (7 cases among over 2,000 patients) was similar to that of interferon alpha with or without alisporivir (0.35% and 0.41%, respectively). [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
Jun 12, 2015
Review on therapeutic strategies for the treatment of Middle East respiratory syndrome coronavirus infection. Safety issues are listed. [Journal]
Interferon gamma
Interferon gamma receptor
Interleukin 1 receptor, type I
Interleukin-4 receptor subunit alpha
Interleukin-6 receptor, alpha subunit
Sep 22, 2020
Phase III study of Actemra/RoActemra (tocilizumab; interleukin-6 receptor, alpha subunit antagonist) for COVID-19 associated pneumonia. The most common adverse events reported in patients receiving tocilizumab were constipation (5.6%), anxiety (5.2%) and headache (3.2%). [Data from a Roche communication announcing results from a phase III study of Actemra/RoActemra for COVID-19 associated pneumonia] [Company Communication]
Aug 27, 2020
Retrospective analysis of the infectious complications observed in adult patients with COVID-19 receiving tocilizumab (interleukin-6 receptor, alpha subunit antagonist). The overall rate of infections did not differ between the tocilizumab and control groups, but there was a higher rate of late infections (>48 hours after admission) in the tocilizumab group (23% vs 8%; P = 0.03). Types of infections and other adverse events observed in patients receiving tocilizumab are listed. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 17, 2020
Review of cutaneous adverse reactions of drugs under investigation for the management of COVID-19. Safety issues are listed. [Journal]
Aug 10, 2020
Case report of severe ulcerative disease in a 43-year-old COVID-19 patient on tocilizumab (interleukin-6 receptor, alpha subunit antagonist; 800 mg) for cytokine release syndrome. Concomitant hydrocortisone was administered for shock. [Journal]
Aug 07, 2020
Retrospective study of abnormal liver tests in patients with COVID-19. Drugs used for the treatment of COVID-19 (lopinavir/ritonavir, hydroxychloroquine, remdesivir and tocilizumab) were significantly associated with peak hospitalization levels of ALT and AST. [Journal]
Aug 06, 2020
Retrospective study of 224 patients hospitalized for COVID-19. Patients receiving tocilizumab (interleukin-6 receptor, alpha subunit antagonist) compared to those not receiving tocilizumab had a higher rate of fungal infections (13.0% vs 1.1%; p < 0.001). [Journal]
Aug 06, 2020
Retrospective study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in 20 patients with severe acute respiratory syndrome coronavirus-2 pneumonia. 55% of patients had asymptomatic transaminitis. 1 patient had 8 times the upper limit of normal SGPT levels, 1 had leukopenia and neutropenia, and 1 had enterococcus faecium bacteremia. [Journal]
Aug 04, 2020
Review on the adverse drug reactions associated with emerging treatments for COVID-19. [Journal]
Jul 29, 2020
Phase III study of Actemra (tocilizumab; interleukin-6 receptor, alpha subunit antagonist) in patients with Covid-19 pneumonia. The most common adverse events in patients treated with Actemra were hypertension (6.4%), pneumonia, acute kidney injury and diarrhea (5.8% each). The study did not identify any new safety signals for Actemra. [Data from a Genentech communication announcing results from a phase III study of Actemra for Covid-19 pneumonia] [Company Communication]
Jul 24, 2020
Retrospective cohort study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) added to standard protocol (hydroxychloroquine, lopinavir plus ritonavir) for COVID-19. Increases in alanine aminotransferase were reported, a known effect of tocilizumab. [Journal]
Jul 20, 2020
Disproportionality analysis of FAERS assessing serious adverse with tocilizumab (interleukin-6 receptor, alpha subunit antagonist). Designated medical events (DMEs) reported with tocilizumab included intestinal perforation (ROR=9.83 [8.37-11.54]), anaphylactic reaction (ROR=4.43 [3.94-4.98]), drug-induced liver injury (ROR=3.77 [3.07-4.64]), anaphylactic shock (ROR= 2.71 [2.21-3.32]), pancytopenia (ROR=2.11 [1.82-2.45]), acute pancreatitis (ROR=1.99 [1.55-2.56]) and pancreatitis (ROR=1.65 [1.41-1.94]). DMEs observed in patients receiving tocilizumab concomitantly with hepatotoxic drugs included acute hepatic failure, autoimmune hepatitis, drug-induced liver injury, hepatic failure, hepatic necrosis and fulminant hepatitis. [Journal]
Jul 17, 2020
Study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in patients with COVID-19 requiring mechanical ventilation. Superinfections were significantly more common in patients receiving tocilizumab than in those receiving placebo (54% vs 26%; p < 0.001), mostly due to an increase in ventilator-associated pneumonia (45% vs 26%; p < 0.001; 51% by Staphylococcus aureus). [Journal]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jul 08, 2020
Single-center study evaluating compassionate use of tocilizumab (interleukin-6 receptor, alpha subunit antagonist; 400 mg) in 27 patients with SARS-CoV-2 pneumonia. One patient developed thrombocytopenia, considered possibly related to tocilizumab. [Journal]
Jul 03, 2020
In a phase III study of Kevzara (sarilumab; interleukin-6 receptor, alpha subunit antagonist; 400 mg) in 194 critically ill patients with COVID-19, serious adverse events (≥3% and more frequent among Kevzara patients) were multi organ dysfunction syndrome (6% with Kevzara vs 5% with placebo) and hypotension (4% vs 3%). [Data from a Sanofi and Regeneron communication announcing that the U.S. phase III study of Kevzara in patients with COVID-19 did not meet its primary and key secondary endpoints] [Company Communication]
Jun 29, 2020
Retrospective, case-control study of patients with severe-to-critical COVID-19 treated with tocilizumab (interleukin-6 receptor, alpha subunit antagonist). Fungemia was more common in patients receiving tocilizumab than in the control group, although the difference was not significant (4.2% vs 3.1%; p = 0.72). [Journal]
Jun 24, 2020
Retrospective study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in 51 patients with severe COVID-19. Hospital-acquired infections reported with tocilizumab were ventilator-associated pneumonia (4/28 patients), fungemia and colitis (1 patient each). [Journal]
Jun 24, 2020
Review on immunotherapy for COVID-19 treatment. Use of tocilizumab for cytokine release syndrome has been associated with a low incidence of infusion reactions. [Congress Alert]
Jun 18, 2020
Observational study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) for cytokine release syndrome in patients with Covid-19. Tocilizumab was associated with elevated transaminase levels (including ALT and AST). Other adverse events included neutropenia (6/239 patients) and bacteremia (4). [Journal]
Jun 15, 2020
Description of 5 transplant recipients with SARS-CoV-2 infection treated with tocilizumab (interleukin-6 receptor, alpha subunit antagonist). There were 4 bacterial infections that may have been related to tocilizumab. [Journal]
Jun 15, 2020
Prospective study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in 51 patients with severe COVID-19. The most common adverse events were increased hepatic enzymes (29%), thrombocytopenia (14%), neutropenia (6%) and cutaneous rash (2%). Bacteremia was observed in 14 patients (27%; 86% of whom were admitted to the ICU). Serious bacterial and fungal infections included Enterococcus spp. (8 patients), Klebsiella pneumoniae (5), Staphylococci (4), Candida spp., Staphylococcus aureus (3 each), Pseudomonas aeruginosa, E. coli and Enterobacter aerogenes (1 each). [Journal]
Jun 12, 2020
Study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist; 8 mg/kg) for COVID-19. Adverse events included superinfections (42/78 [54%]), pneumonia (35 [45%]) and bloodstream infection (11 [14%]). [Journal]
Jun 05, 2020
Case report of a 68-year-old patient hospitalized for COVID-19. He experienced neutropenia due to tocilizumab. [Journal]
May 29, 2020
First case report of drug-induced liver injury, marked by a 40‐fold increase in transaminases, associated with tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in a patient with severe COVID-19 pneumonia. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 27, 2020
Review of clinical trials of potential treatments for COVID-19. Side effects of chloroquine, azithromycin, lopinavir/ritonavir and tocilizumab are listed. [Journal]
May 26, 2020
Article stating that clinicians using tocilizumab (interleukin-6 receptor, alpha subunit antagonist) to treat COVID-19 should be aware of the risk of intestinal perforation. [Journal]
May 25, 2020
Study of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in 100 patients with COVID-19. 3 patients had severe adverse events: 2 developed septic shock resulting in death, while 1 had a gastrointestinal perforation requiring surgery. [Journal]
May 25, 2020
Study reporting that the use of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in patients with COVID-19 could increase the risk of candidemia. 3 cases of candidemia were reported in 43 patients treated with tocilizumab for severe COVID-19 pneumonia, including 1 with endophthalmitis and endocarditis. [Journal]
May 23, 2020
Review on the cardiovascular safety of potential drugs for the treatment of COVID-19, including chloroquine, hydroxychloroquine, azithromycin, remdesivir, lopinavir in combination with ritonavir, and interferon alpha-2b. Safety data is listed. [Journal]
May 21, 2020
Case report of a COVID‐19 patient who developed toxic erythema and eosinophilia due to tocilizumab (interleukin-6 receptor, alpha subunit antagonist). [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 13, 2020
Case reports of 2 patients with COVID-19 treated with tocilizumab (interleukin-6 receptor, alpha subunit antagonist). 1 patient developed viral myocarditis, which may have been promoted by tocilizumab. [Journal]
May 12, 2020
Retrospective review of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in 25 Covid-19 patients. The most common adverse events (AEs) were anemia (16 any grade; 6 grade 3), increased alanine aminotransferase (11; 3), QT interval prolongation (5; 5) and increased aspartate aminotransferase (3; 0). 8 patients had Candida in their respiratory cultures. Other AEs of tocilizumab and of the concomitant agents used are listed. [Journal]
Mar 31, 2020
Article describing a potential risk of osteonecrosis of the jaw with tocilizumab (interleukin-6 receptor antagonist), a drug that is being investigated for the treatment of COVID-19. Other medications linked to this adverse event include tyrosine kinase inhibitors, monoclonal antibodies, mTOR inhibitors, radiopharmaceuticals, estrogen receptor modulators and immunosuppressants. [Journal]
JAK
Aug 28, 2020
Observational study of ruxolitinib (JAK1/JAK2 inhibitor; 5 or 10 mg bid) in 34 patients with Covid-19 infection. The most common adverse events (AEs) were anemia (19 [55.9%]), urinary tract infection (10 [29.4%]), increased creatinine (8 [23.5%]), thrombocytopenia and increased aminotransferase (5 [14.7%]). Grade 3 AEs included anemia (10 [29.4%]), increased creatinine (3 [8.8%]), bleeding, sepsis, stroke, thrombocytopenia and thrombosis (1 [2.9%]). Other AEs are listed. [Journal]
Aug 25, 2020
Article discussing the potential impact of baricitinib (JAK1/JAK2 inhibitor) on COVID-19-associated coagulopathy. Baricitinib has been linked to an increased risk of arterial and venous thromboembolic events (VTE), which could negatively impact the course of COVID-19. VTE could be caused by an increase in platelet counts; however, tofacitinib has also been associated with VTE and does not increase platelet counts. Other side effects of baricitinib are listed. [Journal]
Aug 24, 2020
Case report of a 72-year-old woman with COVID-19 receiving dexamethasone and baricitinib in addition to atracurium, midazolam, propofol and enoxaparin. She suffered pancreatitis, which may have been caused by baricitinib. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 06, 2020
Case report of a patient taking off-label ruxolitinib (JAK1/2 inhibitor; 7.5 mg bid) for COVID-19 who experienced grade 3 liver toxicity. [Journal]
Aug 04, 2020
Review on the adverse drug reactions associated with emerging treatments for COVID-19. [Journal]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jun 24, 2020
Review of baricitinib (JAK1/JAK2 inhibitor) and safety considerations for its use for the treatment of COVID-19. Side effects associated with baricitinib and other JAK inhibitors are listed. [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
Jun 23, 2020
Study of ruxolitinib (JAK1/JAK2 inhibitor) in patients with COVID-19 and severe systemic hyperinflammation. Increases in transaminases indicative of liver dysfunction were reported, including 1 patient with grade 3 liver toxicity. Grade 3 anemia was observed in 2 patients who had pre-existing anemia. [Journal]
Jun 15, 2020
Prospective phase II trial of ruxolitinib (JAK1/2 inhibitor) in 43 patients with COVID-19. Adverse events (AEs) included anemia (55% on ruxolitinib versus 42.9% on placebo), ALT increase (35% versus 9.5%), thrombocytopenia (20% versus 14.3%) and neutropenia (5% versus 4.8%). Grade 3 hypertension was reported in 1 patient. Other AEs are listed. [Journal]
Jun 05, 2020
Case reports associating ruxolitinib (JAK1/JAK2 inhibitor) with purpuric lesions, reduction in platelet levels, deep tissue infection, herpes labialis, progressive reduction of hemoglobin values and erythrodermic rash in 2 patients with SARS-CoV-2 infection. [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
Apr 27, 2020
Article describing arguments against the use of baricitinib (JAK1/JAK2 inhibitor) for managing COVID-19. Baricitinib is known to cause adverse events that could complicate the course of COVID-19, such as lymphocytopenia, neutropenia, anemia, increases in creatine kinase and viral reactivation (including varicella zoster, herpes simplex and Epstein-Barr virus). [Journal]
Apr 27, 2020
Review of adverse infection events (AIEs) observed in clinical trials of JAK inhibitors to identify potential risks for patients with COVID-19 taking these drugs. AIEs of tofacitinib, baricitinib, ruxolitinib, upadacitinib and adalimumab are listed. [Journal]
JAK1
Aug 28, 2020
Observational study of ruxolitinib (JAK1/JAK2 inhibitor; 5 or 10 mg bid) in 34 patients with Covid-19 infection. The most common adverse events (AEs) were anemia (19 [55.9%]), urinary tract infection (10 [29.4%]), increased creatinine (8 [23.5%]), thrombocytopenia and increased aminotransferase (5 [14.7%]). Grade 3 AEs included anemia (10 [29.4%]), increased creatinine (3 [8.8%]), bleeding, sepsis, stroke, thrombocytopenia and thrombosis (1 [2.9%]). Other AEs are listed. [Journal]
Aug 25, 2020
Article discussing the potential impact of baricitinib (JAK1/JAK2 inhibitor) on COVID-19-associated coagulopathy. Baricitinib has been linked to an increased risk of arterial and venous thromboembolic events (VTE), which could negatively impact the course of COVID-19. VTE could be caused by an increase in platelet counts; however, tofacitinib has also been associated with VTE and does not increase platelet counts. Other side effects of baricitinib are listed. [Journal]
Aug 24, 2020
Case report of a 72-year-old woman with COVID-19 receiving dexamethasone and baricitinib in addition to atracurium, midazolam, propofol and enoxaparin. She suffered pancreatitis, which may have been caused by baricitinib. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 06, 2020
Case report of a patient taking off-label ruxolitinib (JAK1/2 inhibitor; 7.5 mg bid) for COVID-19 who experienced grade 3 liver toxicity. [Journal]
Aug 04, 2020
Review on the adverse drug reactions associated with emerging treatments for COVID-19. [Journal]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jun 24, 2020
Review of baricitinib (JAK1/JAK2 inhibitor) and safety considerations for its use for the treatment of COVID-19. Side effects associated with baricitinib and other JAK inhibitors are listed. [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
Jun 23, 2020
Study of ruxolitinib (JAK1/JAK2 inhibitor) in patients with COVID-19 and severe systemic hyperinflammation. Increases in transaminases indicative of liver dysfunction were reported, including 1 patient with grade 3 liver toxicity. Grade 3 anemia was observed in 2 patients who had pre-existing anemia. [Journal]
Jun 15, 2020
Prospective phase II trial of ruxolitinib (JAK1/2 inhibitor) in 43 patients with COVID-19. Adverse events (AEs) included anemia (55% on ruxolitinib versus 42.9% on placebo), ALT increase (35% versus 9.5%), thrombocytopenia (20% versus 14.3%) and neutropenia (5% versus 4.8%). Grade 3 hypertension was reported in 1 patient. Other AEs are listed. [Journal]
Jun 05, 2020
Case reports associating ruxolitinib (JAK1/JAK2 inhibitor) with purpuric lesions, reduction in platelet levels, deep tissue infection, herpes labialis, progressive reduction of hemoglobin values and erythrodermic rash in 2 patients with SARS-CoV-2 infection. [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
Apr 27, 2020
Article describing arguments against the use of baricitinib (JAK1/JAK2 inhibitor) for managing COVID-19. Baricitinib is known to cause adverse events that could complicate the course of COVID-19, such as lymphocytopenia, neutropenia, anemia, increases in creatine kinase and viral reactivation (including varicella zoster, herpes simplex and Epstein-Barr virus). [Journal]
Apr 27, 2020
Review of adverse infection events (AIEs) observed in clinical trials of JAK inhibitors to identify potential risks for patients with COVID-19 taking these drugs. AIEs of tofacitinib, baricitinib, ruxolitinib, upadacitinib and adalimumab are listed. [Journal]
JAK2
Aug 28, 2020
Observational study of ruxolitinib (JAK1/JAK2 inhibitor; 5 or 10 mg bid) in 34 patients with Covid-19 infection. The most common adverse events (AEs) were anemia (19 [55.9%]), urinary tract infection (10 [29.4%]), increased creatinine (8 [23.5%]), thrombocytopenia and increased aminotransferase (5 [14.7%]). Grade 3 AEs included anemia (10 [29.4%]), increased creatinine (3 [8.8%]), bleeding, sepsis, stroke, thrombocytopenia and thrombosis (1 [2.9%]). Other AEs are listed. [Journal]
Aug 25, 2020
Article discussing the potential impact of baricitinib (JAK1/JAK2 inhibitor) on COVID-19-associated coagulopathy. Baricitinib has been linked to an increased risk of arterial and venous thromboembolic events (VTE), which could negatively impact the course of COVID-19. VTE could be caused by an increase in platelet counts; however, tofacitinib has also been associated with VTE and does not increase platelet counts. Other side effects of baricitinib are listed. [Journal]
Aug 24, 2020
Case report of a 72-year-old woman with COVID-19 receiving dexamethasone and baricitinib in addition to atracurium, midazolam, propofol and enoxaparin. She suffered pancreatitis, which may have been caused by baricitinib. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 06, 2020
Case report of a patient taking off-label ruxolitinib (JAK1/2 inhibitor; 7.5 mg bid) for COVID-19 who experienced grade 3 liver toxicity. [Journal]
Aug 04, 2020
Review on the adverse drug reactions associated with emerging treatments for COVID-19. [Journal]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jun 24, 2020
Review of baricitinib (JAK1/JAK2 inhibitor) and safety considerations for its use for the treatment of COVID-19. Side effects associated with baricitinib and other JAK inhibitors are listed. [Journal]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
Jun 23, 2020
Study of ruxolitinib (JAK1/JAK2 inhibitor) in patients with COVID-19 and severe systemic hyperinflammation. Increases in transaminases indicative of liver dysfunction were reported, including 1 patient with grade 3 liver toxicity. Grade 3 anemia was observed in 2 patients who had pre-existing anemia. [Journal]
Jun 15, 2020
Prospective phase II trial of ruxolitinib (JAK1/2 inhibitor) in 43 patients with COVID-19. Adverse events (AEs) included anemia (55% on ruxolitinib versus 42.9% on placebo), ALT increase (35% versus 9.5%), thrombocytopenia (20% versus 14.3%) and neutropenia (5% versus 4.8%). Grade 3 hypertension was reported in 1 patient. Other AEs are listed. [Journal]
Jun 05, 2020
Case reports associating ruxolitinib (JAK1/JAK2 inhibitor) with purpuric lesions, reduction in platelet levels, deep tissue infection, herpes labialis, progressive reduction of hemoglobin values and erythrodermic rash in 2 patients with SARS-CoV-2 infection. [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
Apr 27, 2020
Article describing arguments against the use of baricitinib (JAK1/JAK2 inhibitor) for managing COVID-19. Baricitinib is known to cause adverse events that could complicate the course of COVID-19, such as lymphocytopenia, neutropenia, anemia, increases in creatine kinase and viral reactivation (including varicella zoster, herpes simplex and Epstein-Barr virus). [Journal]
Apr 27, 2020
Review of adverse infection events (AIEs) observed in clinical trials of JAK inhibitors to identify potential risks for patients with COVID-19 taking these drugs. AIEs of tofacitinib, baricitinib, ruxolitinib, upadacitinib and adalimumab are listed. [Journal]
Kelch-like ECH-associated protein 1
Kir6.x/SUR
Kv11.1
Leucine zipper transcription factor-like protein 1
MAO
MAO-A
Mdm2
Meningococcal proteins-directed
Mineralocorticoid receptor
mTOR
Mucosa-associated lymphoid tissue lymphoma translocation protein 1
Na-Cl symporter
NET
Neuraminidase (viral)
NF-kappaB
Nicotinic receptor
NMDA receptor
Opioid delta receptor
Opioid kappa receptor
Opioid mu receptor
Opioid receptor
P2Y12 receptor
p53/MDM proteins
PD-1
PDE3
PDE3A
PDE4
PGP1
Potassium channel
PPARgamma
Protease
Pyruvate synthase (protozoan)
Replicase polyprotein 1a
RET
Reverse transcriptase/ribonuclease H
RNA polymerase (viral)
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 03, 2020
Review on remdesivir (viral RNA polymerase inhibitor) for COVID-19 in pediatric patients. Remdesivir is not recommended in pediatric patients with hepatic impairment or hepatotoxicity at baseline as it increases liver aminotransferase levels (11.7%). Increased ALT was observed in a 5-year-old child with acute lymphoblastic leukemia receiving remdesivir for concomitant SARS-CoV-2 infection. Drug-drug interactions have also been reported with remdesivir in combination with P-glycoprotein inhibitors such as hydroxychloroquine, azithromycin, cyclosporine, tacrolimus and amiodarone, which may have caused the hepatocellular toxicity. [Journal]
Aug 31, 2020
Review of the accumulated evidence supporting remdesivir (viral RNA polymerase inhibitor) for COVID-19. The most common adverse events across clinical experience include anemia, deranged liver function tests, impaired renal function and hyperglycemia. [Journal]
Aug 25, 2020
Article highlighting potential adverse events of nafamostat mesylate (tryptase inhibitor) and favipiravir (viral RNA polymerase inhibitor) in COVID-19 patients. 2 patients receiving favipiravir suffered neuroleptic malignant syndrome. The drug has also been linked to serotonin syndrome. 1 patient receiving nafamostat mesylate (200 mg/day) suffered a cerebral hemorrhage. [Journal]
Aug 25, 2020
Phase III study of remdesivir (viral RNA polymerase inhibitor; 100 mg) in patients with Covid-19. Adverse events occurring more frequently than with placebo included nausea, hypokalemia and headache. Grade 3 laboratory abnormalities were observed. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 18, 2020
Case report of a 67-year-old man who developed symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) after 4 days on compassionate remdesivir (viral RNA polymerase inhibitor) for COVID-19. [Journal]
Aug 17, 2020
Phase II/III clinical trial of favipiravir (viral RNA polymerase inhibitor) in patients with COVID-19. 7/40 patients (17.5%) experienced adverse drug reactions to favipiravir, including diarrhea, nausea, vomiting, chest pain and increased transaminase levels. [Journal]
Aug 17, 2020
Review of cutaneous adverse reactions of drugs under investigation for the management of COVID-19. Safety issues are listed. [Journal]
Aug 12, 2020
Case report of a 42-year-old man with COVID-19 who presented with elevated uric acid levels and acute gouty arthritis after 14 days on compassionate favipiravir (viral RNA polymerase inhibitor; 1,800 mg bid day 1 followed by 800 mg bid). [Journal]
Aug 07, 2020
Article describing patterns of liver toxicity in 5 COVID-19 patients. Lopinavir/ritonavir caused increases in bilirubin in 4/5 patients, while remdesivir caused increases in AST and ALT in 4/5 patients suggestive of hepatocellular injury. Remdesivir was discontinued in 1 patient due to torsade de pointes requiring cardiac resuscitation. [Journal]
Aug 07, 2020
Retrospective study of abnormal liver tests in patients with COVID-19. Drugs used for the treatment of COVID-19 (lopinavir/ritonavir, hydroxychloroquine, remdesivir and tocilizumab) were significantly associated with peak hospitalization levels of ALT and AST. [Journal]
Aug 06, 2020
Analysis of VigiBase to describe hepatic disorder reports with remdesivir (viral RNA polymerase inhibitor) in patients with COVID-19. 130 hepatic adverse events were reported for remdesivir as compared to other drugs prescribed for COVID-19 patients, with remdesivir showing a significantly increased risk for hepatic disorders (ROR=1.94 [1.54-2.45]). [Journal]
Aug 04, 2020
Review on the adverse drug reactions associated with emerging treatments for COVID-19. [Journal]
Jul 26, 2020
Retrospective case series from an open-label phase III trial on the use of remdesivir (viral RNA polymerase inhibitor) for the treatment of severe acute respiratory syndrome in 10 Asian patients with COVID-19. The most common adverse event (AE) was elevated liver transaminases (50% of patients). Other AEs included nausea (30%), diarrhea, chest discomfort and insomnia (10% each). [Journal]
Jul 24, 2020
Phase III trial of favipiravir (viral RNA polymerase inhibitor; 1,800 mg bid day 1 and 800 mg bid thereafter) in patients with mild-to-moderate COVID-19. The most common adverse event was increased uric acid (12 patients on favipiravir vs 0 on placebo). Gastrointestinal disturbance was minimal. [Data from a Glenmark Pharmaceuticals communication announcing results of a phase III trial of favipiravir for COVID-19] [Company Communication]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jul 14, 2020
Reports of 5 patients with COVID-19 treated with remdesivir (viral RNA polymerase inhibitor). Adverse events leading to remdesivir discontinuation included ALT increase, maculopapular rash and acute kidney injury (increased levels of creatinine up to 396 micromol/L). [Journal]
Jul 13, 2020
Results from 2 phase I trials assessing the safety and pharmacokinetics of remdesivir (viral RNA polymerase inhibitor; 3-225 mg) in healthy subjects. In the single-dose escalation study, treatment-related adverse events (TRAEs) were dizziness, pruritus, infusion site extravasation, medical device site dermatitis, ecchymosis, presyncope and medical device site irritation (1 subject each). In the multiple-dose study, TRAEs were pain in extremity (3 subjects), infusion site extravasation, infusion site pain, infusion site hemorrhage, ecchymosis, nausea, headache, vomiting, tremor, decreased appetite and constipation (1 each). [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jul 07, 2020
Case report of a patient with COVID-19 who suffered drug-induced liver injury due to a potential interaction between remdesivir and P-glycoprotein inhibitors (amiodarone and chloroquine). He suffered elevations in ALT and AST. Amiodarone was given to treat the new-onset atrial fibrillation which appeared after starting remdesivir. [Journal]
Jun 19, 2020
Review evaluating the use of remdesivir (viral RNA polymerase inhibitor) for the treatment of COVID-19 in patients with kidney diseases. Adverse events of remdesivir include transaminase elevations (including increased ALT) and infusion-related reactions. Kidney toxicities may occur after prolonged exposures to remdesivir. In monkeys, kidney injury and casts were observed at doses of 5, 10 and 20 mg/kg. [Journal]
Jun 18, 2020
Systematic review and meta-analysis of the safety and efficacy of antivirals for COVID-19. Safety issues potentially associated with the different treatments are listed. [Journal]
Jun 16, 2020
The FDA has issued a warning about a potential drug interaction between remdesivir and chloroquine or hydroxychloroquine, that could result in reduced antiviral activity of remdesivir. Data from the clinical setting is being evaluated as no instances of this drug interaction have been identified. The FDA has also updated the fact sheet of remdesivir to include additional information about possible allergic reactions. [Regulatory Agency Communication]
Jun 15, 2020
Benefit-risk assessment of remdesivir (viral RNA polymerase inhibitor) for the treatment of COVID-19. Risks included cardiac events (including hypotension, arrhythmias and cardiac arrest - fatal in 1 patient with Ebola), gastrointestinal disorders (such as diarrhea and lower gastrointestinal tract hemorrhage), increased liver transaminases, and thrombocytopenia. Acute respiratory distress syndrome was more common in patients taking remdesivir than in those in comparator groups. Multiple organ dysfunction, septic shock and acute kidney injury have been reported in clinical trials. [Journal]
Jun 08, 2020
Article discussing the possibility of combining IV and pulmonary delivery of remdesivir (viral RNA polymerase inhibitor) in patients with COVID-19. The dose cannot exceed 200 mg/day due to the risk of systemic adverse events such as hepatotoxicity. [Journal]
Jun 02, 2020
Phase III study of remdesivir (viral RNA polymerase inhibitor) in patients with COVID-19 pneumonia. The most common adverse events (>5%) were nausea, diarrhea and headache. [Data from a Gilead communication announcing phase III results of remdesivir for COVID-19 infection] [Company Communication]
May 29, 2020
Review of antivirals being investigated for COVID-19. In a trial of remdesivir, adverse events (AEs) included increased hepatic transaminases (23%), diarrhea (9%), rash, renal impairment and hypotension (8% each). AEs of Kaletra (lopinavir/ritonavir) included QTc prolongation, weight gain, fat redistribution, hepatotoxicity, increased cholesterol, hyperglycemia, pancreatitis, skin rash and gastrointestinal disorders. Oseltamivir has been associated with vomiting, nausea and headache. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 28, 2020
Clinical study of remdesivir (viral RNA polymerase inhibitor; 100 mg/day) in 35 patients with Covid-19 pneumonia. Grade 2/3 adverse events included hypertransaminasemia (15 [42.8%]), acute kidney injury (8 [22.8%]), increased total bilirubin levels (7 [20%]) and rash (2 [5.7%]). Hepatotoxicity was frequent, with grade 3/4 increased transaminases levels reported in 42.8% patients. 1 patient discontinued due to maculopapular rash. [Journal]
May 28, 2020
Phase III clinical trial of remdesivir (viral RNA polymerase inhibitor; 100 mg/day) in patients with severe Covid-19. Common adverse events (AEs) included nausea (20/200 patients [10%] in the 5-day group; 17/197 [9%] in the 10-day group), acute respiratory failure (12 [6%]; 21 [11%]), increased ALT (11 [6%]; 15 [8%]), constipation (13 [6%]; 13 [7%]), increased AST (10 [5%]; 13 [7%]), hypokalemia (10 [5%]; 12 [6%]) and insomnia (10 [5%]; 11 [6%]). Other AEs are listed. [Journal]
May 27, 2020
Adverse reactions reported in clinical trials with remdesivir were hepatic adverse reactions, including transaminase elevations (ALT and AST) in healthy volunteers, and liver function test abnormalities in patients with COVID-19 (including transaminase elevations, serious liver-related laboratory abnormality and one case of serious blood bilirubin increased). [Data from MHRA Early Access to Medicines Scheme Information for Healthcare Professionals for remdesivir (RNA polymerase (viral) inhibitor)] [Regulatory Agency Communication]
May 27, 2020
The special warnings and precautions for use section of the MHRA Early Access to Medicines Scheme (EAMS) information for remdesivir indicates that transaminase elevations were observed in clinical studies in both healthy volunteers and patients with COVID-19. [Data from MHRA Early Access to Medicines Scheme Information for Healthcare Professionals for remdesivir (RNA polymerase (viral) inhibitor)] [Regulatory Agency Communication]
May 25, 2020
Preliminary results from a clinical study evaluating the safety and efficacy of intravenous remdesivir (viral RNA polymerase inhibitor) in patients with Covid-19. Adverse events occurring more frequently than with placebo included pyrexia (27/541 patients [5%] with remdesivir vs 17/522 [3.3%] with placebo), decreased glomerular filtration rate (20 [3.7%] vs 17 [3.3%]), increased blood glucose (12 [2.2%] vs 6 [1.1%]), hypotension (12 [2.2%] vs 7 [1.3%]), hypertension (11 [2%] vs 4 [0.8%]), pneumonia (8 [1.5%] vs 2 [0.4%]), increased creatinine (8 [1.5%] vs 4 [0.8%]), prolonged prothrombin time (7 [1.3%] vs 3 [0.6%]), decreased blood albumin, dyspnea (6 [1.1%] vs 3 [0.6%] each) and alkalosis (4 [0.7%] vs 2 [0.4%]). [Journal]
May 23, 2020
Review on the cardiovascular safety of potential drugs for the treatment of COVID-19, including chloroquine, hydroxychloroquine, azithromycin, remdesivir, lopinavir in combination with ritonavir, and interferon alpha-2b. Safety data is listed. [Journal]
May 19, 2020
Review of the cutaneous adverse events associated with potential treatments for COVID-19. Dermatological side effects are listed. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 16, 2020
Review of preclinical and clinical studies of remdesivir (viral RNA polymerase inhibitor) for the treatment of COVID-19. Adverse events reported in clinical trials are listed. [Journal]
May 11, 2020
Side effects reported in clinical studies of Veklury in healthy subjects or patients with SARS-CoV-2 infection are listed. [Data from PMDA package insert (emergency approval) for Veklury (remdesivir; viral RNA polymerase inhibitor)] [Regulatory Agency Communication]
May 05, 2020
Phase III clinical trial of remdesivir (viral RNA polymerase inhibitor) in 237 patients with severe COVID-19. Adverse events (AEs; ≥2% and higher than with placebo) included rash (11/155 [7%] with remdesivir vs 2/78 [3%] with placebo), thrombocytopenia (16 [10%] vs 5 [6%]), increased total bilirubin (15 [10%] vs 7 [9%]), increased neutrophil (10 [6%] vs 4 [5%]), nausea (8 [5%] vs 2 [3%]) and increased serum potassium (4 [3%] vs 1 [1%]). Serious AEs included respiratory failure or acute respiratory distress syndrome (16 [10%] vs 6 [8%]), cardiac arrest, thrombocytopenia, hemorrhage of lower digestive tract and acute kidney injury (1 [1%] vs 0 each). AEs leading to drug discontinuation are listed. [Journal]
May 04, 2020
Review of clinical trials of favipiravir (viral RNA polymerase inhibitor) to evaluate its safety for treating COVID-19. Favipiravir had a similar rate of adverse events to comparators except for gastrointestinal side effects (8.7% vs 11.5%; P = 0.003) and increased uric acid (5.8% vs 1.3%; P < 0.0001). [Journal]
May 04, 2020
Study of remdesivir (viral RNA polymerase inhibitor) in patients with severe COVID-19. Side effects occurred in 32/53 patients (60%), most commonly increased liver enzymes, diarrhea, rash, renal dysfunction and hypotension. [Journal]
May 04, 2020
The FDA has issued an emergency use authorization for remdesivir (viral RNA polymerase inhibitor) for the treatment of suspected or laboratory-confirmed COVID-19. Possible adverse events of remdesivir include increased levels of liver enzymes (which may be a sign of inflammation or damage to liver cells) and infusion-related reactions, including low blood pressure, nausea, vomiting, sweating and shivering. [Regulatory Agency Communication]
Apr 30, 2020
Phase III trial of remdesivir (viral RNA polymerase inhibitor) for severe COVID-19. The most common adverse events (>10% patient in 1 of the groups) were nausea (5-day group: 10.0%; 10-day: 8.6%) and acute respiratory failure (5-day: 6.0%; 10-day: 10.7%). Grade ≥3 ALT elevations occurred in 28/385 patients (7.3%). 12/397 patients (3.0%) discontinued treatment due to elevated liver tests. [Company Communication]
Apr 22, 2020
Remdesivir (viral RNA polymerase inhibitor) can cause gastrointestinal symptoms (including nausea and vomiting), increased transaminases and elevation of the prothrombin time. [Data from the NIH COVID-19 Treatment Guidelines] [Website Reference]
Apr 15, 2020
Study of remdesivir (viral RNA polymerase inhibitor) in 53 patients with severe Covid-19. The most common adverse events (AEs) were increased hepatic enzymes (12 patients [23%]), diarrhea (5 [9%]), rash, renal impairment and hypotension (4 [8%] each). Serious AEs included multiple organ dysfunction syndrome, septic shock, acute kidney injury and hypotension (2 [4%] each). 4 patients discontinued remdesivir due to elevated aminotransferases (2), worsening of preexisting renal failure and multiple organ failure (1 each). Other AEs are listed. [Journal]
Apr 07, 2020
Hepatotoxicity is an identified risk of remdesivir (viral RNA polymerase inhibitor). [Data from the conditions of use of remdesivir in compassionate use for Covid-19] [Regulatory Agency Communication]
Apr 07, 2020
Pooled data of 4 phase I trials of remdesivir (viral RNA polymerase inhibitor) in 138 healthy subjects. Adverse events (AEs) reported in ≥5 subjects included phlebitis (8), constipation (7), headache (6), ecchymosis, nausea and pain in extremity (5 each). Elevations in AST/ALT levels were also observed. A serious AE of hypotension leading to fatal cardiac arrest was considered related to remdesivir. [Data from an EMA summary on compassionate use of remdesivir in patients with Covid-19] [Regulatory Agency Communication]
Apr 07, 2020
The special warnings and precautions for use section of remdesivir (viral RNA polymerase inhibitor) indicates that it may cause elevations in AST/ALT levels and prolong prothrombin time. Kidney injury and dysfunction were observed in preclinical studies. [Data from the conditions of use of remdesivir in compassionate use for Covid-19] [Regulatory Agency Communication]
Mar 29, 2020
Review discussing the potential use of remdesivir and GS-441524 (viral RNA polymerase inhibitors) for the treatment of coronavirus infections. Injection-site discomfort was observed in cats receiving GS-441524. 3 patients treated with remdesivir experienced gastrointestinal upset and elevated aminotransferase levels. [Journal]
Mar 26, 2020
Randomized clinical trial comparing the efficacy and safety of favipiravir (viral RNA polymerase inhibitor) and Arbidol (umifenovir) in 236 patients with COVID-19. Antiviral-associated adverse events were digestive tract reactions (including nausea and flatulence; 16/116 [13.8%] with favipiravir vs 14/120 [11.7%] with Arbidol), raised serum uric acid (16 [13.8%] vs 3 [2.5%]), abnormal liver function tests (increased ALT and/or AST; 9 [7.8%] vs 12 [10%]) and psychiatric symptom reactions (2 [1.7%] vs 1 [0.8%]). [Journal]
Mar 24, 2020
Clinical study comparing favipiravir (viral RNA polymerase inhibitor) to lopinavir plus ritonavir for the treatment of COVID-19. Adverse reactions in the favipiravir group were diarrhea (2/35) and liver and kidney injury (1/35). In the lopinavir/ritonavir group, adverse reactions included nausea (6/45), diarrhea, vomiting (5/45 each), rash (4/45), liver and kidney injury (3/45) and chest tightness and palpitations (1/45 each). [Journal]
Mar 16, 2020
Description of the first 12 patients with Covid-19 in the U.S. 3 patients received remdesivir (viral RNA polymerase inhibitor) for 4-10 days; all experienced increases in aminotransferase levels and gastrointestinal symptoms, including nausea, vomiting, gastroparesis and rectal bleeding. [Journal]
Mar 16, 2020
Remdesivir (viral RNA polymerase inhibitor) is being evaluated for the treatment of Covid-19. In phase I clinical studies of the drug for treating Ebola, remdesivir caused transient low-grade elevations in liver transaminases, the clinical significance of which is unknown. [Website Reference]
S1P receptor
S1P1 receptor
S1P5 receptor
SARS-CoV-2 proteins-directed
Sep 17, 2020
In a phase I clinical trial of the COVID-19 mRNA vaccine BNT162b2, adverse events reported after the second dose of 30 mcg BNT162b2 included fatigue (75% patients aged 18-55-years-old; 42% patients aged 65-85-years-old), headache (67%; 25%), muscle pain (58%; 25%), chills (58%; 17%), fever and joint pain (17%; 8% each). Diarrhea was observed after the first dose in 8% patients aged 18-55-years-old. [Data from a Pfizer presentation summarizing the company’s COVID-19 programs] [Company Communication]
Sep 14, 2020
Preclinical studies evaluating the safety and immunogenicity of BBV152 (SARS-CoV-2 proteins-directed immunity inducer; 3-6 mcg) adjuvated with Algel or Algel-IMDG in mice, rats and rabbits. Histopathological examination of the injection site showed local inflammatory reactions likely caused by the aluminum salt of the vaccine adjuvant preparation. Other safety issues are listed. [Journal]
Sep 09, 2020
A phase III study of AZD1222 (SARS-CoV-2 proteins-directed immunity inducer) has been put on clinical hold after a patient experienced an unexplained illness. Other sources suggest that the patient could have been diagnosed with transverse myelitis. [Company Communication]
Sep 09, 2020
A phase III trial of AstraZeneca’s COVID-19 vaccine AZD1222 was put on clinical hold after a woman experienced neurological symptoms consistent with transverse myelitis, although her diagnosis has not been confirmed. [Website Reference]
Sep 07, 2020
2 phase I/II studies assessing the safety and immunogenicity of 2 formulations of Gam-COVID-Vac, a vector-based COVID-19 vaccine carrying the rAd26-S and rAd5-S genes, in 76 healthy subjects. The most common systemic and local reactions were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]) and muscle and joint pain (18 [24%]). Other changes in laboratory parameters and systemic and local adverse events are listed. [Journal]
Sep 03, 2020
Phase I results of a phase I/II trial of NVX-CoV2373 (SARS-CoV-2 proteins-directed immunity inducer; 5-25 mcg) in 131 healthy adults. Common adverse events (AE) included injection site pain and tenderness, fatigue, malaise, muscle pain, myalgia, nausea and vomiting. Grade 3 AEs included arthralgia and headache. Abnormal levels of hemoglobin, ALT, AST, sodium, bilirubin and urea were noted. Other AEs are listed. [Journal]
Aug 27, 2020
Results from the phase I clinical trial of mRNA-1273 vaccine (SARS-CoV-2 proteins-directed immunity inducer; 25-250 mcg) against SARS-CoV-2 in healthy volunteers. Systemic symptoms reported after vaccination were arthralgia, fatigue, fever, chills, headache, myalgia and nausea. Local symptoms included induration, swelling and pain. Grade 3 fatigue, erythema and redness were reported. [Data from a Moderna presentation on the updated clinical results of its COVID-19 vaccine candidate] [Company Communication]
Aug 21, 2020
Phase I clinical study comparing BNT162b1 and BNT162b2 (SARS-CoV-2 proteins-directed immunity inducers; 10-30 mcg) in healthy adults. The most common local reactions were injection site pain, redness and swelling; while the most common systemic events were fever, fatigue and chills. Transient lymphocyte count decreases were observed with both vaccines after the first dose. Other adverse reactions are listed. [Journal]
Aug 17, 2020
Results from 2 phase I/II trials assessing the safety and immunogenicity of Sinopharm's COVID-19 vaccine in Chinese healthy adults. The most common adverse reactions were injection-site pain (14 subjects in phase I; 21 in phase II) and fever (2; 8). Other adverse events are listed. [Journal]
Aug 17, 2020
Study of the S-2P vaccine against SARS-CoV-2 combined with different adjuvants. There was an increase in body temperature at 4 and 24 hours after administration to rats, which returned to baseline after 48 hours. [Journal]
Aug 13, 2020
Phase I/II clinical trial of BNT162b1 (SARS-CoV-2 protein-directed immunity inducer; 10, 30 or 100 mcg) in healthy adults. The most common local reaction was injection-site pain, whereas the most frequent systemic adverse events (AEs) were fatigue and headache. Other AEs are listed. [Journal]
Aug 11, 2020
First-in-human phase I trial of NVX-CoV2373 (SARS-CoV-2 proteins-directed immunity inducer; 5-25 mcg) in 131 healthy subjects. The most common adverse events (≥40% in any group and higher than with placebo) were local tenderness, local pain, fatigue, headache and muscle pain/myalgia. Other adverse events are listed. [Journal]
Aug 05, 2020
Phase I data from the phase I/II trial of NVX-CoV2373 (SARS-CoV-2 proteins-directed immunity inducer; 5-25 mcg) in 131 healthy subjects. Following 5 mcg dose, tenderness and pain were the most common local events. Headache, fatigue and myalgia were the most common systemic effects. [Data from a Novavax communication announcing positive phase I data from its COVID-19 vaccine candidate] [Company Communication]
Aug 03, 2020
Study assessing the immunogenicity and protective efficacy of single-shot Ad26.COV2.S (SARS-CoV-2 protein-directed immunity inducer; 10E11 viral particles) in 52 rhesus macaques. Ad26.COV2.S vaccine elicited Th1-biased rather than Th2-biased T-cell responses, while animals with sub-protective neutralizing antibody titers did not show enhanced viral replication or clinical disease. [Journal]
Jul 29, 2020
Study evaluating mRNA-1273 (SARS-CoV-2 proteins-directed immunity inducer; 10-100 mcg) in nonhuman primates. Soft stools and decreased appetite were noticed in several animals. No pathologic changes in the lungs or vaccine-associated enhanced respiratory disease was observed. [Journal]
Jul 22, 2020
Preliminary results from an ongoing phase I/II study of BNT162b1 (COVID-19 mRNA vaccine; 1-50 mcg) in 60 healthy adults. The most common solicited event in the 10-mcg and 30-mcg groups was reactogenicity, including fatigue, headache and occasional grade 3 events such as fever, chills, headache, muscle pain, joint pain and injection-site pain and tenderness. The main injection-site reactions within 7 days of the prime or boost injection were pain and tenderness. A dose-dependent transient increase in C-reactive protein and temporary reduction of blood lymphocyte counts were also observed. [Journal]
Jul 21, 2020
Phase I/II study of the AZD1222 vaccine against SARS-CoV-2 and comparison with MenACWY in 1,077 healthy adults. Fatigue and headache were the most common systemic adverse events (AEs). Administration of prophylactic paracetamol reduced the rates of pain, feeling feverish, chills, muscle ache, headache and malaise in patients receiving AZD1222. Other AEs are listed. [Journal]
Jul 21, 2020
Phase II trial of a recombinant adenovirus type-5-vectored COVID-19 vaccine in 508 healthy adults. The most common systemic adverse events (AEs) included fatigue, fever and headache. Injection-site reactions included pain, induration, swelling and itch. The most common grade 3 AE was fever, occurring in 20 (8%) participants in the 1E11 viral particles dose group, and 1 (1%) in the 5E10 viral particles dose group. Other AEs are listed. [Journal]
Jul 15, 2020
First-in-human phase I study evaluating the safety and immunogenicity of mRNA-1273 vaccine (SARS-CoV-2 proteins-directed immunity inducer; 25, 100 or 250 mcg) in 45 healthy adults. Systemic adverse events (AEs) were more common after the second vaccination and included arthralgia, fatigue, fever, chills, headache, myalgia and nausea. The most common local AE was injection-site pain. After the second vaccination, 6 (40%) participants in the 100 mcg group and 8 (57%) in the 250 mcg group reported fever (severe in 1 patient in the 250 mcg group). 1 participant in the 25 mcg group was withdrawn due to transient urticaria related to the first vaccination. Other local AEs are listed. [Journal]
Jul 04, 2020
Phase I study of INO-4800, a vaccine candidate against SARS-CoV-2. The most common adverse event (AE) was local injection-site redness. No serious AEs were reported. [Data from an Inovio communication announcing interim data from a phase I study of INO-4800] [Company Communication]
Jul 02, 2020
Phase I/II trial of BNT162b1 (COVID-19 mRNA vaccine; 10-100 mcg) in 45 subjects. The most common local reaction was pain at the injection site (including 1 severe case at 100 mcg). The most common systemic adverse events (AEs) were fatigue and headache (more common with BNT162b1 than with placebo). Fever was common among the different dose groups (incidences ranging from 8.3% to 75%). Severe systemic AEs were reported in 2 subjects: pyrexia (grade 3; 30 mcg dose group) and sleep disturbance (100 mcg dose group). Chills, muscle pain, and joint pain were only seen in the BNT162b1 group. The most common laboratory changes were decreases in lymphocyte counts (incidences ranging from 8.3% to 50% among dose groups; including grade 3). Grade 2 neutropenia was noted in 2 patients receiving 10 and 30 mcg of BNT162b1. [Journal]
May 27, 2020
Preliminary results of the first-in-human phase I trial of CanSino’s adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV; 5x10^10 - 1.5x10^11 viral particles) in 108 subjects. The most common adverse events (AEs) were injection site pain (58%), fever (46%), fatigue (44%), headache (39%) and muscle pain (17%). Grade 3 AEs included fever (8%), fatigue (2%), joint pain, dyspnea and muscle pain (1% each). Other AEs and laboratory abnormalities are listed. [Journal]
May 21, 2020
Moderna communication announcing interim phase I data of mRNA-1273 vaccine (SARS-CoV-2 proteins-directed immunity inducer; 25-250 microg) against SARS-CoV-2 in 8 subjects. 1 subject in the 100 microg group developed grade 3 erythema around the injection site. 3 subjects in the 250 microg group developed grade 3 systemic symptoms. [Company Communication]
Serine protease
SERT
sigma1 receptor
SLC6A20
Sodium channel
Sphingosine kinase
Sphingosine kinase 2
Spike glycoprotein
Stem cell therapy
Steroid 5-alpha-reductase
Steroid 5-alpha-reductase 1
Steroid 5-alpha-reductase 2
Thiamine transporter 2
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 02, 2020
Review evaluating the cardiovascular risk associated with the use of chloroquine or hydroxychloroquine for COVID-19 treatment. Both drugs have been associated with QTc interval prolongation, ventricular arrhythmias, polymorphic ventricular tachycardia and torsades de pointes. When combined with azithromycin, mortality was increased and the rate of QTc prolongation was higher than that observed with either drug as monotherapy. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 19, 2020
Review evaluating the possibility of ocular toxicity due to chloroquine/hydroxychloroquine therapy for COVID-19. [Journal]
Aug 17, 2020
Review of cutaneous adverse reactions of drugs under investigation for the management of COVID-19. Safety issues are listed. [Journal]
Jul 25, 2020
Safety data from clinical trials of chloroquine and hydroxychloroquine. Gastrointestinal discomfort is the most common side effect of both drugs, manifesting as nausea, vomiting, diarrhea, loss of appetite and stomach pain. Other toxicities included hypoglycemia, rash, itching and hemolytic anemia (serious). Retinal toxicity is a well-described adverse effect of hydroxychloroquine. Chloroquine and hydroxychloroquine are associated with QT prolongation. [Journal]
Jul 17, 2020
Retrospective observational study assessing the risk of QTc interval prolongation in 397 patients with COVID-19 receiving chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor). The mean prolongation in QT interval during treatment with chloroquine was 33 ms. 19 patients discontinued or required dose adjustments due to QT prolongation. [Journal]
Jul 12, 2020
Literature review evaluating psychiatric aspects of chloroquine and hydroxychloroquine treatment in patients with COVID-19. Chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications. These drugs may also prolong the QT interval. Neuropsychiatric side effects are listed. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jul 07, 2020
Case report of a patient with COVID-19 who suffered drug-induced liver injury due to a potential interaction between remdesivir and P-glycoprotein inhibitors (amiodarone and chloroquine). He suffered elevations in ALT and AST. Amiodarone was given to treat the new-onset atrial fibrillation which appeared after starting remdesivir. [Journal]
Jun 24, 2020
Review of antiviral therapy for treating COVID-19. The FDA has warned of the risk of heart rhythm problems associated with chloroquine and hydroxychloroquine. Side effects observed in trials of hydroxychloroquine and lopinavir/ritonavir are listed. [Congress Alert]
Jun 16, 2020
The FDA has issued a warning about a potential drug interaction between remdesivir and chloroquine or hydroxychloroquine, that could result in reduced antiviral activity of remdesivir. Data from the clinical setting is being evaluated as no instances of this drug interaction have been identified. The FDA has also updated the fact sheet of remdesivir to include additional information about possible allergic reactions. [Regulatory Agency Communication]
Jun 16, 2020
The FDA has revoked the emergency use authorization for chloroquine phosphate and hydroxychloroquine sulfate in patients with COVID-19. This follows recent data showing that these drugs are unlikely to be effective and may lead to serious cardiac adverse events and other potential serious side effects. The known and potential benefits no longer outweigh the known and potential risks for the authorized use. [Regulatory Agency Communication]
Jun 05, 2020
Case report of a 57-year-old woman receiving escitalopram for subsyndromal anxiety and self-medicated with chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor) for COVID-19. She experienced a first episode of psychosis induced by chloroquine. [Journal]
Jun 03, 2020
The EMA reminds healthcare professionals to closely monitor patients with COVID-19 who are receiving hydroxychloroquine or chloroquine considering the serious adverse events that can result from these medications. An increased risk of heart problems (including cardiac arrhythmias and cardiac arrest) has been reported with these drugs (alone and combined with azithromycin). Neuropsychiatric disorders may also appear, including agitation, insomnia, confusion, psychosis and suicidal ideation. These medications are also known to affect the liver, cause neuronal damage (leading to seizures) and lower blood sugar. Some EU countries have suspended or stopped clinical trials investigating these drugs for COVID-19. [Regulatory Agency Communication]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 27, 2020
Review of clinical trials of potential treatments for COVID-19. Side effects of chloroquine, azithromycin, lopinavir/ritonavir and tocilizumab are listed. [Journal]
May 27, 2020
Review on chloroquine and hydroxychloroquine for the treatment of COVID-19. In a pilot study assessing the efficacy and safety of chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor; 500 mg) in 10 in-patients with COVID-19, adverse events included vomiting, abdominal pain, nausea, diarrhea, rash/itch, cough and shortness of breath. [Journal]
May 27, 2020
The WHO has announced that it will stop a global study of hydroxychloroquine in patients with COVID-19 due to recent discouraging findings. Results from a study in 96,000 patients receiving hydroxychloroquine or chloroquine with or without an antibiotic showed a higher risk of deaths and heart problems than those who did not receive this medication. The death rate was 1/6 in patients taking hydroxychloroquine or chloroquine alone, 1/5 in patients taking chloroquine and an antibiotic, 1/4 in patients taking hydroxychloroquine and an antibiotic, and 1/11 in patients not taking any investigational drug. Serious cardiac arrythmias were increased in all treatment groups. [Website Reference]
May 26, 2020
Multinational registry analysis of 96,032 patients with COVID-19 treated with chloroquine or hydroxychloroquine, alone or in combination with a macrolide. Compared to the control group, the risk of death and de-novo ventricular arrhythmia was significantly increased in patients receiving hydroxychloroquine, hydroxychloroquine with a macrolide, chloroquine or chloroquine with a macrolide. [Journal]
May 23, 2020
Review on the cardiovascular safety of potential drugs for the treatment of COVID-19, including chloroquine, hydroxychloroquine, azithromycin, remdesivir, lopinavir in combination with ritonavir, and interferon alpha-2b. Safety data is listed. [Journal]
May 22, 2020
Article alerting of a possible synergistic retinal toxicity in COVID-19 patients treated with combinations of drugs known to cause macular toxicity, including ritonavir, chloroquine, hydroxychloroquine and tamoxifen. Ritonavir is known to cause hypertrophy of the retinal pigmented epithelium. [Journal]
May 22, 2020
The AEMPS has warned of neuropsychiatric disorders related to chloroquine and hydroxychloroquine, including psychosis and attempted and completed suicide. A literature search found reports of other psychiatric disorders with these drugs, including agitation, insomnia, confusion, mania, hallucinations, paranoia, depression, catatonia, psychosis and suicidal ideation. These events have been observed in COVID-19 patients receiving hydroxychloroquine (800 mg first dose followed by 400 mg/day), including serious cases. A review is ongoing. [Data from an update of an AEMPS communication on possible adverse events in patients with COVID-19] [Regulatory Agency Communication]
May 20, 2020
Case report of an 84-year-old woman who developed torsade de pointes after 5 days on chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor; 500 mg twice daily) for COVID-19. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 18, 2020
Study of the effects of chloroquine/hydroxychloroquine with or without azithromycin on the QTc interval in 201 patients with SARS-CoV-2 infection. 7 patients (3.5%) discontinued treatment due to QTc prolongation. The maximum QTc was significantly longer in patients who received azithromycin than in those receiving chloroquine or hydroxychloroquine alone (470.4 ± 45.0 ms vs 453.3 ± 37.0 ms; p = 0.004). [Journal]
May 18, 2020
Systematic review of 14 studies assessing the risk of QT prolongation, torsades de pointes, ventricular arrhythmia and sudden death related to chloroquine or hydroxychloroquine in patients with COVID-19. Approximately 10% hospitalized COVD-19 patients taking chloroquine or hydroxychloroquine developed severe QT prolongation. In other studies, QTc prolongation was observed in 12% of 84 patients treated with hydroxychloroquine plus azithromycin and in healthy volunteers treated with chloroquine phosphate and/or azithromycin. 2 patients treated with chloroquine developed ventricular arrhythmia, while atrioventricular block and left bundle branch block was reported in 2 patients on hydroxychloroquine. No sudden deaths were reported with chloroquine in malaria. [Journal]
May 11, 2020
Pharmacovigilance study assessing the cardiac safety of hydroxychloroquine, azithromycin, lopinavir/ritonavir and chloroquine when used off-label for COVID-19. 120 reports of cardiac adverse drug reactions were identified by the French Pharmacovigilance Network, including 103 cases associated with hydroxychloroquine (alone or combined with azithromycin). 17 events were caused by lopinavir/ritonavir. Chloroquine was involved in 3 cases. Hydroxychloroquine-related reactions are listed. [Journal]
May 11, 2020
Phase IIb study of high-dose vs low-dose chloroquine for SARS-CoV-2 infection in patients taking azithromycin and ceftriaxone. 1 patient suffered severe rhabdomyolysis, which could be attributed to chloroquine or to the virus. Other adverse events included hemoglobin decrease, increased creatinine, increased creatine phosphokinase, increased creatine phosphokinase-MB and prolongation of the QTcF interval. 2 patients suffered ventricular tachycardia. [Journal]
May 11, 2020
Retrospective study of QTc prolongation in patients with COVID-19 treated with chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor). Chloroquine was linked to a mean QTc prolongation of 35 ms (95% CI 28-43 ms) using computerized interpretation and 34 ms (95% CI 25-43 ms) on manual interpretation. 23% patients had a QTc interval >500 ms during treatment. [Journal]
Apr 28, 2020
Editorial article discussing the use of chloroquine for COVID-19 infection. The adverse effects of chloroquine and hydroxychloroquine are well known and can be severe, including psychiatric effects, arrhythmia and sudden death. [Journal]
Apr 27, 2020
Health Canada has issued a communication warning against self-medication with chloroquine or hydroxychloroquine for COVID-19. These drugs can cause serious heart rhythm problems, which can be exacerbated when they are combined with azithromycin. [Regulatory Agency Communication]
Apr 27, 2020
The FDA has issued a drug safety communication warning against the use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting and clinical trials. This warning is based on the known serious heart rhythm problems that can be caused by intake of these drugs, including QT interval prolongation, ventricular tachycardia and ventricular fibrillation (including fatal cases). Combination with azithromycin can increase the risk of heart rhythm problems. [Regulatory Agency Communication]
Apr 24, 2020
The EMA has issued a communication reminding the risk of serious side effects associated with chloroquine and hydroxychloroquine, as their use may be increased due to its potential efficacy for Covid-19. Both drugs can cause serious or fatal heart rhythm problems (including QT prolongation), which may be exacerbated at high doses or when combined with azithromycin. Other adverse events of chloroquine and hydroxychloroquine include liver and kidney problems, nerve cell damage leading to seizures and hypoglycemia. [Regulatory Agency Communication]
Apr 23, 2020
In vitro and in vivo data assessing the efficacy and safety of hydroxychloroquine (TLR7/9 antagonist) for treating COVID-19. Adverse events associated with hydroxychloroquine included QTc prolongation (by hERG blockage), retinopathy and gastrointestinal toxicity. Chloroquine was used as a model to predict the risk of QT prolongation. [Journal]
Apr 22, 2020
The NIH recommends monitoring the QTc interval in patients with COVID-19 treated with chloroquine or hydroxychloroquine. Hydroxychloroquine is better tolerated but both drugs have a similar safety profile, including QTc prolongation, torsade de pointes, ventricular arrhythmia, cardiac death, hypoglycemia, rash, nausea, retinopathy and bone marrow suppression. Other safety considerations and adverse events observed in clinical trials of COVID-19 are listed. [Data from the NIH COVID-19 Treatment Guidelines] [Website Reference]
Apr 15, 2020
Article discussing the use of chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor) as a prophylactic agent against COVID-19. High dosage chloroquine may have severe side effects including cardiac toxicity. The most frequent side effects with chloroquine/proguanil are epigastralgia, diarrhea and nausea. [Journal]
Apr 14, 2020
Phase IIb clinical study of chloroquine diphosphate (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor; 600 mg twice daily for 10 days or 450 mg twice the first day, once daily for 4 days) in 81 patients with severe respiratory syndrome due to SARS-CoV-2 infection. Adverse events were decreased hemoglobin (7/20 patients [35%]), increased creatinine (13/18 [72.2%]), prolonged QTc (10/56 [17.9%]), ventricular tachycardia (2/56 [3.5%]) and severe rhabdomyolysis (1 case). [Journal]
Apr 10, 2020
Review of the safety considerations regarding the use of chloroquine, hydroxychloroquine and azithromycin for SARS-CoV2 infection. Common adverse events (AEs) of chloroquine and hydroxychloroquine include pruritus, nausea and headache. Both drugs have been linked with life-threatening arrhythmias, serious hypoglycemia, hypersensitivity reactions and serious cutaneous toxicities, and are extremely toxic in overdose. Other AEs are listed. [Journal]
Apr 06, 2020
Study comparing chloroquine with lopinavir/ritonavir for treating COVID-19. Adverse events (AEs) with chloroquine included vomiting, diarrhea (5/10 patients [50%] each) and nausea (4/10 [40%]). With lopinavir/ritonavir, AEs included diarrhea (8/12 [66.67%]), cough (6/12 [50%]) and nausea (5/12 [41.67%]). Other AEs are listed. [Journal]
Mar 30, 2020
Review of the literature regarding chloroquine and hydroxychloroquine for the treatment of COVID-19. Both drugs have shown potential to prolong the QTc interval, a risk that is increased when azithromycin is added to hydroxychloroquine. Concurrent use of chloroquine/hydroxychloroquine and lopinavir/ritonavir can increase the risk of hypoglycemia. There have been reports of cardiomyopathy and reversible heart failure in patients treated with chloroquine. [Journal]
Mar 28, 2020
Article discussing possible harmful effects of chloroquine/hydroxychloroquine for COVID-19. In nonhuman primate models, chloroquine enhanced Chikungunya virus infection, while in a clinical study it increased the risk of chronic complications of Chikungunya virus infection. [Journal]
Mar 26, 2020
Article discussing the importance of QTc monitoring during treatment for COVID-19. Some drugs being tested for COVID-19, such as chloroquine, hydroxychloroquine, lopinavir and ritonavir, carry a known risk for drug-induced ventricular arrhythmias and sudden cardiac death. Hydroxychloroquine has the potential to cause prolongation of the QT interval. [Website Reference]
Mar 17, 2020
Systematic review of chloroquine (ferriprotoporphyrin IX/thiamine transporter 2 inhibitor) for the treatment of patients infected with COVID-19. Patients administered chloroquine should be monitored for the development of anemia, thrombocytopenia, leukopenia, electrolyte disturbances, hepatic/renal dysfunction, QT interval prolongation, bradycardia and visual/mental impairment. [Journal]
Thrombin
TLR7
Sep 21, 2020
Review of the ocular presentations of COVID-19. Hydroxychloroquine (TLR7/TLR9 antagonist) can cause retinal toxicity and retinopathy. [Journal]
Sep 18, 2020
Review assessing the risk of drug-induced long QT syndrome associated with drugs repurposed for COVID-19. Chloroquine, favipiravir, hydroxychloroquine, remdesivir and lopinavir/ritonavir were associated with moderate-to-very high risk of long QT syndrome. Some cases of torsades de pointes have been reported with azithromycin. Other safety issues are listed. [Journal]
Sep 14, 2020
Case report of ocular myasthenia gravis induced by hydroxychloroquine (TLR7/9 antagonist). Hydroxychloroquine had been administered as a prophylaxis against Covid-19. [Journal]
Sep 09, 2020
Review of azithromycin (50S ribosomal protein inhibitor), as monotherapy or in combination, for the treatment of COVID-19. The most common adverse effects (AEs) of azithromycin are gastrointestinal, but it has also been associated with an increased risk of cardiac events such as QTc prolongation, torsade de pointes, ventricular tachycardia and sudden cardiac death. Other AEs of azithromycin, hydroxychloroquine and the combination of both drugs are listed. [Journal]
Sep 08, 2020
Phase III study comparing azithromycin/hydroxychloroquine combination to hydroxychloroquine alone in 397 patients with severe COVID-19. Serious adverse events (SAEs) included acute kidney failure (147/241 patients [61%] with azithromycin/hydroxychloroquine vs 103/198 [52%] with hydroxychloroquine), gastrointestinal intolerance (61 [25%] vs 48 [24%]), QTc prolongation (47 [20%] vs 42 [21%]), decreased lymphocytes (27 [11%] vs 21 [11%]) and cardiac arrest (16 [7%] vs 13 [7%]). 2 (1%) patients in the azithromycin group and 3 (2%) in the control group died due to acute kidney failure. Other SAEs are listed. [Journal]
Sep 03, 2020
Review on remdesivir (viral RNA polymerase inhibitor) for COVID-19 in pediatric patients. Remdesivir is not recommended in pediatric patients with hepatic impairment or hepatotoxicity at baseline as it increases liver aminotransferase levels (11.7%). Increased ALT was observed in a 5-year-old child with acute lymphoblastic leukemia receiving remdesivir for concomitant SARS-CoV-2 infection. Drug-drug interactions have also been reported with remdesivir in combination with P-glycoprotein inhibitors such as hydroxychloroquine, azithromycin, cyclosporine, tacrolimus and amiodarone, which may have caused the hepatocellular toxicity. [Journal]
Sep 02, 2020
Review evaluating the cardiovascular risk associated with the use of chloroquine or hydroxychloroquine for COVID-19 treatment. Both drugs have been associated with QTc interval prolongation, ventricular arrhythmias, polymorphic ventricular tachycardia and torsades de pointes. When combined with azithromycin, mortality was increased and the rate of QTc prolongation was higher than that observed with either drug as monotherapy. [Journal]
Aug 31, 2020
Systematic review and meta-analysis of treatments used for COVID-19. A higher rate of all-cause mortality was noted with hydroxychloroquine (alone and in combination with azithromycin) than in control groups. [Journal]
Aug 26, 2020
Analysis of clinical trials evaluating the efficacy and safety of hydroxychloroquine (TLR7/TLR9 antagonist) in Covid-19 patients. Adverse events are listed. [Journal]
Aug 22, 2020
Review summarizing the pharmacogenomic literature involving drugs being tested for COVID-19. Adverse events of hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir + ritonavir, darunavir + cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib and corticosteroids are listed. [Journal]
Aug 20, 2020
Real-life study comparing hydroxychloroquine (TLR7/9 antagonist) and lopinavir/ritonavir in 67 patients with severe COVID-19. Side effects included nausea (1/20 patients [5%] with hydroxychloroquine vs 12/47 [25.2%] with lopinavir/ritonavir), diarrhea (0 vs 7 [14.9%]) and elevated liver enzymes (2 [10%] vs 7 [14.9%]). [Journal]
Aug 19, 2020
Review evaluating the possibility of ocular toxicity due to chloroquine/hydroxychloroquine therapy for COVID-19. [Journal]
Aug 17, 2020
Review of cutaneous adverse reactions of drugs under investigation for the management of COVID-19. Safety issues are listed. [Journal]
Aug 07, 2020
Retrospective study of abnormal liver tests in patients with COVID-19. Drugs used for the treatment of COVID-19 (lopinavir/ritonavir, hydroxychloroquine, remdesivir and tocilizumab) were significantly associated with peak hospitalization levels of ALT and AST. [Journal]
Aug 03, 2020
Retrospective study evaluating the safety, tolerability and clinical outcomes of hydroxychloroquine (TLR7/9 antagonist) in 153 hospitalized patients with COVID-19. 47 patients (36%) had a QTc increase, 13 (9%) developed arrhythmia (including supraventricular tachycardia) and 1 (0.7%) developed non-sustained monomorphic ventricular tachycardia. Grade 3-4 adverse events (AEs) included anemia (20 [14.9%] grade 3; 0 grade 4), lymphopenia (13 [10.4%]; 2 [1.6%]), increased AST (10 [8.2%]; 3 [2.5%]) and increased ALT (8 [6.5%]; 2 [1.6%]). Other AEs are listed. [Journal]
Jul 30, 2020
Clinical trial of hydroxychloroquine with or without azithromycin in 667 patients with mild-to-moderate COVID-19. Prolongation of the QTc interval was observed in the combination group (14.7% patients) and the hydroxychloroquine group (14.6%). Other adverse events (AEs) included increased ALT/AST (10.9% and 8.5% in the combination and hydroxychloroquine groups, respectively), anemia (9.6% and 7%) and low lymphocyte levels (12.1% and 8.5%). Other AEs are listed. [Journal]
Jul 25, 2020
Safety data from clinical trials of chloroquine and hydroxychloroquine. Gastrointestinal discomfort is the most common side effect of both drugs, manifesting as nausea, vomiting, diarrhea, loss of appetite and stomach pain. Other toxicities included hypoglycemia, rash, itching and hemolytic anemia (serious). Retinal toxicity is a well-described adverse effect of hydroxychloroquine. Chloroquine and hydroxychloroquine are associated with QT prolongation. [Journal]
Jul 20, 2020
Randomized trial of hydroxychloroquine (TLR7/TLR9 antagonist) in symptomatic, non-hospitalized patients with early COVID-19. Adverse events (AEs) were more common with hydroxychloroquine than with placebo (43.4% vs 21.8%; P < 0.001), and were mostly gastrointestinal, including upset stomach/nausea, abdominal pain, diarrhea and vomiting. Other AEs are listed. [Journal]
Jul 16, 2020
Review evaluating the safety of various drugs used in the treatment of SARS-CoV-2 infection. Adverse drug reactions reported in clinical trials and postmarketing surveillance are listed. [Journal]
Jul 14, 2020
Retrospective study of hydroxychloroquine (HCQ; 200 mg tid) and azithromycin (AZ; 250 mg qd), alone or in combination, in patients with COVID-19. Common adverse events (AEs) considered possibly related to HCQ/AZ included diarrhea (1.6%), nausea, vomiting (0.8% each), abdominal pain (0.7%) and prolonged QTc interval (0.6%). AEs considered related to HCQ monotherapy included skin disorders, abdominal pain/digestive disorders (3% each), prolonged QTc interval and headache (2% each). AEs considered possibly related to AZ included prolonged QTc (2.2%) and neuropsychiatric signs (0.7%). Other AEs considered treatment-related are listed. [Journal]
Jul 14, 2020
Retrospective study of the incidence of arrythmias and electrocardiographic abnormalities in patients with COVID-19 treated with various drugs. Treatment with hydroxychloroquine, with or without azithromycin was associated with a prolongation of the QTc interval. [Journal]
Jul 12, 2020
Literature review evaluating psychiatric aspects of chloroquine and hydroxychloroquine treatment in patients with COVID-19. Chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications. These drugs may also prolong the QT interval. Neuropsychiatric side effects are listed. [Journal]
Jul 08, 2020
Observational study of hydroxychloroquine in combination with baricitinib in 15 patients with COVID-19. 1 patient developed hydroxychloroquine-related rhabdomyolysis. [Journal]
Jul 08, 2020
Review evaluating the risk of neurologic adverse drug reactions associated with potential treatments for COVID-19. Adverse reactions reported with chloroquine, hydroxychloroquine, umifenovir, lopinavir/ritonavir, interferon alpha, favipiravir, tocilizumab and corticosteroids are listed. [Journal]
Jul 07, 2020
Case reports of 4 patients who developed cutaneous side effects (including urticaria, maculopapular rash and palmoplantar itching) after receiving hydroxychloroquine (TLR7/9 antagonist) as a prophylactic against COVID-19. [Journal]
Jun 24, 2020
Review of antiviral therapy for treating COVID-19. The FDA has warned of the risk of heart rhythm problems associated with chloroquine and hydroxychloroquine. Side effects observed in trials of hydroxychloroquine and lopinavir/ritonavir are listed. [Congress Alert]
Jun 23, 2020
Review on the potential hepatotoxicity induced by drugs used as treatment for COVID-19. [Journal]
Jun 19, 2020
Retrospective study comparing lopinavir/ritonavir to hydroxychloroquine in patients with mild-to-moderate COVID-19. Adverse events (AEs) were more common with lopinavir/ritonavir (93.5% vs 76.5%), and included anemia (51.6% vs 44.1%), increased ALT (32.3% vs 29.4%) and diarrhea (22.6% vs 17.6%). Other AEs are listed. [Journal]
Jun 18, 2020
Article discussing the importance of screening for G6PD deficiency before treatment with hydroxychloroquine (HC) for COVID-19. The FDA has issued a warning about the risk of hemolysis in G6PD-deficient patients receiving HC. A case of HC-induced serious hemolysis has been reported. Other AEs of HC include neutropenia, pancytopenia, hypoglycemia, delirium, epithelial keratopathy, renal failure and long QT syndrome. Other drugs linked to hemolysis in patients with G6PD deficiency are listed. [Journal]
Jun 18, 2020
Systematic review and meta-analysis of the safety and efficacy of antivirals for COVID-19. Safety issues potentially associated with the different treatments are listed. [Journal]
Jun 16, 2020
Case report of a patient with G6PD deficiency who suffered serious hemolysis leading to acute renal failure due to hydroxychloroquine (TLR7/TLR9 antagonist). He was receiving combined hydroxychloroquine and azithromycin for COVID-19. [Journal]
Jun 16, 2020
The FDA has issued a warning about a potential drug interaction between remdesivir and chloroquine or hydroxychloroquine, that could result in reduced antiviral activity of remdesivir. Data from the clinical setting is being evaluated as no instances of this drug interaction have been identified. The FDA has also updated the fact sheet of remdesivir to include additional information about possible allergic reactions. [Regulatory Agency Communication]
Jun 16, 2020
The FDA has revoked the emergency use authorization for chloroquine phosphate and hydroxychloroquine sulfate in patients with COVID-19. This follows recent data showing that these drugs are unlikely to be effective and may lead to serious cardiac adverse events and other potential serious side effects. The known and potential benefits no longer outweigh the known and potential risks for the authorized use. [Regulatory Agency Communication]
Jun 08, 2020
Randomized, placebo-controlled trial of hydroxychloroquine as a prophylaxis after exposure to COVID-19. Adverse events (AEs) more common in the hydroxychloroquine group than in the placebo group included nausea/upset stomach (22.9% vs 7.7%), diarrhea/abdominal discomfort/vomiting (23.2% vs 4.3%), irritability/dizziness/vertigo (5.4% vs 3.7%) and headache (3.7% vs 2.3%). Other AEs are listed. [Journal]
Jun 03, 2020
The EMA reminds healthcare professionals to closely monitor patients with COVID-19 who are receiving hydroxychloroquine or chloroquine considering the serious adverse events that can result from these medications. An increased risk of heart problems (including cardiac arrhythmias and cardiac arrest) has been reported with these drugs (alone and combined with azithromycin). Neuropsychiatric disorders may also appear, including agitation, insomnia, confusion, psychosis and suicidal ideation. These medications are also known to affect the liver, cause neuronal damage (leading to seizures) and lower blood sugar. Some EU countries have suspended or stopped clinical trials investigating these drugs for COVID-19. [Regulatory Agency Communication]
May 31, 2020
Article stating that azithromycin (50S ribosomal protein inhibitor) should not be used to treat COVID-19 patients. Compared to hydroxychloroquine alone, the combination of azithromycin with hydroxychloroquine has been associated with an increased risk of cardiovascular mortality, chest pain/angina and heart failure. Both drugs can cause QT prolongation, torsade de pointes and sudden cardiac death. [Journal]
May 29, 2020
Review of safety considerations associated with psychotropic treatment in patients with COVID-19. Relevant adverse events (AEs) of psychotropics and neuropsychiatric AEs of potential COVID-19 treatments are listed. [Journal]
May 28, 2020
Observational study of hydroxychloroquine (TLR7/9 antagonist; 600 mg/day) in patients with Covid-19 pneumonia. 8/84 patients treated with hydroxychloroquine experienced electrocardiographic modifications leading to treatment discontinuation (7 QTc interval prolongations (>60 ms)). 1 patient suffered a first degree atrioventricular block. 1 patient on lopinavir/ritonavir developed left bundle branch block. [Journal]
May 27, 2020
Study of hydroxychloroquine and azithromycin, as monotherapies or in combination, in patients with COVID-19 in New York State. Cardiac arrest and abnormal electrocardiogram findings were more common in the hydroxychloroquine + azithromycin group (15.5% and 27.1%, respectively) and hydroxychloroquine alone group (13.7% and 27.3) than in the azithromycin alone group (6.2% and 16.1%) or in patients not treated with either drug (6.8% and 14.0%). Other side effects are listed. [Journal]
May 27, 2020
Swissmedic, together with Sanofi and Helvepharm, have issued a Direct Healthcare Professional Communication warning about the risk of QT prolongation and subsequent arrhythmias (such as torsades de pointes) associated with hydroxychloroquine (TLR7/9 antagonist). The risk of QT prolongation and other hydroxychloroquine-related serious and life-threatening adverse events (including torsade de pointes, syncope, cardiac arrest and sudden death) was increased in patients receiving hydroxychloroquine combined with other drugs known to prolong QT interval, such as azithromycin. Therefore, doctors must be cautious when using hydroxychloroquine to treat Covid-19. [Regulatory Agency Communication]
May 27, 2020
The WHO has announced that it will stop a global study of hydroxychloroquine in patients with COVID-19 due to recent discouraging findings. Results from a study in 96,000 patients receiving hydroxychloroquine or chloroquine with or without an antibiotic showed a higher risk of deaths and heart problems than those who did not receive this medication. The death rate was 1/6 in patients taking hydroxychloroquine or chloroquine alone, 1/5 in patients taking chloroquine and an antibiotic, 1/4 in patients taking hydroxychloroquine and an antibiotic, and 1/11 in patients not taking any investigational drug. Serious cardiac arrythmias were increased in all treatment groups. [Website Reference]
May 26, 2020
Analysis of VigiBase assessing the risk of cardiovascular adverse drug reactions of proposed treatments for COVID-19 (hydroxychloroquine and azithromycin). QT prolongation and/or ventricular tachycardia including Torsades-de-Pointes were more frequently reported with each drug than with any other drug in the database (IC025 = 1.04 for hydroxychloroquine; 1.67 for azithromycin). Hydroxychloroquine was also associated with conduction disorders (1.04; including atrioventricular and bundle branch blocks) and heart failure (0.06; including fatal cases). QT prolongation and/or ventricular tachycardia including Torsades-de-Pointes were reported significantly more frequently with the combination of both drugs than with either monotherapy (ROR = 2.48 [1.28-4.79]). Whilst lethal cases of ventricular tachycardia and Torsades-de-Pointes were seen with both drugs, lethal cases of prolonged QT were only seen with azithromycin. [Journal]
May 26, 2020
Multinational registry analysis of 96,032 patients with COVID-19 treated with chloroquine or hydroxychloroquine, alone or in combination with a macrolide. Compared to the control group, the risk of death and de-novo ventricular arrhythmia was significantly increased in patients receiving hydroxychloroquine, hydroxychloroquine with a macrolide, chloroquine or chloroquine with a macrolide. [Journal]
May 25, 2020
Systematic review and meta-analysis of hydroxychloroquine (TRL7/TRL9 antagonist) in 2,354 patients with COVID-19. Adverse events were significantly more common with hydroxychloroquine than in the control group (OR: 4.1 [95% CI: 1.42-11.88]). 1 study reported cardiac arrest and abnormal ECG findings. [Journal]
May 23, 2020
Review on the cardiovascular safety of potential drugs for the treatment of COVID-19, including chloroquine, hydroxychloroquine, azithromycin, remdesivir, lopinavir in combination with ritonavir, and interferon alpha-2b. Safety data is listed. [Journal]
May 22, 2020
Article alerting of a possible synergistic retinal toxicity in COVID-19 patients treated with combinations of drugs known to cause macular toxicity, including ritonavir, chloroquine, hydroxychloroquine and tamoxifen. Ritonavir is known to cause hypertrophy of the retinal pigmented epithelium. [Journal]
May 22, 2020
The AEMPS has warned of neuropsychiatric disorders related to chloroquine and hydroxychloroquine, including psychosis and attempted and completed suicide. A literature search found reports of other psychiatric disorders with these drugs, including agitation, insomnia, confusion, mania, hallucinations, paranoia, depression, catatonia, psychosis and suicidal ideation. These events have been observed in COVID-19 patients receiving hydroxychloroquine (800 mg first dose followed by 400 mg/day), including serious cases. A review is ongoing. [Data from an update of an AEMPS communication on possible adverse events in patients with COVID-19] [Regulatory Agency Communication]
May 21, 2020
Study assessing conduction abnormalities of hydroxychloroquine (HCQ; TLR7/TLR9 antagonist) as add on therapy to lopinavir/ritonavir in 11 patients with COVID-19. 3 patients (27.3%) developed prolonged QTc, including 1 with associated right bundle brunch block, 1 with bradycardia and 1 thrombocytopenia. 2 patients with pre-HCQ QTc prolongation were on lopinavir/ritonavir. [Journal]
May 19, 2020
Review on potential therapies for COVID-19. Safety issues are listed. [Journal]
May 18, 2020
Study of the effects of chloroquine/hydroxychloroquine with or without azithromycin on the QTc interval in 201 patients with SARS-CoV-2 infection. 7 patients (3.5%) discontinued treatment due to QTc prolongation. The maximum QTc was significantly longer in patients who received azithromycin than in those receiving chloroquine or hydroxychloroquine alone (470.4 ± 45.0 ms vs 453.3 ± 37.0 ms; p = 0.004). [Journal]
May 18, 2020
Systematic review of 14 studies assessing the risk of QT prolongation, torsades de pointes, ventricular arrhythmia and sudden death related to chloroquine or hydroxychloroquine in patients with COVID-19. Approximately 10% hospitalized COVD-19 patients taking chloroquine or hydroxychloroquine developed severe QT prolongation. In other studies, QTc prolongation was observed in 12% of 84 patients treated with hydroxychloroquine plus azithromycin and in healthy volunteers treated with chloroquine phosphate and/or azithromycin. 2 patients treated with chloroquine developed ventricular arrhythmia, while atrioventricular block and left bundle branch block was reported in 2 patients on hydroxychloroquine. No sudden deaths were reported with chloroquine in malaria. [Journal]
May 13, 2020
Case report of a 68-year-old Congolese man hospitalized for COVID-19. The patient had a G6PD deficiency and suffered hemolysis, which was worsened by hydroxychloroquine. [Journal]
May 12, 2020
Retrospective review of tocilizumab (interleukin-6 receptor, alpha subunit antagonist) in 25 Covid-19 patients. The most common adverse events (AEs) were anemia (16 any grade; 6 grade 3), increased alanine aminotransferase (11; 3), QT interval prolongation (5; 5) and increased aspartate aminotransferase (3; 0). 8 patients had Candida in their respiratory cultures. Other AEs of tocilizumab and of the concomitant agents used are listed. [Journal]
May 11, 2020
Pharmacovigilance study assessing the cardiac safety of hydroxychloroquine, azithromycin, lopinavir/ritonavir and chloroquine when used off-label for COVID-19. 120 reports of cardiac adverse drug reactions were identified by the French Pharmacovigilance Network, including 103 cases associated with hydroxychloroquine (alone or combined with azithromycin). 17 events were caused by lopinavir/ritonavir. Chloroquine was involved in 3 cases. Hydroxychloroquine-related reactions are listed. [Journal]
May 05, 2020
New Zealand’s Medsafe and Sanofi have issued a safety communication about hydroxychloroquine (TLR7/9 antagonist) for the treatment of COVID-19. Hydroxychloroquine has been associated with QT prolongation and subsequent arrhythmias (including torsade de pointes). QT prolongation can be exacerbated when hydroxychloroquine is combined with other drugs with known cardiac risks, such as azithromycin. Some cases of serious and life-threatening QT prolongation, torsade de pointes, syncope, cardiac arrest and sudden death have been reported in patients receiving concomitant treatment with hydroxychloroquine and azithromycin for COVID-19. [Regulatory Agency Communication]
May 05, 2020
Retrospective study of hydroxychloroquine (HC; TLR7/TLR9 antagonist) in patients with COVID-19. Compared to the group not treated with HC, HC-treated patients had a significantly higher risk of death from any cause (adjusted HR 2.61; 95% CI 1.10-6.17; P = 0.03). This was not observed in the group of patients treated with HC and azithromycin (adjusted HR 1.14; 95% CI 0.56-2.32; P = 0.72). [Journal]
May 04, 2020
Study analyzing the risk of QT interval prolongation in 90 patients with COVID-19 treated with hydroxychloroquine with or without azithromycin. 19% patients treated with hydroxychloroquine monotherapy and 21% treated with the combination experienced a prolongation of the QTc interval, which led to treatment discontinuation in 11 and 1 patients, respectively. Other adverse events of hydroxychloroquine included nausea, premature ventricular contractions and bundle branch block. In the combination group, 1 patient suffered torsades de pointes and ventricular arrhythmia. The change in the QTc interval was greater when hydroxychloroquine was coadministered with azithromycin than with hydroxychloroquine alone (P = 0.03). [Journal]
Apr 28, 2020
Editorial article discussing the use of chloroquine for COVID-19 infection. The adverse effects of chloroquine and hydroxychloroquine are well known and can be severe, including psychiatric effects, arrhythmia and sudden death. [Journal]
Apr 27, 2020
Health Canada has issued a communication warning against self-medication with chloroquine or hydroxychloroquine for COVID-19. These drugs can cause serious heart rhythm problems, which can be exacerbated when they are combined with azithromycin. [Regulatory Agency Communication]
Apr 27, 2020
The FDA has issued a drug safety communication warning against the use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting and clinical trials. This warning is based on the known serious heart rhythm problems that can be caused by intake of these drugs, including QT interval prolongation, ventricular tachycardia and ventricular fibrillation (including fatal cases). Combination with azithromycin can increase the risk of heart rhythm problems. [Regulatory Agency Communication]
Apr 24, 2020
The EMA has issued a communication reminding the risk of serious side effects associated with chloroquine and hydroxychloroquine, as their use may be increased due to its potential efficacy for Covid-19. Both drugs can cause serious or fatal heart rhythm problems (including QT prolongation), which may be exacerbated at high doses or when combined with azithromycin. Other adverse events of chloroquine and hydroxychloroquine include liver and kidney problems, nerve cell damage leading to seizures and hypoglycemia. [Regulatory Agency Communication]
Apr 23, 2020
In vitro and in vivo data assessing the efficacy and safety of hydroxychloroquine (TLR7/9 antagonist) for treating COVID-19. Adverse events associated with hydroxychloroquine included QTc prolongation (by hERG blockage), retinopathy and gastrointestinal toxicity. Chloroquine was used as a model to predict the risk of QT prolongation. [Journal]
Apr 22, 2020
The NIH recommends monitoring the QTc interval in patients with COVID-19 treated with chloroquine or hydroxychloroquine. Hydroxychloroquine is better tolerated but both drugs have a similar safety profile, including QTc prolongation, torsade de pointes, ventricular arrhythmia, cardiac death, hypoglycemia, rash, nausea, retinopathy and bone marrow suppression. Other safety considerations and adverse events observed in clinical trials of COVID-19 are listed. [Data from the NIH COVID-19 Treatment Guidelines] [Website Reference]
Apr 21, 2020
Article describing the outbreak response strategy against COVID-19 in long-term care hospitals in Korea, including post-exposure prophylaxis using hydroxychloroquine (TLR7/TLR9 antagonist). 32 (15%) participants reported an adverse event, most commonly diarrhea/loose stool (9%), skin rash (4.3%), gastrointestinal upset and bradycardia (0.95% each). 2 patients discontinued hydroxychloroquine due to gastrointestinal upset, and 2 due to bradycardia. [Journal]
Apr 21, 2020
Real-world data of hydroxychloroquine (TLR7/TLR9 antagonist) in 181 patients hospitalized for COVID-19. 8/84 patients receiving hydroxychloroquine needed to discontinue the drug due to electrocardiogram changes (7 patients with QTc interval prolongation and 1 with first-degree atrioventricular block). 1 patient treated with lopinavir/ritonavir developed left bundle branch block. [Journal]
Apr 19, 2020
Systematic review and meta-analysis of hydroxychloroquine for COVID-19. Adverse events (AEs) included nausea, vomiting, diarrhea, abnormal liver function tests, rash and headache. When hydroxychloroquine was used in combination with azithromycin, AEs included QT interval prolongation, blurred vision, nausea, vomiting and diarrhea. [Journal]
Apr 16, 2020
Clinical trial of hydroxychloroquine (TLR7/9 antagonist; 800 mg daily) in COVID-19 patients. The most common adverse events (AEs) were diarrhea (7) and vomiting (2). 1 patient discontinued treatment due to blurred vision. Other AEs are listed. [Journal]
Apr 15, 2020
Clinical study evaluating the optimal dosing regimen of hydroxychloroquine (TLR7/9 antagonist) for COVID-19 patients. 2/13 patients discontinued hydroxychloroquine due to QT interval prolongation. [Journal]
Apr 15, 2020
Observational study evaluating the safety of hydroxychloroquine (TLR7/9 antagonist) in patients with rheumatoid arthritis, alone or in combination with azithromycin or amoxicillin, in light of rapid wide-spread use for COVID-19. Risk of cardiovascular mortality was increased in patients receiving hydroxychloroquine alone (calibrated hazard ratio = 1.65; 95% CI [1.12-2.44]) or combined with azithromycin (2.19 [1.22-3.94]). Hydroxychloroquine plus azithromycin was also associated with an increased risk of heart failure (1.22 [1.02-1.45]) and chest pain/angina (1.15 [1.05-1.26]). Other adverse events are listed. [Journal]
Apr 13, 2020
Article discussing research strategies for treatments for COVID-19. Hydroxychloroquine (TLR7/TLR9 antagonist), a potential candidate, has been linked to cardiac disorders. [Journal]
Apr 10, 2020
Review of the safety considerations regarding the use of chloroquine, hydroxychloroquine and azithromycin for SARS-CoV2 infection. Common adverse events (AEs) of chloroquine and hydroxychloroquine include pruritus, nausea and headache. Both drugs have been linked with life-threatening arrhythmias, serious hypoglycemia, hypersensitivity reactions and serious cutaneous toxicities, and are extremely toxic in overdose. Other AEs are listed. [Journal]