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2.
Medicine (Baltimore) ; 100(31): e26787, 2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1354339

ABSTRACT

BACKGROUND: Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir. METHODS: In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies. RESULTS: We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment. CONCLUSION: Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.


Subject(s)
Atazanavir Sulfate/adverse effects , Long QT Syndrome/etiology , Lopinavir/adverse effects , Ritonavir/adverse effects , Saquinavir/adverse effects , Adult , Atazanavir Sulfate/therapeutic use , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Electrocardiography/methods , Humans , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Saquinavir/therapeutic use
3.
J Clin Pharm Ther ; 46(3): 724-730, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-991463

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Initial treatment recommendations of COVID-19 were based on the use of antimicrobial drugs and immunomodulators. Although information on drug interactions was available for other pathologies, there was little evidence in the treatment of COVID-19. The objective of this study was to analyse the potential drug-drug interactions (pDDIs) derived from the medication used in COVID-19 patients in the first pandemic wave and to evaluate the real consequences of such interactions in clinical practice. METHODS: Cohort, retrospective and single-centre study carried out in a third-level hospital. Adult patients, admitted with suspected COVID-19, that received at least one dose of hydroxychloroquine, lopinavir/ritonavir, interferon beta 1-b or tocilizumab and with any pDDIs according to "Liverpool Drug Interaction Group" between March and May 2020 were included. The possible consequences of pDDIs at the QTc interval level or any other adverse event according to the patient's medical record were analysed. A descriptive analysis was carried out to assess possible factors that may affect the QTc interval prolongation. RESULTS AND DISCUSSION: Two hundred and eighteen (62.3%) patients of a total of 350 patients admitted with COVID-19 had at least one pDDI. There were 598 pDDIs. Thirty-eight pDDIs (6.3%) were categorized as not recommended or contraindicated. The mean value difference between baseline and pDDI posterior ECG was 412.3 ms ± 25.8 ms vs. 426.3 ms ± 26.7 ms; p < 0.001. Seven patients (5.7%) had a clinically significant alteration of QTc. A total of 44 non-cardiological events (7.3%) with a possible connection to a pDDI were detected. WHAT IS NEW AND CONCLUSION: The number of pDDIs in patients admitted for COVID-19 in the first pandemic wave was remarkably high. However, clinical consequences occurred in a low percentage of patients. Interactions involving medications that would be contraindicated for concomitant administration are rare. Knowledge of these pDDIs and their consequences could help to establish appropriate therapeutic strategies in patients with COVID-19 or other diseases with these treatments.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Interferon beta-1b/adverse effects , Lopinavir/adverse effects , Ritonavir/adverse effects , Adjuvants, Immunologic/adverse effects , Aged , COVID-19/complications , Cohort Studies , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Drug Interactions , Enzyme Inhibitors/adverse effects , Female , Humans , Male , Prevalence , Retrospective Studies , Risk Factors , SARS-CoV-2
5.
Eur Heart J Acute Cardiovasc Care ; 9(3): 215-221, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-186680

ABSTRACT

More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.


Subject(s)
Antimalarials/adverse effects , Betacoronavirus/drug effects , Chloroquine/adverse effects , Coronavirus Infections/drug therapy , Drug Monitoring/methods , Hydroxychloroquine/adverse effects , Pneumonia, Viral/drug therapy , Anti-Bacterial Agents/adverse effects , Antibodies, Monoclonal/adverse effects , Antimalarials/pharmacokinetics , Antimalarials/toxicity , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/complications , COVID-19 , Cardiomyopathies/chemically induced , Cardiomyopathies/complications , Cardiotoxicity/epidemiology , Chloroquine/pharmacokinetics , Chloroquine/toxicity , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Humans , Hydroxychloroquine/pharmacokinetics , Hydroxychloroquine/toxicity , Off-Label Use/statistics & numerical data , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Torsades de Pointes/chemically induced , Torsades de Pointes/epidemiology
6.
Transpl Infect Dis ; 22(4): e13286, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-47858

ABSTRACT

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.


Subject(s)
Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Graft Rejection/prevention & control , Immunosuppressive Agents/adverse effects , Kidney Transplantation , Lopinavir/adverse effects , Pneumonia, Viral/drug therapy , Ritonavir/adverse effects , Tacrolimus/adverse effects , Adult , Antiviral Agents/therapeutic use , Betacoronavirus , C-Reactive Protein/immunology , COVID-19 , Ciliopathies/complications , Cobicistat/therapeutic use , Common Cold/etiology , Common Cold/physiopathology , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Cough/etiology , Cough/physiopathology , Darunavir/therapeutic use , Deprescriptions , Drug Combinations , Drug Interactions , Enzyme Inhibitors/therapeutic use , Fatigue/etiology , Fatigue/physiopathology , Female , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunocompromised Host/immunology , Interleukin-10/immunology , Interleukin-1beta/immunology , Interleukin-6/immunology , Interleukin-8/immunology , Kidney Diseases, Cystic/complications , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/surgery , Leber Congenital Amaurosis/complications , Methylprednisolone/therapeutic use , Optic Atrophies, Hereditary/complications , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Severity of Illness Index
7.
N Engl J Med ; 382(19): 1787-1799, 2020 05 07.
Article in English | MEDLINE | ID: covidwho-9371

ABSTRACT

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/drug therapy , Cytochrome P-450 CYP3A Inhibitors/therapeutic use , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Aged , Antiviral Agents/adverse effects , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Drug Therapy, Combination , Female , Hospital Mortality , Humans , Intention to Treat Analysis , Lopinavir/adverse effects , Male , Middle Aged , Pandemics , Patient Acuity , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Proportional Hazards Models , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/adverse effects , SARS-CoV-2 , Time-to-Treatment , Treatment Failure , Viral Load
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