Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 629
Filtrar
1.
Pharmacol Res Perspect ; 9(1): e00705, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421347

RESUMO

Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.


Assuntos
Antivirais/uso terapêutico , /tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Cloroquina/uso terapêutico , Interações Medicamentosas , Humanos , Lopinavir/uso terapêutico , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
3.
Clin Exp Pharmacol Physiol ; 48(2): 203-210, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33090501

RESUMO

The coronavirus disease 2019 (COVID-19) is an epidemic disease caused by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) and spreading throughout the world rapidly. Here we evaluated the efficacy of the Lopinavir/Ritonavir (LPV/r) and its combination with other drugs in the treatment of COVID-19. We included 170 confirmed COVID-19 patients who had been cured and discharged. Their antiviral therapies were LPV/r alone or combinations with interferon (IFN), Novaferon and Arbidol. We evaluated the medication efficacy by comparing the time of the negative nucleic acid conversion and the length of hospitalization mainly. The LPV/r + Novaferon [6.00 (4.00-8.00) and 7.50 (5.00-10.00) days] had shorter time of the negative nucleic acid conversion (P = .0036) and shorter time of hospitalization (P < .001) compared with LPV/r alone [9.00 (5.00-12.00) and 12.00 (11.00-15.00) days] and LPV/r + IFN [9.00 (7.25-11.00) and 12.00 (10.00-13.50) days]. On the contrary, LPV/r + IFN [9.00 (7.25-11.00) and 12.00 (10.00-13.50) days] had shorter time of the negative nucleic acid conversion (P = .031) and shorter time of hospitalization (P < .001) compared with LPV/r + IFN +Novaferon [10.00 (8.00-11.25) and 13.50 (11.50-17.00) days] and LPV/r + IFN +Arbidol [14.00 (9.75-19.00) and 19.50 (13.25-24.00) days]. In conclusion, the combination of LPV/r and Novaferon may have better efficacy against COVID-19. However, adding IFN based on LPV/r + Novaferon or adding Arbidol based on LPV/r + IFN may not improve the efficacy.


Assuntos
/tratamento farmacológico , Lopinavir/farmacologia , Ritonavir/farmacologia , Adulto , Interações Medicamentosas , Feminino , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/uso terapêutico , Resultado do Tratamento
4.
Rheumatology (Oxford) ; 60(1): 399-407, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020836

RESUMO

OBJECTIVES: The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia. METHODS: This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) <200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW). RESULTS: A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P < 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P < 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group. CONCLUSIONS: . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone. TRIAL REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).


Assuntos
Azetidinas/uso terapêutico , Glucocorticoides/uso terapêutico , Hipóxia/terapia , Inibidores de Janus Quinases/uso terapêutico , Metilprednisolona/uso terapêutico , Oxigenoterapia/estatística & dados numéricos , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Antivirais/uso terapêutico , /fisiopatologia , Estudos de Coortes , Combinação de Medicamentos , Quimioterapia Combinada , Endotélio Vascular , Inibidores Enzimáticos/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Pulmão/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Oximetria , Estudos Prospectivos , Ritonavir/uso terapêutico , Índice de Gravidade de Doença
5.
Phytomedicine ; 81: 153367, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33260064

RESUMO

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Lopinavir/efeitos adversos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Ritonavir/efeitos adversos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Biol Trace Elem Res ; 199(2): 550-558, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32458149

RESUMO

The current COVID-19 pandemic caused by SARS-CoV-2 has prompted investigators worldwide to search for an effective anti-viral treatment. A number of anti-viral drugs such as ribavirin, remdesivir, lopinavir/ritonavir, antibiotics such as azithromycin and doxycycline, and anti-parasite such as ivermectin have been recommended for COVID-19 treatment. In addition, sufficient pre-clinical rationale and evidence have been presented to use chloroquine for the treatment of COVID-19. Furthermore, Zn has the ability to enhance innate and adaptive immunity in the course of a viral infection. Besides, Zn supplement can favour COVID-19 treatment using those suggested and/or recommended drugs. Again, the effectiveness of Zn can be enhanced by using chloroquine as an ionophore while Zn inside the infected cell can stop SARS-CoV-2 replication. Given those benefits, this perspective paper describes how and why Zn could be given due consideration as a complement to the prescribed treatment of COVID-19.


Assuntos
/tratamento farmacológico , Zinco/uso terapêutico , Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Humanos , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico
7.
J Infect Chemother ; 27(1): 99-102, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33023821

RESUMO

We present three patients affected by pulmonary squamous cell carcinoma, metastatic esophageal cancer and advanced non-Hodgkin lymphoma, who incurred in coronavirus 2019 (COVID-19) infection during the early phase of epidemic wave in Italy. All patients presented with fever. Social contact with subject positive for COVID-19 was declared in only one of the three cases. In all cases, laboratory findings showed lymphopenia and elevated C-reactive protein (CRP). Chest x-ray and computed tomography showed bilateral ground-glass opacities, shadowing, interstitial abnormalities, and "crazy paving" pattern which evolved with superimposition of consolidations in one patient. All patients received antiviral therapy based on ritonavir and lopinavir, associated with hydroxychloroquine. Despite treatment, two patients with advanced cancers died after 39 and 17 days of hospitalization, while the patient with lung cancer was dismissed at home, in good conditions.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Neoplasias/complicações , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Surtos de Doenças , Quimioterapia Combinada , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/tratamento farmacológico , Evolução Fatal , Humanos , Itália , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Swiss Med Wkly ; 150: w20446, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33382449

RESUMO

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.


Assuntos
Antivirais/uso terapêutico , /epidemiologia , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Criança , Pré-Escolar , Comorbidade , Combinação de Medicamentos , Quimioterapia Combinada , Gastos em Saúde , Mortalidade Hospitalar/tendências , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Lactente , Tempo de Internação/estatística & dados numéricos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Terapias em Estudo/métodos , Adulto Jovem
9.
Adv Chronic Kidney Dis ; 27(5): 434-441, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33308510

RESUMO

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Insuficiência Renal Crônica/metabolismo , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , /prevenção & controle , /uso terapêutico , Cloroquina/uso terapêutico , Creatinina/metabolismo , Citidina/análogos & derivados , Citidina/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Interações Medicamentosas , Humanos , Hidroxicloroquina/uso terapêutico , Hidroxilaminas/uso terapêutico , Imunização Passiva , Interferons/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Eliminação Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
10.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334760

RESUMO

We present the case of a 39-year-old man with epigastric pain, nausea and vomiting. The patient scored 4 in the Visual Triage Checklist of acute respiratory symptoms; a COVID-19 swab was taken. Prompt review of the peripheral blood smear showed evidence of microangiopathic haemolytic anaemia and thrombocytopenia. Because the patient had a picture of thrombotic thrombocytopenic purpura, plasma exchange and corticosteroids were started immediately. After 3 days, he developed severe ischaemic stroke and his swabs came back positive for COVID-19 by reverse transcription PCR. Therefore, triple therapy was started (lopinavir/ritonavir, ribavirin and interferon beta-1b). White blood cell count reached 50×109/L (normal range, 4.5-11×109/L), mainly neutrophils. All the workup for autoimmune diseases was negative. The patient showed delayed improvement in lactate dehydrogenase, haemoglobin and platelet count until we increased the volume of plasma exchange and subsided the inflammatory response of COVID-19. After that, the patient showed an excellent recovery.


Assuntos
/diagnóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Adulto , /tratamento farmacológico , Combinação de Medicamentos , Humanos , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Troca Plasmática/métodos , Púrpura Trombocitopênica Trombótica/etiologia , Ritonavir/uso terapêutico
11.
Washington; PAHO; Dec. 18, 2020. 163 p.
Não convencional em Inglês | LILACS, PIE | ID: biblio-1145577

RESUMO

This is the thirteenth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, pregnant women, those with immune conditions, etc.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pandemias/prevenção & controle , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Plasma/imunologia , Ivermectina/uso terapêutico , Dexametasona/uso terapêutico , Metilprednisolona/uso terapêutico , Ensaios Clínicos como Assunto , Lopinavir/uso terapêutico , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/imunologia
12.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336780

RESUMO

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , /tratamento farmacológico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antiparasitários/uso terapêutico , Canabinoides/uso terapêutico , Cloroquina/uso terapêutico , Inativadores do Complemento/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferons/uso terapêutico , Ivermectina/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico , Teicoplanina/uso terapêutico , Tetraciclinas/uso terapêutico , Tiazóis/uso terapêutico
13.
Sci Rep ; 10(1): 20958, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262433

RESUMO

The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69-85%) patients, and in 33 (26%, 95% CI 19-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10-731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.


Assuntos
Antivirais/efeitos adversos , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , Inibidores de Proteases/efeitos adversos , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Estudos Transversais , Combinação de Medicamentos , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , Espanha
14.
Trials ; 21(1): 999, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276811

RESUMO

OBJECTIVES: A severe epidemic of COVID-19 has broken out in China and has become a major global public health event. We focus on the Acute Respiratory Distress Syndrome (ARDS)-like changes and overactivation of Th17 cells (these produce cytokines) in patients with COVID-19. We aim to explore the safety and efficacy of ixekizumab (an injectable drug for the treatment of autoimmune diseases) to prevent organ injury caused by the immune response to COVID-19. Ixekizumab is a human monoclonal antibody that binds to interleukin-17A and inhibits the release of pro-inflammatory cytokines and chemokines. TRIAL DESIGN: The experiment is divided into two stages. In the first stage, the open trial, 3 patients with COVID-19 are treated with ixekizumab, and the safety and efficacy are observed for 7 days. In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. This is a two-center, open-label, randomized controlled pilot trial with 2-arm parallel group design (1:1 ratio). PARTICIPANTS: Patients with COVID-19 aged 18-75 with increased Interleukin (IL)-6 levels will be enrolled, but patients with severe infections requiring intensive care will be excluded. The trial will be undertaken in two centers. The first stage is carried out in Xiangya Hospital of Central South University, and the second stage is carried out simultaneously in the Third Xiangya Hospital of Central South University. INTERVENTION AND COMPARATOR: In the first stage, three subjects are given ixekizumab ("Taltz") (80 mg/ml, 160 mg as a single hypodermic injection) and antiviral therapy (α-interferon (administer 5 million U by aerosol inhalation twice daily), lopinavir/ritonavir (administer 100mg by mouth twice daily, for the course of therapy no more than 10 days), chloroquine (administer 500mg by mouth twice daily, for the course of therapy no more than 10 days), ribavirin (administer 500mg by intravenous injection two to three times a day, for the course of therapy no more than 10 days), or arbidol (administer 200mg by mouth three times a day, for the course of therapy no more than 10 days), but not more than 3 types). The treatment course of the first stage is 7 days. In the second stage, 40 randomized patients will receive the following treatments--Group 1: ixekizumab (80 mg/ml, 160 mg as a single hypodermic injection) with antiviral therapy (the same scheme as in the first stage); Group 2: antiviral therapy alone (the same scheme as in the first stage). The length of the second treatment course is 14 days. MAIN OUTCOMES: The primary outcome is a change in pulmonary CT severity score (an imaging tool for assessing COVID-19, which scores on the basis of all abnormal areas involved). Pulmonary CT severity score is assessed on the 7th day, 14th day, or at discharge. RANDOMISATION: In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. The eLite random system of Nanjing Medical University is used for randomization. BLINDING (MASKING): The main efficacy indicator, the CT results, will be evaluated by the third-party blinded and independent research team. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. TRIAL STATUS: Trial registration number is ChiCTR2000030703 (version 1.7 as of March 19, 2020). The recruitment is ongoing, and the date recruitment was initiated in June 2020. The anticipated date of the end of data collection is June 2021. TRIAL REGISTRATION: The name of the trial register is the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2000030703 ( http://www.chictr.org.cn/ ). The date of trial registration is 10 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , /efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , /prevenção & controle , Estudos de Casos e Controles , China/epidemiologia , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Quimioterapia Combinada , Humanos , Indóis/administração & dosagem , Indóis/uso terapêutico , Interleucina-17/imunologia , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Segurança , Células Th17/imunologia , Resultado do Tratamento
15.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33305554

RESUMO

Coronavirus Disease-2019 (COVID-19) is the worst worldwide pandemic with more than 12,000,000 cases and 560,000 deaths until 14th July 2020. Men were more infected by COVID-19 than women, and male subjects with underlying conditions, including diabetes, hypertension, and cardiovascular diseases developed a severe form of the affection, with increased mortality rate. Many factors can contribute to the disparity in disease outcomes, such as hormone-specific reaction and activity of X-linked genes, which modulate the innate and adaptive immune response to virus infection. Until now, only the Remdesivir was approved by FDA (Food Drug Administration) for COVID-19 treatment, although several clinical trials are ongoing worldwide also on other drugs. In this review, we analyzed published studies on several drugs (chloroquine or hydroxychloroquine, remdesivir, favipiravir, lopinavir-ritonavir in combination, tocilizumab, plasma, and immunoglobulins) with some efficacy to COVID-19 in humans, and evaluated if there were a gender analysis of the available data. In our opinion, it is essential to report data about COVID-19 disaggregated by sex, age, and race, because the knowledge of gender differences is fundamental to identify effective and customized treatments to reduce hospitalizations, admissions to intensive care units, and mortality.


Assuntos
/tratamento farmacológico , /genética , Caracteres Sexuais , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , /terapia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Cloroquina/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Complicações do Diabetes/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Imunidade/genética , Imunização Passiva/métodos , Imunoglobulinas/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico
16.
BMC Infect Dis ; 20(1): 954, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317461

RESUMO

BACKGROUND: Treatment of patients with COVID-19 has included supportive care to mainly relief symptoms of the disease. Although World Health Organization (WHO) has not recommended any effective treatments for COVID-19, there are some reports about use of antiviral drugs. The aim of this study is to determine the effect of Arbidol (ARB) on COVID-19 disease. METHODS: Using an open-label randomized controlled trial, we examined the efficacy of ARB in patients with COVID-19 in a teaching hospital. One hundred eligible patients with diagnosis of COVID-19 were recruited in the study and assigned randomly to two groups of either hydroxychloroquine followed by KALETRA (Lopinavir/ritonavir) or hydroxychloroquine followed by ARB. The primary outcome was hospitalization duration and clinical improvement 7 days after admission. The criteria of improvement were relief of cough, dyspnea, and fever. Time to relief from fever was also assessed across the two groups. Without any dropouts, 100 patients were entered into the study for the final analysis at significance level of 0.05. RESULTS: The mean age of patients was 56.6 (17.8) years and 56.2 (14.8) years in ARB and KALETRA groups, respectively. Majority of patients were male across two groups (66 and 54%). The duration of hospitalization in ARB group was significantly less than KALETRA arm (7.2 versus 9.6 days; P = 0.02). Time to relief fever was almost similar across two groups (2.7 versus 3.1 days in ARB and KALETRA arms, respectively). Peripheral oxygen saturation rate was significantly different after 7 days of admission across two groups (94% versus 92% in ARB and KALETRA groups respectively) (P = 0.02). Based on multiple linear regression analysis, IHD, Na level, and oxygen saturation at the time of admission and type of therapy were the independent adjusted variables that determined the duration of hospitalization in patients with COVID-19. CONCLUSION: Our findings showed that Arbidol, compared to KALETRA, significantly contributes to clinical and laboratory improvements, including peripheral oxygen saturation, requiring ICU admissions, duration of hospitalization, chest CT involvements, WBC, and ESR. We suggest further studies on ARB against COVID-19 using larger sample size and multicenter design. TRIAL REGISTRATION: IRCT20180725040596N2 on 18 April 2020.


Assuntos
Antivirais/uso terapêutico , Indóis/uso terapêutico , Adulto , Idoso , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Ritonavir/uso terapêutico
17.
Eur Rev Med Pharmacol Sci ; 24(22): 11939-11944, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33275267

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency; unfortunately, there is currently no treatment for improving outcomes or reducing viral-clearance times in infected patients. The aim of the present study was to evaluate the efficacy of interferon (IFN) with or without lopinavir and ritonavir as antiviral therapeutic option for treating COVID-19 infection. PATIENTS AND METHODS: The present study enrolled 148 patients that received either standard care, treatment with IFN alfa-2b, or IFN alfa-2b combined with lopinavir plus ritonavir. Viral testing was performed using Reverse-Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: There was no significant difference in the viral-clearance time at 28 days after treatment between patients receiving standard care and those receiving anti-viral treatments. However, the average viral-clearance time of patients receiving standard care (14 days) was shorter than that for patients receiving IFN alfa-2b or IFN alfa-2b combined with lopinavir plus ritonavir (15.5 or 17.5 days) (p<0.05). Patients treated with IFN alfa-2b within five days or IFN alfa-2b combined with lopinavir plus ritonavir after three days of symptoms exhibited shorter viral-clearance times than the other groups (p<0.05). Moreover, viral-clearance times were significantly longer in patients receiving standard care or anti-viral treatment 5 days after symptoms appeared than those of patients who received these treatments within five days of symptom onset (p<0.05). CONCLUSIONS: Early symptomatic treatment is most critical for maximizing amelioration of COVID-19 infection. Anti-viral treatment might have complicated effect on viral-clearance.


Assuntos
Antivirais/uso terapêutico , Intervenção Médica Precoce , Interferon alfa-2/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
18.
Eur Rev Med Pharmacol Sci ; 24(22): 11977-11981, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33275275

RESUMO

Researchers have found many similarities between the 2003 severe acute respiratory syndrome (SARS) virus and SARS-CoV-19 through existing data that reveal the SARS's cause. Artificial intelligence (AI) learning models can be created to predict drug structures that can be used to treat COVID-19. Despite the effectively demonstrated repurposed drugs, more repurposed drugs should be recognized. Furthermore, technological advancements have been helpful in the battle against COVID-19. Machine intelligence technology can support this procedure by rapidly determining adequate and effective drugs against COVID-19 and by overcoming any barrier between a large number of repurposed drugs, laboratory/clinical testing, and final drug authorization. This paper reviews the proposed vaccines and medicines for SARS-CoV-2 and the current application of AI in drug repurposing for COVID-19 treatment.


Assuntos
Inteligência Artificial , Desenvolvimento de Medicamentos , Reposicionamento de Medicamentos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Ácido Ascórbico/uso terapêutico , /uso terapêutico , Cloroquina/uso terapêutico , Aprendizado Profundo , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Lopinavir/uso terapêutico , Aprendizado de Máquina , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Vitaminas/uso terapêutico
19.
Drugs Aging ; 37(12): 925-933, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33150470

RESUMO

BACKGROUND: Patients hospitalised with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2; coronavirus 2019 disease (COVID-19)] infection are frequently older with co-morbidities and receiving polypharmacy, all of which are known risk factors for drug-drug interactions (DDIs). The pharmacological burden may be further aggravated by the addition of treatments for COVID-19. OBJECTIVE: The aim of this study was to assess the risk of potential DDIs upon admission and during hospitalisation in patients with COVID-19 treated at our hospital. METHODS: We retrospectively analysed 502 patients with COVID-19 (mean age 61 ± 16 years, range 15-99) treated at our hospital with a proven diagnosis of SARS-CoV-2 infection hospitalised between 21 February and 30 April 2020 and treated with at least two drugs. RESULTS: Overall, 68% of our patients with COVID-19 were exposed to at least one potential DDI, and 55% were exposed to at least one potentially severe DDI. The proportion of patients experiencing potentially severe DDIs increased from 22% upon admission to 80% during hospitalisation. Furosemide, amiodarone and quetiapine were the main drivers of potentially severe DDIs upon admission, and hydroxychloroquine and particularly lopinavir/ritonavir were the main drivers during hospitalisation. The majority of potentially severe DDIs carried an increased risk of cardiotoxicity. No potentially severe DDIs were identified in relation to tocilizumab and remdesivir. CONCLUSIONS: Among hospitalised patients with COVID-19, concomitant treatment with lopinavir/ritonavir and hydroxychloroquine led to a dramatic increase in the number of potentially severe DDIs. Given the high risk of cardiotoxicity and the scant and conflicting data concerning their efficacy in treating SARS-CoV-2 infection, the use of lopinavir/ritonavir and hydroxychloroquine in patients with COVID-19 with polypharmacy needs to be carefully considered.


Assuntos
/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Encaminhamento e Consulta , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Interações Medicamentosas , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Itália/epidemiologia , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Polimedicação , Estudos Retrospectivos , Fatores de Risco , Ritonavir/uso terapêutico , Adulto Jovem
20.
Washington; PAHO; Nov. 13, 2020. 128 p.
Não convencional em Inglês | LILACS, PIE | ID: biblio-1140054

RESUMO

This is the twelfth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pandemias/prevenção & controle , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Plasma/imunologia , Ivermectina/uso terapêutico , Dexametasona/uso terapêutico , Metilprednisolona/uso terapêutico , Ensaios Clínicos como Assunto , Lopinavir/uso terapêutico , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA