ritonavir and baricitinib

Topics: Animals; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Embryonic Development; Female; Humans; Pharmaceutical Preparations; Pregnancy; Pregnancy Complications, Infectious; Ritonavir; SARS-CoV-2; Zebrafish

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.

Topics: Adenosine Monophosphate; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azetidines; Chloroquine; COVID-19; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferons; Ivermectin; Lopinavir; Nitro Compounds; Oseltamivir; Purines; Pyrazines; Pyrazoles; Ribavirin; Ritonavir; Sulfonamides; Thiazoles

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azetidines; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Immunomodulation; Interferon-alpha; Lopinavir; Nelfinavir; Nitro Compounds; Pandemics; Pneumonia, Viral; Purines; Pyrazoles; Ribavirin; Ritonavir; SARS-CoV-2; Sulfonamides; Thiazoles

SARS-CoV-2 is the agent responsible for COVID-19. The infection can be dived into three phases: mild infection, the pulmonary phase and the inflammatory phase. Treatment options for the pulmonary phase include: Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir. The inflammatory phase includes therapeutic options like Tocilizumab, Anakinra, Baricitinib, Eculizumab, Emapalumab and Heparin. Human clinical trials are starting to show some results, in some cases like that of Remdesivir and corticosteroids these are controversial. Coagulopathy is a common complication in severe cases, inflammation and coagulation are intertwined and cross-talking between these two responses is known to happen. A possible amplification of this cross-talking is suggested to be implicated in the severe cases that show both a cytokine storm and coagulopathy.

Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Anticoagulants; Antiviral Agents; Azetidines; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Disseminated Intravascular Coagulation; Drug Combinations; Heparin; Humans; Hydroxychloroquine; Inflammation; Interleukin 1 Receptor Antagonist Protein; Lopinavir; Pandemics; Pneumonia, Viral; Purines; Pyrazoles; Ritonavir; SARS-CoV-2; Sulfonamides

Cancer patients with Covid-19 are exposed to treatment combinations that can potentially result in interactions that adversely affect patient outcomes. This study aimed to identify potential drug-drug interactions between antineoplastic agents and medicines used to treat Covid-19.. We conducted a search for potential interactions between 201 antineoplastic agents and 26 medicines used to treat Covid-19 on the Lexicomp. A total of 388 "major" or "contraindicated" drug-drug interactions were detected. Eight drugs or combinations (baricitinib, lopinavir/ritonavir, atazanavir, darunavir, azithromycin, chloroquine, hydroxychloroquine, and sirolimus) accounted for 91.5% of these interactions. The class of antineoplastic agents with the greatest potential for interaction was tyrosine kinase inhibitors (accounting for 46.4% of all interactions). The findings show that atazanavir, baricitinib, and lopinavir/ritonavir can affect the treatment of all common types of cancer. The most common pharmacokinetic effect of the potential drug-drug interactions was increased plasma concentration of the antineoplastic medicine (39.4%).. Covid-19 is a recent disease and pharmacological interventions are undergoing constant modification. This study identified a considerable number of potential drug-drug interactions. In view of the vulnerability of patients with cancer, it is vital that health professionals carefully assess the risks and benefits of drug combinations.

Topics: Antineoplastic Agents; Antiviral Agents; Atazanavir Sulfate; COVID-19 Drug Treatment; Drug Combinations; Drug Interactions; Humans; Lopinavir; Ritonavir

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.. 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).. 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.. . 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.. European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).

Topics: Aged; Antiviral Agents; Azetidines; Cohort Studies; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Therapy, Combination; Endothelium, Vascular; Enzyme Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Glucocorticoids; Humans; Hydroxychloroquine; Hypoxia; Immunoglobulins, Intravenous; Immunologic Factors; Interferon beta-1b; Janus Kinase Inhibitors; Lopinavir; Lung; Male; Methylprednisolone; Middle Aged; Oximetry; Oxygen Inhalation Therapy; Prospective Studies; Purines; Pyrazoles; Ritonavir; SARS-CoV-2; Severity of Illness Index; Sulfonamides

A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.

Topics: Acute Disease; Aged; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azetidines; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Lopinavir; Male; Pandemics; Pneumonia, Viral; Purines; Pyrazoles; Respiratory Insufficiency; Ritonavir; SARS-CoV-2; Sulfonamides; Treatment Outcome