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Molnupiravir in COVID-19: A systematic review of literature.
Singh, AK, Singh, A, Singh, R, Misra, A
Diabetes & metabolic syndrome. 2021;(6):102329
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Abstract
BACKGROUND AND AIMS Molnupiravir is a newer oral antiviral drug that has recently been tested in COVID-19. We aim to conduct a systematic review of literature to find out the efficacy and safety of molnupiravir in patients with COVID-19. METHODS We systematically searched the electronic database of PubMed, MedRxiv and Google Scholar from inception until October 15, 2021, using MeSH keywords. Ongoing trials of molnupiravir in COVID-19 were additionally searched from the ClinicalTrials.Gov and ctri.nic.in/Clinicaltrials. We retrieved all the available granular details of phase 1 to 3 studies of molnupiravir in COVID-19. Subsequently we reviewed the results narratively. RESULTS Two phase 1 double-blind, randomized, placebo-controlled (DBRPC) studies of molnupiravir showed that 1600 mg daily dose is safe and tolerable, without any serious adverse events up to 5.5 days. One phase 2 DBPRC study found significantly lower time to clearance (RNA negativity) with molnupiravir 800 mg twice daily compared to the placebo (log-rank p value = 0.013) in mild to moderate COVID-19. Interim report of one phase 3 DBRPC study in non-hospitalized COVID-19 found a significant reduction in the risk of hospital admission or death by 50% (p = 0.0012). However, no significant benefit was observed with molnupiravir in the later stage of moderate to severe COVID-19. CONCLUSION Molnupiravir is first oral antiviral drug to demonstrate a significant benefit in reducing hospitalization or death in mild COVID-19 and could be an important weapon in the battle against SARS-CoV-2. However, its role in moderate to severe COVID-19 is questionable and more studies are needed.
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Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.
Marra, F, Smolders, EJ, El-Sherif, O, Boyle, A, Davidson, K, Sommerville, AJ, Marzolini, C, Siccardi, M, Burger, D, Gibbons, S, et al
Drugs in R&D. 2021;(1):9-27
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INTRODUCTION In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing. METHODS COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases. FINDINGS Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities. CONCLUSION Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.
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Clinical trial: low plasma cholesterol and oxidative stress predict rapid virological response to standard therapy with peginterferon and ribavirin in HCV patients.
Angelico, F, Francioso, S, Del Ben, M, Feole, K, Carbone, M, Pignatelli, P, Violi, F, Angelico, M
Alimentary pharmacology & therapeutics. 2009;(5):444-51
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BACKGROUND Rapid virological response (RVR) is the best predictor of sustained response to standard HCV treatment. AIM: To evaluate predictive factors of RVR. METHODS Sixty-five patients (mean age 52.6 +/- 13.8; 37 genotype-1, and 28 genotypes-2/3) were consecutively treated with pegIFN-alpha 2a or 2b once weekly plus daily ribavirin based on body weight for 24 or 48 weeks, according to genotype. RVR was defined as undetectable HCV-RNA at week 4. RESULTS Twenty-seven percent of patients achieved RVR in genotypes 1 and 60.7% in genotypes 2/3 (P < 0.01). Rapid responders had higher mean serum baseline total and LDL-cholesterol levels (P < 0.01). RVR was 20.0% in the bottom tertile of total cholesterol and 63.6% in the top tertile (P < 0.01). HCV-RNA levels at week 4 were positively correlated with baseline serum insulin (P < 0.01), HOMA-IR (P < 0.01), body mass index (P < 0.05) and number of components of metabolic syndrome (P < 0.01) and negatively correlated with cholesterol levels (P < 0.05). At multivariate analysis, age, LDL-cholesterol, HCV genotype and serum 8-iso-PGF 2 alpha, a marker of oxidative stress, were independent predictors of RVR. CONCLUSIONS Our prospective study supports a role of low serum total and LDL-cholesterol and of oxidative stress as positive independent predictive factors of poor RVR in HCV patients.