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Hepatitis C
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Rebecca Pierce-Williams, Neil Silverman, Raja Dhanekula, Jonathan M. Fenkel, Danielle Tholey
Historically, treatment consisted of pegylated interferon (PEG-IFN), ribavirin and protease inhibitors. Ribavirin is contraindicated in pregnancy due to teratogenicity concerns. Treatment has changed dramatically since 2011 with the development of DAAs.For any genotype, in a treatment-naïve patient without cirrhosis, the preferred therapy is either 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir.Treatments are associated with few and mild side effects (headache, nausea, fatigue, insomnia).Ongoing research into HCV treatment (ledipasvir/sofosbuvir) during pregnancy is promising, as many women could be cured while receiving prenatal care.Until treatment in pregnancy is approved, women should be referred to a hepatologist in the postpartum treatment for antiviral therapy and long-term follow-up.
Anti-Infective Agents
Published in Radhwan Nidal Al-Zidan, Drugs in Pregnancy, 2020
Risk Summary: The reproduction studies in animals have shown no evidence of fetal harm or impaired fertility. The pregnancy experience in humans is adequate to exhibit that the embryo-fetal risk is nonexistent or very low. However, Sofosbuvir is contraindicated during pregnancy if taken in combination with Ribavirin and peginterferon alfa.
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Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Singh T, Guirquis J, Anthony S, et al. Sofosbuvir-based treatment is safe and effective in patients with chronic hepatitis C infection and end-stage renal disease: a case series. Liver Int. 2016; 36(6): 802–6.
The preclinical discovery and development of molnupiravir for the treatment of SARS-CoV-2 (COVID-19)
Published in Expert Opinion on Drug Discovery, 2022
Pasquale Pagliano, Carmine Sellitto, Tiziana Ascione, Giuliana Scarpati, Veronica Folliero, Ornella Piazza, Gianluigi Franci, Amelia Filippelli, Valeria Conti
Besides these well-investigated nucleoside analogues, other drugs interacting with RdRp have been evaluated in limited trials for coronavirus treatment. Sofosbuvir, a well-known antiviral drug, which has been employed in the treatment of HCV infection, has broad-spectrum antiviral activity against many RNA viruses. It is administered as a prodrug and needs to be converted into a triphosphate form prior to being incorporated into the RNA chain. Based on preliminary data and meta-analysis, sofosbuvir containing regimens allowed a reduction in terms of mortality. Starting from sofosbuvir, other antiviral agents have been developed, one of these is AT-511 (orally administered as the prodrug AT527), which was evaluated in human airway epithelial cells infected with SARS-CoV-2 demonstrating a favorable antiviral effect and low toxicity [48,49]. Table 1 summarizes the nucleoside analogues proposed for COVID-19 treatment and their pharmacodynamics.
Clinical outcomes of sofosbuvir-based antivirals in patients with COVID-19: a systematic review and meta-analysis of randomized trials
Published in Expert Review of Anti-infective Therapy, 2022
Chia Siang Kow, Amaan Javed, Dinesh Ramachandram, Syed Shahzad Hasan
Sofosbuvir–daclatasvir is an effective direct-acting antiviral agent against the hepatitis C virus. Sofosbuvir inhibits NS5B-RdRp, a crucial enzyme in replicating hepatitis C virus, while ledipasvir inhibits NS5A, an essential protein for RdRp function. An in-silico study reported that sofosbuvir and daclatasvir could have theoretical antiviral activity against SARS-CoV-2 due to their predictive ability to bind to RdRp and Mpro with high energy. Therefore, they are attractive to be repurposed for the treatment of COVID-19 [3,4]. Indeed, in an in vitro study [5], sofosbuvir and daclatasvir demonstrated antiviral activity against SARS-CoV-2-infected Huh-7 and Calu-3 cells. In the same study [5], daclatasvir demonstrated antiviral activity against Vero E6-infected cells but not for sofosbuvir. Sofosbuvir has also exhibited neutralizing activity against SARS-CoV-2-infected brain organoids, suggesting its potential protective effects against COVID-19 related neurological complications [6].
Successes, failures, and future prospects of prodrugs and their clinical impact
Published in Expert Opinion on Drug Discovery, 2019
Sofosbuvir is a recently approved antiviral prodrug with has a promising potential. It is a nucleotide analogue and specific inhibitor of hepatitis C viral non-structural protein 5B (NS5B) RNA-dependent polymerase. Original therapeutic options for hepatitis C infections were peginterferon-α and ribavirin. However, with the discovery of protease inhibitors, telaprevir and boceprevir became part of the combination. This combination suffers from high potential for resistance, complicated regimens, and high rates of adverse effects [52]. Sofosbuvir is rapidly absorbed following oral administration with Cmax at ~0.5–2h. It undergoes extensive intracellular metabolism to pharmacologically active uridine triphosphate (GS-461,203) in human hepatocytes. The active metabolite is then incorporated into viral RNA by NS5B polymerase [53]. Several studies have determined that sofosbuvir has a high genetic barrier to resistance [54,55]. Sofosbuvir is now used primarily in combination therapy with ledipasvir, ribavirin, or velpatasvir.