Simeprevir and Sofosbuvir for Treatment of Chronic Hepatitis C Infection

Childs‐Kean, Lindsey M.; Hand, Elizabeth

doi:10.1016/j.clinthera.2014.12.012

Cited by 30 publications

(26 citation statements)

References 21 publications

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“…Ledipasvir solubility can be reduced at higher gastric pH, so the concomitant administration of medications such as H2 receptor blockers or proton pump inhibitors may decrease its concentration. [37][38][39] Similarly, concurrent administration of Velpatasvir/ Sofosbuvir with the proton pump inhibitor omeprazole is not recommended, or taken 4 hours before it is necessary, as the concentration and activity of velpatasvir is reduces with increase in gastric pH value.…”

Section: Pharmacologic Basis Of Direct Acting Antiviral Drug Interactionmentioning

confidence: 99%

Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction

Geddawy

Ibrahim

Elbahie

et al. 2017

Journal of Translational Internal Medicine

151

103

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Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction.

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Section: Pharmacologic Basis Of Direct Acting Antiviral Drug Interactionmentioning

confidence: 99%

Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction

Geddawy

Ibrahim

Elbahie

et al. 2017

Journal of Translational Internal Medicine

151

103

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“…Sofosbuvir and GS-33100, its inactive nucleoside metabolite, neither inhibit nor induce the CYP enzyme system; therefore, these molecules are not expected to affect the concentrations of methadone [7]. Conversely, simeprevir is metabolized primarily by CYP3A, is a substrate for several drug transporters including the organic anion transporting polypeptides, and is a mild inhibitor of CYP1A2 and intestinal CYP3A [7]. It is, therefore, theoretically susceptible to DDIs with drugs that share the same pathways of absorption, transport, or metabolism, as methadone.…”

Section: Sirmentioning

confidence: 98%

“…However, evidence is available that it mainly undergoes oxidative metabolism to inactive metabolites by cytochrome P450 3A (CYP3A), by CYP2D6, and, to a lesser extent, by CYP2C8, CYP2B6, and CYP2C19 [6]. Sofosbuvir and GS-33100, its inactive nucleoside metabolite, neither inhibit nor induce the CYP enzyme system; therefore, these molecules are not expected to affect the concentrations of methadone [7]. Conversely, simeprevir is metabolized primarily by CYP3A, is a substrate for several drug transporters including the organic anion transporting polypeptides, and is a mild inhibitor of CYP1A2 and intestinal CYP3A [7].…”

mentioning

confidence: 99%

Simeprevir-induced severe withdrawal syndrome in an HIV/HCV coinfected patient on long-term maintenance methadone therapy

Gervasoni

Peri

Cattaneo

et al. 2015

Eur J Clin Pharmacol

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Sir,The availability of second-generation direct-acting antivirals (DAAs) has further changed the treatment of chronic hepatitis C virus (HCV) infection [1]. The combination of simeprevir and sofosbuvir with or without ribavirin led to sustained virological response (SVR12 rates) close to 90 % in chronic HCV genotype 1 and 4 infected patients and was overall well tolerated [2,3]. Similar results have also been recently observed in HCV patients who are coinfected with human immunodeficiency virus (HIV) [4], which are, however, at higher risk of clinically relevant drug-to-drug interactions (DDI). Here, we report a case of an HIV/HCV patient on HAART and stable methadone maintenance therapy who developed symptoms of opioid withdrawal early after starting the combination of simeprevir and sofosbuvir with ribavirin.A 54-year-old white HIV/HCV infected man was admitted to our outpatient service with shakiness, diaphoresis, body aches, abdominal pain, anxiety, insomnia, and asthenia. He reported that the symptoms had started the previous day. Six days before, the patient had started taking simeprevir 150 mg/day, sofosbuvir 400 mg/day, and ribavirin 800 mg/day to treat chronic HCV genotype 4c/4d infection. The patient was on tenofovir/emtricitabine and raltegravir as antiretroviral therapy and was given methadone at 70 mg/day since 1990 for maintenance of former heroin addiction. No other comedications were reported.Liver function tests and haemoglobin were similar to those prior to the start of DAAs. The patient was diagnosed with methadone withdrawal syndrome. A blood sample drawn the same day retrieved a methadone plasma trough concentration of 300 ng/mL, which was in the usual narcotic stabilization range of 50-1000 ng/mL [5]. The patient was stabilized after administration of alprazolam and an increase in methadone dosage to 80 mg/day. Methadone plasma trough concentrations measured 4 days after the increase in the dose was 365 ng/mL. The dosage of methadone was further increased to 90 mg/day in the next weeks and the patient was fully stabilized.The metabolism of methadone, commonly used as opioid substitution in patients with a history of drug addiction, is not completely understood. However, evidence is available that it mainly undergoes oxidative metabolism to inactive metabolites by cytochrome P450 3A (CYP3A), by CYP2D6, and, to a lesser extent, by CYP2C8, CYP2B6, and CYP2C19 [6]. Sofosbuvir and GS-33100, its inactive nucleoside metabolite, neither inhibit nor induce the CYP enzyme system; therefore, these molecules are not expected to affect the concentrations of methadone [7]. Conversely, simeprevir is metabolized primarily by CYP3A, is a substrate for several drug transporters including the organic anion transporting polypeptides, and is a mild inhibitor of CYP1A2 and intestinal CYP3A [7]. It is, therefore, theoretically susceptible to DDIs with drugs that share the same pathways of absorption, transport, or metabolism,

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“…Raltegravir, maravirok, rilpivirin, tenofovir, emtrisitabin, lamivudin ve abakavirin SMV ile etkileşimi yoktur; dolayısıyla SMV alan hastalarda güvenli bir şekilde kullanılabilirler. SMV ile birlikte alınan bazı antiaritmikler, varfarin, kalsiyum kanal blokerleri, HMG KoA-redük-taz inhibitörleri ve sedatif/anksiyolitiklerde doz ayarlaması gerekmektedir (39,67,89,91).…”

Section: Asunaprevir Ve Daklatasvirunclassified

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases-2017 Update

Aygen¹,

Demirtürk²,

Türker³

et al. 2017

Klimik Dergisi

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Simeprevir and Sofosbuvir for Treatment of Chronic Hepatitis C Infection

Cited by 30 publications

References 21 publications

Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction

Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction

Simeprevir-induced severe withdrawal syndrome in an HIV/HCV coinfected patient on long-term maintenance methadone therapy

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases-2017 Update

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