DDInter704 DDInter1673
Everolimus is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors Everolimus' effect is solely on the mTORC1 protein and not on the mTORC2 protein.
Simeprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated in patient's with HCV genotype 1 for the treatment of chronic hepatitis C virus (HCV) infection. HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients . Like all NS3/4A inhibitors, simeprevir is a serine protease inhibitor in similarity to and but is classified as a second generation protease inhibitor. This class of antiviral drugs were the first direct acting antivirals approved but are associated with lower cure rates than newer drugs. Broad use of simeprevir occurred when it was used in combination with a newer drug, . Inhibiting HCV NS3/4A protease in a potent and highly specific manner, simeprevir is a direct-acting antiviral agent against the hepatitis C virus. Since the viral protease NS3/4A complex is essential for cleaving the HCV encoded polyprotein into individual viral proteins facilitating replication , the drug blocks the viral replication process. It is shown to display synergistic effects with interferon-α and HCV NS5B inhibitor, and additive effects with ribavirin in HCV replicon cells . Unlike first generation serine protease inhibitors, simprevir has a sightly different resistance profile where limited therapeutic efficacy of the drug is observed with NS3 Q80K polymorphic variants and simeprevir-specific amino acid position of 168 also results in higher treatment failure rates . The observed prevalence of the N3 Q80K polymorphism was 30% in subjects infected with HCV genotype 1a and 0.5% in subjects infected with HCV genotype 1b . According to 2017 American Association for the Study of Liver Diseases (AASLD) and 2015 consensus guidelines from the Canadian Association for the Study of the Liver (CASL), simeprevir can be used as first-line or second-line threapies for treatment-naïve patients as adjunct to sofosbuvir treatment for genotype 1 or PEG-Interferon/ribavirin combination therapy for genotype 1 or 4. The combination therapy of simeprevir and other antiviral agents are initiated in HCV-positive patients with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality . Simeprevir was approved by the FDA in November 2014 and is marketed under the brand name Olysio as oral tablets. Administered once daily with food, 150mg simeprevir capsule is used in combination with in patients with HCV genotype 1 without cirrhosis for 12 week duration. In patients with HCV genotype 1 with compensated cirrhosis, the treatment is directed for 24 week duration. Sustained virologic response 12 weeks after planned end of treatment (SVR12) was achieved in 170/176 (97%) subjects without cirrhosis treated with 12 weeks simeprevir in combination with sofosbuvir (FDA Label). The overall SVR12 was 88% (44/50) in treatment-naïve patients with cirrhosis . Simeprevir is also used in treatment of HCV genotype 4 patients with or without cirrhosis and is taken with and ; this triple therapy allows shortening treatment duration from 48 weeks or longer to 12 or 24 weeks depending on prior response status and presence of HIV-1 co-infection. Prior to initiation of treatment with and , screening for the presence of virus with the NS3 Q80K polymorphism is strongly recommended and if detected, alternative treatment should be considered instead to prevent therapeutic failure. The SVR12 was 83% (29/35) in treatment-naïve patients and 86% (19/22) in relapsing patients.
Everolimus {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Simeprevir
Everolimus {u} (Compound) is included by {v} (Pharmacologic Class) P-Glycoprotein Inhibitors
P-Glycoprotein Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Simeprevir
Everolimus {u} (Compound) causes {v} (Side Effect) Mediastinal disorder
Mediastinal disorder {u} (Side Effect) is caused by {v} (Compound) Simeprevir
Everolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Sirolimus {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Simeprevir
Everolimus {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Sirolimus
Sirolimus {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Simeprevir
Everolimus {u} (Compound) is included by {v} (Pharmacologic Class) P-Glycoprotein Inhibitors
P-Glycoprotein Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Clarithromycin
Clarithromycin {u} may lead to a major life threatening interaction when taken with {v} Simeprevir
Everolimus {u} (Compound) causes {v} (Side Effect) Mediastinal disorder
Mediastinal disorder {u} (Side Effect) is caused by {v} (Compound) Sirolimus
Sirolimus {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Simeprevir
Everolimus {u} (Compound) downregulates {v} (Gene) SORBS3
SORBS3 {u} (Gene) interacts with {v} (Gene) ALB
ALB {u} (Gene) is bound by {v} (Compound) Simeprevir
Everolimus {u} (Compound) resembles {v} (Compound) Sirolimus
Sirolimus {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Simeprevir
Everolimus {u} (Compound) causes {v} (Side Effect) Blood bilirubin increased
Blood bilirubin increased {u} (Side Effect) is caused by {v} (Compound) Aminolevulinic acid
Aminolevulinic acid {u} may lead to a major life threatening interaction when taken with {v} Simeprevir
Everolimus (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Simeprevir (Compound)
Everolimus (Compound) is included by P-Glycoprotein Inhibitors (Pharmacologic Class) and P-Glycoprotein Inhibitors (Pharmacologic Class) includes Simeprevir (Compound)
Everolimus (Compound) causes Mediastinal disorder (Side Effect) and Mediastinal disorder (Side Effect) is caused by Simeprevir (Compound)
Everolimus (Compound) resembles Sirolimus (Compound) and Sirolimus may cause a moderate interaction that could exacerbate diseases when taken with Simeprevir
Everolimus (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Sirolimus (Compound) and Sirolimus may cause a moderate interaction that could exacerbate diseases when taken with Simeprevir
Everolimus (Compound) is included by P-Glycoprotein Inhibitors (Pharmacologic Class) and P-Glycoprotein Inhibitors (Pharmacologic Class) includes Clarithromycin (Compound) and Clarithromycin may lead to a major life threatening interaction when taken with Simeprevir
Everolimus (Compound) causes Mediastinal disorder (Side Effect) and Mediastinal disorder (Side Effect) is caused by Sirolimus (Compound) and Sirolimus may cause a moderate interaction that could exacerbate diseases when taken with Simeprevir
Everolimus (Compound) downregulates SORBS3 (Gene) and SORBS3 (Gene) interacts with ALB (Gene) and ALB (Gene) is bound by Simeprevir (Compound)
Everolimus (Compound) resembles Sirolimus (Compound) and Sirolimus (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Simeprevir (Compound)
Everolimus (Compound) causes Blood bilirubin increased (Side Effect) and Blood bilirubin increased (Side Effect) is caused by Aminolevulinic acid (Compound) and Aminolevulinic acid may lead to a major life threatening interaction when taken with Simeprevir