DDInter458 DDInter1695
Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus _Beauveria nivea_. Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).[L11097,L3734,L11118]
Sofosbuvir (tradename Sovaldi) is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). 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 . Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as sofosbuvir. As a prodrug nucleotide analog, Sofosbuvir is metabolized into its active form as the antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate (also known as GS-461203), which acts as a defective substrate for NS5B (non-structural protein 5B) [synthesis]. NS5B, an RNA-dependent RNA polymerase, is essential for the transcription of Hepatitis C viral RNA and for its high replicative rate and genetic diversity . Sofosbuvir and other direct acting antivirals are therefore very potent options for the treatment of Hepatitis C, as they exhibit a high barrier to the development of resistance . This is an important advantage relative to HCV drugs that target other viral enzymes such as the protease, for which rapid development of resistance has proven to be an important cause of therapeutic failure. In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Sofosbuvir as first line therapy in combination with other antivirals for all six genotypes of Hepatitis C . Depending on the genotype, sofosbuvir is often used in combination with other antivirals such as , , , , , , , , or 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 . Treatment with direct acting antivirals such as sofosbuvir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon- and ribavirin-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects . Since 2014, sofosbuvir has been available as a fixed dose combination product with (tradename Harvoni) used for the treatment of chronic Hepatitis C. Approved in October 2014 by the FDA, Harvoni is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without depending on the level of liver damage or cirrhosis [FDA Label]. When combined together, ledipasvir and sofosbuvir as the combination product Harvoni has been shown to achieve a SVR between 93 and 99% after 12 weeks of treatment . Its use has also proven successful in the treatment of HCV in patients co-infected with HIV . Sofosbuvir is also available as a fixed dose combination product with as the commercially available product Epclusa. First approved in June 2016, Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. Epclusa is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis . Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV [L852, A19626]. Notably, sofosbuvir has come under intense scrutiny since its release to market in 2013. With the price per pill set at $1000, a 12-week treatment can cost upwards of $84,000 per patient .
Cyclosporine {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Sofosbuvir
Cyclosporine {u} (Compound) causes {v} (Side Effect) Infestation NOS
Infestation NOS {u} (Side Effect) is caused by {v} (Compound) Sofosbuvir
Cyclosporine {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Enzalutamide
Enzalutamide {u} may lead to a major life threatening interaction when taken with {v} Sofosbuvir
Cyclosporine {u} (Compound) causes {v} (Side Effect) Infestation NOS
Infestation NOS {u} (Side Effect) is caused by {v} (Compound) Enzalutamide
Enzalutamide {u} may lead to a major life threatening interaction when taken with {v} Sofosbuvir
Cyclosporine {u} (Compound) upregulates {v} (Gene) HAX1
HAX1 {u} (Gene) interacts with {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Sofosbuvir
Cyclosporine {u} (Compound) downregulates {v} (Gene) CSK
CSK {u} (Gene) is regulated by {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Sofosbuvir
Cyclosporine {u} (Compound) upregulates {v} (Gene) MLEC
MLEC {u} (Gene) is regulated by {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Sofosbuvir
Cyclosporine {u} (Compound) downregulates {v} (Gene) SPR
SPR {u} (Gene) regulates {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Sofosbuvir
Cyclosporine {u} (Compound) binds {v} (Gene) CYP2C8
CYP2C8 {u} (Gene) is bound by {v} (Compound) Warfarin
Warfarin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Sofosbuvir
Cyclosporine (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Sofosbuvir (Compound)
Cyclosporine (Compound) causes Infestation NOS (Side Effect) and Infestation NOS (Side Effect) is caused by Sofosbuvir (Compound)
Cyclosporine (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Enzalutamide (Compound) and Enzalutamide may lead to a major life threatening interaction when taken with Sofosbuvir
Cyclosporine (Compound) causes Infestation NOS (Side Effect) and Infestation NOS (Side Effect) is caused by Enzalutamide (Compound) and Enzalutamide may lead to a major life threatening interaction when taken with Sofosbuvir
Cyclosporine (Compound) upregulates HAX1 (Gene) and HAX1 (Gene) interacts with ABCB1 (Gene) and ABCB1 (Gene) is bound by Sofosbuvir (Compound)
Cyclosporine (Compound) downregulates CSK (Gene) and CSK (Gene) is regulated by ABCB1 (Gene) and ABCB1 (Gene) is bound by Sofosbuvir (Compound)
Cyclosporine (Compound) upregulates MLEC (Gene) and MLEC (Gene) is regulated by ABCB1 (Gene) and ABCB1 (Gene) is bound by Sofosbuvir (Compound)
Cyclosporine (Compound) downregulates SPR (Gene) and SPR (Gene) regulates ABCB1 (Gene) and ABCB1 (Gene) is bound by Sofosbuvir (Compound)
Cyclosporine (Compound) binds CYP2C8 (Gene) and CYP2C8 (Gene) is bound by Warfarin (Compound) and Warfarin may cause a moderate interaction that could exacerbate diseases when taken with Sofosbuvir