DDInter1233 DDInter841
Mitotane is an adrenolytic isomer of the insecticide dichlorodiphenyldichloroethane (DDD) - itself a metabolite of dichlorodiphenyltrichloroethane (DDT) - that inhibits cells of the adrenal cortex and their production of hormones. It has been in use since 1959 for the treatment of inoperable adrenocortical carcinoma and is used off-label for the management of Cushing's syndrome.
Grazoprevir 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 Grazoprevir. Grazoprevir is an inhibitor of NS3/4A, a serine protease enzyme, encoded by HCV genotypes 1 and 4 [synthesis]. These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS3, NS4A, NS4B, NS5A and NS5B [FDA Label]. The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs . Subtitutions at amino acid positions 155, 156, or 168 are known to confer resistance. The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself. Despite this disadvantage Grazoprevir is still effective against HCV particularly when paired with . 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 Grazoprevir as first line therapy in combination with for genotypes 1a, 1b, and 4 of Hepatitis C . Grazoprevir and are used with or without 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 . Grazoprevir is available as a fixed dose combination product with (tradename Zepatier) used for the treatment of chronic Hepatitis C. Approved in January 2016 by the FDA, Zepatier is indicated for the treatment of HCV genotypes 1 and 4 with or without depending on the the presence of resistance associated amino acid substitutions in the NS5A protein and previous treatment failure with , , , or other NS3/4A inhibitors like , , or [FDA Label]. When combined together, Grazoprevir and as the combination product Zepatier have been shown to achieve a SVR between 94% and 97% for genotype 1 and 97% and 100% for genotype 4 after 12 weeks of treatment . It can be used in patients with compensated cirrhosis, human immunodeficiency virus co-infection, or severe kidney disease.
Mitotane {u} (Compound) is included by {v} (Pharmacologic Class) Cytochrome P450 3A4 Inducers
Cytochrome P450 3A4 Inducers {u} (Pharmacologic Class) includes {v} (Compound) Aprepitant
Aprepitant {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Grazoprevir
Mitotane {u} (Compound) causes {v} (Side Effect) Haematuria
Haematuria {u} (Side Effect) is caused by {v} (Compound) Aprepitant
Aprepitant {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Grazoprevir
Mitotane {u} (Compound) is included by {v} (Pharmacologic Class) Cytochrome P450 3A4 Inducers
Cytochrome P450 3A4 Inducers {u} (Pharmacologic Class) includes {v} (Compound) Enzalutamide
Enzalutamide {u} may lead to a major life threatening interaction when taken with {v} Grazoprevir
Mitotane {u} (Compound) causes {v} (Side Effect) Osteoarthritis
Osteoarthritis {u} (Side Effect) is caused by {v} (Compound) Dexamethasone
Dexamethasone {u} may lead to a major life threatening interaction when taken with {v} Grazoprevir
Mitotane {u} (Compound) upregulates {v} (Gene) EIF4EBP1
EIF4EBP1 {u} (Gene) is upregulated by {v} (Compound) Vemurafenib
Vemurafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Grazoprevir
Mitotane {u} (Compound) upregulates {v} (Gene) EIF4EBP1
EIF4EBP1 {u} (Gene) is upregulated by {v} (Compound) Pazopanib
Pazopanib {u} may lead to a major life threatening interaction when taken with {v} Grazoprevir
Mitotane {u} (Compound) resembles {v} (Compound) Chlorpheniramine
Chlorpheniramine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Vemurafenib
Vemurafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Grazoprevir
Mitotane {u} (Compound) resembles {v} (Compound) Chlorpheniramine
Chlorpheniramine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Eluxadoline
Eluxadoline {u} may lead to a major life threatening interaction when taken with {v} Grazoprevir
Mitotane {u} (Compound) downregulates {v} (Gene) HMGCR
HMGCR {u} (Gene) is upregulated by {v} (Compound) Sunitinib
Sunitinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Grazoprevir
Mitotane {u} (Compound) downregulates {v} (Gene) HMGCR
HMGCR {u} (Gene) is bound by {v} (Compound) Rosuvastatin
Rosuvastatin {u} may lead to a major life threatening interaction when taken with {v} Grazoprevir
Mitotane (Compound) is included by Cytochrome P450 3A4 Inducers (Pharmacologic Class) and Cytochrome P450 3A4 Inducers (Pharmacologic Class) includes Aprepitant (Compound) and Aprepitant may cause a moderate interaction that could exacerbate diseases when taken with Grazoprevir
Mitotane (Compound) causes Haematuria (Side Effect) and Haematuria (Side Effect) is caused by Aprepitant (Compound) and Aprepitant may cause a moderate interaction that could exacerbate diseases when taken with Grazoprevir
Mitotane (Compound) is included by Cytochrome P450 3A4 Inducers (Pharmacologic Class) and Cytochrome P450 3A4 Inducers (Pharmacologic Class) includes Enzalutamide (Compound) and Enzalutamide may lead to a major life threatening interaction when taken with Grazoprevir
Mitotane (Compound) causes Osteoarthritis (Side Effect) and Osteoarthritis (Side Effect) is caused by Dexamethasone (Compound) and Dexamethasone may lead to a major life threatening interaction when taken with Grazoprevir
Mitotane (Compound) upregulates EIF4EBP1 (Gene) and EIF4EBP1 (Gene) is upregulated by Vemurafenib (Compound) and Vemurafenib may cause a moderate interaction that could exacerbate diseases when taken with Grazoprevir
Mitotane (Compound) upregulates EIF4EBP1 (Gene) and EIF4EBP1 (Gene) is upregulated by Pazopanib (Compound) and Pazopanib may lead to a major life threatening interaction when taken with Grazoprevir
Mitotane (Compound) resembles Chlorpheniramine (Compound) and Chlorpheniramine may cause a moderate interaction that could exacerbate diseases when taken with Vemurafenib and Vemurafenib may cause a moderate interaction that could exacerbate diseases when taken with Grazoprevir
Mitotane (Compound) resembles Chlorpheniramine (Compound) and Chlorpheniramine may cause a moderate interaction that could exacerbate diseases when taken with Eluxadoline and Eluxadoline may lead to a major life threatening interaction when taken with Grazoprevir
Mitotane (Compound) downregulates HMGCR (Gene) and HMGCR (Gene) is upregulated by Sunitinib (Compound) and Sunitinib may cause a moderate interaction that could exacerbate diseases when taken with Grazoprevir
Mitotane (Compound) downregulates HMGCR (Gene) and HMGCR (Gene) is bound by Rosuvastatin (Compound) and Rosuvastatin may lead to a major life threatening interaction when taken with Grazoprevir