DDInter1460 DDInter1628
Phenytoin is classified as a hydantoin derivative and despite its narrow therapeutic index, it is one of the most commonly used anticonvulsants.[A33595,A188832,A189219] Since it's introduction about 80 years ago, phenytoin has not only been established as an effective anti-epileptic, but has also been investigated for several other indications such as bipolar disorder, retina protection, and wound healing.[A188826,A188832] Clinicians are advised to initiate therapeutic drug monitoring in patients who require phenytoin since even small deviations from the recommended therapeutic range can lead to suboptimal treatment, or adverse effects.[A189219,A35884] Both parenteral and oral formulations of phenytoin are available on the market.
Ruxolitinib, formerly known as INCB018424 or INC424, is an anticancer drug and a Janus kinase (JAK) inhibitor. It is a potent and selective inhibitor of JAK1 and JAK2, which are tyrosine kinases involved in cytokine signalling and hematopoiesis. Myeloproliferative neoplasms, such as myelofibrosis and polycythemia vera, are often characterized by aberrant activation of the JAK-STAT pathway, leading to abnormal blood cell counts and thrombotic complications. By inhibiting JAK1 and JAK2, ruxolitinib works to block the dysregulated cell signalling pathways and prevents abnormal blood cell proliferation. Due to a large number of patients with myeloproliferative neoplasms who have JAK2 mutations, ruxolitinib was the first ATP-competitive inhibitor of JAK1 and JAK2 ever developed. Ruxolitinib was first approved for the treatment of adult patients with myelofibrosis by the FDA in 2011, followed by EMA's approval in 2012. In 2014, it was approved for the treatment of polycythemia vera in adults who have an inadequate response to or are intolerant of [hydroxyurea] and in 2019, ruxolitinib was approved for use in steroid-refractory acute graft-versus-host disease in adults and children. The topical formulation of ruxolitinib is used to treat atopic dermatitis and vitiligo. It is being investigated for other inflammatory skin conditions. Ruxolitinib has been investigated to treat patients with coronavirus disease 2019 (COVID-19) accompanied by severe systemic hyperinflammation. In phase II clinical trials, ruxolitinib improved chest computed tomography and improved recovery in patients with lymphopenia.[A229713, A229718] However, phase III clinical trials later determined that ruxolitinib was inadequate in meeting its primary endpoint of reducing the number of hospitalized COVID-19 patients who experienced severe complications thus the drug was not approved as a treatment for COVID-19.
Phenytoin {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Phenytoin {u} (Compound) downregulates {v} (Gene) ZDHHC6
ZDHHC6 {u} (Gene) is downregulated by {v} (Compound) Ruxolitinib
Phenytoin {u} (Compound) causes {v} (Side Effect) Anaemia
Anaemia {u} (Side Effect) is caused by {v} (Compound) Ruxolitinib
Phenytoin {u} (Compound) downregulates {v} (Gene) ZDHHC6
ZDHHC6 {u} (Gene) is regulated by {v} (Gene) IRAK1
IRAK1 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Phenytoin {u} may lead to a major life threatening interaction when taken with {v} Nilotinib
Nilotinib {u} (Compound) treats {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is treated by {v} (Compound) Ruxolitinib
Phenytoin {u} may lead to a major life threatening interaction when taken with {v} Bortezomib
Bortezomib {u} (Compound) treats {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is treated by {v} (Compound) Ruxolitinib
Phenytoin {u} may lead to a major life threatening interaction when taken with {v} Nilotinib
Nilotinib {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Phenytoin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Epirubicin
Epirubicin {u} (Compound) treats {v} (Disease) hematologic cancer
hematologic cancer {u} (Disease) is treated by {v} (Compound) Ruxolitinib
Phenytoin {u} may lead to a major life threatening interaction when taken with {v} Bortezomib
Bortezomib {u} (Compound) upregulates {v} (Gene) MAP3K7
MAP3K7 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Phenytoin {u} may lead to a major life threatening interaction when taken with {v} Nilotinib
Nilotinib {u} (Compound) downregulates {v} (Gene) PLK1
PLK1 {u} (Gene) is bound by {v} (Compound) Ruxolitinib
Phenytoin (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ruxolitinib (Compound)
Phenytoin (Compound) downregulates ZDHHC6 (Gene) and ZDHHC6 (Gene) is downregulated by Ruxolitinib (Compound)
Phenytoin (Compound) causes Anaemia (Side Effect) and Anaemia (Side Effect) is caused by Ruxolitinib (Compound)
Phenytoin (Compound) downregulates ZDHHC6 (Gene) and ZDHHC6 (Gene) is regulated by IRAK1 (Gene) and IRAK1 (Gene) is bound by Ruxolitinib (Compound)
Phenytoin may lead to a major life threatening interaction when taken with Nilotinib and Nilotinib (Compound) treats hematologic cancer (Disease) and hematologic cancer (Disease) is treated by Ruxolitinib (Compound)
Phenytoin may lead to a major life threatening interaction when taken with Bortezomib and Bortezomib (Compound) treats hematologic cancer (Disease) and hematologic cancer (Disease) is treated by Ruxolitinib (Compound)
Phenytoin may lead to a major life threatening interaction when taken with Nilotinib and Nilotinib (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ruxolitinib (Compound)
Phenytoin may cause a moderate interaction that could exacerbate diseases when taken with Epirubicin and Epirubicin (Compound) treats hematologic cancer (Disease) and hematologic cancer (Disease) is treated by Ruxolitinib (Compound)
Phenytoin may lead to a major life threatening interaction when taken with Bortezomib and Bortezomib (Compound) upregulates MAP3K7 (Gene) and MAP3K7 (Gene) is bound by Ruxolitinib (Compound)
Phenytoin may lead to a major life threatening interaction when taken with Nilotinib and Nilotinib (Compound) downregulates PLK1 (Gene) and PLK1 (Gene) is bound by Ruxolitinib (Compound)