Drug Interaction Report

Fedratinib has a moderate potential interaction with Anemia.

Adverse hematologic effects including neutropenia, thrombocytopenia, and anemia have been associated with the use of fedratinib. Therapy with fedratinib should only be initiated in patients with a baseline platelet count of at least 50 x 10(9)/L. CBC counts should be monitored at baseline and every 3 months thereafter; treatment should be modified based on platelet levels and active bleeding.

Fedratinib has a moderate potential interaction with Bleeding Associated with Coagulation Defect.

Adverse hematologic effects including neutropenia, thrombocytopenia, and anemia have been associated with the use of fedratinib. Therapy with fedratinib should only be initiated in patients with a baseline platelet count of at least 50 x 10(9)/L. CBC counts should be monitored at baseline and every 3 months thereafter; treatment should be modified based on platelet levels and active bleeding.

Fedratinib has a moderate potential interaction with Bleeding Disorder.

Adverse hematologic effects including neutropenia, thrombocytopenia, and anemia have been associated with the use of fedratinib. Therapy with fedratinib should only be initiated in patients with a baseline platelet count of at least 50 x 10(9)/L. CBC counts should be monitored at baseline and every 3 months thereafter; treatment should be modified based on platelet levels and active bleeding.

Fedratinib has a major potential interaction with Cardiovascular Conditions and Disorders.

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

Ustekinumab has a major potential interaction with High Blood Pressure.

The use of ustekinumab may cause posterior leukoencephalopathy syndrome. One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed in clinical studies of psoriasis and psoriatic arthritis. No cases of RPLS were observed in clinical studies of Crohn's disease. Conditions with which it has been associated include preeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy. Caution and close monitoring is advised when prescribing this agent to patients at risk of RPLS. It is recommended to administer appropriate treatment and discontinue therapy if RPLS is suspected.

Ustekinumab has a moderate potential interaction with History, Tuberculosis.

Before initiating certain interleukin inhibitors, patients should be screened for latent tuberculosis infection with a tuberculin skin test. Do not administer these agents to patients with an active tuberculosis infection. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy. Anti-tuberculosis therapy should be considered prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection.

Ustekinumab has a major potential interaction with Immunodeficiency.

The use of ustekinumab may cause posterior leukoencephalopathy syndrome. One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed in clinical studies of psoriasis and psoriatic arthritis. No cases of RPLS were observed in clinical studies of Crohn's disease. Conditions with which it has been associated include preeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy. Caution and close monitoring is advised when prescribing this agent to patients at risk of RPLS. It is recommended to administer appropriate treatment and discontinue therapy if RPLS is suspected.

Ustekinumab has a moderate potential interaction with Infection.

There have been reports of serious infections, including infections with opportunistic pathogens, and reactivation of latent infections in patients receiving interleukin inhibitors. Treatment with these agents should not be initiated in patients with an active infection until the infection resolves or is adequately treated. Caution is recommended when considering the use of interleukin inhibitors in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections.

Ustekinumab has a major potential interaction with Posterior Reversible Encephalopathy Syndrome.

The use of ustekinumab may cause posterior leukoencephalopathy syndrome. One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed in clinical studies of psoriasis and psoriatic arthritis. No cases of RPLS were observed in clinical studies of Crohn's disease. Conditions with which it has been associated include preeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy. Caution and close monitoring is advised when prescribing this agent to patients at risk of RPLS. It is recommended to administer appropriate treatment and discontinue therapy if RPLS is suspected.

Fedratinib has a moderate potential interaction with Renal Dysfunction.

Due to potential increase of exposure, patients with preexisting-existing moderate renal impairment require more intensive safety monitoring, and if necessary, dose modifications based on adverse reactions when treated with fedratinib. Reduce fedratinib dose when administered to patients with severe renal impairment (CrCl 15 mL/min to 29 mL/min by Cockcroft-Gault). No modification of the starting dose is recommended for patients with mild to moderate renal impairment (CrCl 30 mL/min to 89 mL/min by Cockcroft-Gault).

Ustekinumab has a major potential interaction with Skin Cancer.

In clinical trials malignancies have been observed in patients receiving ustekinumab. Patients should be monitored for non-melanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Caution should be exercised when considering ustekinumab for the treatment of patients with a history of malignancy, those who have a known malignancy, or in continuing treatment in patients who develop malignancy while receiving this agent.

Fedratinib has a major potential interaction with Smoking.

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

Fedratinib has a major potential interaction with Smoking.

Malignancies (including lymphomas and solid tumors) have been reported in patients treated with tofacitinib, baricitinib, upadacitinib, deuruxolitinib and other Janus kinase (JAK) inhibitors used to treat inflammatory conditions. Patients who are current or past smokers are at additional increased risk of malignancies. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, pacritinib, and fedratinib. Before starting or continuing therapy, the benefits and risks for the individual patient should be considered, especially in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), patients who develop a malignancy during therapy, and patients who are current or past smokers. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Fedratinib has a major potential interaction with Thrombotic/Thromboembolic Disorder.

Thrombosis (including deep venous thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, and arterial thrombosis) has occurred in patients treated for inflammatory conditions with Janus kinase (JAK) inhibitors, including baricitinib, tofacitinib, deuruxolitinib and upadacitinib. Many of these adverse events were serious and some resulted in death. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, fedratinib, and pacritinib. In general, JAK inhibitors should be avoided in patients who may be at increased risk of thrombosis. Tofacitinib should be used at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response when treating ulcerative colitis. If symptoms of thrombosis occur in any patients receiving JAK inhibitors, treatment should be discontinued and patients should be evaluated promptly and treated appropriately.

Ustekinumab has a major potential interaction with Toxemia of pregnancy.

The use of ustekinumab may cause posterior leukoencephalopathy syndrome. One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed in clinical studies of psoriasis and psoriatic arthritis. No cases of RPLS were observed in clinical studies of Crohn's disease. Conditions with which it has been associated include preeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy. Caution and close monitoring is advised when prescribing this agent to patients at risk of RPLS. It is recommended to administer appropriate treatment and discontinue therapy if RPLS is suspected.

Ustekinumab has a moderate potential interaction with Tuberculosis, Active.

Before initiating certain interleukin inhibitors, patients should be screened for latent tuberculosis infection with a tuberculin skin test. Do not administer these agents to patients with an active tuberculosis infection. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy. Anti-tuberculosis therapy should be considered prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection.

Ustekinumab has a moderate potential interaction with Tuberculosis, Latent.

Before initiating certain interleukin inhibitors, patients should be screened for latent tuberculosis infection with a tuberculin skin test. Do not administer these agents to patients with an active tuberculosis infection. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy. Anti-tuberculosis therapy should be considered prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection.

Ustekinumab has a moderate potential interaction with Vaccination.

Patients requiring non-live vaccination during a course of ustekinumab may not be protected from the vaccine as the immune response might not be sufficient to prevent the disease. It is recommended to be up-to-date with all required immunizations, as recommended by current immunization guidelines, before initiating therapy with ustekinumab. BCG vaccines should not be given during treatment with ustekinumab or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving ustekinumab because of the potential risk for shedding from the household contact and transmission to patient.

Fedratinib has a major potential interaction with Vitamin B1 Deficiency.

Serious and fatal encephalopathy, including Wernicke's disease, has occurred in patients treated with fedratinib. Wernicke's encephalopathy is a neurologic emergency. Assess thiamine levels in all patients prior to starting treatment, periodically during treatment, and as clinically indicated. Do not start fedratinib in patients with thiamine deficiency; replete thiamine prior to treatment initiation. If encephalopathy is suspected, immediately discontinue fedratinib and initiate parenteral thiamine. Patients who develop any change in their mental status during treatment, including confusion or memory impairment, should be evaluated for potential encephalopathy (e.g., neurologic examination, thiamine level assessment, imaging). Monitor until symptoms resolve or improve and thiamine levels normalize.