Leqselvi Disease Interactions

Serious and sometimes fatal infections, including opportunistic infections such as tuberculosis (TB) and reactivation of viral infections (herpes zoster, hepatitis B and C) have been reported in patients receiving treatment with deuruxolitinib. Avoid the use of this drug in patients with any active, serious infection, including localized infections. Prior to treatment consider the risks and benefits in patients with chronic or recurrent infections, exposed to TB, with a history of opportunistic infections, or that have resided or traveled to areas of endemic TB or endemic mycosis. Closely monitor patients for the development of signs and symptoms of infection during and after treatment, and interrupt therapy if a patient develops a new infection or an opportunistic infection. Appropriate antimicrobial therapy should be initiated, and treatment may be resumed once the infection is controlled.

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.

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.

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.

Treatment with deuruxolitinib was associated with an increased incidence of anemia, neutropenia and lymphopenia. Avoid (or interrupt) treatment in patients with hemoglobin less than 8 g/dL, absolute neutrophil count (ANC) less than 1000 cells/mm3, or absolute lymphocyte count (ALC) less than 500 cells/mm3. It is recommended to evaluate patients for abnormal blood cell counts at baseline and thereafter according to routine patient management.

Gastrointestinal perforation has been reported with the use of deuruxolitinib. Monitor patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs). Promptly evaluate patients with new onset abdominal symptoms for early identification of gastrointestinal perforation.

The use of deuruxolitinib is not recommended in patients with severe hepatic impairment. No dose adjustment is required in patients with mild or moderate hepatic impairment. Evaluate baseline liver function and thereafter according to routine patient management.

Deuruxolitinib is not recommended for use in patients with severe renal impairment or end-stage renal disease (eGFR less than 30 mL/min). No adjustment of dosage is required in patients with mild or moderate renal impairment.