deuruxolitinib 8 MG Oral Tablet

INDICATIONS AND USAGE LEQSELVI™ is indicated for the treatment of adult patients with severe alopecia areata. Limitations of Use LEQSELVI is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants. LEQSELVI is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with severe alopecia areata. ( 1 ) Limitations of Use: LEQSELVI is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants. ( 1 )

DOSAGE AND ADMINISTRATION For recommended testing, evaluations, and procedures prior to and during LEQSELVI treatment, see Full Prescribing Information. ( 2.1 ) Recommended dosage is 8 mg twice daily. ( 2.2 ) For treatment interruption for certain adverse reactions, see Full Prescribing Information. ( 2.3 ) 2.1 Recommended Evaluations and Immunizations Prior to and During Treatment Perform the following prior to treatment with LEQSELVI: CYP2C9 genotype determination: Test patients for CYP2C9 variants to determine CYP2C9 genotype. LEQSELVI is contraindicated in patients who are CYP2C9 poor metabolizers (patients with decreased cytochrome P450 (CYP) 2C9 function) [see Contraindications ( 4 )] . An FDA-cleared or -approved test for the detection of CYP2C9 variants to direct the use of LEQSELVI is not currently available. Evaluation for use of concomitant CYP2C9 inhibitors: LEQSELVI is contraindicated in patients taking moderate or strong CYP2C9 inhibitors [see Warnings and Precautions ( 5.6 )] . Active and latent tuberculosis (TB) evaluation: LEQSELVI treatment is not recommended in patients with active TB. For patients with latent TB or those with a negative latent TB test who are at high risk of TB, start preventive therapy for TB prior to LEQSELVI treatment [ see Warnings and Precautions ( 5.1 ) ]. Viral hepatitis screening in accordance with clinical guidelines: LEQSELVI treatment is not recommended in patients with active hepatitis B or hepatitis C. Hepatitis B infection screening: If hepatitis B infection is discovered, follow hepatitis B clinical guidelines, or refer to a liver specialist. Monitor patients for reactivation in accordance with clinical guidelines during treatment [ see Warnings and Precautions ( 5.1 ) ]. Complete blood count (CBC): LEQSELVI treatment is not recommended in patients with an absolute lymphocyte count (ALC) <500 cells/mm 3 absolute neutrophil count (ANC) <1,000 cells/mm 3 , or hemoglobin level <8 g/dl. Monitor complete blood counts periodically during treatment and modify dosage as recommended [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.8 )] . Complete any necessary immunizations, including herpes zoster vaccinations, according to current immunization guidelines prior to LEQSELVI treatment [see Warnings and Precautions ( 5.9 )] . 2.2 Recommended Dosage The recommended dosage of LEQSELVI for the treatment of severe alopecia areata is 8 mg orally twice daily, with or without food [see Clinical Pharmacology ( 12.3 )] . If a dose is missed, skip the missed dose and resume dosing at the next scheduled dose. 2.3 Treatment Interruption and Resumption Serious or Opportunistic Infections If a patient develops a serious or opportunistic infection, interrupt LEQSELVI treatment until the infection is controlled [see Warnings and Precautions ( 5.1 )] . Hematological Abnormalities Recommendations for LEQSELVI treatment interruption for hematologic abnormalities are described in Table 1 [see Warnings and Precautions ( 5.8 )] . Table 1: Recommendations for LEQSELVI Treatment Interruption for Hematologic Abnormalities and Resumption Laboratory Measure Interruption Criterion Resumption Criterion Absolute Lymphocyte Count (ALC) <500 cells/mm 3 ≥500 cells/mm 3 Absolute Neutrophil Count (ANC) <1000 cells/mm 3 ≥1000 cells/mm 3 Hemoglobin <8 g/dL ≥8 g/dL

WARNINGS AND PRECAUTIONS Increased Risk of LEQSELVI-Associated Serious Adverse Reactions in CYP2C9 Poor Metabolizers or with Concomitant Use of Moderate or Strong CYP2C9 Inhibitors : LEQSELVI is contraindicated in patients who are CYP2C9 poor metabolizers or patients taking a moderate or strong CYP2C9 inhibitor. ( 5.6 ) Gastrointestinal Perforations: Monitor patients who may be at increased risk for gastrointestinal perforation. Evaluate promptly patients presenting with new onset abdominal symptoms. ( 5.7 ) Lipid Elevations, Anemia, Neutropenia, and Lymphopenia: Monitor for changes in lipids, hemoglobin, neutrophils, and lymphocytes. ( 5.8 ) Immunizations: Avoid use of live vaccines during or immediately prior to LEQSELVI treatment. ( 5.9 ) 5.1 Serious Infections Serious infections have been reported in subjects with alopecia areata receiving LEQSELVI [see Adverse Reactions ( 6.1 )] . Avoid use of LEQSELVI in patients with an active, serious infection including localized infections. Prior to LEQSELVI treatment, consider the risks and benefits in patients: with chronic or recurrent infection who have been exposed to tuberculosis with a history of a serious or opportunistic infection who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection Closely monitor patients for the development of signs and symptoms of infection during and after treatment with LEQSELVI. If the patient develops a serious infection, interrupt treatment with LEQSELVI until the infection resolves or is adequately treated. If a patient develops a new infection during treatment with LEQSELVI, initiate complete diagnostic testing appropriate for an immunocompromised patient and appropriate antimicrobial therapy. Tuberculosis Evaluate patients for latent and active tuberculosis (TB) infection prior to LEQSELVI treatment. LEQSELVI is not recommended for use in patients with active TB. Treat patients with latent TB before LEQSELVI treatment. Consider anti-TB therapy prior to LEQSELVI treatment in patients with previously untreated latent TB or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individual patient. Monitor patients receiving LEQSELVI for signs and symptoms of active TB during treatment, including patients who tested negative for latent TB infection prior to treatment. Viral Reactivation Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster) were reported in clinical trials with LEQSELVI [see Adverse Reactions ( 6.1 )] . If a patient develops herpes zoster, consider interrupting LEQSELVI treatment until the episode resolves. The impact of LEQSELVI on chronic viral hepatitis reactivation is unknown. Subjects with positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), or hepatitis C virus (HCV) with detectable HCV RNA at screening were excluded from LEQSELVI clinical trials. Perform screening for viral hepatitis before treatment with LEQSELVI. LEQSELVI is not recommended for use in patients with active hepatitis B or hepatitis C (HCV RNA detected). If non-active hepatitis B infection is discovered, monitoring for reactivation or prophylactic treatment is recommended. Follow hepatitis B clinical guidelines or refer to a liver specialist. Hepatitis B viral load (HBV-DNA titer) increase, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, has been reported in subjects with chronic HBV infections receiving JAK inhibitors used to treat inflammatory conditions. The effect of LEQSELVI on viral replication in patients with chronic HBV infection is unknown. 5.2 Mortality In a large, randomized, postmarketing safety trial of another JAK inhibitor in rheumatoid arthritis (RA) subjects 50 years and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in subjects treated with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to and during treatment with LEQSELVI. 5.3 Malignancy and Lymphoproliferative Disorders Malignancies were observed in clinical trials of LEQSELVI [see Adverse Reactions 6.1 )] . In a large, randomized, postmarketing safety trial of another JAK inhibitor in subjects with RA, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in subjects treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in subjects treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this trial, current or past smokers had an additional increased risk of overall malignancies. Consider the benefits and risks for the individual patient prior to and during treatment with LEQSELVI, particularly in patients with a known malignancy (other than successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers. Non-melanoma skin cancers Non-melanoma skin cancers (NMSCs) have been reported in patients treated with LEQSELVI. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. 5.4 Major Adverse Cardiovascular Events (MACE) In a large, randomized, postmarketing safety trial of another JAK inhibitor in subjects with RA 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to and during treatment with LEQSELVI, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Inform patients about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue LEQSELVI in patients that have experienced a myocardial infarction or stroke. 5.5 Thrombosis Thrombosis, including pulmonary embolism (PE), deep vein thrombosis (DVT) and cerebral venous sinus thrombosis (CVT) have been reported in clinical trials of deuruxolitinib [see Adverse Reactions ( 6.1 )] . There was no clear relationship between platelet count elevations and thrombotic events. Thrombosis, including DVT, PE, and arterial thrombosis have been reported in subjects receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In a large, randomized, postmarketing safety trial of another JAK inhibitor in subjects with RA 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. Avoid LEQSELVI in patients who may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue LEQSELVI and evaluate and treat patients appropriately. 5.6 Increased Risk of LEQSELVI-Associated Serious Adverse Reactions in CYP2C9 Poor Metabolizers or with Concomitant Use of Moderate or Strong CYP2C9 Inhibitors Higher plasma concentrations of deuruxolitinib, which may increase the risk of LEQSELVI-associated serious adverse reactions such as thrombosis, may occur when LEQSELVI is used in patients who: Are CYP2C9

CONTRAINDICATIONS LEQSELVI is contraindicated in patients who: Are CYP2C9 poor metabolizers [see Warnings and Precautions ( 5.6 )] . Are on concomitant moderate or strong CYP2C9 inhibitors [see Warnings and Precautions ( 5.6 )] . LEQSELVI is contraindicated in patients: Who are CYP2C9 poor metabolizers. ( 4 ) Using moderate or strong CYP2C9 inhibitors. ( 4 )

Mechanism of Action Deuruxolitinib is a Janus kinase (JAK) inhibitor. JAKs mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression. In an in vitro kinase activity assay, deuruxolitinib had greater inhibitory potency for JAK1, JAK2 and TYK2 relative to JAK3. The relevance of inhibition of JAK enzymes to therapeutic effectiveness is not currently known.