Brand name: LEQSELVI™
Drug class: Janus Kinase Inhibitors

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Introduction

Deuruxolitinib phosphate is a Janus kinase (JAK) inhibitor.

Uses for Deuruxolitinib Phosphate

Deuruxolitinib has the following uses:

Deuruxolitinib is indicated for the treatment of adults with severe alopecia areata.

Deuruxolitinib is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.

Deuruxolitinib Phosphate Dosage and Administration

General

Deuruxolitinib phosphate is available in the following dosage form(s) and strength(s):

Tablets: 8 mg (of deuruxolitinib)

Dosage

Adults

Dosage and Administration

• Perform the recommended evaluations prior to and during treatment including CYP2C9 genotype determination, evaluation for concomitant CYP2C9 inhibitors, viral hepatitis and TB screening, and complete blood count (CBC).

• Complete any necessary immunizations, including herpes zoster vaccinations, according to current immunization guidelines prior to deuruxolitinib treatment.

• The recommended dosage of deuruxolitinib for the treatment of severe alopecia areata in adults is 8 mg orally twice daily, with or without food.

• See Full Prescribing Information for recommendations on treatment interruption for adverse effects.

Cautions for Deuruxolitinib Phosphate

Contraindications

• Patients who are CYP2C9 poor metabolizers.

• Patients on concomitant moderate or strong CYP2C9 inhibitors.

Warnings/Precautions

Warnings

Serious Infections

Serious infections have been reported in subjects with alopecia areata receiving deuruxolitinib. Avoid use of deuruxolitinib in patients with an active, serious infection including localized infections. Prior to deuruxolitinib treatment, consider the risks and benefits in patients with chronic or recurrent infection; patients who have been exposed to tuberculosis; patients with a history of a serious or opportunistic infection; patients who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or patients 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 deuruxolitinib. If a patient develops a serious infection, interrupt treatment with deuruxolitinib until the infection resolves or is adequately treated. If a patient develops a new infection during treatment with deuruxolitinib, initiate complete diagnostic testing appropriate for an immunocompromised patient and appropriate antimicrobial therapy.

Evaluate patients for latent and active tuberculosis (TB) infection prior to deuruxolitinib treatment. Deuruxolitinib is not recommended for use in patients with active TB. Treat patients with latent TB before deuruxolitinib treatment. Consider anti-TB therapy prior to deuruxolitinib 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 deuruxolitinib for signs and symptoms of active TB during treatment, including patients who tested negative for latent TB infection prior to treatment.

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster) were reported in clinical trials with deuruxolitinib. If a patient develops herpes zoster, consider interrupting deuruxolitinib treatment until the episode resolves. The impact of deuruxolitinib 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 deuruxolitinib clinical trials. Perform screening for viral hepatitis before treatment with deuruxolitinib. Deuruxolitinib 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 deuruxolitinib on viral replication in patients with chronic HBV infection is unknown.

Mortality

In a large, randomized, postmarketing safety trial of another JAK inhibitor in rheumatoid arthritis (RA), subjects 50 years of age 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 deuruxolitinib.

Malignancy and Lymphoproliferative Disorders

Malignancies were observed in clinical trials of deuruxolitinib. 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 deuruxolitinib, 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 (NMSCs) have been reported in patients treated with deuruxolitinib. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

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 deuruxolitinib, 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 deuruxolitinib in patients that have experienced a MI or stroke.

Thrombosis

Thrombosis, including pulmonary embolism (PE), deep-vein thrombosis (DVT) and cerebral venous sinus thrombosis (CVT) have been reported in clinical trials of deuruxolitinib. 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 deuruxolitinib in patients who may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue deuruxolitinib and evaluate and treat patients appropriately.

Increased Risk of Deuruxolitinib-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 deuruxolitinib-associated serious adverse reactions such as thrombosis, may occur when the drug is used in patients who are CYP2C9 poor metabolizers or patients who are on a concomitant moderate or strong CYP2C9 inhibitor.

Prior to deuruxolitinib treatment, test patients for CYP2C9 variants to determine if they are poor metabolizers. An FDA-cleared or FDA-approved test for the detection of CYP2C9 variants to direct the use of deuruxolitinib is not currently available. Deuruxolitinib is contraindicated in patients who are CYP2C9 poor metabolizers or patients who are on concomitant moderate or strong CYP2C9 inhibitors.

GI Perforations

GI perforations have been reported in clinical trials with deuruxolitinib. Monitor patients treated with deuruxolitinib who may be at increased risk for GI perforation (e.g., patients with a history of diverticulitis). Evaluate promptly patients presenting with new onset abdominal symptoms for early identification of GI perforation.

Lipid Elevations, Anemia, Neutropenia, and Lymphopenia

Perform a CBC prior to and periodically during treatment with deuruxolitinib.

Treatment with deuruxolitinib was associated with increases in triglycerides and total cholesterol, including HDL-C and LDL-C. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Perform assessment of lipid parameters at baseline and periodically during treatment with deuruxolitinib. Manage patients according to clinical guidelines for hyperlipidemia.

Treatment with deuruxolitinib was associated with an increased incidence of anemia (hemoglobin less than 8 g/dL) compared to placebo. Avoid or interrupt deuruxolitinib treatment in patients with hemoglobin less than 8 g/dL.

Treatment with deuruxolitinib was associated with an increased incidence of neutropenia (ANC less than 1000 cells/mm³) compared to placebo. Avoid or interrupt deuruxolitinib treatment in patients with an ANC less than 1,000 cells/mm³.

Treatment with deuruxolitinib was associated with an increased incidence of lymphopenia (ALC less than 500 cells/mm³ ) compared to placebo. Avoid or interrupt deuruxolitinib treatment in patients with an ALC less than 500 cells/mm³.

Immunizations

Prior to deuruxolitinib treatment, complete all necessary immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in accordance with current immunization guidelines. Avoid use of live vaccines during or immediately prior to deuruxolitinib treatment.

Specific Populations

Pregnancy

Based on the findings from animal reproduction studies, deuruxolitinib may cause fetal harm during pregnancy. Available data from pregnancies reported in clinical trials with deuruxolitinib are not sufficient to evaluate for a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of deuruxolitinib to pregnant rats during the period of organogenesis at a dose 4.8 times the maximum recommended human dose (MRHD) resulted in reduced fetal weight and increased skeletal malformation. Oral administration of deuruxolitinib to pregnant rabbits during the period of organogenesis at a dose 0.3 times the MRHD resulted in maternal toxicity, reduced fetal weight, and increased post-implantation loss. Oral administration of deuruxolitinib to pregnant rats during pregnancy and lactation periods at a dose 5 times the MRHD resulted in maternal toxicity, decreased pup survival, and adverse effects on postnatal development. Advise pregnant women of the potential risk to a fetus. The background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects is 2 to 4% of the general population and miscarriage occurs in 15 to 20% of clinically recognized pregnancies.

Lactation

There are no data on the presence of deuruxolitinib in human milk, the effects on the breast-fed infant, or the effects on milk production. Deuruxolitinib was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment with deuruxolitinib and for one day after the last dose (approximately 5 to 6 elimination half-lives).

Females and Males of Reproductive Potential

Based on animal studies, deuruxolitinib may cause fetal harm when administered during pregnancy. Consider pregnancy planning and prevention for females of reproductive potential.

Pediatric Use

The safety and effectiveness of deuruxolitinib have not been established in pediatric patients.

Geriatric Use

Of the 600 subjects treated with deuruxolitinib 8 mg in phase 3 clinical trials, 2 (0.3%) were 65 years of age or older. Clinical trials of deuruxolitinib did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

Hepatic Impairment

Deuruxolitinib is not recommended for use in patients with severe hepatic impairment (Child Pugh C). No adjustment of dosage is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. The effect of severe hepatic impairment on deuruxolitinib pharmacokinetics is unknown.

Renal Impairment

Deuruxolitinib is not recommended for use in patients with severe renal impairment or end-stage renal disease (eGFR < 30 ml/min). No adjustment of dosage is required in patients with mild or moderate renal impairment. The effect of severe renal impairment on deuruxolitinib pharmacokinetics is unknown.

CYP2C9 Poor Metabolizers

Based on modeling, higher exposure of deuruxolitinib in patients who are CYP2C9 poor metabolizers is expected, which may increase the risk of deuruxolitinib-associated serious adverse reactions. Before initiation of treatment with deuruxolitinib, test patients to determine CYP2C9 genotype. An FDA-cleared or FDA-approved test for the detection of CYP2C9 variants to direct the use of deuruxolitinib is not currently available.

Common Adverse Effects

Most common adverse reactions (≥1%) are headache, acne, nasopharyngitis, blood creatine phosphokinase increased, hyperlipidemia, fatigue, weight increased, lymphopenia, thrombocytosis, anemia, skin and soft tissue infections, neutropenia, and herpes.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Strong CYP3A and moderate or strong CYP2C9 inducers: Avoid concomitant use of deuruxolitinib with strong CYP3A and moderate or strong CYP2C9 inducers. Deuruxolitinib is a CYP2C9 and CYP3A substrate. Concomitant use with a strong CYP3A and moderate or strong CYP2C9 inducer decreases deuruxolitinib exposure (Cmax and AUC), which may reduce deuruxolitinib efficacy.

Moderate or strong CYP2C9 inhibitors: Deuruxolitinib is contraindicated in patients taking moderate or strong CYP2C9 inbibitors. Deuruxolitinib is a CYP2C9 substrate. Concomitant use with a moderate or strong CYP2C9 inhibitor is estimated to increase deuruxolitinib exposure (Cmax and AUC), which may increase the risk of deuruxolitinib serious adverse reactions such as thrombosis.

Actions

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.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).

• Advise patients that they are more likely to develop infections when taking deuruxolitinib. Advise patients that the risk of herpes zoster is increased in patients treated with deuruxolitinib and some cases can be serious. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection.

• Inform patients that deuruxolitinib may increase the risk of developing certain cancers, including skin cancers, and that periodic skin examinations should be performed while using deuruxolitinib. Instruct patients to inform their healthcare provider if they have ever had any type of cancer.

• Inform patients that deuruxolitinib may increase the risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events.

• Advise patients that events of DVT, PE and CVT have been reported in clinical trials with deuruxolitinib. Instruct patients to seek immediate medical attention if they develop any signs or symptoms of a DVT, PE, or CVT.

• Increased risk of deuruxolitinib-associated serious adverse reactions in CYP2C9 poor metabolizers or with concomitant use of moderate or strong CYP2C9 Inhibitors. Advise patients to inform their healthcare providers of all medications they are taking, including prescription medicines, OTC drugs, vitamins, and herbal products (e.g., St. John's wort).

• Inform patients that GI perforations have been reported in clinical trials with deuruxolitinib. Instruct patients to seek medical care immediately if they experience new onset of abdominal pain, fever, chills, nausea, or vomiting.

• Inform patients that deuruxolitinib may affect certain lab tests, and that blood tests are required before and during deuruxolitinib treatment.

• Advise patients that vaccination with live vaccines is not recommended during or immediately prior to deuruxolitinib treatment. Instruct patients to inform their healthcare practitioner that they are taking deuruxolitinib prior to a potential vaccination.

• Advise pregnant patients and patients of reproductive potential of the potential risk to a fetus and to inform their healthcare provider if they are pregnant or plan to become pregnant during treatment with deuruxolitinib. Inform patients to report their pregnancy to Sun Pharmaceutical Industries, Inc at 1-800-818-4555.

• Advise patients not to breastfeed during treatment with deuruxolitinib and for one day after the last dose.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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