Deuruxolitinib Phosphate

FDA Drug Information • Also known as: Leqselvi

Brand Names: Leqselvi
Route: ORAL
Dosage Form: TABLET, FILM COATED
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS Increased risk of serious bacterial, fungal, viral and opportunistic infections, including tuberculosis (TB), that may lead to hospitalization or death. Interrupt treatment with LEQSELVI if a serious infection occurs until the infection is controlled. LEQSELVI treatment is not recommended in patients with active tuberculosis. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test. ( 5.1 ) Higher rate of all-cause mortality, including sudden cardiovascular death, was observed with another Janus kinase (JAK) inhibitor vs. TNF blockers in rheumatoid arthritis (RA) patients. LEQSELVI is not approved for use in RA patients. ( 5.2 ) Malignancies were reported in patients treated with LEQSELVI. Higher rate of lymphomas and lung cancers was observed with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.3 ) Higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) was observed with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.4 ) Thrombosis, including cerebral venous sinus thrombosis (CVT), deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients treated with LEQSELVI. Increased incidence of pulmonary embolism, venous and arterial thrombosis was observed with another JAK inhibitor vs. TNF blockers. ( 5.5 ) WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) and THROMBOSIS See full prescribing information for complete boxed warning. Increased risk of serious bacterial, fungal, viral and opportunistic infections including tuberculosis (TB), that may lead to hospitalization or death. Interrupt treatment with LEQSELVI if a serious infection occurs until the infection is controlled. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test. ( 5.1 ) Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) vs. TNF blockers in rheumatoid arthritis (RA) patients. LEQSELVI is not approved for use in RA patients. ( 5.2 ) Malignancies have occurred in patients treated with LEQSELVI. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.3 ) Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another Janus kinase inhibitor (JAK) vs. TNF blockers in rheumatoid arthritis (RA) patients. ( 5.4 ) Thrombosis has occurred in patients treated with LEQSELVI. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. ( 5.5 )

Description

11 DESCRIPTION LEQSELVI (deuruxolitinib) tablets contain the phosphate salt of deuruxolitinib, a Janus kinase (JAK) inhibitor, for oral administration. Deuruxolitinib phosphate is a white to off-white crystalline solid with the chemical name 1 H -Pyrazole-1-propanenitrile, β-(cyclopentyl-2,2,3,3,4,4,5,5- d 8 )-4-(7 H -pyrrolo[2,3- d ]pyrimidin-4-yl)-, (β R )-, phosphate (1:1). Deuruxolitinib has high aqueous solubility at low pH. Deuruxolitinib phosphate has a molecular weight of 412.42 g/mol and a molecular formula of C 17 H 13 D 8 N 6 O 4 P. The structural formula is: Each tablet contains 8 mg of deuruxolitinib (equivalent to 10.50 mg of deuruxolitinib phosphate) and the following excipients: colloidal silicon dioxide, lactose monohydrate, low-substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose and povidone. The tablet film coating contains the following excipients: carmine, FD&C blue #2 aluminum lake, glyceryl mono and dicaprylocaprate, polyvinyl alcohol, sodium lauryl sulfate, talc, and titanium dioxide. Chemical Structure

What Is Deuruxolitinib Phosphate Used For?

1 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

2 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions ( 5.1 )] Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions ( 5.3 )] Thrombosis [see Warnings and Precautions ( 5.5 )] Gastrointestinal perforations [see Warnings and Precautions ( 5.7 )] Lipid Elevations, Anemia, Neutropenia and Lymphopenia [see Warnings and Precautions ( 5.8 )] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of LEQSELVI was evaluated in three randomized, placebo-controlled clinical trials (including a dose-ranging trial), two open-label trials, and two long-term extension trials in adult subjects with severe alopecia areata. These subjects had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT) for more than six months. A total of 1,730 subjects with alopecia areata were treated across all trials, representing 1,962.9 patient-years of exposure. There were 974 subjects who were exposed to either LEQSELVI 8 mg or deuruxolitinib 12 mg for at least 1 year and 104 subjects who were exposed for at least 3 years. Deuruxolitinib 12 mg is not approved. Among 1,020 subjects enrolled in the placebo-controlled clinical trials, 640 subjects received LEQSELVI 8 mg twice daily, 380 subjects received deuruxolitinib 12 mg twice daily and 299 subjects received placebo twice daily for up to 24 weeks [see Clinical Studies ( 14 )] . Adverse Reactions occurring at ≥1% in the LEQSELVI 8 mg or deuruxolitinib 12 mg twice daily group and at a higher rate than in the placebo group are presented in Table 2 . A total of 20 (3.1%) of subjects treated with LEQSELVI 8 mg were discontinued from the trials due to adverse reactions. Table 2: Adverse Reactions Reported in ≥1% of Subjects with Alopecia Areata Treated with LEQSELVI 8 mg Twice Daily or Deuruxolitinib 12 mg Twice Daily (and More Frequently than Placebo) in Placebo-Controlled Trials Over 24-Weeks a. %-study size adjusted percentages. b. Acne includes: acne, dermatitis acneiform, and acne pustular. c. Hyperlipidemia includes: blood cholesterol increased, low density lipoprotein increased, blood triglycerides increased, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, and dyslipidaemia. d. Fatigue includes: fatigue, asthenia, hypersomnia, somnolence, and lethargy. e. Skin and soft issue infections includes: folliculitis, impetigo, skin infection, subcutaneous abscess, furuncle, paronychia, and pustule. f. Anemia includes: anemia, hematocrit decreased, hemoglobin decreased, iron deficiency anemia, and red blood cell count decreased. g. Neutropenia includes: neutropenia and neutrophil count decreased. h. Thrombocytosis includes: thrombocytosis and platelet count increased. i. Herpes includes: oral herpes, herpes simplex, genital herpes simplex, and nasal herpes. Placebo N = 299 n (%) a LEQSELVI 8 mg twice daily N = 640 n (%) a Deuruxolitinib 12 mg twice daily N = 380 n (%) a Acne b 13 (4.3) 66 (10.0) 52 (12.6) Headache 30 (9.4) 83 (12.4) 44 (10.5) Nasopharyngitis 21 (6.7) 54 (8.1) 33 (7.7) Blood creatine phosphokinase increased 7 (2.2) 35 (5.3) 27 (7.4) Hyperlipidemia c 10 (3.1) 30 (4.4) 19 (5.2) Fatigue d 12 (3.9) 26 (3.9) 20 (4.9) Skin and soft tissue infections e 2 (0.8) 11 (1.6) 15 (4.0) Anemia f 3...

Drug Interactions

7 DRUG INTERACTIONS Effect of Other Drugs on LEQSELVI Strong CYP3A and moderate or strong CYP2C9 inducers: Avoid concomitant use of LEQSELVI 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 (C max and AUC), which may reduce LEQSELVI efficacy [see Clinical Pharmacology ( 12.3 )] . Moderate or strong CYP2C9 inhibitors: LEQSELVI is contraindicated in patients taking moderate or strong CYP2C9 inhibitors [see Contraindications ( 4 )] . Deuruxolitinib is a CYP2C9 substrate. Concomitant use with a moderate or strong CYP2C9 inhibitor is estimated to increase deuruxolitinib exposure (C max and AUC), which may increase the risk of LEQSELVI serious adverse reactions such as thrombosis [see Clinical Pharmacology ( 12.3 )] . Strong CYP3A4 and moderate or strong CYP2C9 inducers: Avoid concomitant use. ( 7 ) Moderate or strong CYP2C9 inhibitors: Contraindicated. ( 7 )

Contraindications

4 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 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on the findings from animal reproduction studies, deuruxolitinib may cause fetal harm during pregnancy. Available data from pregnancies reported in clinical trials with LEQSELVI 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 (see Data ) . 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. Data Animal Data In an embryo-fetal development study, deuruxolitinib was administered to pregnant rats during the period of organogenesis at oral doses of 15, 30, and 60 mg/kg/day. Reduced fetal weight and increased fetal skeletal malformation were noted at 60 mg/kg/day (4.8 times the MRHD based on AUC comparison) with no maternal toxicity. No embryo-fetal toxicity was observed at doses up to 30 mg/kg/day (equivalent to MRHD based on AUC comparison). In another embryo-fetal development study, deuruxolitinib...

Overdosage

10 OVERDOSAGE There is no experience regarding human overdose with LEQSELVI. There is no specific antidote for overdose with LEQSELVI. Treatment should be symptomatic and supportive and monitor patients for signs and symptoms of adverse reactions [see Adverse Reactions ( 6.1 )] . In case of overdose, consider contacting the Poison Center at 1-800-222-1222 for latest recommendations.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied: LEQSELVI tablets are packaged in white, high-density polyethylene (HDPE) bottles and closed with 24 mm white child-resistant caps with foil liner. Each bottle contains 1 g silica-gel canister. LEQSELVI is available as purple, round, immediate-release tablets debossed with “C” on one side and “8” on the other side: 8 mg: 60 tablets in a bottle; NDC: 47335-108-86 Storage and Handling: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Store in the original bottle to protect from moisture.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.