Deuruxolitinib Phosphate (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- LEQSELVI
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. 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)
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.
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)].
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)]
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 (Cmax 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 (Cmax and AUC), which may increase the risk of LEQSELVI serious adverse reactions such as thrombosis [see Clinical Pharmacology (12.3)].
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.
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.