Posology The recommended dosage of Leqselvi for the treatment of severe alopecia areata is 8 mg orally twice daily, with or without food. If a dose is missed, skip the missed dose and resume dosing at the next scheduled dose. Serious or opportunistic infections If a patient develops a serious or opportunistic infection, interrupt Leqselvi treatment until the infection is controlled.
Haematologic abnormalities Recommendations for Leqselvi treatment interruption for haematologic abnormalities are described in Table 1.
Table 1:
Recommendations for Leqselvi Treatment Interruption for Haematologic Abnormalities and Resumption Laboratory Measure Interruption Criterion Resumption Criterion Absolute Lymphocyte Count (ALC) <500 cells/mm3 ≥500 cells/mm3 Absolute Neutrophil Count (ANC) <1000 cells/mm3 ≥1000 cells/mm3 Haemoglobin <8 g/dL ≥8 g/dL Renal impairment Leqselvi 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. Hepatic Impairment Leqselvi 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. CYP2C9 Poor Metabolizers Based on PBPK modelling, higher exposure of deuruxolitinib in patients who are CYP2C9 poor metabolizers is expected with concomitant use of Leqselvi, which may increase the risk of Leqselvi -associated serious adverse reactions.
Before initiation of treatment with Leqselvi, test patients to determine CYP2C9 genotype. Elderly There are limited data in patients ≥ 65 years of age. Paediatric population The safety and efficacy of Leqselvi in children less than 18 years of age has not been established.
No data are available. Method of administration Oral use Leqselvi should be swallowed with water, with or without food. Precautions to be taken before handling or administering the medicinal product. 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). 5). • 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. • 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.
• Complete blood count (CBC): Leqselvi treatment is not recommended in patients with an absolute lymphocyte count (ALC) <500 cells/mm3 absolute neutrophil count (ANC) <1000 cells/mm3, or haemoglobin level <8 g/dL. Monitor complete blood counts periodically during treatment and modify dosage as recommended.
• Complete any necessary immunizations, including herpes zoster vaccinations, according to current immunization guidelines prior to Leqselvi treatment. Pharmacogenomics Deuruxolitinib is primarily metabolized by CYP2C9 (76%) and CYP3A4 (21%).
CYP2C9 activity is reduced in patients with genetic variants in CYP2C9, such as the CYP2C9*2 and CYP2C9*3 alleles. The impact of CYP2C9 genetic variants on the pharmacokinetics of deuruxolitinib has not been directly evaluated. , *2/*3, *3/*3) may have up to 2-fold higher concentrations of deuruxolitinib, when compared to normal metabolizers.
, individuals with *1/*3 genotype). 5 to 4% in Asian populations, and <1% in Black or African American populations. , *5, *6, *8, *11) are more prevalent in Black or African American populations.