Joenja

Treatment must be initiated by a physician experienced in the management of primary immune deficiencies. Posology The recommended dose is 70 mg leniolisib twice daily approximately 12 hours apart. Joenja is indicated in adults and adolescents 12 years of age and older and weighing 45 kg or more.

Treatment should be continued as long as a benefit is observed or until unacceptable toxicity occurs. Missed dose If a dose is missed by more than 6 hours, the patient should not take the missed dose but resume dosing at the next scheduled time.

If vomiting occurs within 1 hour after taking leniolisib, the patient should take another leniolisib tablet as soon as possible. If vomiting occurs more than 1 hour after dosing, the patient should not take an additional dose. 3 Special populations Paediatric population The safety and efficacy of leniolisib in children aged less than 12 years or below the weight of 45 kg have not yet been established.

No data are available. Elderly There are no data on patients aged 65 years and older. No dosing modifications are recommended for elderly patients. Renal impairment Leniolisib has not been studied in patients with renal impairment (creatinine clearance (CrCL) 15 to 89 mL/min).

No dosing modifications are recommended for patients with renal impairment. Hepatic impairment Leniolisib has not been studied in patients with hepatic impairment. Use of leniolisib in patients with moderate to severe hepatic impairment (Child-Pugh Class B or C) is not recommended.

Method of administration Oral use. Joenja can be taken with or without meals. The tablets should be swallowed whole. Do not split, crush, or chew the tablets. 5).

Summary of safety profile The most commonly reported adverse reactions during leniolisib treatment were headache (32%), vomiting (16%), weight increase (13%), and alopecia (11%). Based on laboratory data from the clinical studies, 33% of patients experienced a decrease in neutrophil counts.

Tabulated list of adverse reactions The safety of leniolisib was evaluated in 38 adolescent and adult patients with APDS who participated in the placebo-controlled portion of Study 2201, and an open label safety study. Thirty-seven of 38 patients received leniolisib 70 mg orally twice daily for at least 60 weeks and 84% were exposed for 108 weeks or longer.

Median duration of leniolisib treatment was approximately 4 years, and 10 patients had more than 5 years of leniolisib exposure. The following list of adverse reactions is based on experience from clinical trials and on postmarketing experience.

Adverse reactions in Table 1 are listed by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), and rare (≥ 1/10 000 to < 1/1 000), and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing frequency. Table 1 Adverse reactions System organ class Adverse reaction Frequency Immune system disorders Hypersensitivity* Not known Nervous system disorders Headache Very common Gastrointestinal disorders Vomiting Very common Dyspepsia Common Skin and subcutaneous tissue disorders Alopecia Very common Atopic dermatitis** Common Rash Common 7 System organ class Adverse reaction Frequency General disorders and administration site conditions Fatigue Common Investigations Weight increased Very common Neutrophil count decreased Very common *Hypersensitivity: including itching, skin redness, hives, rash, difficulty breathing or swallowing (from post-marketing use of Joenja) **Atopic dermatitis: including dermatitis atopic and eczema Description of selected adverse reactions Neutrophil count decreased Seven (33%) patients receiving leniolisib developed a transient absolute neutrophil count (ANC) between 500 and 1500 cells/μL.

Immune-related adverse events Serious, sometimes fatal, immune-related adverse events such as severe infections, severe cutaneous adverse reactions (SCARs), pneumonitis, severe diarrhoea/colitis, and hepatotoxicity have occurred in patients receiving other phosphoinositide 3-kinase delta (PI3Kδ) inhibitors for the treatment of haematological or solid cancers.

These serious events have not been associated with the use of Joenja in APDS patients. Joenja is not approved for treatment of haematological or solid cancers. Combination with CYP3A4 inhibitors Concomitant therapy with a strong cytochrome P450 (CYP)3A4 inhibitor increased leniolisib exposure.

5). If use of strong CYP3A4 inhibitors is required, it is recommended that Joenja be discontinued 2 days before administration of CYP3A4 inhibitor. Joenja may be restarted 7 days after CYP3A4 inhibitor discontinuation. Combination with CYP3A4 inducers Concomitant use may result in reduced leniolisib exposure and thus reduced leniolisib efficacy.

5). 4 Combination with BCRP inhibitors Concomitant use may result in increased leniolisib exposure, which could lead to an increased risk of adverse reactions. 5). Combination with organic anion transporter (OAT)P1B1, OATP1B3, and breast cancer resistance protein (BCRP) substrates When co-administered, leniolisib increased rosuvastatin systemic exposure 2-fold.

5). 5). 5). 5). 6). Joenja is not recommended during pregnancy and in women of childbearing potential not using highly effective methods of contraception. Verify pregnancy status in females of reproductive potential prior to initiating treatment with Joenja.

Excipients with known effect Lactose content This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption must not take this medicine.

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