Source: European Medicines Agency (EU) Revision Year: 2026 Publisher: Pharming Technologies B.V., Darwinweg 24, 2333 CR Leiden, The Netherlands
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
Concomitant therapy with a strong cytochrome P450 (CYP)3A4 inhibitor increased leniolisib exposure. Concomitant use of leniolisib with strong CYP3A4 inhibitors should be avoided (see section 4.5). 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.
Concomitant use may result in reduced leniolisib exposure and thus reduced leniolisib efficacy. Therefore, concomitant use of leniolisib with strong and moderate CYP3A4 inducers should be avoided (see section 4.5).
Concomitant use may result in increased leniolisib exposure, which could lead to an increased risk of adverse reactions. Therefore, concomitant use of leniolisib with strong breast cancer resistance protein (BCRP) transporter inhibitors should be avoided (see section 4.5).
When co-administered, leniolisib increased rosuvastatin systemic exposure 2-fold. Concomitant use of leniolisib with medicinal products that are substrates of these transporters should be avoided (see section 4.5).
For OAT3 substrates with a narrow therapeutic index (e.g., methotrexate), monitor patients for adverse events and consider dose adjustments if co-administration cannot be avoided (See section 4.5).
In vitro, leniolisib is an inhibitor of UGT1A1, and although a relevant clinical interaction is not expected, concomitant administration of leniolisib with a UGT1A1 substrate should be avoided (see section 4.5).
For patients using antacids chronically, the antacid should be taken either 2 hours before or 2 hours after Joenja administration (see section 4.5).
Women of childbearing potential should use highly effective contraception while taking Joenja and for 1 week after the last dose (see section 4.6). 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.
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.
This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially 'sodium-free'.
Leniolisib is cleared primarily through oxidative metabolism (primarily hydroxylation and dealkylation) by CYP isoenzymes (predominantly CYP3A4, 95.4%). In a study of healthy adults, co-administration of leniolisib and itraconazole, a strong CYP3A4 inhibitor, resulted in a 2-fold increase in leniolisib exposure. Concomitant use of leniolisib with strong CYP3A4 inhibitors (e.g., cobicistat, danoprevir, elvitegravir, indinavir, itraconazole, ketoconazole, lopinavir, ombitasvir, paritaprevir, posaconazole, ritonavir, saquinavir, telithromycin, tipranavir, troleandomycin, voriconazole) should be avoided (see sections 4.4 and 5.2).
No interaction studies have been conducted with leniolisib and strong and moderate CYP3A4 inducers. Concomitant use may result in reduced leniolisib exposure and thus reduced leniolisib efficacy. Therefore, concomitant use of leniolisib with strong and moderate CYP3A4 inducers (e.g., avasimibe, carbamazepine, mitotane, phenobarbital, phenytoin, rifabutin, rifampicin, St. John's Wort, bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided (see section 4.4).
Leniolisib is a substrate of BCRP transporters. No interaction studies have been conducted with leniolisib and strong BCRP inhibitors. Concomitant use may result in increased leniolisib exposure, which could lead to an increased risk of adverse effects. Therefore, concomitant use of leniolisib with strong BCRP inhibitors (e.g., curcumin, cyclosporine) should be avoided (see section 4.4).
Leniolisib exhibits pH-dependent solubility, with lower solubility at higher pH-values. Locally acting antacids (e.g., magnesium-, aluminum-, and calcium-based antacids, sodium bicarbonate) should be taken 2 hours before or 2 hours after leniolisib administration (see sections 4.2 and 4.4).
When co-administered, leniolisib increased rosuvastatin exposure 2-fold. Avoid concomitant use of leniolisib with medicinal products that are OATP1B1, OATP1B3, and BCRP substrates (e.g., rosuvastatin, pitavastatin, letermovir).
Leniolisib is an OAT3 inhibitor and may increase systemic exposure to OAT3 substrates (e.g., adefovir, baricitinib, bumetanide, cefaclor, ceftizoxime, ciprofloxacin, famotidine, furosemide, methotrexate, oseltamivir carboxylate, benzylpenicillin [penicillin G], tenofovir). When co-administered, leniolisib increased furosemide exposure 1.4-fold. Avoid concomitant use of leniolisib with medicinal products that are OAT3 substrates with a narrow therapeutic index (e.g., methotrexate).
In vitro, leniolisib is an inhibitor of UGT1A1, and although a relevant clinical interaction is not expected, concomitant administration of leniolisib with a UGT1A1 substrate (e.g., irinotecan) should be avoided.
Administration of leniolisib with a single dose oral contraceptive containing ethinylestradiol and levonorgestrel increased ethinylestradiol exposure by approximately 30% with no effect on levonorgestrel exposure. The increase in ethinylestradiol exposure is unlikely to reduce the effectiveness of a combined oral contraceptive composed of ethinylestradiol and levonorgestrel.
Interaction studies have only been performed in adults.
Women of childbearing potential should use highly effective methods of contraception during treatment with Joenja and for 1 week after the last dose. Leniolisib can cause foetal harm based on findings from animal studies (see section 5.3). Verify pregnancy status in females of reproductive potential prior to initiating treatment with Joenja.
There are no data from the use of leniolisib in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Joenja is not recommended during pregnancy and in women of childbearing potential not using highly effective methods of contraception.
It is unknown whether leniolisib and its metabolites are excreted in human milk. Available pharmacokinetic/toxicological data in animals have shown excretion of leniolisib in milk (see section 5.3). A risk to breastfed newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Joenja.
No human data on the effect of leniolisib on fertility are available. Studies in animals have shown effects on the male reproductive organs (see section 5.3).
Leniolisib has no or negligible influence on the ability to drive and use machines.
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.
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 | |
| 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
Seven (33%) patients receiving leniolisib developed a transient absolute neutrophil count (ANC) between 500 and 1500 cells/μL. No patients developed an ANC <500 cells/μL and there were no reports of infection associated with neutropenia. One case of Grade 3 neutrophil count decrease considered related to leniolisib was reported.
Hypersensitivity reactions have been identified during post-marketing use of Joenja.
Thirteen patients aged 12 to 17 were treated with leniolisib in the clinical trials. Frequency, type, and severity of adverse reactions were similar to adults.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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