Jascayd · 4.8 Undesirable effects · 1

HOS-100850 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most frequent adverse reactions are diarrhoea and weight decreased. Tabulated list of adverse reactions Table 1 shows the frequencies of adverse reactions based on 52-week data from two randomised, placebo-controlled, double-blind Phase III clinical trials (FIBRONEER-IPF in IPF and FIBRONEER-ILD in PPF) with twice daily nerandomilast doses of 9 mg or 18 mg. Adverse reactions are listed by MedDRA System Organ Class (SOC). Frequencies are defined as very common (≥ 1/10); common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data). Table 1. Adverse reactions System Organ Class Adverse reactions Frequency category IPFb PPF Metabolism and nutrition disorders Decreased Common Common appetite Gastrointestinal disorders Diarrhoeaa Very Very common common Nausea Common Common Musculoskeletal and connective tissue Back pain Common Common disorders Investigations Weight Common Common decreaseda a see section Description of selected adverse reactions b Frequencies were calculated excluding patients in the 9 mg dose group receiving concomitantly pirfenidone, as this combination is not recommended due to a clinically relevant drug-drug interaction (see section 4.2 and section 4.5). Description of selected adverse reactions Diarrhoea In most patients treated with nerandomilast, diarrhoea was of mild to moderate intensity and generally occurred within the first 3 months of treatment. Most cases were managed with symptomatic therapy with anti-diarrhoeal medication and, if applicable, with reduction in background therapy with nintedanib or pirfenidone. Severe diarrhoea has been reported more frequently in patients receiving nerandomilast in combination with nintedanib. 7 The frequency of diarrhoea depended on the presen

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HOS-100846 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-100845 · has-indication-information · PDF-Seite 2

Jascayd is indicated for the treatment of adult patients with Idiopathic Pulmonary Fibrosis (IPF). Jascayd is indicated for the treatment of adult patients with Progressive Pulmonary Fibrosis (PPF). 2

HOS-100848 · has-interaction-information · PDF-Seite 5

Based on in vitro assessment, nerandomilast is mainly metabolised by CYP3A and is a substrate of P-glycoprotein (P-gp). Effects of other products on nerandomilast Strong CYP3A inhibitors Clinical When a single dose of 6 mg nerandomilast was co-administered with multiple Impact: doses of itraconazole (a dual strong inhibitor of CYP3A and P-gp) in healthy volunteers, the exposure of nerandomilast increased by 2.2-times for AUC and by 1.3-times for Cmax. Intervention: If used concomitantly with strong CYP3A inhibitors, the dose must be reduced to 9 mg twice daily (see section 4.2). Examples: Clarithromycin, itraconazole, ritonavir Strong or moderate CYP3A inducers Clinical When a single dose of 18 mg nerandomilast was co-administered with multiple Impact: doses of carbamazepine (a strong CYP3A inducer) in healthy volunteers, the exposure of nerandomilast decreased by 51% for AUC and by 31% for Cmax. When a single dose of 18 mg nerandomilast was co-administered with multiple doses of bosentan (a moderate CYP3A inducer) in healthy volunteers, the exposure of nerandomilast decreased by 41% for AUC and by 15% for Cmax. Intervention: If used concomitantly with strong or moderate CYP3A inducers, the recommended dose is 18 mg twice daily and must not be reduced to 9 mg twice daily (see section 4.2). Examples: Carbamazepine, St. John’s wort, rifampicin, phenytoin, bosentan, metamizole Pirfenidone Clinical Concomitant use with pirfenidone decreased exposure of nerandomilast by Impact: approximately 50%, based on Ctrough,ss observed in the phase 3 study in patients with 5  IPF. Based on in vitro data, pirfenidone may induce CYP3A activity, leading to decreased nerandomilast exposure. When nerandomilast was co-administered with pirfenidone in patients with IPF in this phase 3 trial, efficacy was not observed at the 9 mg dose but a reduction in Forced Vital Capacity (FVC) decline was observed with the 18 mg dose (see section 5.1). Intervention: In patients using pirfenidone, the recommended dose is 18 mg twice daily and must not be reduced to 9 mg twice daily (see sectio

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HOS-100849 · has-pregnancy-information · PDF-Seite 6

Contraception Based on findings in animal studies, nerandomilast may cause loss of pregnancy (see section Pregnancy below and section 5.3). Women of childbearing potential should be advised to avoid becoming pregnant and to use effective contraceptive methods during treatment. Pregnancy There are no data from the use of nerandomilast in pregnant women. Based on findings in animal studies, nerandomilast may cause loss of pregnancy (see section 5.3). Women of childbearing potential should be advised to avoid becoming pregnant while taking Jascayd. Jascayd is not recommended during pregnancy and in women of childbearing potential not using contraception. Female patients should be advised to notify their health care provider if they become pregnant or suspect they may be pregnant during therapy with Jascayd. Pregnant women and women of childbearing potential should be advised of the potential risk of foetal loss. Breast-feeding There are no data on the presence of nerandomilast in human milk or its effects on either the breast-fed child or on milk production. Studies in rats have shown evidence of excretion of nerandomilast in milk (see section 5.3). A risk to the breast-fed infant cannot be excluded. Breast-feeding should be discontinued during treatment with Jascayd. 6 Fertility There are no data on the impact of nerandomilast on human fertility. No adverse effects on fertility were observed in male and female rats at 4-times human exposure (see section 5.3).

HOS-100847 · has-warning-information · PDF-Seite 4

Diarrhoea, nausea and decreased appetite In clinical trials, diarrhoea, nausea and decreased appetite were frequently reported adverse reactions (see section 4.8) particularly in patients receiving nerandomilast in combination with nintedanib or pirfenidone. In most patients, these adverse reactions were of mild to moderate intensity. Patients should be monitored and adverse reactions managed with adequate symptomatic treatments such as hydration and anti-diarrhoeal or anti-emetic medicinal products, as applicable. Reduction in background therapy with nintedanib or pirfenidone should be managed in line with the advice in the respective SmPCs. Caution is advised in patients who are debilitated, have existing gastrointestinal symptoms, or have previously experienced significant gastrointestinal adverse reactions with nintedanib or pirfenidone. If patients with severe or persistent diarrhoea, nausea or decreased appetite do not respond to symptomatic treatment, dose reduction (see section 4.2) or treatment interruption, nerandomilast treatment should be discontinued. Weight decrease Treatment with nerandomilast has been associated with dose dependent weight loss particularly with concomitant use of nintedanib. Body weight should be monitored regularly during therapy. If unexplained weight loss becomes progressive or clinically concerning, treatment should be reassessed and dose reduction or discontinuation of treatment should be considered. Nerandomilast should be used with caution in patients who are underweight or have conditions in which additional weight loss may be medically undesirable (see section 4.8). 4 Psychiatric disorders Psychiatric disorders can be a common comorbidity in patients with IPF and PPF. Psychiatric events, including very rare instances of suicidal ideation and behaviour, have been reported in clinical studies of nerandomilast across treatment groups. Routine monitoring for psychiatric disorders is recommended. Excipients with known effect Lactose Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicinal product. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.