Wayrilz · 4.1 Therapeutic indications · 1

HOS-100866 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most common adverse reactions were diarrhoea (34.5%), nausea (25.4%), headache (18.3%), abdominal pain (15.8%), COVID-19 (15.5%), nasopharyngitis (11.6%), and arthralgia (11.3%). The most frequent adverse reactions resulting in discontinuation of rilzabrutinib, which occurred each in 2 patients (0.7%), were diarrhoea, nausea, headache, and pneumonia. Tabulated list of adverse reactions Unless otherwise stated, the following frequencies of adverse reactions are based on the 284 ITP patients exposed to rilzabrutinib in the phase 1/2 and phase 3 clinical trials (see section 5.1). The median duration of exposure was 6.6 months (range: <1 month to 70.8 months). Adverse reactions are organised according to primary system organ class (SOC) for each preferred term in MedDRA. The adverse reactions are ranked by frequency within each SOC, and presented in order of decreasing seriousness. 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) and not known (cannot be estimated from the available data). Table 2: Tabulated list of the adverse drug reactions Frequency MedDRA system organ Adverse reactions (All grades) class COVID-19 Very common Infections and Infestations Nasopharyngitis Very common Pneumonia* Common Headache Very common Nervous system disorders Dizziness Common Respiratory, thoracic, and Cough Common mediastinal disorders Diarrhoea Very common Nausea Very common Gastrointestinal disorders Abdominal pain Very common Vomiting Common Dyspepsia Common Skin and subcutaneous tissue Rash Co

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HOS-100862 · has-contraindication-information · PDF-Seite 4

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

HOS-100861 · has-indication-information · PDF-Seite 2

WAYRILZ is indicated for the treatment of immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments (see section 5.1).

HOS-100864 · has-interaction-information · PDF-Seite 5

Rilzabrutinib is primarily metabolized by CYP3A. Agents that may increase rilzabrutinib plasma concentrations Co-administration of rilzabrutinib with a moderate or strong CYP3A inhibitor increases rilzabrutinib plasma concentrations. Increased rilzabrutinib concentrations may increase the risk of rilzabrutinib adverse reactions. CYP3A inhibitors Co-administration with a strong CYP3A inhibitor (ritonavir) increased the rilzabrutinib Cmax by approximately 5-fold and AUC by 8-fold in healthy subjects. Avoid co-administration of moderate or strong CYP3A inhibitors (e.g., ritonavir, clarithromycin, itraconazole, erythromycin, fluconazole, verapamil, diltiazem) with rilzabrutinib. If these inhibitors will be used short term (such as anti-infectives for seven days or less), interrupt rilzabrutinib (see section 4.2). Avoid co-administration of grapefruit, starfruit and products containing these fruits, and Seville oranges with rilzabrutinib, as these are moderate or strong inhibitors of CYP3A. P-glycoprotein (P-gp) inhibitors After co-administration of rilzabrutinib with a strong P-gp inhibitor (quinidine), a modest increase in exposure to rilzabrutinib, considered not to be clinically meaningful, was observed by 12.7% for AUC, relative to rilzabrutinib alone. Agents that may decrease rilzabrutinib plasma concentrations Co-administration of rilzabrutinib with moderate or strong CYP3A inducers decreases rilzabrutinib plasma concentrations. Co-administration with a PPI decreases the plasma concentrations of rilzabrutinib. Decreased rilzabrutinib plasma concentrations may reduce rilzabrutinib efficacy. CYP3A inducers Co-administration with a strong CYP3A inducer (rifampicin) decreased rilzabrutinib Cmax and AUC by about 80% in healthy subjects. Avoid co-administration of rilzabrutinib with moderate or strong CYP3A inducers (e.g., carbamazepine, rifampicin, phenytoin) (see section 4.2). Gastric acid reducing agents Rilzabrutinib solubility decreases with increasing pH. Co-administration with a PPI (esomeprazole) decreased rilzabrutinib AUC by 51% in healthy subjects. Co-administration of rilzabrutinib with a H2RA (famotidine) reduced rilzabrutinib AUC by approximately 36% and no significant change was 5 observed in rilzabrutinib exposure if rilzabrutinib was administered at least 2 hours prior to famotidine. Avoid co-administration of rilzabrutinib with PPIs. If treatment with a gastric acid reducin

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HOS-100865 · has-pregnancy-information · PDF-Seite 6

Women of childbearing potential Women of child-bearing potential must use highly effective contraception during rilzabrutinib treatment and for 1 month after stopping treatment (see section 4.5 regarding potential interaction with hormonal contraceptives). Pregnancy status of females of child-bearing potential should be verified prior to initiating treatment. Pregnancy Rilzabrutinib should not be used during pregnancy and in women of childbearing potential not using contraception. Based on the available nonclinical animal studies, there may be a risk to the foetus (see section 5.3). There are no available data on rilzabrutinib use in pregnant women. Breast-feeding There are no available data on the presence of rilzabrutinib or its metabolites in human milk, effects on milk production, or the breastfed infant. No conclusions can be drawn regarding whether or not rilzabrutinib is safe for use during breastfeeding. Rilzabrutinib should be used during breastfeeding 6 only if the potential benefits to the mother outweigh the potential risks, including those to the breastfed child. Fertility There are no data on the effect of rilzabrutinib on human fertility. Effects of rilzabrutinib on male and female fertility were studied in rats at doses up to 300 mg/kg/day [Human Equivalent Dose (HED) 48 mg/kg/day]. Animal studies do not indicate any effect on fertility (see section 5.3).

HOS-100863 · has-warning-information · PDF-Seite 4

Serious infections Serious infections (including bacterial, viral, or fungal) have been reported during clinical studies (see section 4.8). Monitor patients for signs and symptoms of infection and treat appropriately. Women of childbearing potential Women of childbearing potential must use highly effective method of contraception while taking rilzabrutinib (see section 4.6). Pregnancy status of females of child-bearing potential should be verified prior to initiating treatment. Hepatic impairment In patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment, rilzabrutinib should not be administered (see section 5.2). Bilirubin and transaminases are to be evaluated at baseline and as clinically indicated during treatment with rilzabrutinib. For patients who develop abnormal liver tests after rilzabrutinib, continue to monitor for liver test abnormalities as well as clinical signs and symptoms as clinically indicated. QT shortening In the clinical trials with ITP patients, there were no clinically meaningful QTc interval changes. In a thorough QT study, rilzabrutinib produced a shortening in the QTc interval (see section 5.1). Although the underlying mechanism and safety relevance of this finding is not known, clinicians should use caution when prescribing rilzabrutinib to patients at risk for further shortening their QTc duration (e.g., Congenital Short QT Syndrome or patients with a family history of such a syndrome). Excipients Sunset yellow FCF 4 This medicinal product contains azo colouring agent sunset yellow FCF (E 110), which may cause allergic reactions. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.