Nexpovio · 4.1 Therapeutic indication · 1

HOS-287797 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile The safety of selinexor in combination with bortezomib and dexamethasone has been evaluated in 195 patients with multiple myeloma. The most frequent adverse reactions (≥30%) were thrombocytopenia (62%), nausea (50%), fatigue (42%), anaemia (37%), decreased appetite (35%), diarrhoea (33%), and peripheral neuropathy (33%). The most commonly reported serious adverse reactions (≥3%) were pneumonia (14.9%), cataract (4.6%), sepsis (4.1%), diarrhoea (3.6%), vomiting (3.6%) and anaemia (3.1%). The safety of selinexor in combination with dexamethasone has been evaluated in 214 patients with multiple myeloma, including 83 patients with penta-refractory disease. The most frequent adverse reactions (≥30%) were nausea (75%), thrombocytopenia (75%), fatigue (66%), anaemia (60%), decreased appetite (56%), decreased weight (49%), diarrhoea (47%), vomiting (43%), hyponatraemia (40%), neutropenia (36%) and leukopenia (30%). The most commonly reported serious adverse reactions (≥3%) were pneumonia (7.5%), sepsis (6.1%) thrombocytopenia (4.7%), acute kidney injury (3.7%), and anaemia (3.3%). Tabulated list of adverse reactions Adverse reactions reported in clinical trials with selinexor in combination with bortezomib and dexamethasone (SVd) are summarised in Table 4. Adverse reactions reported in clinical trials with selinexor in combination with dexamethasone (Sd) are summarised in Table 5. These reactions are presented by system organ class (SOC) and by frequency. Frequency categories 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 9 Table 4: Adverse drug reactions (ADRs) observed in patients with multiple myeloma treated with selinexor in combination with bortezomib and dexamethasone (SVd) System organ class/ All ADRs/frequency Grade 3-4 ADRs/frequency preferred term Infections and infestations Very common Very common Pneumonia*, upper respiratory Pneumonia* tract infection, bronchitis, nasopharyngitis Common

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HOS-287793 · has-contraindication-information · PDF-Seite 6

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

HOS-287792 · has-indication-information · PDF-Seite 2

NEXPOVIO is indicated: • in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. • in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

HOS-287795 · has-interaction-information · PDF-Seite 8

No clinically significant differences in selinexor pharmacokinetics were observed when co- administered with a strong CYP3A4 inducer and UGT inducer, carbamazepine (up to 300 mg twice- daily dose of carbamazepine). No clinically significant differences in selinexor pharmacokinetics were observed when co- administered with a strong CYP3A4 inhibitor, clarithromycin (500 mg PO twice daily for 7 days). No clinically significant differences in selinexor pharmacokinetics were observed when co- administered with up to 1000 mg daily dose of paracetamol.

HOS-287796 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/Contraception in males and females Women of childbearing potential should be advised to avoid becoming pregnant or abstain from sexual intercourse while being treated with selinexor and for at least 1 week following the last dose of selinexor. A pregnancy test is recommended for women of childbearing potential prior to initiating selinexor treatment. Women of childbearing potential and male patients of reproductive potential should be advised to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with selinexor and for at least 1 week following the last dose of selinexor. Pregnancy There are no data from the use of selinexor in pregnant women. Studies in animals have shown selinexor can cause foetal harm (see section 5.3). Selinexor is not recommended during pregnancy and 8 in women of childbearing potential not using contraception. If the patient becomes pregnant while taking selinexor, selinexor should be immediately discontinued, and the patient should be apprised of the potential hazard to the foetus. Breast-feeding It is unknown whether selinexor or its metabolites are excreted in human milk. A risk to breast-fed children cannot be excluded. Breast-feeding should be discontinued during treatment with selinexor and for 1 week after the last dose. Fertility Based on findings in animals, selinexor may impair fertility in females and males (see section 5.3).

HOS-287794 · has-warning-information · PDF-Seite 6

For medicinal products administered in combination with selinexor, the Summary of Product Characteristics (SmPC) of these medicinal products must be consulted prior to initiation of treatment, including for special warnings and precaution for use and recommended concomitant treatments. Recommended concomitant treatments Patients should be advised to maintain adequate fluid and caloric intake throughout treatment. Intravenous hydration should be considered for patients at risk of dehydration. Prophylactic concomitant treatment with a 5-HT3 antagonist and/or other anti-nausea agents should be provided prior to and during treatment with NEXPOVIO (see section 4.8). Haematology 6 Patients should have their complete blood counts (CBC) assessed at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Thrombocytopenia Thrombocytopenic events (thrombocytopenia and platelet count decreased) were frequently reported in patients receiving selinexor which can be severe (Grade 3/4). Grade 3/4 thrombocytopenia can sometimes lead to clinically significant bleeding and in rare cases may lead to potentially fatal haemorrhage (see section 4.8). Thrombocytopenia can be managed with dose interruptions, modifications, platelet transfusions, and/or other treatments as clinically indicated. Patients should be monitored for signs and symptoms of bleeding and evaluated promptly. For dose modification guidelines refer to Table 1 and Table 2 in section 4.2. Neutropenia Neutropenia including severe neutropenia (Grade 3/4) has been reported with selinexor. In a few cases concurrent infections occurred in patients with Grade 3/4 neutropenia (see section 4.8). Patients with neutropenia should be monitored for signs of infection and evaluated promptly. Neutropenia can be managed with dose interruptions, modifications, and colony-stimulating factors as per medical guidelines. For dose modification guidelines refer to Table 1 and Table 2 in section 4.2. Gastrointestinal toxicity Nausea, vomiting, diarrhoea, which sometimes can be severe and require the use of anti-emetic and anti-diarrhoeal medicinal products (see section 4.8). Prophylaxis with 5HT3 antagonists and/or other anti-nausea agents should be provided prior to and during treatment with selinexor. Fluids with electrolytes should be administered to prevent dehydration in patients at risk. Nausea

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