Source: European Medicines Agency (EU) Revision Year: 2026 Publisher: Stemline Therapeutics B.V., Basisweg 10, 1043 AP Amsterdam, Netherlands
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
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).
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.
Thrombocytopenic events (thrombocytopenia and platelet count decreased) were frequently reported in patients receiving selinexor which can be severe (Grade ¾). Grade ¾ 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 including severe neutropenia (Grade ¾) has been reported with selinexor. In a few cases concurrent infections occurred in patients with Grade ¾ 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.
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/vomiting can be managed by dose interruptions, modifications, and/or initiation of other antiemetics medicinal products as clinically indicated. Diarrhoea can be managed with dose interruptions, modifications and/or administration of anti-diarrhoea medicinal products. For dose modification guidelines refer to Table 1 and Table 2 in section 4.2.
Selinexor can cause weight loss and anorexia. Patients should have their body weight, nutritional status and volume checked at baseline, during treatment, and as clinically indicated. Monitoring should be more frequent during the first two months of treatment. Patients experiencing new or worsening decreased appetite and weight may require dose modification, appetite stimulants, and nutritional consultations. For dose modification guidelines refer to Table 1 and Table 2 in section 4.2.
Selinexor can cause confusional state and dizziness. Patients should be instructed to avoid situations where dizziness or confusional state may be a problem and to not take other medicinal products that may cause dizziness or confusional state without adequate medical advice. Patients should be advised not to drive or operate heavy machinery until symptoms resolve (see section 4.7).
Selinexor can cause hyponatraemia. Patients should have their sodium levels checked at baseline, during treatment, and as clinically indicated. Monitoring should be more frequent during the first two months of treatment. Correct sodium levels for concurrent hyperglycaemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Hyponatraemia should be treated as per medical guidelines (intravenous sodium chloride solution and/or salt tablets), including dietary review.
Patients may require selinexor dose interruption and/or modification. For dose modification guidelines refer to Table 1 and Table 2 in section 4.2.
Selinexor can cause new onset or exacerbation of cataract (see section 4.8). Ophthalmologic evaluation may be performed as clinically indicated. Cataract should be treated as per medical guidelines, including surgery if warranted.
Tumour lysis syndrome (TLS) has been reported in patients receiving therapy with selinexor. Patients at a high risk for TLS should be monitored closely. Treat TLS promptly in accordance with institutional guidelines.
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.
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 (see section 4.6).
This medicinal product contains less than 1 mmol sodium (23 mg) per 20 mg tablet, that is to say essentially 'sodium-free'.
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.
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.
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 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.
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.
Based on findings in animals, selinexor may impair fertility in females and males (see section 5.3).
Selinexor may have major influence on the ability to drive and use machines. Selinexor can cause fatigue, confusional state and dizziness. Patients should be instructed to avoid situations where dizziness or confusional state may be a problem and to not take other medicinal products that may cause dizziness or confusional state without adequate medical advice. Patients should be advised not to drive or operate machines if they experience any of these symptoms.
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%).
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.
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/ preferred term | All ADRs/frequency | Grade 3-4 ADRs/frequency |
| Infections and infestations | Very common Pneumonia*, upper respiratory tract infection, bronchitis, nasopharyngitis Common Sepsis*, lower respiratory tract infection | Very common Pneumonia* Common Sepsis*, lower respiratory tract infection, bronchitis, upper respiratory tract infection |
| Blood and lymphatic system disorders | Very common Thrombocytopenia, anaemia, neutropenia* Common Leukopenia, lymphopenia | Very common Thrombocytopenia, anaemia Common Neutropenia*, lymphopenia Uncommon Leukopenia |
| Metabolism and nutrition disorders | Very common Decreased appetite Common Hyponatraemia, dehydration, hypokalaemia, hypocalcaemia, hypophosphataemia, hyperkalaemia, hypomagnesaemia | Common Hyponatraemia, dehydration, decreased appetite, hypokalaemia, hypocalcaemia, hypophosphataemia |
| Psychiatric disorders | Very common Insomnia Common Confusional state | Common Confusional state, insomnia |
| Nervous system disorders | Very common Peripheral neuropathy, dizziness, headache Common Syncope, amnesia*, balance disorder, dysgeusia, ageusia | Common Syncope, peripheral neuropathy Uncommon Headache, dizziness, amnesia* |
| Ear and labyrinth disorders | Common Vertigo | None |
| Eye disorders | Very common Cataract, vision blurred* | Very common Cataract Common Vision blurred* |
| Cardiac disorders | Common Tachycardia | None |
| Vascular disorders | Common Hypotension | Common Hypotension |
| Respiratory, thoracic and mediastinal disorders | Very common Cough Common Dyspnoea*, epistaxis | Common Epistaxis Uncommon Dyspnoea*, cough |
| Gastrointestinal disorders | Very common Nausea, diarrhoea, vomiting, constipation Common Abdominal pain, dyspepsia, dry mouth, flatulence | Common Nausea, diarrhoea, vomiting |
| Skin and subcutaneous tissue disorders | Common Alopecia, night sweats*, pruritus | Uncommon Night sweats* |
| Musculoskeletal and connective tissue disorders | Common Hypercreatinaemia | Common Hypercreatinaemia |
| Renal and urinary disorders | Common Acute kidney injury | Common Acute kidney injury |
| General disorders and administration site conditions | Very common Fatigue, pyrexia, asthenia Common General physical health deterioration, malaise | Very common Fatigue Common Pyrexia, asthenia, general physical health deterioration |
| Investigations | Very common Weight decreased Common Aspartate aminotransferase increased, alanine aminotransferase increased | Common Weight decreased, aspartate aminotransferase increased, alanine aminotransferase increased |
| Injury, poisoning and procedural complications | Common Fall, contusion | Common Fall |
* Grouping of more than one MedDRA preferred term including: Pneumonia: pneumonia, lung infection, pneumonia pneumococcal, pneumonia influenzal, pneumonia parainfluenzae viral, pneumonia bacterial and pneumonia fungal
- Sepsis: sepsis, septic shock, staphylococcal sepsis and urosepsis
- Neutropenia: neutropenia and febrile neutropenia
- Amnesia: amnesia and memory impairment
- Vision blurred: vision blurred, visual impairment and visual acuity reduced
- Dyspnoea: dyspnoea and exertional dyspnoea
- Night sweats: night sweats and hyperhidrosis
Table 5. Adverse drug reactions (ADRs) observed in patients treated with selinexor in combination with dexamethasone (Sd):
| System organ class/ preferred term | All ADRs/frequency | Grade 3-4 ADRs/frequency |
| Infections and infestations | Very common Pneumonia, upper respiratory tract infection Common Sepsis, bacteraemia | Common Pneumonia, sepsis, bacteraemia Uncommon Upper respiratory tract infection |
| Blood and lymphatic system disorders | Very common Thrombocytopenia, anaemia, neutropenia, leukopenia, lymphopenia Common Febrile neutropenia | Very common Thrombocytopenia, anaemia, neutropenia, leukopenia, lymphopenia Common Febrile neutropenia |
| Metabolism and nutrition disorders | Very common Hyponatraemia, dehydration, decreased appetite, hyperglycaemia, hypokalaemia Common Hypocalcaemia, hypophosphataemia, hyperkalaemia, hypomagnesaemia, hyperamylasaemia, hyperuricaemia, hyperlipasaemia Uncommon Tumour lysis syndrome | Very common Hyponatraemia Common Dehydration, decreased appetite, hypokalaemia, hyperglycaemia, hypocalcaemia, hyperkalaemia, hyperamylasaemia, hypophosphataemia hyperuricaemia, hyperlipasaemia Uncommon Tumour lysis syndrome |
| Psychiatric disorders | Very common Confusional state, insomnia Common Delirium, hallucination | Common Confusional state, insomnia Uncommon Delirium, hallucination |
| Nervous system disorders | Very common Dizziness, dysgeusia, headache Common Peripheral neuropathy, syncope, ageusia, taste disorder, balance disorder, cognitive disorder, disturbance in attention, memory impairment Uncommon Encephalopathy | Common Syncope, cognitive disorder Uncommon Peripheral neuropathy, encephalopathy |
| Eye disorders | Very common Vision blurred Common Cataract, visual impairment | Common Cataract Uncommon Vision blurred, visual impairment |
| Cardiac disorders | Common Tachycardia | None |
| Vascular disorders | Common Hypotension | Uncommon Hypotension |
| Respiratory, thoracic and mediastinal disorders | Very common Dyspnoea, epistaxis, cough | Common Dyspnoea Uncommon Epistaxis |
| Gastrointestinal disorders | Very common Nausea, diarrhoea, vomiting, abdominal pain, constipation Common Dyspepsia, dry mouth, abdominal discomfort, flatulence | Common Nausea, diarrhoea, vomiting, constipation Uncommon Abdominal pain |
| Skin and subcutaneous tissue disorders | Common Alopecia, night sweats, pruritus | None |
| Musculoskeletal and connective tissue disorders | Common Muscle spasms, hypercreatinaemia | Uncommon Muscle spasms, hypercreatinaemia |
| Renal and urinary disorders | Common Acute kidney injury | Common Acute kidney injury |
| General disorders and administration site conditions | Very common Fatigue, pyrexia, asthenia Common General physical health deterioration, malaise, gait disturbance, chills | Very common Fatigue Common Asthenia, general physical health deterioration, pain Uncommon Pyrexia |
| Investigations | Very common Weight decreased Common Aspartate aminotransferase increased, alanine aminotransferase increased, blood alkaline phosphatase increased | Common Alanine aminotransferase increased Uncommon Weight decreased; aspartate aminotransferase increased |
| Injury, poisoning and procedural complications | Common Fall | Common Fall |
Infection was the most common non-haematological toxicity.
In patients who received SVd, infections were reported in 70% of patients and 28% of patients had Grade 3 or 4 infections. Serious infections were reported in 28% of patients with fatal infections occurring in 4% of treated patients. Upper respiratory tract infection and pneumonia were the most commonly reported infections in 21% and 15% of patients, respectively. Infection led to dose discontinuation in 1% of patients, treatment interruption in 48% patients, and a dose reduction in 10% of patients.
In patients who received Sd, infections were reported in 53% of patients. Of these, 22% were Grade 3 or 4. Upper respiratory tract infection and pneumonia were the most commonly reported infections (in 15% and 13% of patients, respectively) with 25% of reported infections being serious and fatal infections occurring in 3% of treated patients. Infection led to dose discontinuation in 7% of patients, treatment interruption in 19% patients, and a dose reduction in 1% of patients.
In patients who received SVd, thrombocytopenia occurred in 62% of patients and 41% of patients had Grade 3 or 4 thrombocytopenia. Thrombocytopenia was serious in 2% of patients. Of the 41% patients with Grade 3 or 4 thrombocytopenia, Grade 3 or higher concurrent bleeding events (concurrency defined as ±5 days) were reported in 5% of patients. Fatal haemorrhage occurred in 2% of patients with thrombocytopenia. Thrombocytopenia led to dose discontinuation in 2% of patients, treatment interruption in 35% of patients, and a dose reduction in 33% of patients.
In patients who received Sd, thrombocytopenia occurred in 75% of patients and 65% of these ADRs were Grade 3 or 4. Thrombocytopenia was serious in 5% of patients. Of the 65% patients with Grade 3 or 4 thrombocytopenia, serious/Grade 3 or higher concurrent bleeding events (concurrency defined as ±5 days) were reported in 5% of patients. Thrombocytopenia led to dose discontinuation in 3% of patients, treatment interruption in 22% of patients, and a dose reduction in 32% of patients.
Thrombocytopenia can be managed with dose modifications (see section 4.2), supportive care and platelet transfusions. Patients should be monitored for signs and symptoms of bleeding and evaluated promptly (see section 4.4).
In patients who received SVd, neutropenia occurred in 16% of patients and 10% of patients had Grade 3 or 4 events of neutropenia. Neutropenia was serious in 1% of patients. None of the patients had a dose discontinuation due to neutropenia, and neutropenia led to treatment interruption in 9% of patients, and a dose reduction in 5% of patients.
Febrile neutropenia, reported as serious, occurred in one patient (<1%) who received SVd; and was Grade 4. Febrile neutropenia led to treatment interruption and dose reduction; no dose discontinuation occurred due to febrile neutropenia. Of the 19 patients with Grade 3 or higher neutropenia, serious Grade 3 or higher concurrent infections (concurrency defined as ±5 days) were reported in 3 (16%) patients. Concurrent Grade 3 or higher infections included lower respiratory tract infection, bronchitis and ear infection (1 patient each).
In patients who received Sd, neutropenia occurred in 36% of patients and 25% of these were Grade 3 or 4. Neutropenia was serious in 1% of patients. None of the patients had a dose discontinuation due to neutropenia, and neutropenia led to treatment interruption in 2% of patients, and a dose reduction in 6% of patients.
Febrile neutropenia occurred in 3% of patients who received Sd; all were Grade 3 or 4. Febrile neutropenia was reported to be serious in 2% of patients and led to a dose discontinuation, treatment interruption, or a dose reduction in less than 1% of patients (each). Of the 53 patients with Grade 3 or higher neutropenia, serious/Grade 3 or higher concurrent infections (concurrency defined as ±5 days) were reported in 6 (11%) patients. Most commonly reported Grade 3 or higher concurrent infection included urinary tract infection (3 patients), and sepsis (2 patients).
In patients who received SVd, anaemia occurred in 37% of patients and 16% of patients had Grade 3 anaemia, no patients had Grade 4 or 5 anaemia. Anaemia was serious in 3% of patients. Anaemia led to dose discontinuation in 1% of patients, treatment interruption in 6% of patients, and a dose reduction in 3% of patients.
In patients who received Sd, anaemia occurred in 61% of patients and 44% of these were Grade 3 or 4. Anaemia was serious in 3% of patients. Anaemia led to dose discontinuation in <1% of patients, treatment interruption in 4% of patients, and a dose reduction in 1% of patients.
Anaemia can be managed with dose modifications (see section 4.2) and with blood transfusions and/or erythropoietin administration as per medical guidelines. For dose modification guidelines refer to Table 2 of section 4.2.
In patients who received SVd, nausea occurred in 50% of patients and 8% of patients had Grade 3 or 4 nausea. Nausea was serious in 2% of patients. When anti-nausea treatment was administered, the median duration of nausea improved by 10 days. Nausea led to dose discontinuation in 3% of patients, treatment interruption in 7% of patients, and a dose reduction in 7% of patients.
Vomiting occurred in 21% of patients who received SVd, and 4% of patients had Grade 3 vomiting. No patients had Grade 4 vomiting. Vomiting was serious in 4% of patients. Vomiting led to dose discontinuation in 2% of patients, treatment interruption in 3% of patients, and a dose reduction in 3% of patients.
Diarrhoea occurred in 33% of patients who received SVd and 7% of patients had Grade 3 or 4 diarrhoea. Diarrhoea was serious in 4% of patients. Diarrhoea led to dose discontinuation in 1% of patients, treatment interruption in 8% of patients, and a dose reduction in 2% of patients.
In patients who received Sd, nausea/vomiting occurred in 79% of patients and 10% of these were Grade 3 or 4 and was serious in 3% of patients. When anti-nausea treatment was administered, the median duration of nausea or vomiting improved by 3 days. Nausea/vomiting led to dose discontinuation in 5% of patients, treatment interruption in 8% of patients, and a dose reduction in 5% of patients.
Diarrhoea occurred in 47% of patients who received Sd and 7% were Grade 3 or 4 and diarrhoea was serious in 2% of patients. Diarrhoea led to dose discontinuation in 1% of patients, treatment interruption in 2% of patients, and a dose reduction in 1% of patients.
In patients who received SVd, hyponatraemia occurred in 8% of patients and 5% of patients had Grade 3 or 4 hyponatremia. Hyponatraemia was serious in <1% of patients. Most cases of hyponatraemia were not associated with any symptoms. There were no reports of concurrent seizures. Hyponatraemia did not lead to any dose discontinuation, and it led to treatment interruption in <1% of patients, and a dose reduction in 1% of patients.
In patients who received Sd, hyponatraemia occurred in 40% of patients and 24% were Grade 3 or 4. Hyponatraemia was serious in 3% of patients. Most cases of hyponatraemia were not associated with any symptoms. There were no reports of concurrent seizures. Hyponatraemia did not lead to any dose discontinuation, and it led to treatment interruption in 6% of patients, and a dose reduction in 1% of patients.
In patients receiving SVd, the incidence of new onset or worsening cataracts requiring clinical intervention was reported in 24% of patients. The median time to new onset of cataract was 233 days. The median time for worsening of cataract in patients presenting with cataract at start of selinexor therapy was 261 days (SVd). Cataract did not lead to treatment discontinuation, it led to treatment interruption in 4% of patients and a dose reduction in 3% of patients. Cataract should be treated as per medical guidelines, including surgery if warranted (see sections 4.4 and 4.2).
Tumour lysis syndrome (TLS) occurred in one (<1%) patient (who received Sd) which was considered Grade 3 and serious. Patients at a high risk for TLS should be monitored closely. Treat TLS promptly in accordance with institutional guidelines (see section 4.4).
Among patients with multiple myeloma who received SVd, 56% were 65 years of age and over, while 17% were 75 years of age and over. When comparing patients 65 years of age and older to younger patients, older patients had a higher incidence of discontinuation due to an adverse reaction (28% vs 13%) and higher incidence of serious adverse reactions (57% vs 51%).
Among patients with multiple myeloma who received Sd, 47% were 65 years of age and over, while 11% were 75 years of age and over. When comparing patients 75 years of age and older to younger patients, older patients had a higher incidence of discontinuation due to an adverse reaction (52% vs 25%), higher incidence of serious adverse reactions (74% vs 59%), and higher incidence of fatal adverse reactions (22% vs 8%).
Reporting of 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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