Xpovio
Selinexor · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE XPOVIO is a nuclear export inhibitor indicated: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy ( 1.1 ). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody ( 1.1 ). 1.1 Multiple Myeloma XPOVIO in combination with bortezomib and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. XPOVIO in combination with dexamethasone is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
Dosage and administration
Multiple Myeloma in Combination with Bortezomib and Dexamethasone (XVd) : Recommended dosage of XPOVIO is 100 mg taken orally once weekly in combination with bortezomib and dexamethasone ( 2.1 ). Multiple Myeloma in Combination with Dexamethasone (Xd) : Recommended dosage of XPOVIO is 80 mg taken orally on Days 1 and 3 of each week in combination with dexamethasone ( 2.1 ). See Full Prescribing Information for dosage in patients with severe hepatic impairment ( 2.5 , 8.6 ). 2.1 Recommended Dosage for Multiple Myeloma In Combination with Bortezomib and Dexamethasone (XVd) The recommended dosage of XPOVIO is 100 mg taken orally once weekly on Day 1 of each week until disease progression or unacceptable toxicity in combination with: Bortezomib 1.3 mg/m 2 administered subcutaneously once weekly on Day 1 of each week for 4 weeks followed by 1 week off. Dexamethasone 20 mg taken orally twice weekly on Days 1 and 2 of each week. Refer to Clinical Studies ( 14.1 ) and the prescribing information of bortezomib and dexamethasone for additional dosing information. In Combination with Dexamethasone (Xd) The recommended dosage of XPOVIO is 80 mg taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity in combination with dexamethasone 20 mg taken orally with each dose of XPOVIO on Days 1 and 3 of each week. For additional information regarding the administration of dexamethasone, refer to its prescribing information. 2.2 Recommended Monitoring for Safety Monitor complete blood count (CBC) with differential, standard blood chemistries, body weight, nutritional status, and volume status at baseline and during treatment as clinically indicated. Monitor more frequently during the first three months of treatment [see Warning and Precautions (5.1, 5.2, 5.3, and 5.4)] . Assess the need for dosage modifications of XPOVIO for adverse reactions [see Dosage and Administration ( 2.4 )] . 2.3 Recommended Concomitant Treatments Advise patients to maintain adequate fluid and caloric intake throughout treatment. Consider intravenous hydration for patients at risk of dehydration [see Warnings and Precautions ( 5.3 , 5.4 )] . Provide prophylactic antiemetics. Administer a 5-HT3 receptor antagonist and other anti-nausea agents prior to and during treatment with XPOVIO [see Warnings and Precautions ( 5.3 )] . 2.4 Dosage Modifications for Adverse Reactions Recommended XPOVIO dosage reduction steps are presented in Table 1 . Table 1: XPOVIO Dosage Reduction Steps for Adverse Reactions Recommended Starting Dosage Multiple Myeloma In Combination with Bortezomib and Dexamethasone (XVd) Multiple Myeloma In Combination with Dexamethasone (Xd) 100 mg once weekly 80 mg Days 1 and 3 of each week (160 mg total per week) First Reduction 80 mg once weekly 100 mg once weekly Second Reduction 60 mg once weekly 80 mg once weekly Third Reduction 40 mg once weekly 60 mg once weekly Fourth Reduction Permanently discontinue Permanently discontinue Recommended dosage modifications for hematologic adverse reactions in patients with multiple myeloma are presented in Table 2 . Recommended dosage modifications for non-hematologic adverse reactions are presented in Table 3 . Table 2: XPOVIO Dosage Modification Guidelines for Hematologic Adverse Reactions in Patients with Multiple Myeloma Adverse Reaction Occurrence Action Thrombocytopenia [see Warning and Precautions ( 5.1 )] Platelet count 25,000 to less than 75,000/mcL Any Reduce XPOVIO by 1 dose level (see Table 1 ). Platelet count 25,000 to less than 75,000/mcL with concurrent bleeding Any Interrupt XPOVIO. Restart XPOVIO at 1 dose level lower (see Table 1 ) after bleeding has resolved. Administer platelet transfusions per clinical guidelines. Platelet count less than 25,000/mcL Any Interrupt XPOVIO. Monitor until platelet count returns to at least 50,000/mcL. Restart XPOVIO at 1 dose level lower (see Table 1 ). Neutropenia [see Warning and Precautions ( 5.2 )] Absolute neutrophil count of 0.5 to 1 x 10 9 /L without fever Any Reduce XPOVIO by 1 dose level (see Table 1 ). Absolute neutrophil count less than 0.5 x 10 9 /L OR febrile neutropenia Any Interrupt XPOVIO. Monitor until neutrophil counts return to 1 x 10 9 /L or higher. Restart XPOVIO at 1 dose level lower (see Table 1 ). Anemia Hemoglobin less than 8 g/dL Any Reduce XPOVIO by 1 dose level (see Table 1 ). Administer blood transfusions per clinical guidelines. Life-threatening consequences Any Interrupt XPOVIO. Monitor hemoglobin until levels return to 8 g/dL or higher. Restart XPOVIO at 1 dose level lower (see Table 1 ). Administer blood transfusions per clinical guidelines. Table 3: XPOVIO Dosage Modification Guidelines for Non-Hematologic Adverse Reactions Adverse Reaction Occurrence Action Nausea and Vomiting [see Warning and Precautions ( 5.3 )] Grade 1 or 2 nausea (oral intake decreased without significant weight loss, dehydration or malnutrition) OR Grade 1 or 2 vomiting (5 or fewer episodes per day) Any Maintain XPOVIO and initiate additional anti-nausea medications. Grade 3 nausea (inadequate oral caloric or fluid intake) OR Grade 3 or higher vomiting (6 or more episodes per day) Any Interrupt XPOVIO. Monitor until nausea or vomiting has resolved to Grade 2 or lower or baseline. Initiate additional anti-nausea medications. Restart XPOVIO at 1 dose level lower (see Table 1 ). Diarrhea [see Warning and Precautions ( 5.3 )] Grade 2 (increase of 4 to 6 stools per day over baseline) 1 st Maintain XPOVIO and institute supportive care. 2 nd and subsequent Reduce XPOVIO by 1 dose level (see Table 1 ). Institute supportive care. Grade 3 or higher (increase of 7 stools or more per day over baseline; hospitalization indicated) Any Interrupt XPOVIO and institute supportive care. Monitor until diarrhea resolves to Grade 2 or lower. Restart XPOVIO at 1 dose level lower (see Table 1 ).
Dosage forms and strengths
Tablets: 10 mg, blue, round, bi-convex, film-coated tablets with “X10” debossed on one side and nothing on the other side. 20 mg, blue, round, bi-convex, film-coated tablets with “K20” debossed on one side and nothing on the other side. 40 mg tablets, blue, oval, film-coated, debossed on both sides with “X40”. 50 mg tablets, blue, oval, film-coated, debossed on both sides with “X50”. 60 mg tablets, blue, oval, film-coated, debossed on both sides with “X60”. 80 mg tablets, blue, oval, film-coated, debossed on both sides with “X80”. Tablets:10 mg, 20 mg, 40 mg, 50 mg, 60 mg, 80 mg ( 3 ).
Contraindications
None. None ( 4 ).
Warnings and precautions
Thrombocytopenia : Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care ( 2.4 , 5.1 ). Neutropenia : Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony-stimulating factors ( 2.4 , 5.2 ). Gastrointestinal Toxicity : Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care ( 2.4 , 5.3 ). Hyponatremia : Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care ( 2.4 , 5.4 ). Serious Infection : Monitor for infection and treat promptly ( 5.2 , 5.5 ). Neurological Toxicity : Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes ( 5.6 ). Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception ( 5.7 , 8.1 , 8.3 ). Cataract : Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract ( 5.8 ). 5.1 Thrombocytopenia XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia is the leading cause of dosage modifications [see Adverse Reactions ( 6.1 )] . In patients with multiple myeloma who received XPOVIO 100 mg once weekly (BOSTON, n=195), thrombocytopenia was reported in 92% of patients and severe (Grade 3-4) thrombocytopenia was reported in 43% of patients. The median time to first onset was 22 days for any grade thrombocytopenia and 43 days for Grade 3 or 4 thrombocytopenia. Bleeding occurred in 16% of patients with thrombocytopenia, clinically significant bleeding (Grade ≥3 bleeding) occurred in 4% of patients with thrombocytopenia, and fatal hemorrhage occurred in 2% of patients with thrombocytopenia. Permanent discontinuations of XPOVIO due to thrombocytopenia occurred in 2% of patients. In patients with multiple myeloma who received XPOVIO 80 mg twice weekly (STORM, n=202), thrombocytopenia was reported as an adverse reaction in 74% of patients and severe (Grade 3-4) thrombocytopenia was reported in 61% of patients. The median time to onset of the first event was 22 days. Bleeding occurred in 23% of patients with thrombocytopenia, clinically significant bleeding occurred in 5% of patients with thrombocytopenia, and fatal hemorrhage occurred in <1% of patients. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first three months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction [see Dosage and Administration ( 2.4 )]. 5.2 Neutropenia XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection [see Adverse Reactions ( 6.1 )] . In patients with multiple myeloma who received XPOVIO 100 mg once weekly (BOSTON, n=195), neutropenia was reported in 48% of patients and severe neutropenia (Grade 3-4) was reported in 12% of patients. The median time to onset of the first event was 23 days for any grade neutropenia and 40 days for Grade 3-4 neutropenia. Febrile neutropenia was reported in <1% of patients. In patients with multiple myeloma who received XPOVIO 80 mg twice weekly (STORM, n=202), neutropenia was reported as an adverse reaction in 34% of patients and severe (Grade 3-4) neutropenia was reported in 21% of patients. The median time to onset of the first event was 25 days. Febrile neutropenia was reported in 3% of patients. Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first three months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose or permanently discontinue based on severity of adverse reaction [see Dosage and Administration ( 2.4 )]. 5.3 Gastrointestinal Toxicity XPOVIO can cause severe gastrointestinal toxicities [see Adverse Reactions ( 6.1 )] . Nausea/Vomiting In patients with multiple myeloma who received XPOVIO once weekly (BOSTON, n=195) with use of antiemetic prophylaxis (88% of patients), nausea was reported in 50% of patients and Grade 3 nausea was reported in 8% of patients. The median time to onset of the first event was 6 days. Vomiting was reported in 21% of patients and Grade 3 vomiting was reported in 4.1% of patients. The median time to onset of the first event was 8 days. Permanent discontinuation due to nausea occurred in 3.1% of patients and due to vomiting occurred in 2.1% of patients. In patients with multiple myeloma receiving XPOVIO 80 mg twice weekly (STORM, n=202) with use of antiemetic prophylaxis, nausea was reported as an adverse reaction in 72% of patients and Grade 3 nausea occurred in 9%. The median time to first onset of nausea was 3 days. Vomiting was reported in 41% of patients and Grade 3 vomiting occurred in 4% of patients. The median time to first onset of vomiting was 5 days. Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose or permanently discontinue based on severity of adverse reaction [see Dosage and Administration ( 2.4 )] .
Side effects
The following clinically significant adverse reactions are described in detail in other labeling sections: Thrombocytopenia [see Warnings and Precautions ( 5.1 )] . Neutropenia [see Warnings and Precautions ( 5.2 )] . Gastrointestinal Toxicity [see Warnings and Precautions ( 5.3 )] . Hyponatremia [see Warnings and Precautions ( 5.4 )] . Serious Infection [see Warnings and Precautions ( 5.5 )] . Neurological Toxicity [see Warnings and Precautions ( 5.6 )] . Cataract [see Warnings and Precautions ( 5.8 )] . The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, weight decreased, cataract, and vomiting. Grade 3-4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia ( 6.1 ). The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, weight decreased, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Multiple Myeloma XPOVIO in Combination with Bortezomib and Dexamethasone (XVd) The safety of XPOVIO in combination with bortezomib and dexamethasone was evaluated in BOSTON [see Clinical Studies ( 14.1 )]. Patients were randomized to receive XPOVIO 100 mg orally once weekly in combination with bortezomib and dexamethasone (XVd) (n=195) or bortezomib and dexamethasone (Vd) (n=204). Among patients who received XPOVIO, the median duration of XPOVIO treatment was 29 weeks (range: 1 to 120 weeks) and the median dose was 80 mg (range: 30 to 137 mg) per week. Serious adverse reactions occurred in 52% of patients who received XPOVIO in combination with bortezomib and dexamethasone. Serious adverse reactions in >3% of patients included pneumonia (14%), sepsis, diarrhea and vomiting (4% each). Fatal adverse reactions occurred in 6% of patients within 30 days of last treatment, including pneumonia (n=3) and sepsis (n=3). Grade ≥2 peripheral neuropathy, a pre-specified key secondary endpoint, was lower in the XVd arm (21%) compared to the Vd arm (34%); odds ratio 0.50 [95% CI: 0.32, 0.79]. The median treatment duration was 30 weeks (range: 1-120 weeks) in patients who received once weekly XVd as compared to 32 weeks (range: 1-122 weeks) in patients who received twice weekly Vd. Permanent discontinuation of XPOVIO due to an adverse reaction occurred in 19% of patients. Adverse reactions which resulted in permanent discontinuation of XPOVIO in >2% of patients included fatigue (3.6%), nausea (3.1%), thrombocytopenia, decreased appetite, peripheral neuropathy, and vomiting (2.1% each). Dosage interruptions of XPOVIO due to an adverse reaction occurred in 83% of patients. Adverse reactions which required dosage interruption in >5% of patients included thrombocytopenia (33%), fatigue (13%), asthenia (12%), pneumonia (11%), upper respiratory tract infection (10%), decreased appetite (9%), neutropenia (8%), pyrexia (8%), nausea (7%), bronchitis (7%), diarrhea (6%), weight decreased (6%), and anemia (5%). Dose reductions of XPOVIO due to an adverse reaction occurred in 64% of patients. Adverse reactions which required dose reductions in >5% of patients included thrombocytopenia (31%), decreased appetite (8%), nausea, fatigue, weight decreased (7% each), and asthenia (6%). The most common adverse reactions (≥20% with a difference between arms of >5% compared to Vd) were fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, weight decreased, cataract, and vomiting. Grade 3-4 laboratory abnormalities (≥10%) were thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia. Table 6 summarizes the adverse reactions in BOSTON. Table 6: Adverse Reactions (≥10%) in Patients with Multiple Myeloma Who Received XPOVIO in Combination with Bortezomib and Dexamethasone (XVd) with a Difference Between Arms of >5% Compared to Vd in BOSTON Key: X=XPOVIO, Vd=bortezomib-dexamethasone a. Fatigue includes fatigue and asthenia. b. Peripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, polyneuropathy, peripheral sensorimotor neuropathy, toxic neuropathy, and peripheral motor neuropathy. c. Upper respiratory tract infection includes upper respiratory infection, nasopharyngitis, pharyngitis, respiratory syncytial virus infection, respiratory tract infection, rhinitis, and viral upper respiratory tract infection. d. Vision blurred includes blurred vision, visual acuity reduced, and visual impairment. Adverse Reaction Weekly XVd (n=195) Twice Weekly Vd (n=204) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal Nausea 50 8 10 0 Diarrhea 32 6 25 <1 Vomiting 21 4.1 4.4 0 General Conditions Fatigue a 59 21 28 5 Pyrexia 15 1.5 11 1 Metabolism and Nutrition Decreased appetite 35 3.6 5 0 Weight decreased 26 2.1 12 1 Nervous System Peripheral neuropathy b 32 4.6 47 9 Dizziness 12 <1 3.9 0 Infections Upper respiratory tract infection c 29 3.6 22 1.5 Eye Disorders Cataract 22 9 6 1.5 Vision blurred d 13 <1 6 0 Clinically relevant adverse reactions in <10% of patients who received XPOVIO in combination with bortezomib and dexamethasone included: Neurologic disorders: mental status changes (9%) and syncope (3.6%) Table 7 summarizes selected laboratory abnormalities in BOSTON.
Use in specific populations
Lactation : Advise not to breastfeed ( 8.2 ). 8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , XPOVIO can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of selinexor to pregnant rats during organogenesis resulted in structural abnormalities and alterations to growth at exposures that were below those occurring clinically at the recommended dose (see Data ) . Advise pregnant women of the risks to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data In an embryo-fetal development study in pregnant rats, daily oral administration of selinexor at 0, 0.25, 0.75, or 2 mg/kg throughout organogenesis caused incomplete or delayed ossification, skeletal variations, and reduced fetal weight compared with controls at a dose of 0.75 mg/kg (approximately 0.08-fold of human area under the curve [AUC] at the recommended dose). Malformations were observed at 2 mg/kg, including microphthalmia, fetal edema, malpositioned kidney, and persistent truncus arteriosus. 8.2 Lactation Risk Summary There is no information regarding the presence of selinexor or its metabolites in human milk, or their effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with XPOVIO and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential XPOVIO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating XPOVIO [see Use in Specific Populations ( 8.1 )] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose. Males Advise males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose. Infertility Females and Males Based on findings in animals, XPOVIO may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology ( 13.1 )] . 8.4 Pediatric Use The safety and effectiveness of XPOVIO have not been established in pediatric patients. 8.5 Geriatric Use In BOSTON, of the 195 patients with multiple myeloma who received XPOVIO in combination with bortezomib and dexamethasone, 56% were 65 years of age and older, while 17% were 75 years of age and older. No overall differences in effectiveness were observed between these patients and younger patients. 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 a higher incidence of serious adverse reactions (56% vs 47%). In STORM, of the 202 patients with multiple myeloma who received XPOVIO, 49% were 65 years of age and older, while 11% were 75 years of age and older. No overall difference in effectiveness was observed in patients over 65 years of age, including patients over 75 years of age, when compared with younger patients. 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 (44% vs 27%), higher incidence of serious adverse reactions (70% vs 58%), and higher incidence of fatal adverse reactions (17% vs 9%). 8.6 Hepatic Impairment No dose adjustment for selinexor is required for mild (total bilirubin ≤1x ULN and AST >1x ULN, or total bilirubin >1.0 to 1.5x ULN and any AST) or moderate (total bilirubin >1.5x to 3.0x ULN, and any AST) hepatic impairment. Reduce the starting dose in patients with severe (total bilirubin >3.0x ULN, and any AST) hepatic impairment [see Dosage and Administration ( 2.5 ) and Clinical Pharmacology ( 12.3 )] .
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , XPOVIO can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of selinexor to pregnant rats during organogenesis resulted in structural abnormalities and alterations to growth at exposures that were below those occurring clinically at the recommended dose (see Data ) . Advise pregnant women of the risks to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data In an embryo-fetal development study in pregnant rats, daily oral administration of selinexor at 0, 0.25, 0.75, or 2 mg/kg throughout organogenesis caused incomplete or delayed ossification, skeletal variations, and reduced fetal weight compared with controls at a dose of 0.75 mg/kg (approximately 0.08-fold of human area under the curve [AUC] at the recommended dose). Malformations were observed at 2 mg/kg, including microphthalmia, fetal edema, malpositioned kidney, and persistent truncus arteriosus.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of XPOVIO have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use In BOSTON, of the 195 patients with multiple myeloma who received XPOVIO in combination with bortezomib and dexamethasone, 56% were 65 years of age and older, while 17% were 75 years of age and older. No overall differences in effectiveness were observed between these patients and younger patients. 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 a higher incidence of serious adverse reactions (56% vs 47%). In STORM, of the 202 patients with multiple myeloma who received XPOVIO, 49% were 65 years of age and older, while 11% were 75 years of age and older. No overall difference in effectiveness was observed in patients over 65 years of age, including patients over 75 years of age, when compared with younger patients. 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 (44% vs 27%), higher incidence of serious adverse reactions (70% vs 58%), and higher incidence of fatal adverse reactions (17% vs 9%).
Description
Selinexor is a nuclear export inhibitor. Selinexor is (2 Z )-3-{3-[3,5-bis(trifluoromethyl)phenyl]-1 H -1,2,4-triazol-1-yl}- N '-(pyrazin-2-yl)prop-2-enehydrazide. It is a white to off-white powder and has the molecular formula C 17 H 11 F 6 N 7 O and a molecular mass of 443.31 g/mol. The molecular structure is shown below: XPOVIO tablets for oral dosing are supplied in six strengths, with each tablet containing 10 mg, 20 mg, 40 mg, 50 mg, 60 mg, or 80 mg of selinexor as the active ingredient. The inactive ingredients are colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, Opadry 200 clear, Opadry II blue, povidone K30, and sodium lauryl sulfate. Molecular Structure
Mechanism of action
12.1 Mechanism of Action In nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus and reductions in several oncoproteins, such as c-myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells. Selinexor demonstrated pro-apoptotic activity in vitro in multiple myeloma cells and showed anti-tumor activity in murine xenograft models of multiple myeloma. The combination of selinexor and dexamethasone or bortezomib demonstrated synergistic cytotoxic effects in multiple myeloma in vitro and increased anti-tumor activity in murine xenograft multiple myeloma models in vivo, including those resistant to proteasome inhibitors.
How supplied
10 mg tablets are blue, round, bi-convex, film-coated debossed with “X10” on one side and nothing on the other side. XPOVIO 20 mg tablets are blue, round, bi-convex, film-coated debossed with “K20” on one side and nothing on the other side. XPOVIO 40 mg tablets are blue, oval, film-coated, debossed on both sides with “X40”. XPOVIO 50 mg tablets are blue, oval, film-coated, debossed on both sides with “X50”. XPOVIO 60 mg tablets are blue, oval, film-coated, debossed on both sides with “X60”. XPOVIO 80 mg tablets are blue, oval, film-coated, debossed on both sides with “X80”. Tablets are packaged in a child-resistant blister pack. Four blister packs are supplied per carton. The following seven dose presentations are available: Weekly dose Strength per tablet Carton (28-day supply) Blister Pack NDC 100 mg once weekly 50 mg 4 blister packs (8 tablets total in the carton) Each blister has two 50 mg tablets Outer carton NDC 72237-103-05 Blister pack NDC 72237-103-15 80 mg once weekly 40 mg 4 blister packs (8 tablets total in the carton) Each blister has two 40 mg tablets Outer carton NDC 72237-102-02 Blister pack NDC 72237-102-12 80 mg once weekly 80 mg 4 blister packs (4 tablets total in the carton) Each blister has one 80 mg tablet Outer carton NDC 72237-105-01 Blister pack NDC 72237-105-11 60 mg once weekly 60 mg 4 blister packs (4 tablets total in the carton) Each blister has one 60 mg tablet Outer carton NDC 72237-104-01 Blister pack NDC 72237-104-11 40 mg once weekly 10 mg 4 blister packs (16 tablets total in the carton) Each blister has four 10 mg tablets Outer carton NDC 72237-106-01 Blister pack NDC 72237-106-11 40 mg once weekly 40 mg 4 blister packs (4 tablets total in the carton) Each blister has one 40 mg tablet Outer carton NDC 72237-102-07 Blister pack NDC 72237-102-17 80 mg twice weekly 20 mg 4 blister packs (32 tablets total in the carton) Each blister has eight 20 mg tablets Outer carton NDC 72237-101-04 Blister pack NDC 72237-101-14 Store at or below 30°C (86°F).
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Dosing Instructions [see Dosage and Administration ( 2 )]: Instruct patients to take XPOVIO exactly as prescribed. Advise patients to swallow the tablet whole with water. The tablet should not be broken, chewed, crushed, or divided. If a patient misses a dose, advise them to take their next dose at its regularly scheduled time. If a patient vomits or misses a dose of XPOVIO, advise them to take the next dose on the next regularly scheduled day. Advise patients that XPOVIO comes in a child-resistant blister pack. Advise patients to take their prescribed dexamethasone (if applicable) and prophylactic anti-nausea medications as directed [see Dosage and Administration ( 2.1 , 2.2 )] . Advise patients that blood tests and body weight will be monitored at baseline and during treatment as clinically indicated, with more frequent monitoring during the first three months of treatment [see Dosage and Administration ( 2.2 )] . Advise patients to maintain appropriate fluid and caloric intake throughout their treatment [see Dosage and Administration ( 2.3 )] . Hematologic Adverse Reactions Thrombocytopenia Advise patients that they may develop low platelet counts (thrombocytopenia). Symptoms of thrombocytopenia may include bleeding and easy bruising. Advise patients that platelet counts will be monitored at baseline, during treatment, and as clinically indicated, with more frequent monitoring during the first 3 months of treatment. Advise patients to report signs of bleeding right away [see Warnings and Precautions ( 5.1 )] . Anemia Advise patients that they may develop anemia. Symptoms of anemia may include fatigue and shortness of breath. Advise patients to report signs or symptoms of anemia [see Adverse Reactions ( 6.1 )] . Neutropenia Advise patients that they may develop low neutrophil counts which may increase their susceptibility to infection [see Warnings and Precautions ( 5.2 )]. Advise patients that neutrophil counts will be monitored at baseline, during treatment, and as clinically indicated, with more frequent monitoring during the first 3 months of treatment. Gastrointestinal Adverse Reactions Advise patients they may experience nausea/vomiting or diarrhea and to contact their physician if these adverse reactions occur or persist [see Warnings and Precautions ( 5.3 )] . Advise patients that they may experience weight loss or decreased appetite. Advise patients to report decreased appetite and weight loss [see Warnings and Precautions ( 5.3 )] . Hyponatremia Advise patients that they may develop low sodium levels (hyponatremia). Most cases of hyponatremia were not associated with specific symptoms. Advise patients that levels of sodium will be monitored at baseline and during treatment as clinically indicated, with more frequent monitoring during the first two months of treatment [see Warnings and Precautions ( 5.4 )]. Serious Infection Advise patients of the possibility of serious infections. Instruct patients to immediately report infection-related signs or symptoms (e.g., chills, fever) [see Warnings and Precautions ( 5.5 )] . Neurotoxicity Advise patients that they may experience confusion and dizziness. Advise patients to report symptoms of neurological toxicity right away. Advise patients not to drive or operate hazardous machinery until the neurological toxicity fully resolves. Advise patients to use fall prevention measures as warranted [see Warnings and Precautions ( 5.6 )] . Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to contact their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the final dose [see Use in Specific Populations ( 8.3 )] . Cataract Advise patients of the potential risk of worsening or new onset of cataract, that may require surgery. Advise patients to readily inform their healthcare professionals of changes in vision (i.e. blurred vision) and that ophthalmologic evaluation may be performed as clinically indicated [see Warnings and Precautions ( 5.8 )] . Fatigue Advise patients that they may experience fatigue [see Adverse Reactions ( 6.1 )]. Lactation Advise women not to breastfeed during treatment with XPOVIO and for 1 week after the last dose [see Use in Specific Populations ( 8.2 )] . Concomitant Medications Advise patients to take 5-HT3 antagonist prophylactic treatment and other anti-nausea agents prior to and during treatment with XPOVIO [see Dosage and Administration ( 2.3 )] . Advise patients to speak with their physician about other medications they are currently taking and before starting any new medication. Manufactured for and marketed by: Karyopharm Therapeutics Inc., 85 Wells Avenue, Newton, MA, 02459. XPOVIO is a registered trademark of Karyopharm Therapeutics Inc. ©2026 Karyopharm Therapeutics Inc. For more information, call 1-888-209-9326 or go to www.XPOVIO.com.
Label text from the FDA structured product label by Karyopharm Therapeutics Inc. (revised May 12, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Selinexor in 6 products
Xpovio NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 72237-101 | Selinexor 20 mg/1 Tablet, Film Coated | Karyopharm Therapeutics Inc. | NDA |
| 72237-102 | Selinexor 40 mg/1 Tablet, Film Coated | Karyopharm Therapeutics Inc. | NDA |
| 72237-103 | Selinexor 50 mg/1 Tablet, Film Coated | Karyopharm Therapeutics Inc. | NDA |
| 72237-104 | Selinexor 60 mg/1 Tablet, Film Coated | Karyopharm Therapeutics Inc. | NDA |
| 72237-105 | Selinexor 80 mg/1 Tablet, Film Coated | Karyopharm Therapeutics Inc. | NDA |
| 72237-106 | Selinexor 10 mg/1 Tablet, Film Coated | Karyopharm Therapeutics Inc. | NDA |
Frequently asked questions
What is Xpovio used for?
1 INDICATIONS AND USAGE XPOVIO is a nuclear export inhibitor indicated: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy ( 1.1 ). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and…
What are the side effects of Xpovio?
The following clinically significant adverse reactions are described in detail in other labeling sections: Thrombocytopenia [see Warnings and Precautions ( 5.1 )] . Neutropenia [see Warnings and Precautions ( 5.2 )] . Gastrointestinal Toxicity [see Warnings and Precautions ( 5.3 )] . Hyponatremia [see Warnings and Precautions ( 5.4 )] . Serious Infection [see Warnings and Precautions ( 5.5 )] .… See the full label for the complete list.
Who makes Xpovio?
Xpovio is listed by 1 labeler in the FDA NDC directory, including Karyopharm Therapeutics Inc..