XPOVIO

XPOVIO is an FDA-registered drug product whose active ingredient is SELINEXOR. It is labelled by Karyopharm Therapeutics Inc. taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 72237-101, application NDA212306, label effective 20260512. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing SELINEXOR are most often described in connection with: multiple myeloma, treatment adult, received least, one prior, relapsed refractory, two proteasome, immunomodulatory agents, anti-cd monoclonal. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

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.

2 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 ). Weight Loss and Anorexia [see Warning and Precautions ( 5.3 )] Weight loss of 10% to less than 20% OR Anorexia associated with significant weight loss or malnutrition Any Interrupt XPOVIO and institute supportive care. Monitor until weight returns to more than 90% of baseline weight. Restart XPOVIO at 1 dose level lower (see Table 1 ). Hyponatremia [see Warning and Precautions ( 5.4 )] Sodium level 130 mmol/L or less Any Interrupt XPOVIO, evaluate, and provide supportive care. Monitor until sodium levels return to greater than 130 mmol/L. Restart XPOVIO at 1 dose level lower (see Table 1 ). Fatigue Grade 2 lasting greater than 7 days OR Grade 3 Any Interrupt XPOVIO. Monitor until fatigue resolves to Grade 1 or baseline. Restart XPOVIO at 1 dose level lower (see Table 1 ). Ocular Toxicity [see Warning and Precautions ( 5.8 )] Grade 2, excluding cataract Any Perform ophthalmologic evaluation. Interrupt XPOVIO and provide supportive care. Monitor until ocular symptoms resolve to Grade 1 or baseline. Restart XPOVIO at 1 dose level lower (see Table 1 ). Grade ≥3, excluding cataract Any Permanently discontinue XPOVIO. Perform ophthalmologic evaluation. Other Non-Hematologic Adverse Reactions [see Warning and Precautions ( 5.6 )] Grade 3 or 4 Any Interrupt XPOVIO. Monitor until resolved to Grade 2 or lower; restart XPOVIO at 1 dose level lower (see Table 1 ). 2.5 Starting Dosage and Dosage Modifications for Adverse Reactions in Patients with Severe Hepatic Impairment For patients with severe hepatic impairment, defined by NCI-ODWG (National Cancer Institute Organ Dysfunction Working Group) criteria as total bilirubin >3x upper limit of normal with any level of AST, use the starting dosage of XPOVIO as shown in Table 4 [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. See Table 5 for dosage modifications for adverse reactions in patients with severe hepatic impairment. Table 4: XPOVIO Starting Dosage in Patients with Severe Hepatic Impairment AST = aspartate aminotransferase; ULN = upper limit of normal Total Bilirubin Levels XPOVIO Dosage Multiple Myeloma in Combination with Bortezomib and Dexamethasone (XVd) Multiple Myeloma in Combination with Dexamethasone (Xd) >3x ULN (and any AST) 80 mg once weekly 100 mg once weekly Table 5: XPOVIO Dosage Modifications for Adverse Reactions for Patients with Severe Hepatic Impairment Multiple Myeloma In Combination with Bortezomib and Dexamethasone (XVd) Multiple Myeloma In Combination with Dexamethasone (Xd) Recommended Starting Dosage 80 mg once weekly 100 mg once weekly First Reduction 60 mg once weekly 80 mg once weekly Second Reduction 40 mg once weekly 60 mg once weekly Third Reduction Permanently discontinue Permanently discontinue 2.6 Administration Each XPOVIO dose should be taken at approximately the same time of day and each tablet should be swallowed whole with water. Do not break, chew, crush, or divide the tablets. If a dose of XPOVIO is missed or delayed, instruct patients to take their next dose at the next regularly scheduled time. If a patient vomits a dose of XPOVIO, the patient should not repeat the dose and the patient should take the next dose on the next regularly scheduled day.

4 CONTRAINDICATIONS None. None ( 4 ).

6 ADVERSE REACTIONS 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. Table 7: Select Laboratory Abnormalities (≥15%) That Worsened from Baseline in Patients with Multiple Myeloma Who Received XPOVIO in Combination with Bortezomib and Dexamethasone (XVd) in BOSTON Laboratory Abnormality Weekly XVd Twice Weekly Vd All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) The denominator used to calculate the rate varied from 91 to 201 based on the number of patients with at least one post-treatment value. a. Includes one fatal anemia. Hematologic Platelet count decrease 92 43 51 19 Lymphocyte count decrease 77 38 70 27 Hemoglobin decrease 71 17 51 a 12 Neutrophil count decrease 48 12 19 7 Chemistry Glucose increase 62 3.8 47 4.1 Phosphate decrease 61 23 42 11 Sodium decrease 58 14 25 3 Calcium decrease 55 2.1 47 1 Blood urea nitrogen increase 41 5 40 5 Creatinine increase 28 3.6 24 1.5 Potassium decrease 27 6 22 3.5 Magnesium decrease 27 <1 23 1.5 Potassium increase 18 4.1 21 2.5 Hepatic ALT increase 33 3.1 30 <1 Albumin decrease 27 <1 35 <1 AST increase 24 1.5 19 <1 Bilirubin increase 16 1 13 2 ALP increase 12 0 16 <1 XPOVIO in Combination with Dexamethasone (Xd) The safety of XPOVIO in combination with dexamethasone was evaluated in STORM [see Clinical Studies ( 14.1 )]. Patients received XPOVIO 80 mg orally with dexamethasone 20 mg on Days 1 and 3 of every week (n=202). The median duration of XPOVIO treatment was 8 weeks (range: 1 to 60 weeks). The median dose was 115 mg (range: 36 to 200 mg) per week. Fatal adverse reactions occurred in 9% of XPOVIO treated patients. Serious adverse reactions occurred in 58% of patients. The treatment discontinuation rate due to adverse reactions was 27%; 53% of patients had a reduction in the XPOVIO dose, and 65% had the dose of XPOVIO interrupted. Thrombocytopenia was the leading cause of dose modification, resulting in dose reduction and/or interruption in >25% of patients. The most frequent adverse reactions requiring permanent discontinuation in 4% or greater of patients who received XPOVIO included fatigue, nausea, and thrombocytopenia. Table 8 summarizes the adverse reactions in STORM. Table 8: Adverse Reactions (≥10%) in Patients Who Received XPOVIO in STORM Adverse Reaction XPOVIO 80 mg twice weekly + Dexamethasone (n=202) a. Thrombocytopenia includes thrombocytopenia and platelet count decreased. b. Fatigue includes fatigue and asthenia. c. Anemia includes anemia and hematocrit decreased. d. Neutropenia includes neutropenia and neutrophil count decreased. e. Dyspnea includes dyspnea, dyspnea exertional, and dyspnea at rest. f. Upper respiratory tract infection includes upper respiratory tract infection, respiratory tract infection, pharyngitis, nasopharyngitis, bronchitis, bronchiolitis, respiratory syncytial virus infection, parainfluenza virus infection, rhinitis, rhinovirus infection, and adenovirus infection. g. Cough includes cough, productive cough, and upper-airway cough syndrome. h. Mental status changes includes mental status changes, confusional state, and delirium. i. Hypercreatininemia includes hypercreatininemia and hypercreatinemia. j. Pneumonia includes pneumonia, atypical pneumonia, lung infection, lower respiratory tract infection, pneumocystis jirovecii pneumonia, pneumonia aspiration, pneumonia influenzal, and pneumonia viral. k. Includes fatal event. All Grades (%) Grades ≥3 (%) Thrombocytopenia a 74 61 Fatigue b 73 22 Nausea 72 9 Anemia c 59 40 Decreased appetite 53 4.5 Weight decreased 47 0.5 Diarrhea 44 6 Vomiting 41 3.5 Hyponatremia 39 22 Neutropenia d 34 21 Leukopenia 28 11 Constipation 25 1.5 Dyspnea e 24 3.5 k Upper respiratory tract infection f 21 3 Cough g 16 0 Mental status changes h 16 7 Pyrexia 16 0.5 Hyperglycemia 15 7 Dizziness 15 0 Insomnia 15 2 Lymphopenia 15 10 Dehydration 14 3.5 Hypercreatininemia i 14 2 Pneumonia j 13 9 k Epistaxis 12 0.5 Hypokalemia 12 3.5 Dysgeusia 11 0 Vision blurred 10 0.5 Headache 10 0

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 …

Who makes XPOVIO?
Karyopharm Therapeutics Inc. is the labeler of record for XPOVIO.

What form does XPOVIO come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is XPOVIO prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has XPOVIO been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.