Selinexor

FDA Drug Information • Also known as: Xpovio

Brand Names: Xpovio
Dosage Form: TABLET, FILM COATED
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION Selinexor is a nuclear export inhibitor. Selinexor is (2 Z )-3-{3-[3,5-bis(trifluoromethyl)phenyl]-1 H -1,2,4-triazol-1yl}- 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

What Is Selinexor 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 whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody ( 1.1 ). For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s) ( 1.2 ). 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. 1.2 Diffuse Large B-Cell Lymphoma XPOVIO is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate [see Clinical Studies ( 14.2 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dosage and Administration

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 ). DLBCL: Recommended dosage of XPOVIO is 60 mg taken orally on Days 1 and 3 of each week ( 2.2 ). See Full Prescribing Information for dosage in patients with severe hepatic impairment ( 2.6 , 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 Dosage for Diffuse Large B-Cell Lymphoma The recommended dosage of XPOVIO is 60 mg taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity. 2.3 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 ( 2.5 )] . 2.4 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 )] . 2.5 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...

Side Effects (Adverse Reactions)

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 ). The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, decreased appetite, weight decreased, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia ( 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%),...

Contraindications

4 CONTRAINDICATIONS None. None ( 4 ).

Pregnancy and Breastfeeding

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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING XPOVIO 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 nine 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...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.