Selinexor: Drug information

(For additional information see "Selinexor: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Xpovio (100 MG Once Weekly);
Xpovio (40 MG Once Weekly);
Xpovio (40 MG Twice Weekly);
Xpovio (60 MG Once Weekly);
Xpovio (60 MG Twice Weekly);
Xpovio (80 MG Once Weekly);
Xpovio (80 MG Twice Weekly)

Brand Names: Canada

Xpovio (100 MG Once Weekly)

Pharmacologic Category

Antineoplastic Agent, Nuclear Export Inhibitor

Dosing: Adult

Note: Selinexor is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]).

Diffuse large B-cell lymphoma, relapsed or refractory

Diffuse large B-cell lymphoma, relapsed or refractory: Oral: 60 mg/dose twice weekly on days 1 and 3 each week; continue until disease progression or unacceptable toxicity (Kalakonda 2020). Total selinexor dose per week: 120 mg.

Multiple myeloma, relapsed/refractory

Multiple myeloma, relapsed/refractory:

Selinexor/dexamethasone (Sd) regimen (in patients who have received at least 4 prior therapies): Oral: 80 mg/dose twice weekly on days 1 and 3 each week (in combination with dexamethasone); continue until disease progression or unacceptable toxicity (Chari 2019). Total selinexor dose per week: 160 mg.

Selinexor/bortezomib/dexamethasone (SVd) regimen (in patients who have received at least 1 prior therapy): Oral: 100 mg once weekly on day 1 of each week (in combination with bortezomib and dexamethasone); continue until disease progression or unacceptable toxicity (Grosicki 2020).

Missed doses: If a selinexor dose is missed or delayed, administer the next dose at the next regularly scheduled time. If a dose is vomited, administer the next dose at the next regularly scheduled day (do not repeat the dose).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated by the Cockcroft-Gault equation.

CrCl ≥15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, there are no clinically significant effects on selinexor pharmacokinetics.

End-stage kidney disease (CrCl <15 mL/minute): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Mild impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, there are no clinically significant effects on selinexor pharmacokinetics.

Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Adjustment for Toxicity: Adult

**Recommended Selinexor Dosage Reduction Levels**
	Multiple myeloma (in combination with bortezomib and dexamethasone [SVd regimen])	Multiple myeloma (in combination with dexamethasone [Sd regimen])	Diffuse large B-cell lymphoma
Recommended starting dose	100 mg once weekly	80 mg on days 1 and 3 (total weekly selinexor dose is 160 mg)	60 mg on days 1 and 3 (total weekly selinexor dose is 120 mg)
1st dose reduction	80 mg once weekly	100 mg once weekly	40 mg on days 1 and 3 (total weekly selinexor dose is 80 mg)
2nd dose reduction	60 mg once weekly	80 mg once weekly	60 mg once weekly
3rd dose reduction	40 mg once weekly	60 mg once weekly	40 mg once weekly
4th dose reduction	Permanently discontinue selinexor.	Permanently discontinue selinexor.	Permanently discontinue selinexor.

**Selinexor Dosage Adjustment for Hematologic Toxicity in Diffuse Large B-Cell Lymphoma**
Toxicity	Occurrence	Action
Thrombocytopenia
Platelets 50,000/mm³ to <75,000/mm³	Any	Withhold 1 selinexor dose. Restart selinexor at the same dose level.
Platelets 25,000/mm³ to <50,000/mm³ without bleeding	First occurrence	Interrupt selinexor treatment and monitor until platelets return to ≥50,000/mm³ and then restart selinexor with the dose reduced by 1 dose level.
Platelets 25,000/mm³ to <50,000/mm³ with concurrent bleeding	Any	Interrupt selinexor treatment and monitor until platelets return to ≥50,000/mm³ and bleeding has resolved, then restart selinexor with the dose reduced by 1 dose level. Administer platelet transfusions per clinical guideline recommendations.
Platelets <25,000/mm³	Any	Interrupt selinexor treatment and monitor until platelets return to ≥50,000/mm³ and then restart selinexor with the dose reduced by 1 dose level. Administer platelet transfusions per clinical practice guideline recommendations.
Neutropenia
ANC 500/mm³ to <1,000/mm³ without fever	First occurrence	Interrupt selinexor treatment and monitor until ANC returns to ≥1,000/mm³ and then restart selinexor at the same dose level.
ANC 500/mm³ to <1,000/mm³ without fever	Recurrence	Interrupt selinexor treatment and monitor until ANC returns to ≥1,000/mm³ and then restart selinexor with the dose reduced by 1 dose level. Administer growth factor support per clinical guidelines. Consider antimicrobials if indicated.
ANC <500/mm³ or neutropenic fever	Any	Interrupt selinexor treatment and monitor until ANC returns to ≥1,000/mm³ and then restart selinexor with the dose reduced by 1 dose level. Administer growth factor support and antimicrobials per clinical guidelines.
Anemia
Hemoglobin <8 g/dL	Any	Reduce selinexor dose by 1 dose level. Administer blood transfusions per clinical guideline recommendations.
Life-threatening anemia	Any	Interrupt selinexor treatment and monitor until hemoglobin returns to ≥8 g/dL and then restart selinexor with the dose reduced by 1 dose level. Administer blood transfusions per clinical guideline recommendations.

**Selinexor Dosage Adjustment for Hematologic Toxicity in Multiple Myeloma**
Toxicity	Occurrence	Action
Thrombocytopenia
Platelets 25,000/mm³ to <75,000/mm³	Any	Reduce selinexor dose by 1 dose level.
Platelets 25,000/mm³ to <75,000/mm³ with concurrent bleeding	Any	Interrupt selinexor treatment. After bleeding has resolved, restart selinexor with the dose reduced by 1 dose level. Administer platelet transfusions per clinical guideline recommendations.
Platelets <25,000/mm³	Any	Interrupt selinexor treatment and monitor until platelets return to ≥50,000/mm³ and then restart selinexor with the dose reduced by 1 dose level.
Neutropenia
ANC 500/mm³ to 1,000/mm³without fever	Any	Reduce selinexor dose by 1 dose level.
ANC <500/mm³ or neutropenic fever	Any	Interrupt selinexor treatment and monitor until ANC returns to ≥1,000/mm³ and then restart selinexor with the dose reduced by 1 dose level. Consider supportive measures including WBC growth factors and/or antimicrobials if indicated.
Anemia
Hemoglobin <8 g/dL	Any	Reduce selinexor dose by 1 dose level. Administer blood transfusions per clinical guideline recommendations.
Life-threatening anemia	Any	Interrupt selinexor treatment and monitor until hemoglobin returns to ≥8 g/dL and then restart selinexor with the dose reduced by 1 dose level. Administer blood transfusions per clinical guideline recommendations.

**Selinexor Dosage Adjustment for Nonhematologic Adverse Reactions in Diffuse Large B-Cell Lymphoma and Multiple Myeloma**
Adverse reaction	Occurrence	Action
^aAdminister IV fluids to prevent dehydration and electrolyte replacement as clinically indicated.
^bProvide standard antidiarrheal agents as clinically indicated.
Fatigue: Grade 2 lasting >7 days or grade 3	Any	Interrupt selinexor treatment and monitor until fatigue returns to grade 1 or baseline and then restart selinexor with the dose reduced by 1 dose level.
Hyponatremia: Sodium level ≤130 mmol/L	Any	Interrupt selinexor treatment and provide appropriate supportive care (including IV saline and/or salt tablets along with dietary review per clinical guidelines). Monitor until sodium levels return to >130 mmol/L and restart selinexor with the dose reduced by 1 dose level.
Diarrhea^a,b
Grade 2 (increase of 4 to 6 stools/day over baseline)	First occurrence	Maintain selinexor dose and initiate supportive care.
Grade 2 (increase of 4 to 6 stools/day over baseline)	Second and subsequent occurrences	Reduce selinexor dose by 1 dose level and initiate supportive care.
≥ Grade 3 (increase of ≥7 stools/day over baseline; hospitalization indicated)	Any	Interrupt selinexor treatment and initiate supportive care. Monitor until diarrhea resolves to ≤ grade 2 and restart selinexor with the dose reduced by 1 dose level.
Nausea and vomiting^a
Grade 1 or 2 nausea (oral intake decreased without significant weight loss, dehydration, or malnutrition) or grade 1 or 2 vomiting (≤5 episodes/day)	Any	Maintain selinexor dose and initiate additional antinausea medications.
Grade 3 nausea (inadequate oral caloric or fluid intake) or ≥ grade 3 vomiting (≥ 6 episodes per day)	Any	Interrupt selinexor treatment and monitor until nausea or vomiting has resolved to ≤ grade 2 or baseline and restart selinexor with the dose reduced by 1 dose level. Also initiate additional antinausea medications.
Weight loss and anorexia: Weight loss of 10% to <20% or anorexia associated with significant weight loss or malnutrition	Any	Interrupt selinexor treatment and initiate supportive care. Monitor until weight returns to >90% of baseline weight and restart selinexor with the dose reduced by 1 dose level. Administer IV fluids, electrolyte replacement, and/or nutritional support as clinically indicated.
Ocular toxicity
Grade 2 (excluding cataract)	Any	Interrupt selinexor treatment and perform ophthalmologic evaluation. Provide supportive care. Monitor until ocular symptoms resolve to grade 1 or baseline and restart selinexor with the dose reduced by 1 dose level.
≥ Grade 3 (excluding cataract)	Any	Permanently discontinue selinexor and perform ophthalmologic evaluation.
Cataract	New onset or exacerbation	Generally requires surgical removal of cataract.
Infection	Any	Evaluate and treat promptly.
Neurotoxicity	Any	Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbation of dizziness or mental status changes. Institute fall precautions as appropriate.
Other nonhematologic adverse reactions
Grade 3 or 4	Any	Interrupt selinexor treatment and monitor until resolved to ≤ grade 2 and restart selinexor with the dose reduced by 1 dose level.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions may be in combination with dexamethasone.

>10%:

Cardiovascular: Edema (17%), hypotension (13%)

Endocrine & metabolic: Decreased serum albumin (25%), decreased serum calcium (30%), decreased serum magnesium (30%), decreased serum phosphate (34%), dehydration (7% to 14%), hyperglycemia (15%), hypokalemia (12%), hyponatremia (39% to 62%), increased serum potassium (26%), weight loss (30% to 47%)

Gastrointestinal: Anorexia (37% to 53%), constipation (25% to 29%), decreased appetite (37% to 53%), diarrhea (37% to 44%), dysgeusia (11% to 13%), nausea (57% to 72%), vomiting (28% to 41%)

Hematologic & oncologic: Anemia (59%; grades ≥3: 40%), leukopenia (28%; grades ≥3: 11%), lymphocytopenia (15%; grades ≥3: 10%; grade 4: 5%), neutropenia (34%; grades ≥3: 21%; grade 4: 9%), thrombocytopenia (74% to 86%; grades ≥3: 49% to 61%; grade 4: 18%)

Hepatic: Increased serum alanine aminotransferase (29%), increased serum aspartate aminotransferase (24%), increased serum bilirubin (16%)

Infection: Infection (49% to 52%; serious infection: 21%)

Nervous system: Dizziness (15% to 16%), fatigue (≤73%), insomnia (15%), mental status changes (11% to 16%, including amnesia, confusion, delirium, memory impairment), neurological signs and symptoms (25% to 30%, including cognitive dysfunction, drowsiness, hallucination, and impaired consciousness)

Neuromuscular & skeletal: Asthenia (≤73%), increased creatinine phosphokinase in blood specimen (21%), musculoskeletal pain (15%)

Ophthalmic: Blurred vision (10% to 11%)

Renal: Increased serum creatinine (14% to 47%)

Respiratory: Cough (16% to 18%), dyspnea (10% to 24%), epistaxis (12%), pneumonia (10% to 13%, including fungal), upper respiratory tract infection (17% to 21%)

Miscellaneous: Fever (16% to 22%)

1% to 10%:

Cardiovascular: Cardiac failure (3%), syncope (2%)

Gastrointestinal: Abdominal pain (10%)

Genitourinary: Urinary tract infection (10%)

Hematologic & oncologic: Febrile neutropenia (3%), hemorrhage (10%)

Infection: Herpes virus infection (3%), sepsis (6%)

Nervous system: Falling (8%), headache (5% to 10%), peripheral sensory neuropathy (10%)

Ophthalmic: Cataract (4%)

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to selinexor or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Selinexor may cause life-threatening thrombocytopenia (potentially leading to hemorrhage); grade 3 and 4 events occurred in ~40% to 60% of patients. The median time to onset (first event) was 22 to 28 days. In patients with diffuse large B-cell lymphoma (DLBCL), the median time to onset of grade 3 or 4 thrombocytopenia was 33 days. In patients with multiple myeloma who received 100 mg once weekly, the median time to onset of grade 3 or 4 thrombocytopenia was 43 days. Bleeding has occurred in patients with thrombocytopenia, including clinically significant bleeding and (rare) fatal hemorrhage. Selinexor is also associated with neutropenia, including grade 3 and 4 events; neutropenia may potentially increase the risk of infection. The median time to onset (first neutropenic event) was 23 to 25 days in patients with multiple myeloma; the median time to first onset of grade 3 or 4 neutropenia was 32 days in patients with DLBCL. Neutropenic fever has also been reported.

• GI toxicity: GI toxicities have occurred in patients treated with selinexor; may be severe. Nausea and vomiting were commonly reported; grade 3 nausea and vomiting have occurred, despite the use of prophylactic antiemetics. The median time to nausea onset (first event) was 3 to 6 days; the median time to the first vomiting event was 5 to 8 days. Diarrhea has been reported, including grade 3 diarrhea; the median time to diarrhea onset was 12 to 50 days. Anorexia was reported in approximately one-third to one-half of patients receiving selinexor, with grade 3 anorexia occurring in some patients. The median time to onset of anorexia was 8 to 35 days in patients with multiple myeloma. Weight loss was reported in nearly one-third to one-half of patients receiving selinexor, with grade 3 weight loss occurring rarely. In patients with multiple myeloma, the median time to weight loss onset was 15 to 58 days.

• Hyponatremia: Selinexor may cause hyponatremia, including grades 3 and 4 hyponatremia, which may be severe or life-threatening. The median time to onset of the first event was 8 to 21 days in patients with multiple myeloma. In some cases, hyponatremia occurred in those experiencing nausea, vomiting, diarrhea, dehydration, and anorexia. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels.

• Infection: Serious and potentially fatal infections may occur; infection (any grade) occurred in approximately half of patients treated with selinexor. Grade 3 or higher infections were reported in up to one-third of patients; some were fatal. The most commonly reported grade 3 or higher infections were pneumonia, sepsis, and upper respiratory infection. When reported, the median time to onset of infection ranged from 42 to 54 days. Most infections were not associated with ≥ grade 3 neutropenia; atypical infections such as fungal pneumonia and herpes virus were reported.

• Neurotoxicity: Selinexor may cause life-threatening neurotoxicity. Neurologic toxicities (including dizziness, syncope, decreased consciousness, cognitive disorders, somnolence, hallucination, mental status changes [including delirium and confusion], vertigo, and amnesia) have occurred. Grade 3 and 4 events have been reported. The median time to the first event was 15 to 29 days. In patients with DLBCL, ~70% of patients recovered with a median time to recovery of 14 days. Patients should avoid driving or operating heavy or dangerous machinery until neurotoxicity fully resolves.

• Ocular toxicity: New onset or exacerbation of cataract has occurred during selinexor treatment. Nearly one-fourth of patients with multiple myeloma who received selinexor 100 mg once weekly experienced new or worsening cataract requiring clinical intervention. The median time to new onset of cataract was 228 days, and the median time to worsening cataract was 237 days.

Special populations:

• Older age: Patients ≥75 years of age experienced a higher incidence of serious adverse reactions, fatal adverse events, and a higher incidence of treatment discontinuation (due to adverse events) when compared to younger patients in one multiple myeloma trial. In another multiple myeloma trial, patients ≥65 years of age experienced a higher incidence of serious adverse reactions and a higher discontinuation rate due to adverse events (compared to younger patients).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet Therapy Pack, Oral:

Xpovio (100 MG Once Weekly): 20 mg (5 ea [DSC]); 50 mg (2 ea)

Xpovio (40 MG Once Weekly): 20 mg (2 ea [DSC]); 40 mg (1 ea)

Xpovio (40 MG Twice Weekly): 20 mg (4 ea [DSC]); 40 mg (2 ea)

Xpovio (60 MG Once Weekly): 20 mg (3 ea [DSC]); 60 mg (1 ea)

Xpovio (60 MG Twice Weekly): 20 mg (6 ea)

Xpovio (80 MG Once Weekly): 20 mg (4 ea [DSC]); 40 mg (2 ea)

Xpovio (80 MG Twice Weekly): 20 mg (8 ea)

Generic Equivalent Available: US

Pricing: US

Tablet Therapy Pack (Xpovio (100 MG Once Weekly) Oral)

50 mg (per each): $4,600.50

Tablet Therapy Pack (Xpovio (40 MG Once Weekly) Oral)

40 mg (per each): $9,201.00

Tablet Therapy Pack (Xpovio (40 MG Twice Weekly) Oral)

40 mg (per each): $4,600.50

Tablet Therapy Pack (Xpovio (60 MG Once Weekly) Oral)

60 mg (per each): $9,201.00

Tablet Therapy Pack (Xpovio (60 MG Twice Weekly) Oral)

20 mg (per each): $1,533.50

Tablet Therapy Pack (Xpovio (80 MG Once Weekly) Oral)

40 mg (per each): $4,600.50

Tablet Therapy Pack (Xpovio (80 MG Twice Weekly) Oral)

20 mg (per each): $1,150.13

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Therapy Pack, Oral:

Xpovio (100 MG Once Weekly): 20 mg (20 ea) [contains fd&c blue #1 (brill blue) aluminum lake, fd&c blue #2 (indigotine,indigo carmine)]

Prescribing and Access Restrictions

Selinexor is available through specialty pharmacies; access information is available at https://www.xpovio.com/hcp/wp-content/uploads/sites/3/2019/07/XPO_DistributionFactSheet.pdf.

Administration: Adult

Oral: Administer at approximately the same time of day on the scheduled day(s) of the week. Swallow whole with water; do not break, chew, crush, or divide tablets.

Selinexor is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]). Administer a 5-HT3 antagonist and other antiemetics as clinically appropriate prior to and during selinexor treatment. Maintain adequate hydration and caloric intake throughout treatment; consider IV hydration in patients at risk of dehydration.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Selinexor may cause teratogenicity and reproductive toxicity.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212306s005lbl.pdf#page=32, must be dispensed with this medication.

Use: Labeled Indications

Diffuse large B-cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, in adults after at least 2 lines of systemic therapy.

Multiple myeloma, relapsed or refractory:

Treatment of multiple myeloma (in combination with bortezomib and dexamethasone) in adults who have received at least 1 prior therapy.

Treatment of relapsed or refractory multiple myeloma (in combination with dexamethasone) in adults who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Medication Safety Issues

Sound-alike/look-alike issues:

Selinexor may be confused with selegiline, selexipag, selpercatinib, selumetinib.

Xpovio may be confused with Xalkori, Xeloda, Xgeva, Xofigo, Xospata, Xtandi.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Food Interactions

Concomitant administration of a high-fat meal (800 to 1,000 calories with ~50% of total caloric content of the meal from fat) did not have a clinically significant effect on selinexor pharmacokinetics.

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 1 week after the last selinexor dose. Patients with partners who could become pregnant should also use effective contraception during treatment and for 1 week after the last selinexor dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to selinexor may cause fetal harm.

Breastfeeding Considerations

It is not known if selinexor is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 week after the last selinexor dose.

Monitoring Parameters

Monitor CBC with differential and standard blood chemistries (including sodium levels) at baseline and as clinically indicated during treatment (monitor more frequently during the first 3 treatment months). Evaluate pregnancy status prior to treatment initiation (in patients who could become pregnant). Assess body weight, nutritional status, and hydration/volume status at baseline and as clinically indicated during treatment (monitor more frequently during the first 3 treatment months). Monitor for signs/symptoms of bleeding, infection, neurotoxicity, ocular toxicity, and GI toxicity. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Selinexor reversibly inhibits nuclear export of tumor suppressor proteins, growth regulators, and mRNAs of oncogenic proteins via blockage of exportin 1. Inhibition of exportin 1 results in accumulation of tumor suppressor proteins (in the nucleus), oncoproteins reduction, cell cycle arrest, and cancer cell apoptosis. The combination of selinexor with dexamethasone or bortezomib demonstrated synergistic cytotoxicity and increased antitumor activity in multiple myeloma models.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: 133 L.

Protein binding: 95%.

Metabolism: Hepatic via CYP3A4, multiple UDP-glucuronosyltransferases, and glutathione S-transferases.

Half-life elimination: 6 to 8 hours.

Time to peak: Within 4 hours.

Excretion: Clearance: 18.6 L/hour.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AT) Austria: Nexpovio;
(AU) Australia: Xpovio;
(DE) Germany: Nexpovio;
(PR) Puerto Rico: Xpovio

<800> Hazardous Drugs–Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727-738. doi:10.1056/NEJMoa1903455 [PubMed 31433920]
Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3 [PubMed 33189178]
Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
Kalakonda N, Maerevoet M, Cavallo F, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):e511-e522. doi:10.1016/S2352-3026(20)30120-4 [PubMed 32589977]
US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in health care settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed July 8, 2019.
Xpovio (selinexor) [prescribing information]. Newton, MA: Karyopharm Therapeutics Inc; July 2022.
Xpovio (selinexor) [product monograph]. Oakville, Ontario, Canada: Forus Therapeutics Inc; May 2022.

Topic 121843 Version 127.0

خرید پکیج

Selinexor: Drug information