Selinexor

Dosage Forms

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

Tablet Therapy Pack, Oral:

Xpovio (100 MG Once Weekly): 20 mg (5 ea)

Xpovio (60 MG Once Weekly): 20 mg (3 ea)

Xpovio (80 MG Once Weekly): 20 mg (4 ea)

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

Pharmacology

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.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 125 L

Metabolism

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

Excretion

Clearance: 17.9 L/hour

Time to Peak

Within 4 hours

Half-Life Elimination

6 to 8 hours

Protein Binding

95%

Use: Labeled Indications

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

Contraindications

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

Dosage and Administration

Dosing: Adult

Multiple myeloma (relapsed or refractory): 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.

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).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Recommended selinexor dosage reduction levels:

Initial (usual) dose: 80 mg/dose twice weekly (on days 1 and 3); total weekly selinexor dose is 160 mg.

First dose reduction level: 100 mg once weekly.

Second dose reduction level: 80 mg once weekly.

Third dose reduction level: 60 mg once weekly.

If further dose reductions are required, discontinue selinexor.

Hematologic toxicity:

Thrombocytopenia (any occurrence):

Platelets 25,000/mm³ to <75,000/mm³: Reduce selinexor dose by 1 dose level.

Platelets 25,000/mm³ to <75,000/mm³ with concurrent bleeding: Interrupt selinexor treatment. After bleeding has resolved, restart selinexor with the dose reduced by 1 dose level.

Platelets <25,000/mm³: 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 (any occurrence):

ANC 500/mm³ to 1,000/mm³: Reduce selinexor dose by 1 dose level.

ANC <500/mm³ or neutropenic fever: Interrupt selinexor treatment and monitor until ANC returns to ≥1,000/mm³ and then restart selinexor with the dose reduced by 1 dose level.

Anemia (any occurrence):

Hemoglobin <8 g/dL: Reduce selinexor dose by 1 dose level. Administer blood transfusion and/or other treatments per clinical guideline recommendations.

Life-threatening anemia (urgent intervention indicated): 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 transfusion and/or other treatments per clinical guideline recommendations.

Nonhematologic toxicity:

Fatigue, grade 2 lasting >7 days or grade 3 (any occurrence): 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 occurrence): Interrupt selinexor treatment and provide appropriate supportive care. Monitor until sodium levels return to ≥130 mmol/L and restart selinexor with the dose reduced by 1 dose level.

Gastrointestinal toxicity:

Diarrhea:

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 or higher (increase of ≥7 stools/day over baseline; hospitalization indicated), any occurrence: 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 (any occurrence):

Grade 1 or 2 nausea (oral intake decreased without significant weight loss, dehydration, or malnutrition) or grade 1 or 2 vomiting (≤5 episodes/day): 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): 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 (any occurrence): Weight loss of 10% to <20% or anorexia associated with significant weight loss or malnutrition: 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.

Other nonhematologic toxicities: Grade 3 or 4 (life-threatening; any occurrence): Interrupt selinexor treatment and monitor until resolved to ≤ grade 2 and restart selinexor with the dose reduced by 1 dose level.

Administration

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

Selinexor may be associated with nausea and vomiting; antiemetics are recommended prior to and during treatment to prevent nausea and vomiting. Maintain adequate hydration and caloric intake throughout treatment; consider IV hydration in patients at risk of dehydration.

Storage

Store at or below 30°C (86°F).

Drug Interactions

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

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

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

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

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

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

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

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

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

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

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

>10%:

Central nervous system: Fatigue (73%), neurological signs and symptoms (≤30%), mental status changes (16%), dizziness (15%), insomnia (15%)

Endocrine & metabolic: Weight loss (47%), hyponatremia (39%), hyperglycemia (15%), dehydration (14%), hypokalemia (12%)

Gastrointestinal: Nausea (72%), decreased appetite (53%), diarrhea (44%), vomiting (41%), constipation (25%), dysgeusia (11%)

Hematologic & oncologic: Thrombocytopenia (74%; grades ≥3: 61%), anemia (59%; grades ≥3: 40%), neutropenia (34%; grades ≥3: 21%), leukopenia (28%; grades ≥3: 11%), lymphocytopenia (15%; grades ≥3: 10%)

Infection: Infection (52%)

Renal: Increased serum creatinine (14%)

Respiratory: Dyspnea (24%), upper respiratory tract infection (21%), cough (16%), pneumonia (13%), epistaxis (12%)

Miscellaneous: Fever (16%)

1% to 10%:

Central nervous system: Headache (10%)

Infection: Sepsis (6%)

Ophthalmic: Blurred vision (10%)

Frequency not defined:

Central nervous system: Confusion, delirium, impaired consciousness

Cardiovascular: Syncope

Hematologic & oncologic: Hemorrhage

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Selinexor may commonly cause thrombocytopenia; grade 3 and 4 events occurred in over half of patients. The median time to onset (first event) was 22 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 25 days. Neutropenic fever has also been reported. Monitor CBC (including neutrophils and platelets) at baseline, during treatment, and as clinically indicated (monitor more frequently during the first 2 treatment months). May require platelet transfusion (and/or other treatments) as clinically indicated. Monitor for signs/symptoms of bleeding or concomitant infection and evaluate promptly. Based on the severity, may require treatment interruption, dose reduction, and/or permanent discontinuation. Consider supportive measures including antimicrobials for signs of infection and WBC growth factors. Anemia and lymphopenia may also occur.
• Gastrointestinal toxicity: GI toxicities have occurred in patients treated with selinexor. Nausea and vomiting were commonly reported; grade 3 nausea and vomiting have occurred. The median time to nausea onset (first event) was 3 days; the median time to the first vomiting event was 5 days. Provide prophylactic 5-HT3 antagonists and/or other antinausea agents prior to and during selinexor treatment. Nausea or vomiting may require treatment interruption, dose reduction, and/or discontinuation. Administer IV fluids and electrolyte replacement to prevent dehydration in patients at risk. Additional antinausea medications may be required as clinically indicated. Diarrhea has been reported, including grade 3 diarrhea; the median time to diarrhea onset was 15 days. Diarrhea may be managed with dose modifications and/or standard antidiarrheal agents; administer IV fluids to prevent dehydration in patients at risk. Anorexia was reported in over half of patients receiving selinexor, with grade 3 anorexia occurring in some patients. The median time to onset of anorexia was 8 days. Weight loss was reported in nearly half of patients receiving selinexor, with grade 3 weight loss occurring rarely. The median time to weight loss onset was 15 days. Monitor weight at baseline, during treatment, and as clinically indicated (monitor more frequently during the first 2 treatment months). Manage anorexia and weight loss with dose modifications, appetite stimulants, and/or nutritional support.
• Hyponatremia: Selinexor may cause hyponatremia, including grades 3 and 4 hyponatremia. The median time to onset of the first event was 8 days. Monitor sodium level at baseline, during treatment, and as clinically indicated (monitor more frequently during the first 2 treatment months). Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Manage hyponatremia with IV saline and/or salt tablets per clinical guidelines, including dietary review. Based on the severity, hyponatremia may require treatment interruption, dose reduction, and/or permanent discontinuation.
• Infection: Infection (any grade) occurred in over half of patients treated with selinexor. Infections included upper respiratory tract infection, pneumonia, and sepsis. Grade 3 or higher infections were reported in one-fourth of patients; some were fatal. The most commonly reported grade 3 or higher infections were pneumonia and sepsis. The median time to onset was 54 days (for pneumonia) and 42 days (for sepsis). Most infections were not associated with neutropenia and were caused by nonopportunistic organisms.
• Neurotoxicity: Neurologic toxicities (including dizziness, syncope, decreased consciousness, and mental status changes [including delirium and confusion]) have occurred in patients who received selinexor. Grade 3 and 4 events have been reported. The median time to the first event was 15 days. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbation of dizziness or mental status changes.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: 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.

Monitoring Parameters

Monitor CBC with differential and standard blood chemistries at baseline and as indicated during treatment (monitor more frequently during the first 2 treatment months); evaluate pregnancy status (in females of reproductive potential) prior to treatment initiation. Assess body weight at baseline and as indicated during treatment (monitor more frequently during the first 2 treatment months). Monitor hydration status. Monitor for signs/symptoms of bleeding, infection, neurotoxicity, and gastrointestinal toxicity. Monitor adherence.

Pregnancy

Pregnancy Considerations

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

Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment and for 1 week after the last selinexor dose. Males with a female partner of reproductive potential should also use effective contraception during treatment and for 1 week after the last selinexor dose.

Patient Education

What is this drug used for?

• It is used to treat multiple myeloma.

Frequently reported side effects of this drug

• Constipation
• Common cold symptoms
• Trouble sleeping
• Change in taste
• Headache
• Diarrhea
• Loss of appetite
• Nausea
• Vomiting
• Weight loss

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding
• Dehydration like dry skin, dry mouth, dry eyes, increased thirst, fast heartbeat, dizziness, fast breathing, or confusion
• Infection
• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Dizziness
• Passing out
• Confusion
• Severe loss of strength and energy
• Shortness of breath
• Blurred vision
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.