selinexor (Rx)

Brand and Other Names:Xpovio
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 20mg

Multiple Myeloma

Indicated in combination with dexamethasone for adults with relapsed or refractory multiple myeloma (RRMM) 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

80 mg PO plus dexamethasone 20 mg PO on Days 1 and 3 of each week

Continue until disease progression or unacceptable toxicity

Concomitant treatment

  • Maintain adequate fluid and caloric intake throughout treatment
  • Consider IV hydration for patients at risk of dehydration
  • Provide prophylactic concomitant treatment with a 5–HT3 antagonist and/or other antinausea agents before and during treatment

Dosage Modifications

Dosage reduction steps for adverse effects

  • Starting dose: 80 mg on Days 1 and 3 each week (160 mg/week)
  • First reduction: 100 mg once weekly
  • Second reduction: 80 mg once weekly
  • Third reduction: 60 mg once weekly
  • Discontinue if fourth reduction needed

Thrombocytopenia

  • Platelet count 25,000-75,000/mcL: Reduce by 1 dose level
  • Platelet count 25,000-75,000/mcL with bleeding: Interrupt dosing; restart at 1 dose level lower after bleeding resolved
  • Platelet count <25,000/mcL: Interrupt dosing; monitor until platelet count returns to ≥50,000/mcL, then restart at 1 dose level lower

Neutropenia

  • ANC 0.5-1 x 10^9/L without fever: Reduce by 1 dose level
  • ANC <0.5 x 10^9/L or febrile neutropenia: Interrupt dosing; monitor until neutrophil count returns to ≥1 x 10^9/L, then restart at 1 dose level lower

Anemia

  • Hemoglobin <8 g/dL: Reduce by 1 dose level; administer blood transfusion and/or other treatments per clinical guidelines
  • Life-threatening consequences (urgent intervention indicated): Interrupt dosing; monitor until hemoglobin ≥8 g/dL, then restart at 1 dose level lower; administer blood transfusion and/or other treatments per clinical guidelines

Hyponatremia

  • Serum sodium <130 mmol/L: Interrupt dosing and provide supportive care
  • Monitor until sodium returns to ≥130 mmol/L
  • Restart at 1 dose level lower

Fatigue

  • Grade 2 lasting >7 days or Grade 3: Interrupt dosing
  • Monitor until fatigue resolves to Grade 1 or baseline
  • Restart at 1 dose level lower

Nausea & vomiting

  • Grade 1 or 2
    • Grade 1 or 2 nausea (decrease oral intake without significant weight loss, dehydration, or malnutrition) OR
    • Grade 1 or 2 vomiting (≤5 episodes/day)
    • Maintain dose and initiate additional antinausea medications
  • ≥Grade 3
    • Grade 3 nausea (inadequate oral caloric or fluid intake) OR
    • Grade ≥3 vomiting (≥6 episodes/day)
    • Interrupt dosing; monitor until nausea/vomiting resolved to ≤Grade 2; initiate additional antinausea medications; restart at 1 dose level lower

Diarrhea

  • Grade 2 (inrease of 4-6 stools/day over baseline): If 1st episode, maintain dose and institute supportive care
  • Grade 2 (2nd and subsequent episodes): Reduce by 1 dose level; institute supportive care
  • ≥Grade 3 (increase ≥7 stools/day over baseline; hospitalization indicated): Interrupt dosing and institute supportive care; monitor until resolved to ≤Grade 2; restart at 1 dose level lower

Weight loss and anorexia

  • Weight loss of 10-20% or anorexia associated with significant weight loss or malnutrition
  • Interrupt and institute supportive care
  • Monitor until weight returns to >90% baseline
  • Restart at 1 dose level lower

Other nonhematologic adverse effects

  • Grade 3 or 4 (life-threatening)
    • Interrupt dosing
    • Monitor until resolved to ≤Grade 2
    • Restart at 1 dose level lower

Renal impairment

  • Mild-to-severe (CrCl 15-89 mL/min): No significant differences in pharmacokinetics observed
  • ESRD (CrCl <15 mL/min) or hemodialysis: Effect on pharmacokinetics unknown

Hepatic impairment

  • Mild: No significant differences in pharmacokinetics observed
  • Moderate-to-severe: Effect on pharmacokinetics unknown

Dosing Considerations

Monitor CBC count, standard blood chemistry, and body weight at baseline and during treatment as clinically indicated; monitor more frequently during the first 2 months of treatment

Safety and efficacy not established

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Adverse Effects

>10% (All Grades)

Thrombocytopenia (74%)

Fatigue (73%)

Nausea (72%)

Anemia (59%)

Decreased appetite (53%)

Weight decreased (47%)

Diarrhea (44%)

Vomiting (41%)

Hyponatremia (39%)

Neutropenia (34%)

Leukopenia (28%)

Constipation (25%)

Dyspnea (24%)

Upper respiratory tract infection (21%)

Cough (16%)

Mental status changes (16%)

Pyrexia (16%)

Hyperglycemia (15%)

Dizziness (15%)

Insomnia (15%)

Lymphopenia (15%)

Dehydration (14%)

Hypercreatinemia (14%)

Pneumonia (13%)

Epistaxis (12%)

Hypokalemia (12%) Dysgeusia (11%)

>10% (Grades ≥3)

Thrombocytopenia (61%)

Anemia (40%)

Fatigue (22%)

Hyponatremia (22%)

Neutropenia (21%)

Leukopenia (11%)

1-10% (All Grades)

Blurred vision (10%)

Headache (10%)

1-10% (Grades ≥3)

Lymphopenia (10%)

Nausea (9%)

Pneumonia (9%)

Mental status changes (7%)

Hyperglycemia (7%)

Diarrhea (6%)

Decreased appetite (4.5%)

Vomiting (3.5%)

Dyspnea (3.5%)

Dehydration (3.5%)

Hypokalemia (3.5%)

Upper respiratory tract infection (3%)

Insomnia (2%)

Hypercreatinemia (2%)

Constipation (1.5%)

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Warnings

Contraindications

None

Cautions

See dosage modifications for guidance regarding dose interruption/reduction if adverse effects occur

High incidence of thrombocytopenia reported; median time to onset of first event was 22 days; some patients experienced bleeding; rare reports of death resulting from fatal hemorrhage

Neutropenia commonly reported, potentially increasing infection risk

Nausea and/or vomiting commonly occurs; follow recommendations for adequate hydration and prophylactic antiemetics

Diarrhea commonly reported; monitor for dehydration and provide supportive care as required

Anorexia and weight loss reported

Hyponatremia may rapidly occur (median onset 8 days) and may be severe

Infections reported; most infections were not associated with neutropenia and were caused by nonopportunistic organisms

Neurological toxicity may occur, including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confused state)

Embryofetal toxicity can occur

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Pregnancy

Pregnancy

Based on animal studies and its mechanism of action, selinexor can cause fetal harm if administered to pregnant women

Verify pregnancy status of females of reproductive potential before initiating selinexor

Animal studies

  • Administration to pregnant rats during organogenesis resulted in structural abnormalities and alterations to growth at exposures below those clinically recommended for humans

Contraception

  • Females of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose
  • Males with female partner of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose

Infertility

  • Based on animal studies, selinexor may impair fertility in females and males

Lactation

No data are available regarding the presence of selinexor or its metabolites in human milk, or their effects on the breastfed child or milk production

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 week after the last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Selective inhibitor of nuclear export (SINE) of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1)

XPO1 inhibition leads to accumulation of TSPs in the nucleus, reductions in several oncoproteins (eg, c–myc, cyclin D1), cell cycle arrest, and apoptosis of cancer cells

Selinexor demonstrated proapoptotic activity in vitro in multiple myeloma cell lines, patient tumor samples, and murine xenograft model

Absorption

Peak plasma time: 4 hr

Peak plasma concentration: 124 ng/mL (single-dose)

AUC: 5,386 ng·hr/mL (single-dose)

Distribution

Protein bound: 95%

Vd: 125 L

Metabolism

Metabolized by CYP3A4, multiple UGTs, and glutathione S-transferases

Elimination

Half-life: 6-8 hr

Total clearance: 17.9 L/hr

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Administration

Oral Administration

May take with or without food

Swallow tablet whole; do not break, chew, crush, or divide

On scheduled administration day, take tablet at about the same time of day

Missed, delayed, or vomited dose

  • Take next dose at the next regularly scheduled time
  • Vomited dose: Do not repeat dose; wait until next scheduled dose

Storage

Store at or below 30°C (86°F)

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
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  • Compare formulary status to other drugs in the same class.
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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.