Dosing & Uses
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
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%)
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
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.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
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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Patient Handout
Formulary
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