Dosing & Uses
Dosage Forms & Strengths
tablet
- 20mg
Multiple Myeloma
In combination with bortezomib and dexamethasone (SVd)
- Indicated, in combination with bortezomib and dexamethasone, for multiple myeloma (MM) have received ≥1 prior therapy
-
35-day cycle
- Selinexor 100 mg PO qWeek on Day 1; continue until disease progression or unacceptable toxicity
- Bortezomib 1.3 mg/m2 SC qWeek on Day of each week x 4 weeks followed by 1 week off
- Dexamethasone 20 mg PO twice weekly on Days 1 and 2 of each week
- Refer to prescribing information of bortezomib and dexamethasone for additional dosing information
In combination with dexamethasone (Sd)
- 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
- Selinexor 80 mg PO plus dexamethasone 20 mg PO on Days 1 and 3 of each week
- Continue until disease progression or unacceptable toxicity
- Refer to prescribing information of dexamethasone for additional dosing information
Diffuse Large B-Cell Lymphoma
Indicated for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, in patients previously treated with at least 2 lines of systemic therapy
60 mg PO on Days 1 and 3 of each week
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dosage reduction recommendations for adverse effects
-
SVd
- Starting dose: 100 mg once weekly
- First reduction: 80 mg once weekly
- Second reduction: 60 mg once weekly
- Third reduction: 40 mg once weekly
- Fourth reduction: Permanently discontinue
-
Sd
- 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
- Fourth reduction: Permanently discontinue
-
DLBCL
- Starting dose: 60 mg on Days 1 and 3 each week (120 mg/week)
- First reduction: 40 mg Days 1 and 3 of each week (80 mg total per week)
- Second reduction: 60 mg once weekly
- Third reduction: 40 mg once weekly
- Fourth reduction: Permanently discontinue
Thrombocytopenia (Sd and SVd)
- 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
Thrombocytopenia (DLBCL)
- Platelet count 50,000 to <75,000/mcL: Interrupt 1 dose; restart at the same dose level
-
Platelet count 25,000 to <50,000/mcL without bleeding
- First occurrence: Interrupt dose; monitor until platelet count returns to ≥50,000/mcL
- Reduce by 1 dose level
-
Platelet count 25,000 to <50,000/mcL with concurrent bleeding
- Interrupt dose; monitor until platelet count returns to ≥50,000/mcL
- Restart at 1 dose level lower, after bleeding has resolved
- Administer platelet transfusions per clinical guidelines
-
Platelet count <25,000/mcL
- Interrupt dose; monitor until platelet count returns to ≥50,000/mcL
- Restart at 1 dose level lower
- Administer platelet transfusions per clinical guidelines
Neutropenia (Sd and SVd)
- ANC 0.5-1 x 109/L without fever: Reduce by 1 dose level
- ANC <0.5 x 109/L or febrile neutropenia: Interrupt dosing; monitor until neutrophil count returns to ≥1 x 109/L, then restart at 1 dose level lower
Neutropenia (DLBCL)
-
ANC 0.5 to <1 x 10^9/L without fever
- First occurrence: Interrupt dose; monitor until neutrophil counts return to ≥1 x 109/L; restart at the same dose level
- Recurrence: Interrupt dose; monitor until neutrophil counts return to ≥1 x 109/L; administer growth factors per clinical guidelines; restart at 1 dose level lower
- ANC <0.5 x 109/L or febrile neutropenia: Interrupt dosing; monitor until neutrophil count returns to ≥1 x 109/L; administer growth factors per clinical guidelines; 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
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
Monitor parameters
- Monitor at baseline and as clinically indicated
- Monitor more frequently during the first 3 months of treatment
- Assess the need for dosage modifications for adverse reaction
- CBC with differential
- Standard blood chemistries
- Body weight
- Nutritional status
- Volume status
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
All grades
-
SVd
- Platelet count decrease (92%)
- Lymphocyte count decreased (77%)
- Hemoglobin decrease (71%)
- Glucose increase (62%)
- Phosphate increase (61%)
- Fatigue (59%)
- Sodium decrease (58%)
- Calcium decrease (55%)
- Nausea (50%)
- Neutrophil count decrease (48%)
- BUN increase (41%)
- ALT increase (33%)
- Peripheral neuropathy (32%)
- Diarrhea (32%)
- Upper respiratory tract infection (29%)
- Creatinine increase (28%)
- Albumin decrease (27%)
- Potassium decrease (27%)
- Magnesium decrease (27%)
- Appetite decrease (26%)
- AST increase (24%)
- Cataract (22%)
- Vomiting (21%)
- Potassium increase (18%)
- Bilirubin increase (16%)
- Pyrexia (15%)
- Blurred vision (13%)
- Dizziness (12%)
- ALP increase (12%)
-
Sd
- 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%)
-
DLBCL
- Fatigue (63%)
- Nausea (57%)
- Diarrhea (37%)
- Appetite decrease (37%)
- Weight decrease (30%)
- Constipation (29%)
- Vomiting (28%)
- Pyrexia (22%)
- Cough (18%)
- Edema (17%)
- Upper respiratory tract infection (17%)
- Dizziness (16%)
- Musculoskeletal pain (15%)
- Taste disorder (13%)
- Hypotension (13%)
- Mental status changes (11%)
Grade 3 or 4
-
SVd
- Platelet count decrease (43%)
- Lymphocyte count decrease (38%)
- Fatigue (28%)
- Phosphate decrease (23%)
- Hemoglobin decrease (17%)
- Sodium decrease (14%)
- Neutrophil count decrease (12%)
- Sd H5
- Thrombocytopenia (61%)
- Anemia (40%)
- Fatigue (22%)
- Hyponatremia (22%)
- Neutropenia (21%)
- Leukopenia (11%)
- DLBCL H5
- Fatigue (15%)
1-10%
All grades
-
Sd
- Vision blurred (10%)
- Headache (10%)
-
DLBCL
- Abdominal pain (10%)
- Dyspnea (10%)
- Pneumonia (10%)
- Urinary tract infection (10%)
- Peripheral neuropathy, sensory (10%)
- Hemorrhage (10%)
Grade 3 or 4
-
SVd
- Cataract (9%)
- Mental status changes (9%)
- Nausea (8%)
- Diarrhea (6%)
- Potassium decrease (6%)
- BUN increase (5%)
- Peripheral neuropathy (4.6%)
- Vomiting (4.1%)
- Potassium increase (4.1%)
- Glucose increase (3.8%)
- Decreased appetite (3.6%)
- Creatinine increase (3.6%)
- Syncope (3.6%)
- ALT increase (3.1%)
- Decreased weight (2.1%)
- Calcium decrease (2.1%)
- Pyrexia (1.5%)
- AST increase (1.5%)
- Bilirubin increase (1%)
-
Sd
- 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%)
-
DLBCL
- Nausea (6%)
- Pneumonia (6%)
- Pyrexia (4.5%)
- Appetite decrease (3.7%)
- Mental status changes (3.7%)
- Diarrhea (3%)
- Urinary tract infection (3%)
- Hypotension (3%)
- Edema (2.2%)
- Musculoskeletal pain (2.2%)
- Vomiting (1.5%)
- Dyspnea (1.5%)
- Upper respiratory tract infection (1.5%)
<1%
Grade 3 or 4
-
SVd
- Dizziness
- Blurred vision
- Albumin decrease
- Magnesium decrease
-
Sd
- Weight decreased
- Pyrexia
- Epistaxis
- Vision blurred
-
DLBCL
- Hemorrhage
- Dizziness
- Blurred vision
Warnings
Contraindications
None
Cautions
Life-threatening thrombocytopenia, potentially leading to hemorrhage may occur; monitor platelet counts at baseline and during treatment; institute platelet transfusion and/or other treatments as clinically indicated; monitor patients for signs and symptoms of bleeding and evaluate promptly; interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction
Neutropenia commonly reported, potentially increasing infection risk; obtain white blood cell counts with differential at baseline and throughout treatment; monitor more frequently during first three months of treatment; monitor patients for signs and symptoms of concomitant infection and evaluate promptly; consider supportive measures, including antimicrobials and growth factors (eg, G-CSF); interrupt, reduce dose or permanently discontinue based on severity of adverse reaction
Nausea and/or vomiting commonly occurs; follow recommendations for adequate hydration and prophylactic antiemetics; provide prophylactic antiemetics; administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment; interrupt, reduce dose or permanently discontinue based on severity of adverse reaction; administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated
Diarrhea commonly reported; monitor for dehydration and provide supportive care as required; interrupt, reduce dose or permanently discontinue based on severity of adverse reaction; provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated
Anorexia and weight loss reported; monitor weight, nutritional status, and volume status at baseline and throughout treatment; monitor more frequently during first three months of treatment; interrupt, reduce dose or permanently discontinue based on severity of adverse reaction; provide nutritional support, fluids, and electrolyte repletion as clinically indicated
Hyponatremia may rapidly occur (median onset 8 days) and may be severe; monitor sodium level at baseline and throughout treatment; monitor more frequently during first two months of treatment; correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels; assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review; interrupt, reduce dose or permanently discontinue based on severity of adverse reaction
Serious and fatal infections reported; most infections were not associated with neutropenia and were caused by nonopportunistic organisms; monitor for signs and symptoms of infection, evaluate and treat promptly
Neurological toxicity may occur, including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confused state); advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until neurological toxicity fully resolves; optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes; institute fall precautions as appropriate
Embryofetal toxicity can occur
New onset or exacerbation of cataracts has occurred; median time to new onset was 228 days and 237 days for worsening of cataract in patients with cataract at start of therapy; treatment usually requires surgical removal of cataract
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
- 60 mg-dose: 442 ng/mL
- 80 mg-dose: 680 ng/mL
AUC
- 60 mg-dose: 4,096 ng⋅hr/mL
- 80 mg-dose: 5,386 ng⋅hr/mL
Distribution
Vd: 133 L
Protein bound: 95%
Metabolism
Metabolized by CYP3A4, multiple UGTs, and glutathione S-transferases
Elimination
Half-life: 6-8 hr
Clearance: 18.6 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 30ºC (86ºF)
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Patient Handout
Formulary
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