dverse Reactions
Recommended XPOVIO dosage reductions and dosage modifications for adverse reactions arepresented in Table 1 and Table 2, respectively.
Refer to the dexamethasone prescribing information for dexamethasone dosage modifications due toadverse reactions.
Table 1: XPOVIO Dosage Reduction Steps for Adverse Reactions
Recommended Starting
Dosage
First Reduction Second Reduction Third Reduction
80 mg Discontinue
Days 1 and 3 of each week
(160 mg total per week)
100 mg
once weekly
80 mg
once weekly
60 mg
once weekly
Table 2: XPOVIO Dosage Modification Guidelines for Adverse Reactions
Adverse Reactiona Occurrence Action
Hematologic Adverse Reactions
Thrombocytopenia
Platelet count 25,000 to
less than 75,000/mcL
Any • Reduce XPOVIO by 1 dose level (see Table 1).
Platelet count 25,000 to
less than 75,000/mcL with
concurrent bleeding
Any • Interrupt XPOVIO.
• Restart XPOVIO at 1 dose level lower (see Table 1), after bleeding has
resolved.
Platelet count less than
25,000/mcL
Any • Interrupt XPOVIO.
• Monitor until platelet count returns to at least 50,000/mcL.
• Restart XPOVIO at 1 dose level lower (see Table 1).
Neutropenia
Absolute neutrophil count
of 0.5 to 1.0 x 109
/L
without fever
Any • Reduce XPOVIO by 1 dose level (see Table 1).
Absolute neutrophil count
less than 0.5 x 109
/L
OR febrile neutropenia
Any • Interrupt XPOVIO.
• Monitor until neutrophil counts return to 1.0 x 109
/L or higher.
• Restart XPOVIO at 1 dose level lower (see Table 1).
Anemia
Hemoglobin less than
8.0 g/dL
Any • Reduce XPOVIO by 1 dose level (see Table 1).
• Administer blood transfusions and/or other treatments per clinical guidelines.
Life‐threatening
consequences
(urgent intervention
indicated)
Any • Interrupt XPOVIO.
• Monitor hemoglobin until levels return to 8 g/dL or higher.
• Restart XPOVIO at 1 dose level lower (see Table 1).
• Administer blood transfusions and/or other treatments per clinical guidelines.
Non‐Hematologic Adverse Reactions
Hyponatremia
Sodium level 130 mmol/Lor less
Any • Interrupt XPOVIO and provide appropriate supportive care.
• Monitor until sodium levels return to 130 mmol/L or higher.
• Restart XPOVIO at 1 dose level lower (see Table 1).
Fatigue
Grade 2 lasting greater
than 7 days
OR Grade 3
Any • Interrupt XPOVIO.
• Monitor until fatigue resolves to Grade 1 or baseline.
• Restart XPOVIO at 1 dose level lower (see Table 1).
Nausea and Vomiting
Grade 1 or 2 nausea (oral
intake decreased without
significant weight loss,
dehydration or
malnutrition)
OR Grade 1 or 2 vomiting
(5 or fewer episodes per
day)
Any • Maintain XPOVIO and initiate additional anti‐nausea medications.
Grade 3 nausea
(inadequate oral caloric or
fluid intake)
OR Grade 3 or higher
vomiting (6 or more
episodes per day)
Any • Interrupt XPOVIO.
• Monitor until nausea or vomiting has resolved to Grade 2 or lower or
baseline.
• Initiate additional anti‐nausea medications.
• Restart XPOVIO at 1 dose level lower (see Table 1).
Diarrhea
Grade 2 (increase of 4 to 6
stools per day over
baseline)
1st
• Maintain XPOVIO and institute supportive care.
2nd and
subsequent
• Reduce XPOVIO by 1 dose level (see Table 1).
• Institute suppor |
