XPOVIO

XPOVIO- selinexor tablet, film coated
Karyopharm Therapeutics Inc.

1 INDICATIONS AND USAGE

XPOVIO is indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended starting dosage of XPOVIO is 80 mg (four 20 mg tablets) taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity [see Clinical Studies (14.1)].

The recommended starting dosage of dexamethasone is 20 mg taken orally with each dose of XPOVIO on Days 1 and 3 of each week. For additional information regarding the administration of dexamethasone, refer to its prescribing information.

Each XPOVIO dose should be taken at approximately the same time of day, and each tablet should be swallowed whole with water. Do not break, chew, crush, or divide the tablets.

If a dose of XPOVIO is missed or delayed, instruct patients to take their next dose at the next regularly scheduled time. If a patient vomits a dose of XPOVIO, the patient should not repeat the dose and the patient should take the next dose on the next regularly scheduled day.

2.2 Recommended Monitoring for Safety

Monitor complete blood count (CBC), standard blood chemistry, and body weight at baseline and during treatment as clinically indicated. Monitor more frequently during the first two months of treatment [see Warning and Precautions (5.1, 5.2, 5.3, and 5.4)].

2.3 Recommended Concomitant Treatments

Advise patients to maintain adequate fluid and caloric intake throughout treatment.

Consider intravenous hydration for patients at risk of dehydration.

Provide prophylactic concomitant treatment with a 5-HT3 antagonist and/or other anti-nausea agents prior to and during treatment with XPOVIO [see Warnings and Precautions (5.3)].

2.4 Dosage Modification for Adverse Reactions

Recommended XPOVIO dosage reductions and dosage modifications for adverse reactions are presented in Table 1 and Table 2, respectively.

Refer to the dexamethasone prescribing information for dexamethasone dosage modifications due to adverse reactions.

Table 1: XPOVIO Dosage Reduction Steps for Adverse Reactions
Recommended Starting Dosage First Reduction Second Reduction Third Reduction Discontinue
80 mgDays 1 and 3 of each week(160 mg total per week) 100 mgonce weekly 80 mgonce weekly 60 mgonce weekly
Table 2: XPOVIO Dosage Modification Guidelines for Adverse Reactions

a. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Adverse Reaction a 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 /LOR 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/L or 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 daysOR 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 supportive care.
Grade 3 or higher (increase of 7 stools or more per day over baseline; hospitalization indicated) Any
  • Interrupt XPOVIO and institute supportive care.
  • Monitor until diarrhea resolves to Grade 2 or lower.
  • Restart XPOVIO at 1 dose level lower (see Table 1).
Weight Loss and Anorexia
Weight loss of 10% to less than 20% OR anorexia associated with significant weight loss or malnutrition Any
  • Interrupt XPOVIO and institute supportive care.
  • Monitor until weight returns to more than 90% of baseline weight.
  • Restart XPOVIO at 1 dose level lower (see Table 1).
Other Non-Hematologic Adverse Reactions
Grade 3 or 4 (life threatening) Any
  • Interrupt XPOVIO.
  • Monitor until resolved to Grade 2 or lower, restart XPOVIO at 1 dose level lower (see Table 1).
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