Xpovio (Selinexor)

Dosage and Administration, Starting Dosage and Dosage Modifications for Adverse Reactions in Patients with Severe Hepatic Impairment (

XPOVIO is a nuclear export inhibitor indicated:

• In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (
  1.1 Multiple Myeloma

  • XPOVIO in combination with bortezomib and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
  • XPOVIO in combination with dexamethasone is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma 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.
  ).
• In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma 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 (
  1.1 Multiple Myeloma

  • XPOVIO in combination with bortezomib and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
  • XPOVIO in combination with dexamethasone is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma 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.
  ).
• For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. 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 confirmatory trial(s) (
  1.2 Diffuse Large B-Cell Lymphoma

  XPOVIO is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.

  This indication is approved under accelerated approval based on response rate

  [see Clinical Studies ]

  . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
  ).

• Multiple Myeloma in Combination with Bortezomib and Dexamethasone (XVd):
  Recommended dosage of XPOVIO is 100 mg taken orally once weekly in combination with bortezomib and dexamethasone (
  2.1 Recommended Dosage for Multiple Myeloma

  In Combination with Bortezomib and Dexamethasone (XVd)

  The recommended dosage of XPOVIO is 100 mg taken orally once weekly on Day 1 of each week until disease progression or unacceptable toxicity in combination with:

  • Bortezomib 1.3 mg/m²administered subcutaneously once weekly on Day 1 of each week for 4 weeks followed by 1 week off.
  • Dexamethasone 20 mg taken orally twice weekly on Days 1 and 2 of each week.

  Refer to

  Clinical Studies

  and the prescribing information of bortezomib and dexamethasone for additional dosing information.

  In Combination with Dexamethasone (Xd)

  The recommended dosage of XPOVIO is 80 mg taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity in combination with dexamethasone 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.
  ).
• Multiple Myeloma in Combination with Dexamethasone (Xd):
  Recommended dosage of XPOVIO is 80 mg taken orally on Days 1 and 3 of each week in combination with dexamethasone (
  2.1 Recommended Dosage for Multiple Myeloma

  In Combination with Bortezomib and Dexamethasone (XVd)

  The recommended dosage of XPOVIO is 100 mg taken orally once weekly on Day 1 of each week until disease progression or unacceptable toxicity in combination with:

  • Bortezomib 1.3 mg/m²administered subcutaneously once weekly on Day 1 of each week for 4 weeks followed by 1 week off.
  • Dexamethasone 20 mg taken orally twice weekly on Days 1 and 2 of each week.

  Refer to

  Clinical Studies

  and the prescribing information of bortezomib and dexamethasone for additional dosing information.

  In Combination with Dexamethasone (Xd)

  The recommended dosage of XPOVIO is 80 mg taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity in combination with dexamethasone 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.
  ).
• DLBCL:
  Recommended dosage of XPOVIO is 60 mg taken orally on Days 1 and 3 of each week (
  2.2 Recommended Dosage for Diffuse Large B-Cell Lymphoma

  The recommended dosage of XPOVIO is 60 mg taken orally on Days 1 and 3 of each week until disease progression or unacceptable toxicity.
  ).
• See Full Prescribing Information for dosage in patients with severe hepatic impairment (
  2.6 Starting Dosage and Dosage Modifications for Adverse Reactions in Patients with Severe Hepatic Impairment

  For patients with severe hepatic impairment, defined by NCI-ODWG (National Cancer Institute Organ Dysfunction Working Group) criteria as total bilirubin >3x upper limit of normal with any level of AST, use the starting dosage of XPOVIO as shown in Table 5

  [see Use in Specific Populations and Clinical Pharmacology ].

  See Table 6for dosage modifications for adverse reactions in patients with severe hepatic impairment.

  Table 5: XPOVIO Starting Dosage in Patients with Severe Hepatic Impairment

  AST = aspartate aminotransferase; ULN = upper limit of normal
  Total Bilirubin Levels	XPOVIO Dosage
  	Multiple Myeloma in Combination with Bortezomib and Dexamethasone (XVd)	Multiple Myeloma in Combination with Dexamethasone (Xd)	Diffuse Large B Cell Lymphoma
  >3x ULN (and any AST)	80 mg once weekly	100 mg once weekly	40 mg Days 1 and 3 of each week (80 mg total per week)

  Table 6: XPOVIO Dosage Modifications for Adverse Reactions for Patients with Severe Hepatic Impairment

  	Multiple Myeloma In Combination with Bortezomib and Dexamethasone (XVd)	Multiple Myeloma In Combination with Dexamethasone (Xd)	Diffuse Large B-Cell Lymphoma
  Recommended Starting Dosage	80 mg once weekly	100 mg once weekly	40 mg Days 1 and 3 of each week (80 mg total per week)
  First Reduction	60 mg once weekly	80 mg once weekly	60 mg once weekly
  Second Reduction	40 mg once weekly	60 mg once weekly	40 mg once weekly
  Third Reduction	Permanently discontinue	Permanently discontinue	Permanently discontinue
  ,
  8.6 Hepatic Impairment

  No dose adjustment for selinexor is required for mild (total bilirubin ≤1x ULN and AST >1x ULN, or total bilirubin >1.0 to 1.5x ULN and any AST) or moderate (total bilirubin >1.5x to 3.0x ULN, and any AST) hepatic impairment. Reduce the starting dose in patients with severe (total bilirubin >3.0x ULN, and any AST) hepatic impairment

  [see Dosage and Administration and Clinical Pharmacology ]

  .
  ).

Tablets:

10 mg, blue, round, bi-convex, film-coated tablets with “X10” debossed on one side and nothing on the other side.

20 mg, blue, round, bi-convex, film-coated tablets with “K20” debossed on one side and nothing on the other side.

40 mg tablets, blue, oval, film-coated, debossed on both sides with “X40”.

50 mg tablets, blue, oval, film-coated, debossed on both sides with “X50”.

60 mg tablets, blue, oval, film-coated, debossed on both sides with “X60”.

80 mg tablets, blue, oval, film-coated, debossed on both sides with “X80”.