Xpovio (selinexor) for Multiple Myeloma: Side Effects & Dosage

Generic drug: selinexor

Brand name: Xpovio

What is Xpovio (selinexor), and how does it work?

Xpovio is a prescription medicine used:

• in combination with dexamethasone to treat adults with multiple myeloma (MM) that has come back (relapsed) or that did not respond to previous treatment (refractory), and
  • who have received at least 4 prior therapies, and
  • whose disease did not respond to (refractory) to at least 2 proteasome inhibitor medicines, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody medicine.
• to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory) and who have received at least 2 prior therapies It is not known if Xpovio is safe and effective in children less than 18 years of age.

What are the side effects of Xpovio?

Xpovio can cause serious side effects, including:

• Nausea and vomiting.
  Nausea and vomiting are common with Xpovio and can sometimes be severe.
  Nausea and vomiting may affect your ability to eat and drink well. You can
  lose too much body fluid and body salts (electrolytes) and may be at risk
  for becoming dehydrated. You may need to receive intravenous (IV) fluids or
  other treatments to help prevent dehydration. Your healthcare provider will
  prescribe anti-nausea medicines for you to take before you start and during
  treatment with Xpovio.
• Diarrhea. Diarrhea is common with Xpovio and can sometimes be severe. You can lose too much body fluid and body salts (electrolytes) and may be at risk for becoming dehydrated. You may need to receive IV fluids or other treatments to help prevent dehydration. Your healthcare provider will prescribe anti-diarrhea medicine for you as needed.
• Loss of appetite and weight loss. Loss of appetite and weight loss are common with Xpovio and can sometimes be severe. Tell your healthcare provider if you have a decrease or loss of appetite and if you notice that you are losing weight. Your healthcare provider may prescribe medicines that can help increase your appetite or prescribe other kinds of nutritional support.
• Decreased sodium levels in your blood. Decreased sodium levels in your blood is common with Xpovio but can also sometimes be severe. Low sodium levels in your blood can happen if you have nausea, vomiting, or diarrhea, you become dehydrated, or if you have loss of appetite with Xpovio. You may not have any symptoms of a low sodium level. Your healthcare provider may talk with you about your diet and prescribe IV fluids for you based on the sodium levels in your blood. Your healthcare provider will do blood tests before you start taking Xpovio, and often during the first 2 months of treatment, and then as needed during treatment to monitor the sodium levels in your blood.
• Serious infections. Infections are common with Xpovio and can be serious and can sometimes cause death. Xpovio can cause infections including upper or lower respiratory tract infections, such as pneumonia, and an infection throughout your body (sepsis). Tell your healthcare provider right away if you have any signs or symptoms of an infection such as cough, chills or fever, during treatment with Xpovio.
• Neurologic side effects. Xpovio can cause neurologic side effects that can sometimes be severe and life-threatening.
  • Xpovio can cause dizziness, fainting, decreased alertness, and changes in your mental status including confusion and decreased awareness of things around you (delirium).
  • In some people, Xpovio may also cause problems with thinking (cognitive problems), seeing or hearing things that are not really there (hallucinations), and may become very sleepy or drowsy.

Tell your healthcare provider right away if you get any of these signs or symptoms.

Your healthcare provider may change your dose of Xpovio, stop your treatment for a period of time, or completely stop your treatment if you have certain side effects during treatment with Xpovio.

Common side effects of Xpovio include:

• tiredness
• low red blood cell count (anemia). Symptoms may include tiredness and shortness of breath.
• constipation
• shortness of breath
• increased blood sugar
• changes in body salt and mineral levels in your blood
• changes in kidney and liver function blood tests

Xpovio may cause fertility problems in males and females, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of Xpovio.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the dosage for Xpovio?

Recommended Dosage For Multiple Myeloma

In Combination With Bortezomib And Dexamethasone (SVd)

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/m² administered 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 the prescribing information of bortezomib and dexamethasone for additional dosing information.

In Combination With Dexamethasone (Sd)

• 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.

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.

Recommended Monitoring For Safety

• Monitor complete blood count (CBC) with differential, standard blood chemistries, body weight, nutritional status, and volume status at baseline and during treatment as clinically indicated.
• Monitor more frequently during the first three months of treatment.
• Assess the need for dosage modifications of Xpovio for adverse
  reactions.

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
antiemetics. Administer a 5-HT3 receptor antagonist and other anti-nausea agents
prior to and during treatment with Xpovio.

Dosage Modification For Adverse Reactions

Recommended
Xpovio dosage reduction steps are presented in Table 1.

Table 1:
Xpovio Dosage Reduction Steps for Adverse Reactions

Multiple Myeloma In Combination with Bortezomib and Dexamethasone (SVd)Multiple Myeloma In Combination with Dexamethasone (Sd)Diffuse Large B-Cell LymphomaRecommended Starting Dosage100 mg once weekly80 mg Days 1 and 3 of each week
(160 mg total per week)60 mg Days 1 and 3 of each week
(120 mg total per week)First Reduction80 mg once weekly100 mg once weekly40 mg Days 1 and 3 of each week
(80 mg total per week)Second Reduction60 mg once weekly80 mg once weekly60 mg once weeklyThird Reduction40 mg once weekly60 mg once weekly40 mg once weeklyFourth ReductionPermanently discontinuePermanently discontinuePermanently discontinue

Recommended dosage modifications for hematologic adverse reactions in patients with multiple myeloma and DLBCL are presented in Table 2 and Table 3, respectively. Recommended dosage modifications for nonhematologic adverse reactions are presented in Table 4.

Table 2:
Xpovio Dosage Modification Guidelines for Hematologic Adverse Reactions in Patients with Multiple Myeloma

Adverse ReactionOccurrenceActionThrombocytopenia Platelet count 25,000 to less than 75,000/mcLAny

• Reduce
  Xpovio by 1 dose level (see Table 1).

Platelet count 25,000 to less than 75,000/mcL with concurrent bleedingAny

• Interrupt
  Xpovio.
• Restart Xpovio at 1 dose level lower (see Table 1) after bleeding has resolved.
• Administer platelet transfusions per clinical guidelines.

Platelet count less than 25,000/mcLAny

• 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 x 10⁹/L without feverAny

• Reduce
  Xpovio by 1 dose level (see Table 1).

Absolute neutrophil count less than 0.5 x 10⁹/L
OR
febrile neutropeniaAny

• Interrupt
  Xpovio.
• Monitor until neutrophil counts return to 1 x 10⁹/L or higher.
• Restart
  Xpovio at 1 dose level lower (see Table 1).

AnemiaHemoglobin less than 8 g/dLAny

• Reduce
  Xpovio by 1 dose level (see Table 1).
• Administer blood transfusions per clinical guidelines.

Life-threatening consequencesAny

• 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 per clinical guidelines.

Table 3:
Xpovio Dosage Modification Guidelines for Hematologic Adverse Reactions in Patients with Diffuse Large B-Cell Lymphoma

Adverse ReactionOccurrenceActionThrombocytopenia Platelet count 50,000 to less than 75,000/mcLAny

• Interrupt one dose of
  Xpovio.
• Restart Xpovio at the same dose level.

Platelet count 25,000 to less than 50,000/mcL without bleeding1st

• Interrupt
  Xpovio.
• Monitor until platelet count returns to at least 50,000/mcL.
• Reduce
  Xpovio by 1 dose level (see Table 1).

Platelet count 25,000 to less than 50,000/mcL with concurrent bleedingAny

• Interrupt
  Xpovio.
• Monitor until platelet count returns to at least 50,000/mcL.
• Restart
  Xpovio at 1 dose level lower (see Table 1), after bleeding has resolved.
• Administer platelet transfusions per clinical guidelines.

Platelet count less than 25,000/mcLAny

• Interrupt
  Xpovio.
• Monitor until platelet count returns to at least 50,000/mcL.
• Restart
  Xpovio at 1 dose level lower (see Table 1).
• Administer platelet transfusions per clinical guidelines.

Neutropenia Absolute neutrophil count of 0.5 to less than 1 x 10⁹/L without fever1st occurrence

• Interrupt
  Xpovio.
• Monitor until neutrophil counts return to 1 x 10⁹/L or higher.
• Restart
  Xpovio at the same dose level.

Recurrence

• Interrupt
  Xpovio.
• Monitor until neutrophil counts return to 1 x 10⁹/L or higher.
• Administer growth factors per clinical guidelines.
• Restart
  Xpovio at 1 dose level lower (see Table 1).

Absolute neutrophil count less than 0.5 x 10⁹/L
OR
Febrile neutropeniaAny

• Interrupt
  Xpovio.
• Monitor until neutrophil counts return to 1 x 10⁹/L or higher.
• Administer growth factors per clinical guidelines.
• Restart
  Xpovio at 1 dose level lower (see Table 1).

AnemiaHemoglobin less than 8 g/dLAny

• Reduce
  Xpovio by 1 dose level (see Table 1).
• Administer blood transfusions per clinical guidelines.

Life-threatening consequencesAny

• 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 per clinical guidelines.

Table 4:
Xpovio Dosage Modification Guidelines for Non–Hematologic Adverse Reactions

Adverse ReactionOccurrenceActionNausea 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)1^st

• Maintain
  Xpovio and institute supportive care.

2^nd 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 malnutritionAny

• 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).

Hyponatremia Sodium level 130 mmol/L or lessAny

• Interrupt
  Xpovio, evaluate, and provide supportive care.
• Monitor until sodium levels return to greater than 130 mmol/L.
• Restart
  Xpovio at 1 dose level lower (see Table 1).

FatigueGrade 2 lasting greater than 7 days
OR
Grade 3Any

• Interrupt
  Xpovio.
• Monitor until fatigue resolves to Grade 1 or baseline.
• Restart
  Xpovio at 1 dose level lower (see Table 1).

Ocular Toxicity Grade 2, excluding cataractAny

• Perform ophthalmologic evaluation.
• Interrupt
  Xpovio and provide supportive care.
• Monitor until ocular symptoms resolve to Grade 1 or baseline.
• Restart
  Xpovio at 1 dose level lower (see Table 1).

Grade ≥3, excluding cataractAny

• Permanently discontinue
  Xpovio.
• Perform ophthalmologic evaluation.

Other Non-Hematologic Adverse ReactionsGrade 3 or 4Any

• Interrupt
  Xpovio.
• Monitor until resolved to Grade 2 or lower; restart Xpovio at 1 dose level lower (see Table 1).

Administration

• 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.

What drugs interact with Xpovio?

No Information Provided

Is Xpovio safe to use while pregnant or breastfeeding?

• Based on findings in animal studies and its mechanism of action, Xpovio can cause fetal harm when administered to a pregnant woman.
• There are no available data in pregnant women to inform the drug-associated risk.
• There is no information 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 a breastfed
  child,  women should not breastfeed during treatment with Xpovio and for 1 week after the last dose.