Xpovio

Tell your healthcare provider immediately if you experience any of these signs or symptoms.

Your healthcare provider may adjust your dose of Xpovio, pause your treatment for a period of time, or completely halt your treatment if you experience certain side effects while taking 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 impact your ability to have children. Discuss any concerns about fertility with your healthcare provider.

These are not all the potential side effects of Xpovio.

Contact your doctor for medical guidance about side effects. You can report side effects to the 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/m 2 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

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

• Reduce Xpovio by 1 dose level (see Table 1).
• Interrupt Xpovio.
• Restart Xpovio at 1 dose level lower (see Table 1) after bleeding has resolved.
• Administer platelet transfusions per clinical guidelines.
• Interrupt Xpovio.
• Monitor until platelet count returns to at least 50,000/mcL.
• Restart Xpovio at 1 dose level lower (see Table 1).
• Reduce Xpovio by 1 dose level (see Table 1).
• Interrupt Xpovio.
• Monitor until neutrophil counts return to 1 x 10 9 /L or higher.
• Restart Xpovio at 1 dose level lower (see Table 1).
• Reduce Xpovio by 1 dose level (see Table 1).
• Administer blood transfusions per clinical guidelines.
• 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

• Interrupt one dose of Xpovio.
• Restart Xpovio at the same dose level.
• Interrupt Xpovio.
• Monitor until platelet count returns to at least 50,000/mcL.
• Reduce Xpovio by 1 dose level (see Table 1).
• 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.
• 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.
• Interrupt Xpovio.
• Monitor until neutrophil counts return to 1 x 10 9 /L or higher.
• Restart Xpovio at the same dose level.
• Interrupt Xpovio.
• Monitor until neutrophil counts return to 1 x 10 9 /L or higher.
• Administer growth factors per clinical guidelines.
• Restart Xpovio at 1 dose level lower (see Table 1).
• Interrupt Xpovio.
• Monitor until neutrophil counts return to 1 x 10 9 /L or higher.
• Administer growth factors per clinical guidelines.
• Restart Xpovio at 1 dose level lower (see Table 1).
• Reduce Xpovio by 1 dose level (see Table 1).
• Administer blood transfusions per clinical guidelines.
• 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.

Administration

• Each Xpovio dose should be taken at approximately the same time of day, and each tablet should be swallowed whole with water. The tablets should not be broken, chewed, crushed, or divided.
• 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, they should not take an additional dose. The next dose should be taken on the next regularly scheduled day.