Xpovio

Generic name: selinexor
Drug class: Miscellaneous antineoplastics

Medically reviewed by  A Ras MD.

What is Xpovio?

Xpovio is a prescription medicine used in combination with the medicines Velcade (bortezomib) and dexamethasone to treat adults with multiple myeloma (MM) who have received at least one prior treatment for their disease.

It is 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.

It is used 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.

Description

Selinexor is a nuclear export inhibitor. Selinexor is (2Z)‐3‐{3‐[3,5‐bis(trifluoromethyl)phenyl]‐1H‐1,2,4‐triazol‐1yl}‐N‘‐(pyrazin‐2‐yl)prop‐2‐enehydrazide. It is a white to off‐white powder and has the molecular formula C17H11F6N7O and a molecular mass of 443.31 g/mol. The molecular structure is shown below:

XPOVIO tablets for oral dosing are supplied in four strengths, with each tablet containing 20 mg, 40 mg, 50 mg, or 60 mg of selinexor as the active ingredient. The inactive ingredients are colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, Opadry 200 clear, Opadry II blue, povidone K30, and sodium lauryl sulfate.

Mechanism of Action

In nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus and reductions in several oncoproteins, such as c‐myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells. Selinexor demonstrated pro‐apoptotic activity in vitro in multiple myeloma cells and showed anti‐tumor activity in murine xenograft models of multiple myeloma and diffuse large B cell lymphoma. The combination of selinexor and dexamethasone or bortezomib demonstrated synergistic cytotoxic effects in multiple myeloma in vitro and increased anti‐tumor activity in murine xenograft multiple myeloma models in vivo, including those resistant to proteasome inhibitors.

What is the most important information I should know about Xpovio?

Xpovio can cause serious side effects, including:

• Low platelet counts. Low platelet counts are common with Xpovio and can lead to bleeding which can be severe and can sometimes cause death. Your healthcare provider may prescribe platelet transfusions or other treatments for your low platelet counts.
  Tell your healthcare provider right away if you have any bleeding or easy bruising during treatment with Xpovio.
• Low white blood cell counts. Low white blood cell counts are common with Xpovio and can sometimes be severe. You may have an increased risk of getting bacterial infections during treatment with Xpovio. Your healthcare provider may prescribe antibiotics if you have signs or symptoms of infection, or certain medicines to help increase your white blood cell count, if needed.Your healthcare provider will do blood tests before you start taking Xpovio, and often during the first 3 months of treatment, and then as needed during treatment to monitor you for side effects.

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.

See “What are the possible side effects of Xpovio?” for more information about side effects.

What should I tell my healthcare provider before taking Xpovio?

Before taking Xpovio, tell your healthcare provider about all of your medical conditions, including if you:

• have or have had a recent or active infection
• have or have had bleeding problems
• are pregnant or plan to become pregnant. Xpovio can harm your unborn baby.
  Females who are able to become pregnant:
  • Your healthcare provider will check to see if you are pregnant before you start taking Xpovio.
  • You should use effective birth control (contraception) during treatment with Xpovio and for 1 week after your last dose.
  • Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with Xpovio.

  Males with female partners who are able to become pregnant:

  • You should use effective birth control during treatment with Xpovio and for 1 week after your last dose.
• are breastfeeding or plan to breastfeed. It is not known if Xpovio passes into your breast milk.
  • Do not breastfeed during treatment with Xpovio and for 1 week after your last dose of Xpovio.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Talk with your healthcare provider before taking any new medicines.

How should I take Xpovio?

• Take Xpovio exactly as prescribed by your healthcare provider.
• If you have multiple myeloma, your healthcare provider will prescribe dexamethasone with your Xpovio treatment. Take dexamethasone exactly as prescribed.
• Your healthcare provider will tell you how much Xpovio to take and when to take it. Do not change your dose or stop taking Xpovio without talking to your healthcare provider first.
• Swallow Xpovio tablets whole with water. Do not break, chew, crush, or divide the tablets.
• Be sure to take any medicines prescribed by your healthcare provider before and during treatment with Xpovio to help prevent nausea and vomiting. Tell your healthcare provider if the prescribed medicine does not control your nausea and vomiting.
• It is important for you to drink enough fluids to help prevent dehydration and to eat enough calories to help prevent weight loss during treatment with Xpovio. Talk to your healthcare provider if this is a problem for you. See “What are the possible side effects of Xpovio?”
• If you miss a dose of Xpovio, take your next dose at your next regularly scheduled day and time.
• If you vomit after taking a dose of Xpovio, do not take an extra dose. Take your next dose at your next regularly scheduled day and time.
• If you take too much Xpovio, call your healthcare provider right away.

What should I avoid while taking Xpovio?

Xpovio can cause neurologic side effects.

• See “What are the possible side effects of Xpovio?” below.
• If you have any neurologic side effects with Xpovio, do not drive or operate heavy or dangerous machinery until your neurologic side effects go away.
• Avoid falling. Use care as needed to avoid falling due to neurologic side effects.

What are the possible side effects of Xpovio?

Xpovio can cause serious side effects, including:

• See “What is the most important information I should know about Xpovio?”
• 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. See “How should I take 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.
  • Taking other medicines that can cause dizziness or mental status changes during treatment with XPOVIO may increase your risk of neurologic side effects.
• Tell your healthcare provider right away if you get any of these signs or symptoms.
• New or worsening cataract, a cloudy or loss of transparency of the lens in the eye. New or worsening cataract are common with Xpovio. If a cataract forms, your vision may decrease, and you may need eye surgery to remove the cataract and restore your vision. Tell your healthcare provider right away if you have symptoms of a cataract such as double vision, blurred vision, sensitivity to light or glare.

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
• nausea
• 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-108

General information about the safe and effective use of Xpovio

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Xpovio for a condition for which it was not prescribed. Do not give Xpovio to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Xpovio that is written for health professionals.

How should I store Xpovio?

• Store Xpovio at or below 86°F (30°C).
• Xpovio comes in a child-resistant blister pack.

Keep Xpovio and all medicines out of the reach of children.

What are the ingredients in Xpovio?

Active ingredient: selinexor
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, Opadry 200 clear, Opadry II blue, povidone K30, and sodium lauryl sulfate.

Label

Principal Display Panel – 60 mg (Once Weekly) Blister Pack Label

• XPOVIO®(selinexor tablets)
• 60 mg
  Dose
  (entire pack)
• Push tablets through foil.
• Swallow whole with water.
• IMPORTANT: Take each dose as prescribed by your physician.
• Take only one 60 mg dose in a single day per week.
• Refer to Prescribing Information for dosing instructions.

Principal Display Panel – 80 mg (Once Weekly) Carton Label

• NDC 72237-101-02
• Rx ONLY
• 80 mg
  Once
  Weekly
  Blister Packs
• XPOVIO®
• (selinexor) tablets
• Contents: 4 individual weekly
  blister packs. Each blister pack
  contains 4 tablets (20 mg per tablet).
• 16 film-coated tablets
• Dispense enclosed Medication Guide
  to each patient.
• Karyopharm®
  Therapeutics

SRC: NLM .