What Is Xpovio and How Does It work?

Xpovio, a new medication to treat myeloma, is a “nuclear export inhibitor,” the first compound in this new drug class. Nuclear export inhibitors prevent cancer cells from expelling special genes in the cell nucleus called tumor suppressor proteins that help protect the cell from cancer.

Who Is a Candidate for Xpovio?

Xpovio has been approved 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 drugs, and an anti-CD38 monoclonal antibody.

How Is Xpovio Taken?

Xpovio is an oral medication taken by mouth in the form of round, blue, 20-mg tablets with K20 embossed on one side and nothing on the other side.

What Are the Dose and Schedule of Xpovio?

The recommended starting dose 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. The recommended starting dose of dexamethasone is 20 mg taken orally with each dose of Xpovio on Days 1 and 3 of each week. For more information on dexamethasone, read the IMF’s publication Understanding Dexamethasone and Other Steroids.

Each Xpovio dosage 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 you miss or delay a dose of Xpovio, take your next dosage at the next regularly scheduled time. If you vomit after taking your dosage of Xpovio, do not repeat the dosage. Take your next dosage on the next regularly scheduled day.

Your doctor will monitor your complete blood count (CBC), standard blood chemistry panel, and body weight before you start Xpovio and as needed during treatment, especially during the first two months you are taking Xpovio.

You will receive treatment to prevent nausea and vomiting prior to and during treatment with Xpovio.

It is very important for you to maintain good intake of food and fluids throughout your treatment with Xpovio. You may receive intravenous (IV) hydration if necessary.

What Are Common Side Effects of Xpovio?


Thrombocytopenia, or decreased platelet level (See Myelosuppression for details.)

Xpovio can cause a lowered level of platelets in the blood. Platelets (thrombocytes) help blood to clot; fewer platelets can lead to bleeding. Your doctor will monitor your platelet counts at baseline and during treatment, especially during the first two months. Management of low platelet counts may include interruption, reduction, or permanent discontinuation of your dose of Xpovio; platelet transfusions; or medication to stimulate the production of platelets.

Nausea/Vomiting (See Gastrointestinal Problems for details.)

Many patients in the phase IIb STORM trial of the drug Xpovio experienced nausea and vomiting.To learn more about this, see page 8 of the IMF booklet Understanding Xpovio.

Your doctor will prescribe a required anti-nausea medication along with your prescription for Xpovio. Even if you’re not experiencing nausea, it is very important to start taking your anti-nausea medication as a preventive prior to treatment with Xpovio. Continue taking the anti-nausea medication during treatment with Xpovio, even if you are not experiencing nausea.

Your doctor may also manage your nausea by delaying, reducing ,or stopping your treatment with Xpovio, and may also administer intravenous fluids to replace electrolytes and prevent dehydration.

Fatigue (See Distress, Fatigue, and Sexuality for details.)

Fatigue is commonly associated with cancer and with cancer therapy. Fatigue that is related to cancer and its treatments is different from and more severe than normal fatigue, tends to last longer, and includes the feeling of overall weakness. See the IMF publication Understanding Fatigue for more information.

As with all side effects, let your doctor and/or nurse know how you feel. Your doctor may prescribe a medication to minimize your fatigue. The effects of fatigue may also be minimized by maintaining:

  • A moderate level of activity
  • A healthy diet and proper fluid intake
  • A consistent sleeping schedule
  • Regularly scheduled visits with your doctor to monitor your red blood cell count (low red blood cells, or anemia, can cause fatigue) and to discuss issues that may contribute to your fatigue
  • A careful review of the side effects of any other medications you are taking to ensure that they are not contributing to your fatigue.

Anemia (See Multiple Myeloma and Anemia for details.)

Red blood cells contain hemoglobin, a protein that contains iron and transports oxygen from the lungs to the body’s organs and tissues. A low level of red blood cells results in low levels of oxygen in the body, which may cause shortness of breath and feelings of exhaustion.

Your doctor will determine which treatment regimen for anemia is best suited to and safest for you. The following are options:

  • Interruption, reduction, or discontinuation of your dose of Xpovio
  • Blood transfusions
  • Erythropoietic (red blood cell-making) medication

Decreased appetite

Your doctor will give you a prescription for anti-nausea medication to help prevent loss of appetite and will also manage this side effect by interrupting and/or modifying the dosing and scheduling of Xpovio. You may be asked to weigh yourself daily and report the results to your doctor in order to monitor your condition closely.

Click the following link for the publication by the National Cancer Institute, Eating Hints: Before, During, and After Cancer Treatment. It may help you maintain adequate nutrition.

Diarrhea (See Gastrointestinal Problems for details.)

Your doctor will modify your dose of Xpovio and/or use standard anti- diarrheal medications such as Imodium® (loperamide HCl) to help con- trol diarrhea. Dizziness, light-headedness, or fainting may occur due to dehydration caused by excessive or persistent diarrhea. If you become dehydrated, your doctor will order intravenous fluids for you.

Hyponatremia (a low level of sodium in the blood)

Sodium (Na, the chemical symbol for sodium, is taken from the Latin word “natrium”) is an electrolyte, one of the minerals in the blood and other body fluids that carries an electrical charge and is essential for life. Sodium helps to regulate the amount of water that is in and around the cells, the acidity of the blood (pH), nerve and muscle function (including the heart), and other important processes. Vomiting and diarrhea can lead to reduced concentrations of sodium in the blood.

Your doctor will monitor your levels of sodium before and during the first two months of your treatment with Xpovio. The doctor will review your diet with you and may treat you with intravenous saline or with salt tablets, or may suggest that you eat salty snacks. Your dose of Xpovio may be interrupted, reduced, or permanently discontinued depending upon the severity of the hyponatremia.

Neutropenia (a low level of neutrophils; see also Myelosuppression.)

Neutrophils, the most abundant type of white blood cell, are the body’s “first responders” in fighting bacterial infections. Having too few neutro- phils can lead to infection. Fever is the most common sign of neutropenia. If you have a fever, you need immediate medical attention.

Your doctor will assess your baseline neutrophil count before you start treatment with Xpovio, and will monitor your count during treatment. Your blood count levels will be monitored closely during the first two months of treatment. You will also be monitored closely for signs and symptoms of infection. Call your doctor immediately if you have a fever, and make sure you have an emergency or after-hours number to reach a doctor who is covering the practice.

You may be given antimicrobial therapy if you are showing signs of infection. Your doctor may also give you a white blood cell growth factor (G-CSF, or granulocyte-colony stimulating factor) to increase production of your white blood cells. Your dose of Xpovio may be interrupted, and/or reduced, or permanently discontinued based on the severity of your neutropenia.

Constipation (See Gastrointestinal Problems for details.)

The medical definition of constipation is 3 or fewer bowel movements in one week. The stool may be hard, dry, and difficult to pass. You may also have stomach cramps and bloating. Not eating and drinking enough and being less active can contribute to the problem.

  • To prevent and/or treat constipation:
  • Drink sufficient fluids, 8–12 glasses daily.
  • Try to eat high-fiber foods.
  • Try to be active every day, even if you exercise in a chair.
  • Moving your body increases peristalsis, the rhythmic contractions that move food through the intestines.
  • Report your constipation to your nurse and/or doctor, who will recommend a stool softener or laxative if required.


Tell your doctor immediately if you have any signs and symptoms of infection, including:

  • Fever Flu-like symptoms (body aches, sweating, chills)
  • Sore throat
  • Cough (which may produce phlegm)
  • Shortness of breath
  • Chest pain when you breathe or cough

You must report your symptoms to your doctor, who will determine how the symptoms should be managed and if you need to receive an antibiotic, or other medications. If your doctor or another doctor covering the practice is not available, you should go to an urgent care or emergency facility.

Recommended Adjustments to Dosing If Side
Effects Occur

If you have one or more adverse reactions to Xpovio (discussed above), your doctor will adjust your dose according to the guidelines in the following table:

Recommended Starting Dosage

80 mg – Days 1 & 3 of each week (160 mg total/week)

First Reduction 100 mg – once weekly
Second Reduction  80 mg – once weekly
Third Reduction  60 mg – once weekly
Discontinue  No dosage

Warnings and precautions

Neurological toxicity

Neurological toxicities including dizziness, fainting, depressed levelof consciousness, and mental status changes (including delirium and confusion) occurred in 16% of patients treated in clinical trials with Xpovio 80 mg and dexamethasone 20 mg administered twice weekly (the standard doses); 14% was severe or required hospitalization. You must report any of the above symptoms to your doctor and/or nurse. Your doctor will your check your hydration level, your red blood cell levels, and any other drugs you’re taking that might have similar toxicities. Your dose of Xpovio may be interrupted, lowered, or discontinued.

Embryo-fetal toxicity

Based on data from animal studies, Xpovio might cause harm to a developing child during prenatal development if administered to a pregnant woman or her male partner. If you are pregnant, you should not take Xpovio. Females of childbearing potential and males with a female partner of childbearing potential should use effective contraception during treat- ment with Xpovio and for one week after the last dose.


There is no information about the presence of Xpovio in human milk, or its 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.


Based on findings in animals, Xpovio may harm fertility in males and females of reproductive potential.

Patient Access and Support Services for Xpovio

Karyopharm Therapeutics, the company that developed Xpovio, has established a patient support and resource center called KaryForward. You can enroll in KaryForward to receive help with access to Xpovio, to learn about financial resources that may be available to help you, and to speak with a nurse case manager at a specialty pharmacy to ask questions about Xpovio or to discuss side effects. Contact KaryForward at or 1.877.KARY4WD (1.877.527.9493).

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