Selinexor (Xpovio) is an orally available medicine that acts by reversibly inhibiting the nuclear export of tumor suppressor proteins. It is used in patients with relapsed or refractory multiple myeloma.

Selinexor Uses:

• Relapsed or refractory multiple myeloma:

  • Used for treating relapsed or refractory cases of multiple myeloma (in combination with dexamethasone) in adults who have received ≥4 prior therapies and whose disease has not responded to ≥2 proteasome inhibitors, ≥2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Selinexor (Xpovio) Dose in Adults

Selinexor (Xpovio) Dose in the treatment of Multiple myeloma (relapsed or refractory):

• Oral: 80 mg per dose two times a week on days 1 and 3 each week (in combination with dexamethasone); dose should be continued until disease progression or unacceptable toxicity occurs. Total dose of selinexor per week is 160 mg.

• Missed doses:

  • If a dose of selinexor is missed or delayed or vomited, the next dose should be administered at the next regularly scheduled time(do not repeat the dose).

Use in Children:

Not indicated.

Pregnancy Risk Category: N (Not assigned)

• Fetal harm could result from in utero selinexor exposure, according to data from animal reproduction studies and the mechanism of action.
• Before using contraception in females with reproductive potential, it is important to determine if you are pregnant. Effective contraception should also be used during treatment and for one week after the last dose. Effective contraception should be used during treatment for males who have a female partner with reproductive potential and for one week after the last dose.

Use while breastfeeding

• It is not known if it is present in breast milk.
• Due to the risk of serious adverse reactions in breastfed babies, the manufacturer doesn't recommend that it be used during breastfeeding.

Dose in Kidney Disease:

Note: Kidney function estimated by the Cockcroft-Gault equation.

• CrCl ≥15 mL/minute: No dosage adjustments have been provided in the manufacturer's labeling; however, selinexor pharmacokinetics remain unaffected at this creatinine clearance.
• End-stage kidney disease (CrCl <15 mL/minute): No dosage adjustments have been provided in the manufacturer's labeling (has not been studied).
• Hemodialysis: No dosage adjustments have been provided in the manufacturer's labeling (has not been studied).

Dose in Liver disease:

• Mild impairment: No dosage adjustments have been provided in the manufacturer's labeling; however, selinexor pharmacokinetics remain unaffected at this creatinine clearance.
• Moderate or severe impairment: No dosage adjustments have been provided in the manufacturer's labeling (has not been studied).

Common Side Effects of Selinexor (Xpovio):

• Central Nervous System:

  • Fatigue
  • Neurological Signs and Symptoms
  • Mental Status Changes
  • Dizziness
  • Insomnia

• Endocrine & Metabolic:

  • Weight Loss
  • Hyponatremia
  • Hyperglycemia
  • Dehydration
  • Hypokalemia

• Gastrointestinal:

  • Nausea
  • Decreased Appetite
  • Diarrhea
  • Vomiting
  • Constipation
  • Dysgeusia

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Anemia
  • Neutropenia
  • Leukopenia
  • Lymphocytopenia

• Infection:

  • Infection

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Dyspnea
  • Upper Respiratory Tract Infection
  • Cough
  • Pneumonia
  • Epistaxis

• Miscellaneous:

  • Fever

Less Common Side Effects of Selinexor (Xpovio):

• Central Nervous System:

  • Headache

• Infection:

  • Sepsis

• Ophthalmic:

  • Blurred Vision

Frequency of side effects not defined:

• Central Nervous System:

  • Confusion
  • Delirium
  • Impaired Consciousness

• Cardiovascular:

  • Syncope

• Hematologic & Oncologic:

  • Hemorrhage

Contraindications to Selinexor (Xpovio):

The manufacturer's labeling does not contain any contraindications.

Warnings and precautions

• Suppression of bone marrow

  • Selinexor may be a common cause of thrombocytopenia; more than half of patients are affected by grade 3 or 4 events.
  • The median time it took for a first event to occur (or onset) was 22 days.
  • Patients with low platelet counts have experienced bleeding, including severe bleeding and fatal hemorhage.
  • Selinexor may also cause neutropenia (potentially increasing the risk for infection).
  • The median time it took for a neutropenic event to occur (first onset) was 25 days.
  • There have been cases of neutropenic fever.
  • CBC (including platelets and neutrophils) should be checked at baseline and during treatment. Monitor more often during the first two months.
  • As indicated by the doctor, platelet transfusions may be necessary (and/or other treatments).
  • It is important to be aware of any signs or symptoms that may indicate bleeding or concomitant infections and have them promptly checked.
  • Depending on severity, treatment interruption, dose reduction and/or permanent discontinuation might be necessary.
  • You should consider supporting measures such as antimicrobials to treat signs of infection or WBC growth factors.
  • Also, may cause anemia or lymphopenia.

• Gastrointestinal toxicities:

  • Selinexor can also cause GI toxicity.
  • Nausea, vomiting and nausea were common; there have been cases of grade 3 nausea or vomiting.
  • For nausea and vomiting, the median time it took to experience the first event was 3 days. It took 5 days for the first event to occur.
  • Prophylactic use of 5-HT3 antagonists or other antinausea drugs should be done prior to and during treatment with selinexor.
  • Nausea or vomiting may cause treatment interruptions, dose reductions, and/or discontinuation.
  • Patients at high risk of dehydration should receive IV fluids and electrolyte substitution.
  • As clinically indicated, may require additional anti-nausea medication.
  • There have been reports of diarrhea, including grade 3 diarrhea. The median time for onset was 15 days.
  • To manage diarrhea, you can use dose modifications or standard antidiarrheal medications. Patients at high risk should receive IV fluids to prevent dehydration.
  • More than half of patients who received selinexor suffered from anorexia. Some patients also experienced grade 3 anorexia.
  • Anorexia began in the median time of 8 days.
  • Nearly half the patients who received selinexor reported weight loss. Grade 3 weight loss is rare.
  • The median time it took to lose weight was 15 days.
  • At baseline, during treatment and as indicated by the doctor, weight monitoring should be performed. Monitor more often during the first two months.
  • To manage anorexia or weight loss, you should use appetite stimulants, dose modifications, and/or nutritional supports.

• Hyponatremia

  • Selinexor may be used to treat hyponatremia, including grades 3 through 4.
  • The median time it took for the first event to occur was 8 days.
  • Monitor sodium levels at baseline, throughout treatment, and as indicated by the doctor (monitor more often in the first two months of treatment).
  • Concurrent hyperglycemia (serum glucose greater than 150 mg/dL) or high serum paraprotein levels should be corrected.
  • Hyponatremia should be managed with IV saline or salt tablets, according to clinical guidelines and dietary review.
  • Hyponatremia can lead to treatment interruption, dose reduction and/or permanent discontinuation, depending on severity.

• Infection

  • More than half of patients who were treated with selinexor had an infection (any grade), which included upper respiratory tract infections and pneumonia.
  • Quarter of all patients with grade 3 or higher infection were reported. Some were even fatal.
  • Pneumonia, sepsis and sepsis were two of the most common grade 3 or higher infections.
  • For sepsis, the median time for onset was 42 days.
  • The majority of infections were caused non-opportunistic bacteria and were not associated to neutropenia.

• Neurotoxicity:

  • Selinexor use was associated with neurologic toxicities, including dizziness, syncope and decreased consciousness.
  • Reports of Grade 3 and 4 events were made.
  • The median time to complete the first event was 15 days.
  • Optimizing hydration, hemoglobin levels, and any concomitant medication should be done to avoid dizziness, or exacerbation.

Selinexor: Drug Interaction

Monitoring parameters:

• Monitor blood cp with differential and standard blood chemistries at baseline and as indicated during treatment (more frequently monitor during the first 2 treatment months)
• Pregnancy status should be evaluated(in females of reproductive potential) prior to treatment initiation.
• Bodyweight should be assessed at baseline and as indicated during treatment (more frequently monitor during the first 2 treatment months).
• Hydration status.
• Monitoring should be done for signs/symptoms of bleeding, infection, neurotoxicity, and gastrointestinal toxicity.
• Monitor adherence.

How to administer Selinexor (Xpovio)?

• Oral: Should be administered at approximately the same time of day & swallowed as a whole with water(do not break, chew, crush, or divide tablets).
• Nausea and vomiting may be associated with the use of selinexor; to prevent nausea and vomiting, antiemetics are recommended prior to and during treatment.
• Adequate hydration and caloric intake should be maintained throughout the treatment & IV hydration should be considered in patients at risk of dehydration.

Mechanism of action of Selinexor (Xpovio):

• Selinexor blocks exportin 1 and causes the nuclear export of tumor suppressor protein, growth regulators and mRNAs from oncogenic proteins to be reversibly inhibited. 
• It inhibits exportin 1, which causes tumor suppressor proteins to accumulate in the nucleus, oncoproteins reduction, cell cycles arrest, and cancer cell death.

Protein binding: 95%

Metabolism: In liver via CYP3A4, multiple UDP-glucuronosyltransferases, and glutathione S transferases

Half-life elimination: 6 - 8 hours

Time to peak: Within 4 hours

Excretion: Clearance: 17.9 L per hour

International Brand Names of Selinexor:

• Xpovio (100 MG Once Weekly)
• Xpovio (60 MG Once Weekly)
• Xpovio (80 MG Once Weekly)
• Xpovio (80 MG Twice Weekly)

Selinexor Brand Names in Pakistan:

No Brands Available in Pakistan.