Selinexor is an oral selective inhibitor of nuclear export (SINE) compound. It functions by binding and inhibiting the nuclear export protein exportin 1 (XPO1/CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus, inhibition of NF-κB, reduced levels of oncoprotein mRNA translation, and induction of cancer cell death.

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):

• Swallow an 80 mg pill two times a week, specifically on day 1 and day 3.
• Patient also need to take it with another medicine called dexamethasone.
• Keep taking these pills until the doctor says to stop or if side effects become too bad.
• Every week, you will be taking a total of 160 mg.

If You Miss a Dose:

• If you forget to take the pill, just take it the next time you're supposed to. Don't double up.
• If you throw up after taking it, don't take another one. Just wait until the next scheduled time to take your next pill.

Use in Children:

Not indicated.

Pregnancy Risk Category: N (Not assigned)

• Selinexor can be harmful to unborn babies if taken during pregnancy.
• So, if you're a woman who can become pregnant, make sure you're not pregnant before taking it.
• While using selinexor, you should also use a reliable form of birth control, and continue to do so for a week after your last dose.
• If you're a man and your partner can become pregnant, you should also use contraception during selinexor treatment and for a week after the last dose to prevent pregnancy.

Use while breastfeeding

• We don't know if selinexor is in breast milk.
• To be safe, it's best not to breastfeed while you're taking selinexor.
• This is because there could be serious side effects for the baby if they're exposed to the medication through breast milk.
• It's recommended to avoid breastfeeding during treatment with selinexor and for one week after you've taken your last dose.

Dose in Kidney Disease:

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

• If your kidney function is equal to or greater than 15 mL/minute (CrCl ≥15 mL/minute), you don't need to adjust the dose of selinexor according to the manufacturer's instructions. It means the medication works the same way in people with this level of kidney function, and there are no significant effects on how the body processes selinexor.
• For individuals with end-stage kidney disease, where their kidney function is less than 15 mL/minute (CrCl <15 mL/minute), there are no specific dosage adjustments recommended in the manufacturer's instructions. However, it's important to note that this group has not been studied extensively, so the effects of selinexor in such cases are not well understood.
• In cases where a patient is undergoing hemodialysis, there are also no recommended dosage adjustments according to the manufacturer's instructions. However, it's worth noting that the use of selinexor in people on hemodialysis has not been thoroughly studied, so caution is advised.

Dose in Liver disease:

• For people with mild impairment of liver function, there are no specific dosage adjustments recommended in the manufacturer's instructions. Importantly, studies have shown that mild liver impairment does not significantly affect how the body processes selinexor.
• However, for individuals with moderate or severe impairment of liver function, there are no recommended dosage adjustments according to the manufacturer's instructions. It's essential to note that there hasn't been sufficient research conducted to understand how selinexor behaves in people with significant liver problems.

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):

According to the manufacturer's labeling, there are no specific contraindications listed for selinexor.

Warnings and precautions

Suppression of bone marrow

• Selinexor can lead to problems with your blood, particularly your platelets and neutrophils.
• This might cause bleeding and increase your risk of infections.
• You should get your blood checked before and during treatment, especially in the first two months.
• If your blood counts are low, you might need treatments like platelet transfusions, and your doctor may need to adjust your selinexor dose or even stop the treatment.
• It's essential to keep an eye out for signs of bleeding or infection and let your doctor know if you notice any.
• Selinexor can also cause anemia and low lymphocyte counts.

Gastrointestinal toxicities:

• Selinexor can cause problems in the digestive system.
• Many patients experience nausea and vomiting, and in some cases, it can be severe.
• This usually starts a few days after starting treatment.
• To help prevent this, doctors may give you anti-nausea medications before and during selinexor treatment.
• If you still have nausea or vomiting, your doctor might need to adjust your treatment.
• It's important to stay hydrated, so you might receive fluids through an IV if you're at risk of dehydration.
• Selinexor can also cause diarrhea, which can be managed with dose changes and regular anti-diarrhea medicines.
• Some people may lose their appetite and weight while taking selinexor, and your weight will be monitored regularly.
• If this happens, your doctor can adjust your treatment, give you medications to boost your appetite, or provide nutritional support.

Hyponatremia

• Selinexor can lower the levels of sodium in your blood, which is called hyponatremia.
• This can be severe, even reaching grades 3 and 4.
• It typically happens about 8 days after you start taking selinexor.
• Your doctor will check your sodium levels before and during treatment, especially in the first two months.
• They will also take into account factors like high blood sugar or high levels of certain proteins in your blood when assessing your sodium levels.
• If your sodium levels drop too much, your doctor may give you saline through an IV or suggest taking salt tablets based on medical guidelines.
• Depending on how serious it is, hyponatremia might require changes in your treatment, a lower dose, or even stopping selinexor altogether.

Infection

• When taking Selinexor, there's a risk of getting infections, and more than half of the patients in studies experienced some form of infection.
• These infections can range from mild to severe, and they might include things like upper respiratory tract infections, pneumonia, and even sepsis.
• In about a quarter of patients, these infections were quite serious, and sadly, some were fatal.
• The most common severe infections were pneumonia and sepsis.
• These infections typically occurred after about 54 days for pneumonia and 42 days for sepsis, on average.
• It's important to note that many of these infections happened without low neutrophil counts, and they were caused by regular germs rather than opportunistic ones.
• So, if you're taking Selinexor, it's crucial to watch out for signs of infection and seek medical help if you think you might be getting sick.
• Your healthcare provider will be able to monitor and manage this risk.

Neurotoxicity:

• Selinexor can sometimes lead to problems with the nervous system, causing symptoms like dizziness, fainting, reduced consciousness, and changes in mental status (such as delirium and confusion).
• These issues can be severe, including grade 3 and 4 events.
• On average, they tend to occur around 15 days after starting selinexor treatment.
• To minimize these side effects, it's essential to ensure you're well-hydrated, your hemoglobin levels are within a healthy range, and that you're not taking medications that could make these symptoms worse.

Selinexor: Drug Interaction

Monitoring parameters:

Blood Tests:

• Regularly check your blood counts (CBC with differential) and standard blood chemistries when you start selinexor and as recommended by your doctor, especially in the first 2 months of treatment.

Pregnancy Check:

• If you're a woman who can become pregnant, make sure to determine if you're pregnant before starting treatment.

Body Weight:

• Keep track of your weight when starting selinexor and as directed by your healthcare provider, especially in the first 2 months.

Hydration:

• Ensure you stay well-hydrated; this is essential to prevent dehydration.

Watch for Signs:

• Pay attention to any signs or symptoms of bleeding, infection, neurotoxicity (problems with your nervous system), and gastrointestinal issues.

Medication Adherence:

• Make sure you're taking selinexor as prescribed by your doctor.

How to administer Selinexor (Xpovio)?

• Consistent Timing: Take your selinexor dose at about the same time every day.
• Swallow Whole: Always swallow the tablets whole with water. Don't break, chew, crush, or split them.

Managing Nausea and Vomiting:

• Anti-nausea Medication: To prevent nausea and vomiting, your doctor may recommend antiemetics (medications that help with nausea and vomiting) before and during your treatment.

Staying Hydrated and Nourished:

• Hydration: Make sure to stay well-hydrated throughout your treatment. In some cases, you might receive fluids through an IV if there's a risk of dehydration.
• Caloric Intake: Ensure you're getting enough calories to maintain your energy and health while taking selinexor.

Mechanism of action of Selinexor (Xpovio):

• Selinexor works by stopping certain proteins and messages from leaving the cell's control center (the nucleus).
• This action prevents harmful proteins from growing too much and helps the body's natural defenses against cancer work better.
• It basically puts a brake on the cancer's growth and can make the cancer cells die.

Distribution:

• Selinexor is distributed in the body, and the estimated volume is about 125 liters, which means it can spread throughout the body.

Protein Binding:

• Around 95% of selinexor in the bloodstream binds to proteins. This can affect how it moves through the body.

Metabolism:

• Selinexor is broken down in the liver with the help of enzymes like CYP3A4, multiple UDP-glucuronosyltransferases, and glutathione S transferases.

Half-life Elimination:

• The time it takes for half of the selinexor in the body to be eliminated is about 6 to 8 hours. This tells us how long the drug stays in your system.

Time to Peak:

• After taking selinexor, it reaches its highest concentration in the bloodstream within about 4 hours.

Excretion:

• The body clears selinexor at a rate of approximately 17.9 liters per hour, which is how it gets rid of the drug.

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:

Not available.