Xpovio Selinexor Tablets

1. Indications and Usage
Relapsed or Refractory Multiple Myeloma (RRMM):
Indicated in combination with dexamethasone for adult patients who have received prior therapy.
Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL):
Indicated for the treatment of adult patients with DLBCL, including DLBCL arising from follicular lymphoma, after two or more lines of systemic therapy.
Newly Diagnosed Multiple Myeloma:
Indicated in combination with bortezomib and dexamethasone for adult patients with newly diagnosed multiple myeloma.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage (RRMM):
Dose: 100 mg once weekly.
Schedule: Administer on Days 1, 8, 15, and 22 of a 28-day cycle.
Recommended Dosage (DLBCL):
Dose: 60 mg twice weekly.
Schedule: Administer on Days 1, 3, 5, and 7 of a 28-day cycle.
Administration Instructions:
Swallow tablets whole with water; do not crush, chew, or split.
Administer on an empty stomach (fasting for at least 1 hour before and after administration is recommended).
Premedication: Administer antiemetics (e.g., ondansetron) and antinauseants prior to each dose to manage gastrointestinal toxicity.
Dose Adjustments:
Dose reductions are required for hematologic toxicity (thrombocytopenia, neutropenia, anemia) and non-hematologic toxicity (nausea, vomiting, hyponatremia).
3. Mechanism of Action
XPO1 Inhibition:
Selinexor binds covalently to the cargo-binding pocket of Exportin-1 (XPO1), inhibiting the nuclear export of tumor suppressor proteins (TSPs), growth-regulating factors, and oncogenic mRNAs.
Induction of Apoptosis:
By blocking XPO1, TSPs (e.g., p53, BRCA1) accumulate in the nucleus, restoring their tumor-suppressive function. Simultaneously, it suppresses oncogenic signaling by retaining oncogenic mRNAs (e.g., c-MYC, Cyclin D1) in the nucleus, preventing their translation into proteins. This dual action induces cell cycle arrest and apoptosis in malignant cells.
4. Safety and Warnings
Thrombocytopenia:
Can cause severe and life-threatening thrombocytopenia. Monitor platelet counts weekly. May require dose interruption or reduction.
Gastrointestinal Toxicity:
Nausea, vomiting, anorexia, and diarrhea are very common. Prophylactic antiemetic therapy is mandatory.
Hyponatremia:
Can cause severe hyponatremia. Monitor serum sodium levels prior to initiation and regularly during treatment.
Embryo-Fetal Toxicity:
Can cause fetal harm. Females of reproductive potential must use effective contraception during treatment and for at least 1 week after the final dose.
5. Adverse Reactions
Most Common (Incidence ≥20%):
Thrombocytopenia, fatigue, nausea, anemia, decreased appetite, vomiting, diarrhea, hyponatremia, neutropenia, leukopenia, and dizziness.
6. Drug Interactions
CYP Enzymes:
Selinexor does not significantly inhibit or induce CYP enzymes.
P-gp Inhibitors:
Selinexor is a substrate of P-gp. Concomitant use with strong P-gp inhibitors may increase selinexor exposure, though clinical significance is currently unknown.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Selinexor.
Available Strength: 20 mg tablets.
Appearance: Blue, biconvex, round, film-coated tablets debossed with “K20”.
Storage: Store at room temperature (20°C–25°C / 68°F–77°F). Protect from moisture.