Selinexor

• Relapsed or refractory multiple myeloma:
  For adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL):
  For adult patients with DLBCL, including DLBCL arising from follicular lymphoma, who have received at least two prior lines of systemic therapy.
• Off-label uses:
  Investigational uses in various hematologic malignancies and solid tumors under clinical trials.

• Route: Oral
• Multiple myeloma:
  80 mg orally twice weekly (e.g., Monday and Thursday), with or without food.
• DLBCL:
  60 mg orally twice weekly on a similar schedule.
• Dose adjustments:
  Reduce dose by 20 mg increments for adverse effects; hold therapy if severe toxicity occurs until recovery.
• Special populations:
• Renal impairment: Use with caution; no specific dose adjustment recommended.
• Hepatic impairment: Dose reduction may be necessary in moderate to severe impairment.
• Elderly: Monitor closely due to potential increased toxicity.

Selinexor selectively inhibits exportin 1 (XPO1), a nuclear export protein responsible for transporting tumor suppressor proteins (TSPs) and other growth regulatory proteins out of the nucleus. By blocking XPO1, Selinexor causes accumulation of TSPs in the nucleus, reactivating their tumor suppressive functions. This leads to cell cycle arrest and apoptosis specifically in malignant cells, thereby inhibiting tumor growth.

• Absorption: Rapid oral absorption; peak plasma levels within 2-4 hours.
• Bioavailability: Approximately 80%.
• Distribution: Highly plasma protein bound (~95%).
• Metabolism: Primarily metabolized by hepatic CYP3A4 enzymes.
• Elimination half-life: Approximately 6 to 8 hours.
• Excretion: Mainly via feces (~82%) and minimally via urine (~1%).

• Pregnancy: No formal FDA category assigned; animal studies indicate potential fetal harm. Use only if benefits justify risks.
• Lactation: Unknown if excreted in human milk; breastfeeding is not recommended during treatment and for at least one week after the last dose.

• Primary class: Antineoplastic agent
• Subclass: Selective inhibitor of nuclear export (SINE)

• Known hypersensitivity to Selinexor or any of its excipients.
• Severe hepatic impairment without appropriate monitoring.
• Pregnancy (relative contraindication due to potential fetal risk).

• Myelosuppression: Severe thrombocytopenia, anemia, and neutropenia can occur; frequent CBC monitoring is required.
• Gastrointestinal toxicity: Nausea, vomiting, anorexia, and diarrhea are common; prophylactic antiemetics are recommended.
• Hyponatremia: Monitor serum sodium levels regularly.
• Infections: Increased susceptibility; monitor and treat infections promptly.
• Neurologic effects: Fatigue, dizziness, confusion may affect ability to perform tasks requiring alertness.
• Tumor lysis syndrome: Monitor especially during initial treatment.
• Requires close clinical monitoring and dose modifications based on tolerance.

• Common: Fatigue, nausea, vomiting, anorexia, thrombocytopenia, anemia, neutropenia, diarrhea, hyponatremia, weight loss, altered taste (dysgeusia).
• Serious but less frequent: Severe infections, tumor lysis syndrome, neurological toxicities (confusion, dizziness), electrolyte disturbances.

• CYP3A4 inhibitors (e.g., ketoconazole): May increase Selinexor plasma levels and toxicity risk; use caution or adjust dose.
• CYP3A4 inducers (e.g., rifampin): May reduce Selinexor efficacy by lowering plasma concentration.
• Concomitant use with anticoagulants or agents affecting platelet function may increase bleeding risk.
• Avoid strong CYP3A4 modulators unless necessary.

• FDA granted accelerated approval for use in multiple myeloma and DLBCL with ongoing post-marketing requirements.
• Updated guidelines emphasize management of myelosuppression and gastrointestinal side effects with supportive care.
• New safety alerts highlight monitoring for hyponatremia and early detection of neurological symptoms.
• Trials are ongoing to assess combination regimens and expanded indications.

• Store tablets at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light; keep in original container with desiccant.
• Keep out of reach of children.
• No refrigeration required.