Emend

• Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC):
  For delaying metastasis and progression in men with prostate cancer resistant to androgen deprivation therapy (ADT) but without detectable metastases.
• Metastatic Castration-Sensitive Prostate Cancer (mCSPC):
  Used in combination with ADT to improve survival in patients with newly diagnosed metastatic hormone-sensitive prostate cancer.

• Adults:
  240 mg orally once daily (four 60 mg tablets), with or without food.
• Dose Adjustments:
  No recommended dose adjustment for mild or moderate renal impairment.
  Use with caution in severe renal impairment; data limited.
  Avoid use in severe hepatic impairment (Child-Pugh C).
  No dose adjustment based on age.
• Administration:
  Tablets should be swallowed whole; do not crush or chew.

Apalutamide is a potent, selective androgen receptor (AR) inhibitor. It binds directly to the ligand-binding domain of the AR, inhibiting androgen binding, AR nuclear translocation, and AR-mediated DNA transcription. This blockade reduces androgen-driven prostate cancer cell proliferation and survival, thereby slowing disease progression.

• Absorption:
  Oral bioavailability approximately 100%.
  Peak plasma concentration reached within 2 hours after dosing.
• Distribution:
  Highly protein bound (~95%).
  Volume of distribution approximately 276 L.
• Metabolism:
  Extensively metabolized primarily by CYP2C8 and CYP3A4 into active metabolites.
• Elimination:
  Terminal half-life approximately 3 days.
  Excreted mainly via feces (~65%) and urine (~24%).
• Steady State:
  Achieved within 4 weeks of once-daily dosing.

• Pregnancy:
  Not applicable; drug indicated for males only.
• Lactation:
  Unknown if excreted in human milk; not applicable.
• Use in women is contraindicated.

• Androgen receptor inhibitor
• Antineoplastic agent

• Known hypersensitivity to apalutamide or any component of the formulation.

• Seizure Risk:
  May increase risk of seizures; use caution in patients with seizure history.
• Falls and Fractures:
  Increased risk reported; assess bone health.
• Hypothyroidism:
  Monitor thyroid function periodically.
• Rash:
  Severe rash reported; discontinue if severe or life-threatening.
• Drug Interactions:
  Use caution with strong CYP2C8 and CYP3A4 inhibitors or inducers.

• Common:
  Fatigue, rash, weight loss, hypertension, diarrhea, arthralgia.
• Serious:
  Seizures, severe rash, hypothyroidism, fractures.
• Onset:
  Rash and fatigue often appear within the first months of treatment.

• Metabolized by CYP2C8 and CYP3A4; inhibitors can increase apalutamide levels, inducers decrease levels.
• Apalutamide induces CYP3A4, CYP2C9, and CYP2C19, potentially reducing plasma concentrations of concomitant medications metabolized by these enzymes (e.g., warfarin, certain statins).

• EMA and FDA approvals expanded to include mCSPC treatment.
• Updated warnings on seizure risk and skin reactions added in recent labels.
• Ongoing studies on combination therapies.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Do not freeze.
• Keep out of reach of children.