Erleada Apalutamide Tablets

1. Indications and Usage
Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC):
Indicated for the treatment of adult patients with nmCRPC at high risk of metastasis.
Metastatic Hormone-Sensitive Prostate Cancer (mHSPC):
Indicated for the treatment of adult patients with mHSPC, in combination with androgen deprivation therapy (ADT).
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Dose: 240 mg (four 60 mg tablets) once daily.
Treatment Duration: Continue until disease progression or unacceptable toxicity.
Administration Instructions:
Swallow tablets whole with water; do not crush or split.
Administer with or without food.
Concomitant Therapy: Must be used in combination with a GnRH analogue (continuous medical castration) or in patients who have undergone bilateral orchiectomy.
Missed Dose: If a dose is missed, take it as soon as possible on the same day. Resume the normal schedule the following day. Do not take a double dose.
Dose Adjustments:
Reduce dose (to 180 mg or 120 mg) for intolerable Grade ≥3 adverse reactions.
Permanently discontinue for seizures, severe cutaneous adverse reactions (SCARs), or interstitial lung disease (ILD).
3. Mechanism of Action
Androgen Receptor (AR) Inhibition:
Apalutamide is an androgen receptor inhibitor that binds directly to the ligand-binding domain of the AR.
Blocking Signaling Pathways:
It inhibits multiple steps in the AR signaling pathway:
1. Inhibits the binding of testosterone and dihydrotestosterone (DHT) to the AR.
2. Inhibits the nuclear translocation of the activated AR.
3. Inhibits the binding of the AR to DNA, thereby blocking AR-mediated transcription and tumor cell growth.
4. Safety and Warnings
Seizures:
Can cause seizures. Monitor patients for signs of seizure activity. Permanently discontinue if a seizure occurs.
Falls and Fractures:
Increased risk of falls and fractures due to fatigue and musculoskeletal effects. Assess fall risk and consider bone-modifying agents.
Cardiovascular Events:
May increase the risk of ischemic cardiovascular and cerebrovascular events. Monitor for symptoms and optimize risk factors.
Severe Cutaneous Adverse Reactions (SCARs):
Can cause serious rashes (e.g., Stevens-Johnson Syndrome). Monitor for rash symptoms.
Embryo-Fetal Toxicity:
Males with female partners of reproductive potential must use effective contraception during treatment and for 3 months after the final dose.
5. Adverse Reactions
Most Common (Incidence ≥20%):
Fatigue, arthralgia, rash, decreased appetite, fall, weight decrease, hypertension, and hot flashes.
6. Drug Interactions
CYP Enzyme Induction:
Apalutamide is a strong inducer of CYP3A4 and CYP2C19, and a moderate inducer of CYP2C9.
Impact on Other Drugs:
Concomitant use may significantly decrease the exposure and efficacy of sensitive substrates (e.g., warfarin, certain statins, benzodiazepines). Dose adjustments or alternative therapies may be required.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Apalutamide.
Available Strength: 60 mg tablets.
Appearance: Pale yellow to grayish-green, oval, film-coated tablets debossed with “AR 60”.
Storage: Store at room temperature (20°C–25°C / 68°F–77°F). Protect from moisture.