前列腺癌 Prostate cancer
Treatment of metastatic, castration-sensitive prostate cancer and nonmetastatic, castration-resistant prostate cancer

Antiandrogen Antineoplastic Agent
Apalutamide is a nonsteroidal androgen receptor inhibitor which binds directly to the androgen receptor ligand-binding domain to prevent androgen-receptor translocation, DNA binding, and receptor-mediated transcription. Androgen receptor inhibition results in decreased proliferation of tumor cells and increased apoptosis, leading to a decrease in tumor volume.

Distribution
1. Distribution: ~276 L
2. Protein binding: (Apalutamide) 96%; (N-desmethyl apalutamide) 95%; to plasma proteins
Metabolism
Hepatic; primarily via CYP2C8 and CYP3A4 to form the active metabolite N-desmethyl apalutamide
Excretion
1. Urine: 65%; 1.2% as apalutamide and 2.7% as N-desmethyl apalutamide
2. Feces: 24%; 1.5% as apalutamide and 2% as N-desmethyl apalutamide)
3. Half-life elimination: ~3 days
Time to peak
2 hours (range: 1 to 5 hours)

1. Hypersensitivity to apalutamide or any component of the formulation
2. Females who are or may become pregnant

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to apalutamide may cause fetal harm and potential fetal loss.

It is not known if apalutamide is present in breast milk.

Common:
1. Cardiovascular: Hypertension, peripheral edema
2. Dermatologic: Pruritus, skin rash
3. Endocrine & metabolic: Hot flash, hypercholesterolemia, hyperglycemia, hyperkalemia, hypertriglyceridemia, increased thyroid stimulating hormone level, weight loss
4. Gastrointestinal: Decreased appetite, diarrhea, nausea
5. Hematologic & oncologic: Anemia, leukopenia, lymphocytopenia
6. Nervous system: Falling, fatigue
7. Neuromuscular & skeletal: Arthralgia, bone fracture
Warnings/Precautions
1. Cerebrovascular and ischemic cardiovascular events:
Monitor for signs/symptoms of cerebrovascular disorders and ischemic heart disease; consider discontinuing apalutamide therapy for grade 3 or 4 events.
2. Dermatologic toxicity:
(1)Rashes (usually macular or maculo-papular) were reported in nearly one-fourth of patients who received apalutamide; may require treatment interruption and/or dose reduction.
(2)Cases of fatal and life-threatening severe cutaneous adverse reactions (SCARs) have been reported, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS).
Falls:
Evaluate patients for fall risk; elderly patients are at increased risk for falls.
4. Fractures:
Grade 3 or 4 fractures have been reported. Evaluate patients for fracture risk; consider the use of bone-modifying agents.
5. Seizures:
It is not known if antiepileptic medications can prevent apalutamide-related seizures. Discontinue apalutamide permanently if seizures develop during treatment.
6. Thyroid dysfunction:
Hypothyroidism and elevated thyroid stimulating hormone (TSH) have been reported with apalutamide.
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240 mg once daily (in combination with continuous androgen deprivation therapy)
Note: Continuous androgen deprivation therapy is either treatment with a concurrent gonadotropin-releasing hormone analog agonist/antagonist or prior bilateral orchiectomy.
Dose adjustment
1.Erleada should be temporarily discontinued if Grade 3 or higher adverse reactions or other intolerable adverse reactions occur.
2.Consider permanent discontinuation of Erleada if Grade 3 or 4 cerebrovascular and ischemic cardiovascular events occur.
3.Erleada should be permanently discontinued if a serious skin adverse reaction or other Grade 4 skin reaction is confirmed.
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1. eGFR 30-89 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling. However, no clinically significant pharmacokinetic differences were observed in mild or moderate renal impairment; therefore, dosage adjustment is not likely necessary.
2. eGFR ≤29 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

1. Mild to moderate impairment (Child-Pugh classes A and B): There are no dosage adjustments provided in the manufacturer's labeling. However, no clinically significant pharmacokinetic differences were observed in mild or moderate hepatic impairment; therefore, dosage adjustment is not likely necessary.
2. Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).