Apalutamide

Apalutamide is a selective androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. It prevents AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription, decreasing tumor cell proliferation and increasing apoptosis.

It is indicated for metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (NM-CRPC). The recommended dose is 240 mg (four 60 mg tablets) taken orally once daily.

Common side effects include fatigue, hypertension, rash, diarrhea, nausea, arthralgia, weight loss, hot flush, and fractures. Serious side effects include seizures, falls, and ischemic heart disease.

• Metastatic castration-sensitive prostate cancer (mCSPC)
• Non-metastatic castration-resistant prostate cancer (NM-CRPC)

Apalutamide is an orally administered, selective Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide prevents AR nuclear translocation, inhibits DNA binding, impedes AR-mediated transcription, and lacks androgen receptor agonist activity.

Apalutamide treatment decreases tumor cell proliferation and increases apoptosis, leading to potent antitumor activity in mouse xenograft models of prostate cancer.

Apalutamide binds directly to the ligand-binding domain of the androgen receptor (AR), blocking androgens (male hormones like testosterone) from binding to the AR. This prevents AR from translocating to the nucleus, binding to DNA, and regulating gene expression. As a result, prostate cancer cell growth is reduced and cells undergo apoptosis.

Recommended Dose: 240 mg (four 60 mg tablets) orally once daily.

Concurrent Treatment: Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.

Important: Swallow tablets whole. Do not crush or split the tablets.

May take with or without food. Swallow tablets whole. Do not crush or split.

If you miss a dose, take your normal dose as soon as possible on the same day. Return to your normal schedule on the following day. Do not take extra tablets to make up the missed dose.

Common (>10%):

• Hypercholesterolemia (76%)
• Anemia (70%)
• Hyperglycemia (70%)
• Hypertriglyceridemia (67%)
• Leukopenia (47%)
• Lymphopenia (41%)
• Fatigue (39%)
• Hyperkalemia (32%)
• Hypertension (25%)
• Rash (24%)
• Diarrhea (20%)
• Nausea (18%)
• Arthralgia (16%)
• Fall (16%)
• Weight decreased (16%)
• Hot flush (14%)
• Fracture (12%)
• Decreased appetite (12%)
• Peripheral edema (11%)

Grades 3-4 (>10%): Hypertension (14%)

1-10%: Hypothyroidism (8%), Pruritus (6.2%), Ischemic heart disease (3.7%), Heart failure (2.2%)

Grades 3-4 (1-10%): Rash (5%), Fracture (3%), Fall (2%), Hypertriglyceridemia (2%), Lymphopenia (2%), Hyperkalemia (2%), Hyperglycemia (2%)

Serious Precautions:

• Not recommended in patients with history of seizures or predisposing factors (brain injury, stroke, brain tumors) - permanently discontinue if seizure occurs during treatment
• Falls and fractures risk - evaluate patient for risk; consider bone-targeted agents
• Ischemic heart disease - most patients had cardiac risk factors; monitor for signs and symptoms
• Safety not established in patients with clinically significant cardiovascular disease in the past 6 months
• Androgen deprivation therapy may prolong QT interval
• Contraindicated during pregnancy - may cause fetal harm
• Not indicated for use in females

• Pregnancy or women who may become pregnant
• Hypersensitivity to active substance
• History of seizures (not recommended)

CYP2C8 Inhibitors: Coadministration with strong CYP2C8 inhibitors (e.g., gemfibrozil, clopidogrel) increases active apalutamide AUC by 45%. No initial dose adjustment necessary; consider dose reduction based on tolerability.

CYP3A4 Inhibitors: Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) shows no significant changes. No initial dose adjustment necessary.

CYP3A4/CYP2C19 Effects: Apalutamide is a strong inducer of CYP3A4 and CYP2C19, and weak inducer of CYP2C9. May decrease exposure of medications metabolized by these enzymes.

UGT Substrates: Concomitant use with UGT substrates may decrease exposure.

P-gp/BCRP/OATP1B1: Apalutamide is a weak inducer; may decrease exposure of substrates.

Warfarin: Avoid coadministration with CYP2C9-metabolized anticoagulants; monitor INR if necessary.

May take with or without food.

Contraindicated during pregnancy: Based on its mechanism of action, the drug can cause fetal harm and potential loss of pregnancy. No available data regarding use in pregnant women. Not indicated for use in females.

Contraception: Male patients with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.

Not indicated for use in females. It is unknown whether apalutamide/metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Should not be used during breast-feeding.

Safety and efficacy in pediatric patients have not been established.

No specific dose adjustment needed for elderly patients. However, monitor for cardiovascular risk factors.

No specific dose adjustment needed for renal impairment.

No specific dose adjustment needed for hepatic impairment.

There is no known specific antidote for apalutamide overdose. In the event of an overdose, stop apalutamide, undertake general supportive measures until clinical toxicity has been diminished or resolved.

Store below 30°C. Protect from moisture and light. Keep out of reach of children.

Apalutamide