Apalutamide

🔹 1. Basic Information
Generic name: Apalutamide
Brand name: ERLEADA
Drug class: Androgen receptor inhibitor (anti-androgen)
Pharmacological classification: A.21.12 – Hormone inhibitor
Formulation: Oral film-coated tablets
Strengths: 60 mg
Mechanism of action: Selectively binds to androgen receptors, preventing receptor activation, nuclear translocation, and DNA binding. Inhibits androgen-driven gene expression and prostate cancer cell growth.

🔹 2. Indications
Used in combination with a GnRH analogue or after bilateral orchiectomy for:

• Metastatic castration-sensitive prostate cancer (mCSPC)

• Non-metastatic castration-resistant prostate cancer (nmCRPC)

🔹 3. Dosing
Recommended dose: 240 mg (four 60 mg tablets) once daily
Administration:

• Swallow tablets whole, with or without food

• Take missed dose as soon as possible on the same day — do not double up

• Should be prescribed by a healthcare professional experienced in prostate cancer management

🔹 4. Dose Modifications

If the patient experiences Grade 3 or higher side effects, or side effects that are difficult to tolerate, pause treatment.
Resume at the same or a lower dose once side effects improve to Grade 1 or baseline.

🔹 5. Co-medications

• Must be used with a GnRH analogue (e.g. leuprolide, goserelin, triptorelin) or after bilateral orchiectomy

• No pharmacokinetic interaction with leuprolide (GnRH analogue)

🔹 6. Contraindications

• Hypersensitivity to apalutamide or excipients

• Pregnancy (contraindicated in women who are or may become pregnant)

• History of seizures or epilepsy

🔹 7. Monitoring Requirements

• Thyroid function: Baseline and periodic (risk of hypothyroidism)

• Cardiac: Monitor for ischaemic heart or cerebrovascular disease

• Bone health: Assess fall/fracture risk; consider bone-protective agents

• Neurological: Observe for seizures

• Dermatologic: Monitor for rash and SCAR (SJS/TEN, DRESS)

🔹 8. Side Effects

🔹 9. Drug Interactions

• CYP2C8/3A4 inhibitors (e.g. gemfibrozil, ketoconazole): ↑ apalutamide levels – monitor and reduce dose if needed

• CYP3A4/CYP2C8 inducers (e.g. rifampicin): ↓ levels – avoid

• Strong inducer of CYP3A4, 2C19, 2C9: May ↓ levels of other drugs (e.g. warfarin, omeprazole)

• Monitor INR if on warfarin

• May reduce exposure to drugs transported by P-gp, BCRP, OATP1B1

• No interaction with acid-lowering medicines

🔹 10. Use in Special Populations

• Pregnancy/Lactation: Contraindicated

• Males: May impair fertility

• Elderly (≥65 years): No adjustment needed

• Hepatic impairment: No dose adjustment for mild/moderate; avoid in severe

• Renal impairment: No dose adjustment for mild/moderate; avoid if severe (eGFR ≤29 mL/min/1.73 m²)

• Paediatric: Not indicated

🔹 11. Duration of Use / When to Stop the Drug
Continue until disease progression or unacceptable toxicity.
Discontinue if:

• Seizures occur

• Severe cutaneous adverse reactions (SCAR) develop

• Persistent Grade ≥3 toxicity despite dose reductions

• Patient cannot tolerate 120 mg daily dose

🔹 12. Toxicity Management

REFERENCE: 

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2023/04/ERLEADA-PI_Mar2023.pdf