Androgen Receptor Inhibitor (ARi) — Non-Metastatic CRPC Pregnancy: Contraindicated — teratogenic; male patients must use condoms + second contraception method during and for 3 months after treatment if partner is of childbearing potential

Apalutamide

Brand names: Erleada

Adult dose

Dose: 240 mg once daily (four 60 mg tablets)

Route: Oral

Frequency: Once daily

Max: 240 mg/day

Non-metastatic CRPC (nmCRPC) with PSA doubling time ≤10 months; continue until radiographic progression or unacceptable toxicity; with ongoing LHRH agonist/antagonist

Paediatric dose

Dose: Not applicable N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not licensed in paediatrics

Dose adjustments

Renal

No dose adjustment required

Hepatic

Mild-moderate: no adjustment; severe: limited data — avoid

Paediatric weight-based calculator

Patient weight (kg)

Not licensed in paediatrics

Clinical pearls

SPARTAN trial (Smith et al. NEJM 2018): apalutamide significantly prolonged metastasis-free survival (MFS) in nmCRPC vs placebo (40.5 vs 16.2 months) — MHRA approved; NICE TA578; first ARi to demonstrate MFS benefit in non-metastatic setting
PSA doubling time ≤10 months criterion: identifies highest-risk nmCRPC patients most likely to develop metastases within 2 years — apalutamide delays this by interfering with AR signalling before visible metastases appear on conventional imaging
CYP induction is the dominant drug interaction concern: apalutamide is one of the most potent CYP3A4/2C9 inducers in clinical use — review ALL concurrent medications before starting; particular risk with anticoagulants (warfarin INR falls dramatically), anticonvulsants, and HIV medications
Rash: most common grade 3 toxicity (24%) — typically maculopapular, appearing 2-4 weeks after starting; manage with antihistamines/topical steroids; dose reduction/interruption if severe; rarely requires permanent discontinuation
Hypothyroidism: apalutamide induces thyroid hormone metabolism (CYP3A4 induction increases T4/T3 clearance) — TSH should be checked every 4 months; levothyroxine dose frequently needs adjustment

Contraindications

Women of childbearing potential without effective contraception
Pregnancy
Known hypersensitivity

Side effects

Fatigue
Rash (maculopapular — 24%)
Hypothyroidism (thyroid hormone metabolism increased)
Fractures (bone density loss on ADT)
Seizures (rare — ARi class)
Hypertension
Hot flushes
CYP3A4 induction (many drug interactions)

Interactions

Strong CYP3A4/2C19 substrates — apalutamide is a potent inducer; significantly reduces levels of many drugs (warfarin, statins, azole antifungals, hormonal contraceptives, opioids)
LHRH agonists — continue concurrently
Drugs that lower seizure threshold — avoid

Monitoring

PSA every 3 months
CT and bone scan (radiological MFS assessment)
TFTs (every 4 months — hypothyroidism risk)
LFTs
Blood pressure
Seizure history
Bone density (DEXA — ADT-related fracture risk)

Reference: BNFc; BNF 90; SPARTAN trial (Smith et al. NEJM 2018); NICE TA578; MHRA SPC Erleada; EAU Prostate Cancer Guidelines 2024. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways