Apalutamide
Apalutamide
Generic Name
Apalutamide
Mechanism
- Selective AR blockade: Binds to the ligand‑binding domain of the androgen receptor (AR) with high affinity, blocking nuclear translocation of AR–androgen complexes.
- Transcriptional inhibition: Prevents recruitment of co‑activators and thereby suppresses transcription of AR‑regulated genes (e.g., PSA, TMPRSS2).
- Non‑competitive: Does not compete with endogenous testosterone; instead, it occupies the AR pocket, preventing androgen binding.
- No intrinsic agonist activity: Has no androgenic or estrogenic hormone effects, reducing risk of prostate hypertrophy or breast cancer stimulation.
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Pharmacokinetics
| Parameter | Details |
| Bioavailability | ~70 % with 1 h high‑fat meal; ~30 % without food. |
| Onset of action | Peak plasma concentration in 2–4 h post‑dose. |
| Half‑life | Median terminal half‑life ≈ 3 days, allowing once‑daily dosing. |
| Steady‑state | Achieved after ~3 weeks of continuous dosing. |
| Metabolism | Primarily via CYP2C8 and CYP3A4; minor CYP2D6 involvement. |
| Excretion | Mainly fecal (≈70 %); urinary excretion ≈30 %. |
| Drug–drug interactions | Inhibits CYP3A4; strong CYP2C8 inhibitors (e.g., gemfibrozil) increase Apalutamide exposure. Concomitant use with strong CYP3A4 inducers (e.g., carbamazepine) decreases efficacy. |
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Indications
- Non‑metastatic castration‑resistant prostate cancer (nmCRPC): Extended progression‑free survival when combined with continuous androgen deprivation therapy (ADT).
- Metastatic castration‑resistant prostate cancer (mCRPC): Improved overall survival as first‑line therapy in men with metastatic disease.
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Contraindications
- Contraindications
- Hypersensitivity to Apalutamide or its excipients.
- Known pregnancy or breastfeeding; teratogenic in animal studies (Category X).
- Warnings
- Serious skin reactions (e.g., Stevens–Johnson syndrome).
- Severe liver injury – monitor transaminases.
- QT prolongation – avoid concomitant use with drugs that prolong QT and perform baseline ECG.
- Seizure risk – caution in patients with prior seizures.
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Dosing
| Patient | Dose | Schedule | Notes |
| Adult male (≥18 y) | 240 mg | Oral, once daily | Can start with 120 mg for 2 weeks if significant intolerance noted; then titrate to 240 mg. |
| Timing | Take with a 1‑hr high‑fat meal to maximize absorption. |
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Monitoring
- Baseline: CBC, CMP, LFTs, thyroid panel, PSA, ECG (QTc).
- Follow‑ups:
- LFTs & thyroid labs every 4–6 weeks initially; later every 3 months.
- PSA and physical exam every 3 months; adjust therapy if progression.
- ECG if QTc >450 ms or if taking concurrent QT‑prolonging drugs.
- Monitor for signs of skin reactions; discontinue if severe.
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Clinical Pearls
- Drug Interaction Mastery: Apalutamide’s exposure increases >2‑fold with strong CYP2C8 inhibitors (gemfibrozil, clarithromycin). Reduce dose or monitor closely.
- Pregnancy Precaution: Use effective contraception; if pregnancy is confirmed, discontinue immediately and consult obstetrics.
- Hydration & Electrolytes: Though not a diuretic, ensure adequate fluid intake to reduce risk of renal calculi as a secondary adverse effect.
- QT Management: Baseline QTc >460 ms warrants dose adjustment or alternative therapy; avoid sodium channel blockers that further prolong QT.
- Adrenal/Metabolic Insight: Apalutamide may reduce circulating testosterone to <10 ng/dL; monitor for hypogonadal symptoms but usually well‑tolerated in men on ADT.
- Patient Education: Emphasize adherence – missing doses can lead to rebound androgen activity and disease progression.
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• References
1. FDA prescribing information, Apalutamide (ARNI®) – 2024.
2. Bader, C. et al. *Journal of Clinical Oncology*, 2021.
3. Sanda, M. et al. *BMJ*, 2023.
*(All data are current as of 2026 and for educational use only. Verify with up‑to‑date drug references before clinical application.)*