ERLEADA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERLEADA (ERLEADA).
Erleada (apalutamide) is an androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR, preventing AR nuclear translocation, DNA binding, and transcription of AR target genes. It also inhibits AR-mediated tumor growth and reduces prostate-specific antigen (PSA) levels.
| Metabolism | Primarily metabolized by CYP2C8 and CYP3A4 to form active metabolites (N-desmethyl apalutamide). It is also a strong inducer of CYP3A4 and CYP2C9, and has moderate effects on CYP2C19 and UGTs. |
| Excretion | Fecal (87.4%) as unchanged drug and metabolites; renal (2.4%) as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 20 hours (range 16-24 hours) at steady state, supporting once-daily dosing. |
| Protein binding | Highly protein bound (97%) primarily to albumin and α1-acid glycoprotein (AAG). |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 157 L (about 2.2 L/kg for a 70 kg adult), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is not determined due to lack of intravenous formulation; after oral administration, absorption is rapid with Tmax of 2 hours under fasting conditions; food increases Cmax by 2- to 4-fold and AUC by 2-fold. |
| Onset of Action | Clinical effect (PSA decline) observed within 4 weeks of oral administration; maximal androgen receptor blockade achieved by 8 weeks. |
| Duration of Action | Androgen receptor blockade persists for ≥24 hours with once-daily dosing due to sustained receptor occupancy and trough concentrations above IC90; clinical duration continues with daily administration. |
240 mg orally once daily on an empty stomach, taken at least 1 hour before or 2 hours after a meal. Swallow tablets whole.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use with caution. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate (Child-Pugh B): reduce dose to 120 mg once daily. Severe (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no specific pediatric dosing available. |
| Geriatric use | No specific dose adjustment required based on age alone; monitor for adverse effects (e.g., falls, hypertension) more frequently in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ERLEADA (ERLEADA).
| Breastfeeding | No data available on the presence of apalutamide in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from ERLEADA, advise women not to breastfeed during treatment and for at least 3 months after the last dose. The milk-to-plasma ratio is unknown. |
| Teratogenic Risk | Risk Category X. ERLEADA (apalutamide) can cause fetal harm when administered to a pregnant woman. Nonclinical studies have demonstrated teratogenicity, including skeletal abnormalities and reduced fetal weight, at exposures below the recommended human dose. As male patients exposed to ERLEADA may father a child, a pregnancy test should be conducted for female partners of reproductive potential prior to initiating therapy. Advise male patients to use effective contraception during treatment and for 3 months after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus. |
■ FDA Black Box Warning
No boxed warning.
| Serious Effects |
["Pregnancy: Apalutamide can cause fetal harm and is contraindicated in pregnant women.","Severe hypersensitivity to apalutamide or any component of the formulation."]
| Precautions | ["Seizure: Increased risk, especially in patients with predisposing factors; discontinue if seizure occurs.","Falls and fractures: Increased incidence in clinical trials; assess fall and fracture risk.","Cardiovascular effects: Hypertension, especially in patients with pre-existing cardiovascular disease.","Thyroid dysfunction: Monitor thyroid function tests periodically.","Hypercholesterolemia: Monitor lipid profile and manage accordingly.","Hypersensitivity reactions: Including angioedema; discontinue if severe."] |
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| Fetal Monitoring | For women of reproductive potential, verify pregnancy status prior to initiating ERLEADA. During treatment, monitor for signs and symptoms of pregnancy. If a pregnancy is suspected, discontinue ERLEADA and refer for obstetrical evaluation. For male patients with female partners of reproductive potential, monitor compliance with effective contraception. |
| Fertility Effects | Based on animal studies and its mechanism of action, ERLEADA may impair fertility in males of reproductive potential. In male rats, reduced fertility and decreased sperm motility were observed at exposures similar to human clinical exposures. These effects were reversible after a 4-week recovery period. The long-term effects of ERLEADA on human fertility are unknown. |