Apalutamide is an Androgen Receptor (AR) inhibitor that binds directly to the AR ligand-binding domain to inhibit nuclear translocation, DNA binding, and AR-mediated transcription resulting in tumor growth inhibition and regression.
100%. Apalutamide is completely absorbed after oral administration.
|Time to reach steady state||
|Effects with food||
Food administration has no significant effect on apalutamide exposure, however the median time to reach tmax was delayed approximately 2 hours with food.
|Time to reach steady state||
4 weeks; accumulates approximately 5x relative to a single dose.
|Cross blood brain barrier?||
Apalutamide and N-desmethyl apalutamide has been observed to cross the blood brain barrier in animal studies.
96% Apalutamide; 95% N-desmethyl apalutamide
44% N-desmethyl apalutamide
Apalutamide is primarily metabolized by CYP2C8 and CYP3A4 to form the active metabolite N-desmethyl apalutamide.
65%; 1.2% as apalutamide and 2.7% as N-desmethyl apalutamide
24%; 1.5% as apalutamide and 2% as N-desmethyl apalutamide
~ 3 days
For the treatment of patients with non-metastatic castration-resistant prostate cancer (NM-CRPC).
Extravasation Potential: Not applicable
The following adverse effects were reported in ≥ 10% of patients in the phase III trial comparing apalutamide with androgen deprivation therapy (ADT) to placebo with ADT, where incidence was at least 2% or more compared to placebo. Severe adverse effects from other studies or post-marketing may also be included.
|ORGAN SITE||SIDE EFFECT* (%)||ONSET**|
|Cardiovascular||Arterial thromboembolism (4%)||E|
|QT interval prolonged (rare)||E|
|Dermatological||Rash (24%) (5% severe)||D|
|Gastrointestinal||Anorexia, weight loss (16%)||E|
|Fall (16%)||E D|
|Hematological||Anemia (70%) (mild)||E D|
|Myelosuppression (47%) (mild)||E|
|Metabolic / Endocrine||↑ Cholesterol (76%) (non-fasting)||E|
|Hyperglycemia (70%) (non-fasting)||E|
|Hypothyroidism (8%)||E D|
|↑ K (32%)||E|
|Nervous System||Seizure (<1%)||E|
|Reproductive and breast disorders||Androgen deprivation symptoms (14%)||E|
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common side effects for apalutamide include ↑ cholesterol, anemia, hyperglycemia, myelosuppression, fatigue, ↑ K, hypertension, rash, diarrhea and nausea.
Rash (usually macular or maculopapular) onset typically occurred at a median of 82 days with resolution within a median of 60 days in most patients. Rash recurred in approximately half of patients who were re-challenged with apalutamide.
Hypothyroidism has been reported with apalutamide. Interactions between apalutamide and thyroxine have been reported.
Fall and fractures have been observed in patients receiving apalutamide. The median time to onset of fracture was approximately 10 months. Patients at risk for fractures should be monitored and managed according to established management guidelines. Consider the use of bone targeted agents.
Seizures were observed and may be related to off target effects on GABAA gated channels.
Refer to protocol by which patient is being treated.
Patients should also receive a gonadotropin-releasing hormone (GnRH) analog unless they have had a bilateral orchiectomy.
Patients should be assessed for the risk of fracture and fall and managed according to guidelines.
|Dose Level||Apalutamide Dose (mg/day)|
|Intolerable or ≥ Grade 3||Hold until recover to ≤ Grade 1, resume at the same dose or at ↓ 1 dose level.
If the toxicity recurs at ≥ Grade 3, ↓ 1 dose level.
|Mild or moderate||No adjustment required|
|Mild to moderate (CrCL ≥ 30 mL/min)||No adjustment required|
|Severe (CrCL ≤ 29 mL/min)||No data|
No dose adjustment is necessary for elderly patients. Patients ≥ 65 years treated with apalutamide experienced higher toxicity and lower tolerance. Monitor elderly patients more closely for toxicity and adjust dose when needed.
There is no clinically relevant difference in exposure between White (Caucasian or Hispanic or Latino), Black (of African heritage or African American), Asian (non-Japanese), or Japanese patients. No dose adjustments are necessary.
Safety and effectiveness of apalutamide in pediatric patients have not been evaluated.
Tablets should be swallowed whole with a glass of water.
Tables can be taken with or without food.
Take the dose at around the same time each day.
A missed dose should be taken as soon as possible on the same day with a return to the normal schedule on the following day. The patient should not take extra tablets to make up the missed dose.
Store at 15°C to 30°C, in the original package to protect from light and moisture.
If tablets are provided in a bottle, do not remove the silica gel desiccant from the bottle.
Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
Women who are or may become pregnant.
Exercise caution in patients with:
Cardiac disorders. Patients with clinically significant cardiovascular disease in the past 6 months including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events or clinically significant ventricular arrhythmias were excluded from clinically trials.
Seizures. Patients with a history of seizures or predisposing factors for seizures were excluded from clinical studies; patients on medications known to lower seizure threshold were prohibited while receiving apalutamide.
QT prolongation, risk factors for Torsade de pointes or on medications known to prolong QTc.
Other Drug Properties:
Apalutamide is not recommended for use in pregnancy. Adequate contraception should be used by both sexes of childbearing potential during treatment, and for at least 3 months after the last dose.
Apalutamide is not indicated for use in females. There are no data on the presence of apalutamide or its metabolites in human milk.
Documented in animals
In vitro studies showed that apalutamide and N-desmethyl apalutamide are moderate to strong CYP2B6 inducers and moderate inhibitors of CYP2B6.
Based on in vitro data, inhibition of organic cation transporter 2 (OCT2), organic anion transporter 3 (OAT3) and multidrug and toxin extrusions (MATEs) by apalutamide and its N-desmethyl apalutamide cannot be excluded.
- GABA inhibition is an off-target activity of both apalutamide and N-desmethyl apalutamide. This interaction is considered the mechanism for the seizures/convulsions observed in general toxicology studies at high doses in animals.
|CYP 2C8 strong inhibitors (i.e. gemfibrozil)||↑ apalutamide concentration||↓ metabolism of apalutamide||Caution; consider dose adjustment for apalutamide based on tolerability.|
|CYP3A4 strong inhibitors (i.e. itraconazole, clarithromycin, ritonavir, nelfinavir, etc.)||↑ apalutamide concentration||↓ metabolism of apalutamide||Caution; consider dose adjustment for apalutamide based on tolerability.|
|CYP3A4 strong inducers (i.e. phenytoin, rifampin, carbamazepine, phenobarbital, St. John’s Wort, etc.)||↓ apalutamide concentration||↑ metabolism of apalutamide||Caution, no adjustment needed.|
|CYP 2C8 strong inducers (i.e. rifampicin, phenobarbital)||↓ apalutamide concentration||↓ metabolism of apalutamide||Caution, no adjustment needed.|
|CYP3A4 substrates (e.g. cyclosporine, pimozide, tacrolimus, triazolo-benzodiazepines, dihydropyridine calcium-channel blockers, certain HMG-CoA reductase inhibitors)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Avoid or substitute if possible. Evaluate for loss of efficacy if medication is continued.|
|CYP 2C19 substrates (e.g. omeprazole)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Avoid or substitute if possible. Evaluate for loss of efficacy if medication is continued.|
|CYP 2C9 substrates (e.g. warfarin, meloxicam, fluvastatin)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Avoid or substitute if possible; if not possible monitor closely (e.g. INR).|
|CYP 2C8 substrates (i.e. paclitaxel, sorafenib, amiodarone)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Caution; no adjustment needed.|
|P-glycoprotein substrates (i.e. verapamil, digoxin, morphine, ondansetron)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Caution; evaluate for loss of efficacy if medication is continued.|
|BCRP substrates (i.e. topotecan)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Caution; evaluate for loss of efficacy if medication is continued.|
|OATP1B1 substrates (i.e. rosuvastatin)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Caution; evaluate for loss of efficacy if medication is continued.|
|UGT substrates (i.e. estradiol, irinotecan, levothyroxine, thyroxine)||↓ substrate concentration and/or efficacy||↑ metabolism of substrate||Caution; evaluate for loss of efficacy if medication is continued.|
|Drugs that may prolong QT (i.e. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc.)||↑ risk of QT prolongation and arrhythmias||Additive||Caution|
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
|Monitor Type||Monitor Frequency|
|Baseline and as clinically indicated|
|Baseline and as clinically indicated; more frequent in patients at risk of QTc increase|
|If warfarin cannot be discontinued; baseline and during apalutamide treatment|
Clinical toxicity assessment for androgen withdrawal effects, fatigue, infection, active cardiac disease, seizure, dermatologic toxicity and risk of fracture and falls
|At each visit|
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Exceptional Access Program (EAP Website)
- apalutamide - For the treatment of non-metastatic castration resistant prostate cancer (nmCRPC) according to clinical criteria
Erleada™ (apalutamide) product monograph. Toronto, Ontario, Canada: Janssen Inc; July 2018.
January 2020 Added EAP funding info
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