Apalutamide

• ARN-509
• Erleada
• JNJ-56021927

• Antineoplastic Agent, Antiandrogen

Apalutamide is a nonsteroidal androgen receptor inhibitor; apalutamide binds directly to the androgen receptor ligand-binding domain to prevent androgen-receptor translocation, DNA binding, and receptor-mediated transcription (Smith 2018). Androgen receptor inhibition results in decreased proliferation of tumor cells and increased apoptosis, leading to a decrease in tumor volume.

Distribution

~276 L

Metabolism

Hepatic; primarily via CYP2C8 and CYP3A4 to form the active metabolite N-desmethyl apalutamide

Excretion

Urine (65%; 1.2% as apalutamide and 2.7% as N-desmethyl apalutamide); Feces (24%; 1.5% as apalutamide and 2% as N-desmethyl apalutamide)

Time to Peak

2 hours (range: 1 to 5 hours)

Half-Life Elimination

~3 days

Protein Binding

Apalutamide: 96%; N-desmethyl apalutamide: 95%; to plasma proteins

Prostate cancer, non-metastatic, castration-resistant: Treatment of non-metastatic, castration-resistant prostate cancer (NM-CRPC).

Oral: Administer at the same time each day, either with or without food. Swallow tablets whole.

Monitor thyroid function (eg, TSH) as clinically necessary. Monitor for signs/symptoms of seizure and dermatologic toxicity. Assess for fall and fracture risk. Monitor adherence.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of high potassium levels like a heartbeat that does not feel normal; feeling confused; feeling weak, lightheaded, or dizzy; feeling like passing out; numbness or tingling; or shortness of breath.
• Signs of low thyroid levels like hard stools (constipation); not able to handle cold; memory problems; mood changes; or a burning, numbness, or tingling feeling that is not normal.
• Seizures.
• Swelling in the arms or legs.
• Bone pain.
• Feeling very tired or weak.
• Low white blood cell counts have happened with apalutamide. This may lead to a higher chance of getting an infection. Call your doctor right away if you have signs of infection like fever, chills, or sore throat.

Although apalutamide is not for use by women, this medicine can cause birth defects if a woman is exposed to it during pregnancy.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Call your doctor for instructions if you miss an appointment for your LHRH injection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak.
• Joint pain.
• Not hungry.
• Weight loss.
• Hot flashes.
• Loose stools (diarrhea).
• Upset stomach.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Applies to apalutamide: oral tablet

General

The most frequently reported side effects are fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, appetite decreased, fracture, and peripheral edema.[Ref]

Hematologic

Very common (10% or more): Anemia (up to 70%), leukopenia (up to 47%), lymphopenia (up to 41%)[Ref]

Metabolic

Very common (10% or more): Hypercholesterolemia (up to 76%), hyperglycemia (up to 70%), hypertriglyceridemia (up to 67%), hyperkalemia, (up to 32%), appetite disorder (appetite decreased, early satiety, hypophagia) (up to 12%)[Ref]

Genitourinary

Common (1% to 10%): Hematuria[Ref]

Other

Very common (10% or more): Fatigue/asthenia (up to 39%), fall (up to 16%), weight decreased (up to 16%), edema (peripheral edema, generalized edema, edema, edema genital, penile edema, peripheral swelling, scrotal edema, lymphedema, swelling, localized edema) (11%)
Frequency not reported: Infection[Ref]

Cardiovascular

Very common (10% or more): Hypertension (up to 25%), hot flush (14%)
Common (1% to 10%): Ischemic heart disease, heart failure
Frequency not reported: Myocardial infarction, cardiopulmonary arrest[Ref]

Dermatologic

Very common (10% or more): Rash (maculopapular rash, generalized rash, urticaria, rash pruritic, rash macular, conjunctivitis, erythema multiforme, rash papular, skin exfoliation, genital rash, rash erythematous, stomatitis, drug eruption, mouth ulceration, rash pustular, blister, papule, pemphigoid, skin erosion, and rash vesicular) (up to 24%)
Common (1% to 10%): Pruritus[Ref]

Endocrine

Very common (10% or more): Thyroid stimulating hormone elevated
Common (1% to 10%): Hypothyroidism[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 20%), nausea (18%)[Ref]

Nervous system

Uncommon (0.1% to 1%): Seizure
Frequency not reported: Cerebral hemorrhage[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (16%), fracture (rib fracture, lumbar vertebral fracture, spinal compression fracture, spinal fracture, foot fracture, hip fracture, humerus fracture, thoracic vertebral fracture, upper limb fracture, fractured sacrum, hand fracture, pubis fracture, acetabulum fracture, ankle fracture, compression fracture, costal cartilage fracture, facial bones fracture, lower limb fracture, osteoporotic fracture, wrist fracture, avulsion fracture, fibula fracture, fractured coccyx, pelvic fracture, radius fracture, sternal fracture, stress fracture, traumatic fracture, cervical vertebral fracture, femoral neck fracture, and tibia fracture) (up to 12%)[Ref]

Applies to apalutamide: oral tablet

General

The most frequently reported side effects are fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, appetite decreased, fracture, and peripheral edema.[Ref]

Hematologic

Very common (10% or more): Anemia (up to 70%), leukopenia (up to 47%), lymphopenia (up to 41%)[Ref]

Metabolic

Very common (10% or more): Hypercholesterolemia (up to 76%), hyperglycemia (up to 70%), hypertriglyceridemia (up to 67%), hyperkalemia, (up to 32%), appetite disorder (appetite decreased, early satiety, hypophagia) (up to 12%)[Ref]

Genitourinary

Common (1% to 10%): Hematuria[Ref]

Other

Very common (10% or more): Fatigue/asthenia (up to 39%), fall (up to 16%), weight decreased (up to 16%), edema (peripheral edema, generalized edema, edema, edema genital, penile edema, peripheral swelling, scrotal edema, lymphedema, swelling, localized edema) (11%)
Frequency not reported: Infection[Ref]

Cardiovascular

Very common (10% or more): Hypertension (up to 25%), hot flush (14%)
Common (1% to 10%): Ischemic heart disease, heart failure
Frequency not reported: Myocardial infarction, cardiopulmonary arrest[Ref]

Dermatologic

Very common (10% or more): Rash (maculopapular rash, generalized rash, urticaria, rash pruritic, rash macular, conjunctivitis, erythema multiforme, rash papular, skin exfoliation, genital rash, rash erythematous, stomatitis, drug eruption, mouth ulceration, rash pustular, blister, papule, pemphigoid, skin erosion, and rash vesicular) (up to 24%)
Common (1% to 10%): Pruritus[Ref]

Endocrine

Very common (10% or more): Thyroid stimulating hormone elevated
Common (1% to 10%): Hypothyroidism[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 20%), nausea (18%)[Ref]

Nervous system

Uncommon (0.1% to 1%): Seizure
Frequency not reported: Cerebral hemorrhage[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (16%), fracture (rib fracture, lumbar vertebral fracture, spinal compression fracture, spinal fracture, foot fracture, hip fracture, humerus fracture, thoracic vertebral fracture, upper limb fracture, fractured sacrum, hand fracture, pubis fracture, acetabulum fracture, ankle fracture, compression fracture, costal cartilage fracture, facial bones fracture, lower limb fracture, osteoporotic fracture, wrist fracture, avulsion fracture, fibula fracture, fractured coccyx, pelvic fracture, radius fracture, sternal fracture, stress fracture, traumatic fracture, cervical vertebral fracture, femoral neck fracture, and tibia fracture) (up to 12%)[Ref]

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Medical Disclaimer

Take the missed dose as soon as you remember it. However, if you do not remember until the next day, skip the missed dose and continue your regular dosing schedule. Do not take more than one dose in one day and do not take a double dose to make up for a missed one.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.