Usage
Apalutamide is prescribed for the treatment of:
- Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC): In men at high risk of developing metastatic disease.
- Metastatic Castration-Sensitive Prostate Cancer (mCSPC): In combination with androgen deprivation therapy (ADT).
Pharmacological Classification: Nonsteroidal antiandrogen, androgen receptor inhibitor.
Mechanism of Action: Apalutamide binds to androgen receptors, preventing androgens (like testosterone) from binding and activating them. This inhibits the growth of prostate cancer cells, which rely on androgens for growth and survival.
Alternate Names
- INN: Apalutamide
- Brand name: Erleada
How It Works
Pharmacodynamics: Apalutamide inhibits prostate cancer cell growth by blocking androgen receptor signaling. It affects multiple steps in the androgen receptor pathway, including nuclear translocation, DNA binding, and transcription.
Pharmacokinetics:
- Absorption: Oral bioavailability is approximately 100%.
- Metabolism: Primarily by CYP2C8 and CYP3A4 enzymes in the liver. N-desmethylapalutamide is the major active metabolite.
- Elimination: Primarily via urinary excretion of inactive metabolites. Approximately 65% is excreted in urine (1% as unchanged apalutamide, 3% as N-desmethylapalutamide) and 24% in feces (2% as unchanged apalutamide, 2% as N-desmethylapalutamide).
- Half-life: Approximately 3 days at steady state.
Mode of Action: Apalutamide competitively binds to androgen receptors with high affinity, preventing androgens from binding and activating the receptors. It exhibits no agonist activity, unlike some other antiandrogens.
Receptor Binding/Enzyme Inhibition: Apalutamide specifically targets androgen receptors. Its primary route of metabolism is via CYP2C8 and CYP3A4.
Dosage
Standard Dosage
Adults:
240 mg (one 240 mg tablet or four 60 mg tablets) orally once daily, taken with or without food. Administer concurrently with a gonadotropin-releasing hormone (GnRH) analog or after bilateral orchiectomy.
Children: Not recommended. Safety and efficacy have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No dose adjustment is necessary. However, patients ≥75 years may experience higher toxicity and lower tolerance. Close monitoring is recommended.
- Patients with Renal Impairment: No dose adjustment needed for mild to moderate impairment. Caution is advised in patients with severe renal impairment due to limited data.
- Patients with Hepatic Dysfunction: No dose adjustment needed for mild to moderate impairment. Not recommended in severe hepatic impairment.
- Patients with Comorbid Conditions: Close monitoring is necessary for patients with cardiovascular disease, diabetes, or other conditions. Manage risk factors optimally.
Clinical Use Cases
Apalutamide is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is limited to the specific prostate cancer indications mentioned above.
Dosage Adjustments
For Grade 3 or higher toxicity or intolerable side effects, hold the dose until symptoms improve to Grade 1 or baseline. Then resume at the same or a reduced dose (180 mg or 120 mg). Discontinue for recurrent Grade 3 toxicity after dose reduction. Permanently discontinue if a seizure occurs.
Side Effects
Common Side Effects:
Fatigue, hypertension, rash, diarrhea, nausea, weight loss, arthralgia, falls, hot flashes, decreased appetite, fractures, peripheral edema.
Rare but Serious Side Effects:
Seizures, cardiovascular events (e.g., heart attack, stroke), severe skin reactions (e.g., Stevens-Johnson syndrome).
Long-Term Effects:
Increased risk of fractures, cardiovascular disease, and hypothyroidism.
Adverse Drug Reactions (ADR):
Seizures, severe hypersensitivity reactions, falls, fractures.
Contraindications
- Hypersensitivity to apalutamide or any of its components.
- Women who are or may become pregnant.
Drug Interactions
Apalutamide interacts with numerous medications. Consult a comprehensive drug interaction resource for detailed information.
- CYP450 Interactions: CYP2C8 and CYP3A4 substrates, inducers, and inhibitors may affect apalutamide levels.
- Medications: Clarithromycin, ketoconazole, warfarin, simvastatin, midazolam, and many others.
Pregnancy and Breastfeeding
Pregnancy Safety Category: X. Contraindicated in women who are or may become pregnant due to potential fetal harm.
Breastfeeding: Not recommended due to lack of data on apalutamide excretion in breast milk.
Drug Profile Summary
- Mechanism of Action: Androgen receptor inhibitor.
- Side Effects: Fatigue, hypertension, rash, seizures (rare).
- Contraindications: Pregnancy, hypersensitivity.
- Drug Interactions: Numerous; consult a drug interaction resource.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, not recommended while breastfeeding.
- Dosage: 240 mg orally once daily.
- Monitoring Parameters: PSA levels, cardiovascular function, bone health, thyroid function.
Popular Combinations
Apalutamide is typically used in combination with androgen deprivation therapy (ADT), either a GnRH analog or bilateral orchiectomy.
Precautions
- Monitor for falls and fractures.
- Assess and manage cardiovascular risk factors.
- Monitor for seizures, particularly in patients with predisposing factors.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Apalutamide?
A: 240 mg orally once daily for adults. Not recommended for children.
Q2: What are the most common side effects?
A: Fatigue, hypertension, rash, diarrhea.
Q3: Can Apalutamide be used in women?
A: No, it is contraindicated in women, especially those who are or may become pregnant.
Q4: Are there any serious side effects?
A: Yes, seizures, though rare, are a serious side effect. Cardiovascular events and severe skin reactions can also occur.
Q5: How should Apalutamide be taken?
A: Swallow tablets whole with water, with or without food. Take at the same time each day.
Q6: What should I do if a dose is missed?
A: Take the missed dose as soon as possible on the same day. Do not take extra tablets.
Q7: Does Apalutamide interact with other medications?
A: Yes, many drug interactions are possible. Inform your doctor of all medications you are taking.
Q8: What are the long-term effects of Apalutamide?
A: Long-term use may increase the risk of fractures, cardiovascular disease, and hypothyroidism.
Q9: Should any monitoring be done during treatment?
A: Yes, monitoring PSA levels, cardiovascular function, and bone health are important during treatment. Thyroid function should also be checked.
