Enzalutamide Astellas

Uses

Enzalutamide Astellas is an androgen receptor inhibitor used to treat castration-resistant prostate cancer.

Enzalutamide Astellas is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.

Enzalutamide Astellas is also used to associated treatment for these conditions: Metastatic Castration Resistant Prostate Cancer

How Enzalutamide Astellas works

Enzalutamide Astellas is a competitive androgen receptor inhibitor that effects multiple stages of the signalling pathway. It is able to inhibit androgen binding to its receptor, androgen receptor nuclear translocation, and subsequent interaction with DNA. As a result, proliferation of prostate cancer cells decreases which ultimately leads to apoptosis and decreased tumour volume.

Toxicity

The most common adverse reactions (≥ 5%) are asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension.

Food Interaction

• Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of enzalutamide and may reduce its serum concentration.
• Take with or without food.

Enzalutamide Astellas Drug Interaction

Major: tramadolModerate: fexofenadine, sulfamethoxazole / trimethoprim, celecoxib, atorvastatinUnknown: dicyclomine, calcium / vitamin d, calcium carbonate, docusate, leuprolide, ethanol, leuprolide, morphine, bifidobacterium infantis / lactobacillus acidophilus, calcium carbonate, acetaminophen, cyanocobalamin, cholecalciferol, denosumab, goserelin

Enzalutamide Astellas Disease Interaction

Moderate: renal impairment, seizures

Volume of Distribution

Apparent volume of distribution (Vd/F), single oral dose = 110 L

Elimination Route

The pharmacokinetic profile of enzalutamide and N-desmethyl enzalutamide (its major active metabolite) is described by a linear two-compartment model with first-order absorption. Enzalutamide Astellas also accumulates. Food does not affect its absorption. Tmax, prostate cancer patients = 1 hour (range of 0.5-3 hours); Cmax, steady state, enzalutamide = 16.6 μg/mL; Cmax, steady state, N-desmethyl enzalutamide = 12.7 μg/mL; Time to steady state, daily dosing = 28 days;

Half Life

The mean terminal half-life (t1/2) for enzalutamide in patients after a single oral dose is 5.8 days (range 2.8 to 10.2 days). Following a single 160 mg oral dose of enzalutamide in healthy volunteers, the mean terminal t1/2 for N-desmethyl enzalutamide is approximately 7.8 to 8.6 days.

Clearance

Apparent clearance (CL/F), single oral dose = 0.56 L/h (range of 0.33 - 1.02 L/h)

Elimination Route

Enzalutamide Astellas is primarily eliminated by hepatic metabolism. 71% of the dose is recovered in urine (including only trace amounts of enzalutamide and N-desmethyl enzalutamide), and 14% is recovered in feces (0.4% of dose as unchanged enzalutamide and 1% as N-desmethyl enzalutamide).

Innovators Monograph

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