Xtandi Film-coated

Uses

Xtandi Film-coated is an androgen receptor inhibitor used to treat castration-resistant prostate cancer.

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

Xtandi Film-coated is also used to associated treatment for these conditions: Metastatic Castration Resistant Prostate Cancer

How Xtandi Film-coated works

Xtandi Film-coated 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.

Xtandi Film-coated 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

Xtandi Film-coated 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. Xtandi Film-coated 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

Xtandi Film-coated 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

You find simplified version here Xtandi Film-coated