Enzalutamide is indicated for the treatment of patients with:

• Castration-Resistant Prostate Cancer (CRPC)
• Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Enzalutamide is an androgen receptor inhibitor that blocks several steps in the androgen receptor signaling pathway involved in prostate cancer growth. It competitively prevents androgens (such as testosterone) from binding to androgen receptors. As a result, it inhibits the movement of androgen receptors into the cell nucleus and prevents their interaction with DNA, which blocks the activation of genes responsible for tumor growth.

One of its major metabolites, N-desmethyl enzalutamide, shows similar biological activity to enzalutamide in laboratory studies. In preclinical experiments, enzalutamide reduced the proliferation of prostate cancer cells, promoted cancer cell death, and decreased tumor size in animal models of prostate cancer.

The recommended dosage of Enzalutamide is 160 mg administered orally once daily with or without food. Swallow capsules or tablets whole. Do not chew, dissolve, or open the capsules. Do not cut, crush, or chew the tablets.

Dosage Modifications for Adverse Reactions: If a patient experiences a ≥Grade 3 or an intolerable adverse reaction, withhold Enzalutamide for one week or until symptoms improve to ≤Grade 2, then resume at the same or a reduced dose (120 mg or 80 mg) if warranted.

Strong CYP2C8 Inhibitors: Avoid the coadministration of strong CYP2C8 inhibitors. If the coadministration of a strong CYP2C8 inhibitor cannot be avoided, reduce the Enzalutamide dosage to 80 mg once daily. If the coadministration of the strong inhibitor is discontinued, increase the Enzalutamide dosage to the dosage used prior to initiation of the strong CYP2C8 inhibitor.

Strong CYP3A4 Inducers: Avoid the coadministration of strong CYP3A4 inducers. If the coadministration of a strong CYP3A4 inducer cannot be avoided, increase the Enzalutamide dosage from 160 mg to 240 mg orally once daily. If the coadministration of the strong CYP3A4 inducer is discontinued, decrease the Enzalutamide dosage to the dosage used prior to initiation of the strong CYP3A4 inducer.

Pediatric Use: Safety and effectiveness of Enzalutamide in pediatric patients have not been established.

Renal Impairment: No dosage modification is recommended for patients with mild to moderate renal impairment.

Hepatic Impairment: No dosage modification is recommended for patients with mild, moderate, or severe hepatic impairment.

Strong CYP2C8 Inhibitors: When Enzalutamide is taken together with strong CYP2C8 inhibitors such as gemfibrozil, the blood levels of enzalutamide and its active metabolite (N-desmethyl enzalutamide) may increase. This may raise the risk and severity of side effects. Therefore, coadministration with strong CYP2C8 inhibitors should be avoided. If the combination cannot be avoided, the dose of Enzalutamide should be reduced.

Strong CYP3A4 Inducers: The use of Enzalutamide with strong CYP3A4 inducers, such as rifampin, may decrease the blood concentration of enzalutamide and its active metabolite. This can reduce the effectiveness of the treatment. Such combinations should generally be avoided. If coadministration is necessary, the dose of Enzalutamide may need to be increased.

The most frequently reported adverse reactions (≥10%) that were observed more often (≥2% compared to placebo) in patients treated with XTANDI include asthenia/fatigue, back pain, hot flushes, constipation, arthralgia, reduced appetite, diarrhoea, and hypertension.

The safety and effectiveness of Enzalutamide have not been established in women. Based on animal reproductive studies and its mechanism of action, Enzalutamide may cause fetal harm or pregnancy loss if used during pregnancy. There are no adequate data regarding its use in pregnant women. Animal studies showed developmental toxicity when enzalutamide was administered to pregnant mice during organ development at doses lower than the recommended human dose.

There is also no information available regarding the presence of Enzalutamide in human breast milk, its effect on breastfed infants, or its influence on milk production. However, enzalutamide and its metabolites were found in the milk of lactating rats.

Seizures have been reported in about 0.5% of patients receiving Enzalutamide. In patients with predisposing risk factors, seizures occurred in approximately 2.2% of cases. If a patient experiences a seizure during treatment, Enzalutamide should be permanently discontinued.

Posterior Reversible Encephalopathy Syndrome (PRES): If PRES develops, treatment with Enzalutamide should be discontinued immediately.

Hypersensitivity: Patients who develop serious allergic reactions should discontinue Enzalutamide.

Ischemic Heart Disease: Patients should have their cardiovascular risk factors properly managed. For severe cardiac events (Grade 3–4), treatment with Enzalutamide should be discontinued.

Falls and Fractures: Falls and fractures were reported in 11% and 10% of patients, respectively. Patients should be evaluated for fracture and fall risk, and appropriate bone-protective therapy should be considered.

Embryo-Fetal Toxicity: Enzalutamide may cause fetal harm. Men with female partners who may become pregnant should use effective contraception during treatment.

Cytotoxic Chemotherapy

Store Enzalutamide in a cool and dry place, protected from light. Keep the medicine out of the reach of children.