Zaluta Tablet

Zaluta 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 acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors; and consequently, inhibits nuclear translocation of androgen receptors and their interaction with DNA. A major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to enzalutamide. Enzalutamide decreased proliferation and induced cell death of prostate cancer cells in vitro, and decreased tumor volume in a mouse prostate cancer xenograft model.

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 induce.

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: The coadministration of Zaluta with gemfibrozil (a strong CYP2C8 inhibitor) increases plasma concentrations of Zaluta plus N-desmethyl Zaluta, which may increase the incidence and severity of adverse reactions of Zaluta. Avoid the coadministration of Zaluta with strong CYP2C8 inhibitors. If the coadministration of Zaluta with a strong CYP2C8 inhibitor cannot be avoided, reduce the dosage of Zaluta.

Strong CYP3A4 Inducers: The coadministration of Zaluta with rifampin (a strong CYP3A4 inducer and a moderate CYP2C8 inducer) decreases plasma concentrations of Zaluta plus N-desmethyl Zaluta, which may decrease the efficacy of Zaluta. Avoid the coadministration of Zaluta with strong CYP3A4 inducers. If the coadministration of Zaluta with a strong CYP3A4 inducer cannot be avoided, increase the dosage of Zaluta.

The most common adverse reactions (≥10%) that occurred more frequently (≥2% over placebo) in the XTANDI-treated patients are asthenia/fatigue, back pain, hot flush, constipation, arthralgia, decreased appetite, diarrhea, and hypertension.

The safety and efficacy of Enzalutamide have not been established in females. Based on animal reproductive studies and mechanism of action, Enzalutamide can cause fetal harm and loss of pregnancy. There are no human data on the use of Enzalutamide in pregnant females. In animal reproduction studies, oral administration of enzalutamide in pregnant mice during organogenesis caused adverse developmental effects at doses lower than the maximum recommended human dose.

The safety and efficacy of Enzalutamide have not been established in females. There is no information available on the presence of Enzalutamide in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Enzalutamide and/or its metabolites were present in milk of lactating rats.

Seizure occurred in 0.5% of patients receiving Zaluta. In patients with predisposing factors, seizures were reported in 2.2% of patients. Permanently discontinue Zaluta in patients who develop a seizure during treatment.

Posterior reversible encephalopathy syndrome (PRES): Discontinue Zaluta.

Hypersensitivity: Discontinue Zaluta.

Ischemic Heart Disease: Optimize management of cardiovascular risk factors. Discontinue Zaluta for Grade 3-4 events. Falls and Fractures occurred in 11% and 10% of patients receiving Zaluta, respectively. Evaluate patients for fracture and fall risk, and treat patients with bone-targeted agents according to established guidelines.

Embryo-Fetal Toxicity: Zaluta can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception.

Cytotoxic Chemotherapy

Keep in a cool and dry place, protect from light. Keep out of the reach of children.