Enzalunix: Enzalutamide is an androgen receptor inhibitor. Androgens are a group of hormones that includes testosterone. Androgen receptor inhibitors interfere with the connection between androgens and androgen receptors. This can help slow cancer cell growth.

Mode of Action:
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.

• Enzalutamide is indicated for the treatment of patients with:
• Non-Metastatic Castration-resistant prostate cancer (nmCRPC)
• Metastatic Castration-resistant prostate cancer (mCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

DOSAGE & ADMINISTRATION

Dosing Information: The recommended dose of Enzalutamide is 160 mg (two 80 mg tablets or four 40 mg tablets) administered orally once daily.

Method of administration: Enzalutamide can be taken 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.

Dose Modifications: If a patient experiences a ≥ Grade 3 toxicity or an intolerable side effect, withhold dosing 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.

Concomitant Strong CYP2C8 Inhibitors: The concomitant use of strong CYP2C8 inhibitors should be avoided if possible. If patients must be co-administered a strong CYP2C8 inhibitor, reduce the Enzalutamide dose to 80 mg once daily. If co-administration of the strong inhibitor is discontinued, the Enzalutamide dose should be returned to the dose used prior to initiation of the strong CYP2C8 inhibitor.

Concomitant Strong CYP3A4 Inducers: The concomitant use of strong CYP3A4 inducers should be avoided if possible. If patients must be co-administered a strong CYP3A4 inducer, increase the Enzalutamide dose from 160 mg to 240 mg once daily. If co-administration of the strong CYP3A4 inducer is discontinued, the Enzalutamide dose should be returned to the dose used prior to initiation of the strong CYP3A4 inducer.

Important Administration Instructions : Patients receiving Enzalutamide should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

WARNINGS AND PRECAUTIONS:

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

Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue Enzalutamide in patients who develop PRES.

Hypersensitivity: Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with Enzalutamide in seven randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue Enzalutamide and promptly seek medical care. Permanently discontinue Enzalutamide for serious hypersensitivity reactions.

Ischemic Heart Disease: In the combined data of four randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the Enzalutamide arm compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4 ischemic events occurred in 1.4% of patients on the Enzalutamide arm compared to 0.7% on the placebo arm. Ischemic events led to death in 0.4% of patients on the Enzalutamide arm compared to 0.1% on the placebo arm. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue Enzalutamide for Grade 3-4 ischemic heart disease.

Falls and Fractures: Falls and Fractures occurred in 11% and 10% of patients receiving Enzalutamide, respectively. Evaluate patients for fracture and fall risk and treat patients with bone-targeted agents according to established guidelines.

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

SIDE EFFECTS

Serious side effects:

1. Seizure.

2. Posterior Reversible Encephalopathy Syndrome (PRES).

3. Allergic Reactions.

4. Heart disease.

5. Falls and fractures.

Serious side effects:

1.Weakness or feeling more tired than usual

2. Back pain

3. Hot Flashes

4. Constipation

5. Joint Pain

6. Decreased Appetite

7. Diarrhea

8. High blood pressure

OVERDOSAGE:

In the event of an overdose, stop treatment with Enzalutamide and initiate general supportive measures taking into consideration the half-life of 5.8 days. In a dose escalation study, no seizures were reported at < 240 mg daily, whereas 3 seizures were reported, 1 each at 360 mg, 480 mg, and 600 mg daily. Patients may be at increased risk of seizure following an overdose.