Enzalutamide (Xtandi) FDA Approval History

• FDA Approved: Yes (Initial approval date: August 31, 2012)
• Brand Name: Xtandi
• Active Ingredient: Enzalutamide
• Administration: Soft capsule
• Class: Antiandrogen
• Category: Hormonal agent
• Manufacturer: Astellas
• Distribution in Turkey: Astellas İlaç
• Approved Cancer: Prostate Cancer

The drug containing enzalutamide, Xtandi , is a potent androgen receptor inhibitor used to treat patients with prostate cancer.

1. A Pure Androgen Receptor (AR) Antagonist: It acts directly at different stages of the androgen receptor signaling pathway.
2. Blocks Receptor Binding: It competitively blocks androgen binding to ARs.
3. Inhibits Nuclear Translocation: It stops AR nuclear translocation and coactivator recruitment by the ligand–receptor complex.
4. Provides Dual-Level Suppression: It strongly inhibits the androgen–AR pathway at the receptor and post-receptor ligand-binding levels.
5. Active Metabolite Support: The drug's N-desmethyl enzalutamide metabolite also continues to exhibit antitumor activity similar to enzalutamide.

• August 31, 2012: The FDA approved Xtandi for late-stage castration-resistant prostate cancer.
• July 13, 2018: The FDA Approved Xtandi for Men with Nonmetastatic Castration-Resistant Prostate Cancer.
• December 16, 2019: The FDA Approved Xtandi (enzalutamide) for Metastatic Castration-Sensitive Prostate Cancer.

Xtandi was first licensed on 26.04.2016 by the Republic of Turkey Ministry of Health. Its approved clinical settings in Turkey are:

• mHSPC: In combination with androgen deprivation therapy (ADT) in adult men with metastatic hormone-sensitive prostate cancer without visceral (organ) metastases.
• Nonmetastatic Castration-Resistant Disease: In patients with baseline PSA above 2 ng/ml, PSA doubling time shorter than 6 months, testosterone below 50 ng/dl, no prior cytotoxic chemotherapy, and ECOG performance status 0-1.
• Post-Chemotherapy Metastatic Disease: Until progression in patients with metastatic prostate cancer showing PSA and radiological progression despite hormonal therapy followed by docetaxel-based chemotherapy, with testosterone at castration levels.
• When Chemotherapy Is Contraindicated: Until progression in patients with metastatic prostate cancer showing castration-resistant progression, testosterone <50 ng/dl, and contraindications to chemotherapy, severely reduced bone marrow reserve, and/or Diabetes Mellitus.

Xtandi is covered for reimbursement by the Social Security Institution (SGK) for patients meeting the following clinical criteria:

• Patients with metastatic prostate cancer, demonstrated castration-resistant progression, testosterone <50 ng/dl, and contraindications to chemotherapy or a diagnosis of diabetes mellitus;
• Patients with metastatic prostate cancer resistant to hormonal therapy and docetaxel-based chemotherapy, ECOG performance status 0-1, and proven progression;
• Nonmetastatic castration-resistant patients with baseline PSA above 2 ng/ml, PSA doubling time shorter than 6 months, testosterone at castration levels (<50 ng/dl), no cytotoxic chemotherapy, and ECOG status 0-1;
• Adult men with metastatic hormone-sensitive prostate cancer (mHSPC) without visceral metastases, when used with androgen deprivation therapy (ADT) until progression.

💵 Current Price Information for June 2026: The sale price of Xtandi 40 mg 112 soft capsules is 73,692.23 TL.

• Receptor Gene Rearrangement: Variation in the androgen receptor gene can structurally alter the receptor so that it lacks the ligand-binding domain (LBD).
• NF-κB2/p52 Signaling Activation: The NF-κB2/p52 pathway may mediate resistance through activation of the androgen receptor and its additional variants.
• Reduced Receptor Expression: Reduced androgen receptor expression on the cell surface or inside cells decreases drug efficacy.
• AR Point Mutations: Specific androgen receptor mutations reduce binding affinity for enzalutamide.

Absorption: It is rapidly absorbed after oral administration. Plasma levels peak (Tmax) 0.5 - 3 hours after intake. With regular daily use, steady-state plasma levels are reached on day 28. Food does not affect the extent of absorption.

Distribution: Mean apparent volume of distribution (Vd) after a single oral dose is 110 L. It binds strongly to plasma proteins, primarily albumin (97% - 98%). Its active metabolite, N-desmethyl enzalutamide, also circulates 95% protein-bound.

Metabolism and Elimination: It is metabolized in the liver by CYP2C8 and CYP3A4. CYP2C8 is primarily responsible for forming the active N-desmethyl enzalutamide metabolite. Elimination is mainly hepatic. Mean terminal half-life (t1/2) of enzalutamide is 5.8 days, while its active metabolite has a half-life of 7.8 to 8.6 days.

Standard Dosage Regimen: The recommended treatment dose is 160 mg once daily (4 soft capsules of 40 mg swallowed together). No additional steroid support, such as prednisolone, is required in the treatment protocol.

Critical Drug Interactions:

• CYP2C8 Inhibitors (e.g., Gemfibrozil): Concomitant use increases plasma concentrations of enzalutamide and its active metabolite.
• CYP2C8 Inducers (e.g., Rifampicin): They may alter drug exposure and cause fluctuations in efficacy.
• CYP3A4 Inhibitors (e.g., Itraconazole): Concurrent use may increase drug exposure and the risk of side effects.
• CYP3A4 Inducers (e.g., Carbamazepine, Phenobarbital, Phenytoin, Rifampicin, St. John's Wort): They may significantly reduce plasma enzalutamide concentrations and decrease clinical treatment success.

• Renal Impairment: No initial dose adjustment is needed in mild or moderate renal impairment. Clinical data are limited in severe renal impairment (creatinine clearance <30 mL/min).
• Hepatic Impairment: No dose adjustment is made for mild or moderate hepatic impairment. Studies have not been conducted in patients with severe hepatic impairment (Child-Pugh Class C).
• Seizure (Epilepsy) Risk: Patients should be closely monitored for seizure activity throughout treatment. It is not possible to predict fully who is at high risk.
• Contraception (Birth Control): Male patients with female partners of reproductive potential should use effective contraception throughout treatment and for at least 3 months after the last Xtandi dose.

1. Asthenia and Fatigue

Physical and mental fatigue, weakness, and a general lack of energy are observed in approximately 50% of patients.

2. Musculoskeletal Adverse Effects

Back pain, arthralgia (joint pain), musculoskeletal pain, muscle weakness, joint stiffness, and nonpathological fractures may occur.

3. Gastrointestinal Disorders (Diarrhea)

Approximately 20% of patients may develop diarrhea, which is generally mild.

4. Vasomotor Symptoms (Hot Flashes)

Hot flashes are observed in 20% of patients.
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5. Fluid Retention (Edema)

Fluid accumulation in the body can cause peripheral edema .

6. Central Nervous System (Seizures)

Seizure activity rarely develops in fewer than 1% of patients (<1%) and usually improves clinically when treatment is withheld.