What is XTANDI and how is it used?

XTANDI is a prescription medicine used to treat men with prostate cancer that:

• no longer responds to a hormone therapy or surgical treatment to lower testosterone OR
• has spread to other parts of the body and responds to a hormone therapy or surgical treatment to lower testosterone.

It is not known if XTANDI is safe and effective in females.

It is not known if XTANDI is safe and effective in children.

What are the possible side effects of XTANDI?

XTANDI may cause serious side effects including:

• Seizure. If you take XTANDI you may be at risk of having a seizure. You should avoid activities where a sudden loss of consciousness could cause serious harm to yourself or others. Tell your healthcare provider right away if you have loss of consciousness or seizure.
• Posterior Reversible Encephalopathy Syndrome (PRES). If you take XTANDI you may be at risk of developing a condition involving the brain called PRES. Tell your healthcare provider right away if you have a seizure or quickly worsening symptoms such as headache, decreased alertness, confusion, reduced eyesight, blurred vision or other visual problems. Your healthcare provider will do a test to check for PRES.
• Allergic Reactions. Allergic reactions have happened in people who take XTANDI. Stop taking XTANDI and get medical help right away if you develop swelling of the face, tongue, lip or throat.
• Heart disease. Blockage of the arteries in the heart (ischemic heart disease) that can lead to death has happened in some people during treatment with XTANDI. Your healthcare provider will monitor you for signs and symptoms of heart problems during your treatment with XTANDI. Call your healthcare provider or go to the nearest emergency room right away if you get chest pain or discomfort at rest or with activity or shortness of breath during your treatment with XTANDI.
• Falls and fractures. XTANDI treatment may increase your risk for falls and fractures. Falls were not caused by loss of consciousness (fainting) or seizures. Your healthcare provider will monitor your risks for falls and fractures during treatment with XTANDI.

Your healthcare provider will stop treatment with XTANDI if you have serious side effects.

The most common side effects of XTANDI include:

• weakness or feeling more tired than usual
• back pain
• hot flashes
• constipation
• joint pain
• decreased appetite
• diarrhea
• high blood pressure

XTANDI may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of XTANDI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

DESCRIPTION

Enzalutamide is an androgen receptor inhibitor. The chemical name is 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5- dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide.

The molecular weight is 464.44 and molecular formula is C₂₁H₁₆F₄N₄O₂S. The structural formula is:

Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water.

XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.

INDICATIONS

XTANDI® is indicated for the treatment of patients with:

• castration-resistant prostate cancer (CRPC)
• metastatic castration-sensitive prostate cancer (mCSPC).

DOSAGE AND ADMINISTRATION

Dosing Information

The recommended dose of XTANDI is 160 mg (two 80 mg tablets or four 40 mg tablets or four 40 mg capsules) administered orally once daily. XTANDI can be taken with or without food [see CLINICAL PHARMACOLOGY]. Swallow capsules or tablets whole. Do not chew, dissolve, or open the capsules. Do not cut, crush, or chew the tablets [see HOW SUPPLIED/Storage And Handling].

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 [see WARNINGS AND PRECAUTIONS].

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 XTANDI dose to 80 mg once daily. If co-administration of the strong inhibitor is discontinued, the XTANDI dose should be returned to the dose used prior to initiation of the strong CYP2C8 inhibitor [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

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 XTANDI dose from 160 mg to 240 mg once daily. If co-administration of the strong CYP3A4 inducer is discontinued, the XTANDI dose should be returned to the dose used prior to initiation of the strong CYP3A4 inducer [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Important Administration Instructions

Patients receiving XTANDI should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

HOW SUPPLIED

Dosage Forms And Strengths

XTANDI 40 mg capsules are white to off-white oblong soft gelatin capsules imprinted in black ink with ENZ.

XTANDI 40 mg tablets are yellow, round, film-coated and debossed with E 40.

XTANDI 80 mg tablets are yellow, oval, film-coated and debossed with E 80.

Storage And Handling

XTANDI (enzalutamide) 40 mg capsules are supplied as white to off-white oblong soft gelatin capsules imprinted in black ink with ENZ and are available in the following package size:

Bottles of 120 capsules with child resistant closures (NDC 0469-0125-99)

XTANDI (enzalutamide) 40 mg tablets are supplied as yellow, round, film-coated tablets debossed with E 40, and are available in the following package size:

Bottles of 120 tablets with child resistant closures (NDC 0469-0625-99)

XTANDI (enzalutamide) 80 mg tablets are supplied as yellow, oval, film-coated tablets debossed with E 80, and are available in the following package size:

Bottles of 60 tablets with child resistant closures (NDC 0469-0725-60)

SIDE EFFECTS

The following is discussed in more detail in other sections of the labeling:

• Seizure [see WARNINGS AND PRECAUTIONS]
• Posterior Reversible Encephalopathy Syndrome (PRES) [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity [see WARNINGS AND PRECAUTIONS]
• Ischemic Heart Disease [see WARNINGS AND PRECAUTIONS]
• Falls and Fractures [see WARNINGS AND PRECAUTIONS]

Recommended storage: Store XTANDI capsules and tablets at 20°C to 25°C (68°F to 77°F) in a dry place and keep the container tightly closed. Excursions permitted from 15°C to 30°C (59°F to 86°F).

Swallow capsules or tablets whole. Do not chew, dissolve or open the capsules. Do not cut, crush, or chew the tablets.