Xtandi

Xtandi (enzalutamide) is a prescription hormone therapy used to treat certain types of advanced prostate cancer. It belongs to a class of medicines called androgen receptor inhibitors.

Xtandi works by blocking the effects of androgens, such as testosterone, which can help prostate cancer cells grow and spread. By blocking these hormones, Xtandi may help slow cancer progression and delay the worsening of the disease.

Xtandi is available as tablets or capsules and is usually taken once daily, with or without food.

Xtandi is used to treat several forms of prostate cancer, including:

• Castration-resistant prostate cancer (CRPC): prostate cancer that no longer responds well to hormone therapy
• Metastatic castration-sensitive prostate cancer (mCSPC): prostate cancer that has spread to other parts of the body and still responds to hormone-lowering treatment
• Non-metastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis: prostate cancer that has not spread but has a rising PSA and a high risk of spreading

Xtandi became an FDA-approved medicine on August 31, 2012.

Take Xtandi exactly as prescribed by your doctor.

General instructions

• Take Xtandi once a day
• Take it with or without food
• Take it at the same time each day
• Swallow tablets or capsules whole with enough water to make sure you swallow all of the medicine successfully
• Do not crush, chew, break, open, or dissolve Xtandi

Your healthcare provider may switch you to a smaller tablet size if swallowing is difficult.

Because prostate cancer is sometimes treated with more than one medicine, Xtandi may be used with other therapies. Do not change your dose unless your doctor tells you to.

Xtandi has several important warnings patients and caregivers should know about.

• Seizures: Seizures have occurred in some people taking Xtandi. If a seizure happens during treatment, Xtandi should be stopped permanently.
• PRES: Xtandi may cause a rare but serious brain condition called posterior reversible encephalopathy syndrome (PRES). If this occurs, treatment should be stopped.
• Serious allergic reactions: Xtandi should be stopped if a severe allergic reaction occurs.
• Ischemic heart disease: Patients should have heart-related risk factors monitored and managed carefully.
• Falls and fractures: Patients may need to be evaluated for fall risk and bone health.
• Embryo-fetal toxicity: Xtandi can harm an unborn baby and may cause pregnancy loss. Men with female partners who could become pregnant should use effective birth control. Use a condom and one other form of birth control to prevent pregnancy during your treatment and for at least 3 months after your treatment ends.
• Swallowing problems or choking risk: Smaller Xtandi tablets may be considered for people who have trouble swallowing. If tablets or capsules cannot be swallowed, treatment may need to be stopped.
• Digoxin lab test interference: Xtandi can interfere with certain blood tests used to measure digoxin levels.

You should not take Xtandi if you are allergic to the active ingredient enzalutamide or the inactive ingredients.

Before starting Xtandi, tell your doctor if you have ever had:

• a seizure
• a stroke, brain injury, or brain tumor
• heart disease or circulation problems
• high blood pressure
• diabetes
• high cholesterol or high triglycerides

Xtandi is not intended for use in women, but it can cause harm to an unborn baby if either parent is taking it during conception or pregnancy.

If your partner can become pregnant, use:

• a condom, and
• one other effective form of birth control

Keep using birth control during treatment and for at least 3 months after treatment ends to prevent pregnancy.

You must also use a condom during sex if your partner is pregnant.

Xtandi may also affect male fertility. Talk to your healthcare provider if fertility is a concern.

Like all medicines, Xtandi can cause side effects. Some are mild, while others can be serious.

Common Xtandi side effects

Common side effects of Xtandi may include:

• tiredness or weakness
• muscle pain, back pain, or joint pain
• hot flashes
• constipation
• diarrhea
• decreased appetite
• high blood pressure
• headache
• bleeding
• falls
• fractures

Serious side effects

Stop taking Xtandi and get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Xtandi may cause side effects on your spinal cord.

Stop taking this medicine and call your doctor at once if you have:

• dizziness, spinning sensation;
• a seizure (blackout or convulsions);
• confusion, thinking problems, severe headache, vision problems;
• weakness, loss of consciousness;
• red or pink urine;
• heart problems - chest pain, shortness of breath (even with mild exertion);
• increased blood pressure - severe headache, blurred vision, pounding in your neck or ears, anxiety, nosebleed;
• signs of an infection - such as fever, chills, cough with yellow or green mucus, stabbing chest pain, wheezing, or feeling short of breath; or
• signs of a severe skin reaction - fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual Xtandi dose for prostate cancer

The usual adult dose of Xtandi is:

• 160 mg by mouth once daily

Dose Modifications: Dose may be modified due to side effects of drug interactions

Xtandi comes in:

• 40 mg capsules
• 40 mg tablets
• 80 mg tablets

Some patients may take:

• two 80 mg tablets once daily, or
• four 40 mg tablets or capsules once daily

Important dosage notes

Patients with CRPC or mCSPC who take Xtandi should also receive a GnRH analog, unless they have had bilateral orchiectomy.

Patients with nmCSPC with high-risk biochemical recurrence may take Xtandi with or without a GnRH analog.

In some patients, treatment may be paused if PSA becomes undetectable after 36 weeks and restarted later if PSA rises again.

If you miss a dose of Xtandi, take it later the same day as soon as you remember.

If it is almost time for your next dose, skip the missed dose. Do not take extra medicine to make up for the missed dose.

Seek emergency medical help or call Poison Help right away. An Xtandi overdose may increase the risk of seizure.

Xtandi may increase the risk of seizures, dizziness, and falls.

While taking this medicine:

• avoid driving until you know how it affects you
• avoid hazardous activities if there is a risk of losing consciousness
• use caution in situations where a fall could cause injury

Even without dizziness, Xtandi may increase the risk of bone fractures and falls. Avoid activities or situations that may lead to injury or falls.

Xtandi can interact with many prescription drugs, over-the-counter medicines, vitamins, and herbal supplements. Tell your doctor about all medicines you take, including any medicines you start or stop during treatment.

Strong CYP2C8 inhibitors

These medicines can increase the amount of Xtandi in the body.

• Avoid taking strong CYP2C8 inhibitors with Xtandi if possible
• If they must be used together, the Xtandi dose may need to be reduced to 80 mg once daily
• When the CYP2C8 inhibitor is stopped, the Xtandi dose may be increased back to the previous dose

Strong CYP3A4 inducers

These medicines can lower the amount of Xtandi in the body.

• Avoid taking strong CYP3A4 inducers with Xtandi if possible
• If they must be used together, the Xtandi dose may need to be increased from 160 mg to 240 mg once daily
• When the CYP3A4 inducer is stopped, the Xtandi dose should be reduced back to the previous dose

Certain CYP3A4, CYP2C9, or CYP2C19 substrate drugs

Xtandi can also affect other medicines by lowering their levels in the body.

• This may make some medicines work less well
• The risk is higher for drugs where even a small drop in blood level can cause treatment failure
• In some cases, the dose of the other medicine may need to be adjusted
• Some medicines may also produce increased levels of active metabolites

Not all possible drug interactions are listed here.

Store at 68°F to 77°F (20°C to 25°C).

• Keep capsules and tablets dry
• Store in a tightly closed container
• Keep away from heat and moisture

Active ingredient

• enzalutamide

Inactive ingredients in capsules

• caprylocaproyl polyoxylglycerides
• butylated hydroxyanisole
• butylated hydroxytoluene
• gelatin
• sorbitol sorbitan solution
• glycerin
• purified water
• titanium dioxide
• black iron oxide

Inactive ingredients in tablets

• hypromellose acetate succinate
• microcrystalline cellulose
• colloidal silicon dioxide
• croscarmellose sodium
• magnesium stearate

Tablet film coating

• hypromellose
• talc
• polyethylene glycol
• titanium dioxide
• ferric oxide

Manufactured for and distributed by: Astellas Pharma US, Inc., Northbrook, IL 60062

Marketed by: Astellas Pharma US, Inc., Northbrook, IL 60062Pfizer Inc., New York, NY 10017