Xtandi

Enzalutamide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• weakness
• tiredness
• joint pain
• muscle weakness or stiffness
• headache
• dizziness
• burning, numbness, or tingling in the arms, hands, or feet
• decreased sense of touch or ability to feel sensation
• hot flashes
• difficulty falling asleep or staying asleep
• anxiety
• difficulty remembering, thinking, or paying attention
• diarrhea
• itching
• dry skin
• nosebleeds
• frequent urination

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

• seizures
• swelling of the arms, legs, hands, or feet
• pain in the back and/or legs
• numbness or tingling in the buttocks or legs
• difficulty controlling urination or bowel movements
• difficulty breathing
• falling
• hallucinating (seeing things or hearing voices that do not exist)
• pink or red urine

Enzalutamide may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

XTANDI® is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Xtandi is a prescription medication used to treat men with prostate cancer that no longer responds to a medical or surgical treatment that lowers testosterone, and has spread to other parts of the body.

Xtandi belongs to a group of drugs called androgen receptor inhibitors. These work by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells.

Xtandi comes as a capsule to take by mouth. It is taken once daily, with or without food. Take Xtandi at the same time each day.

Common side effects include weakness, back pain, diarrhea, and joint pains. Xtandi can also cause seizures. Do not drive or operate machinery until you know how this medication affects you.

Xtandi is part of the drug class:

• Anti androgens

Before taking Xtandi,

• tell your doctor and pharmacist if you are allergic to Xtandi, any other medications, or any of the ingredients in Xtandi capsules. Ask your pharmacist or check the manufacturer's information for the patient for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, herbal products, and nutritional supplements you are taking or plan to take.
• tell your doctor if you have or have ever had seizures, a brain injury, a brain tumor, a brain arteriovenous malformation (abnormal connection between arteries and veins in the brain that forms before birth and may cause bleeding in the brain), or a stroke or ministroke.
• you should know that Xtandi is only for use in men. Women should not take this medication, especially if they are or may become pregnant or are breast-feeding. If taken by pregnant women, Xtandi may harm the fetus. If a pregnant woman takes Xtandi, she should call her doctor immediately.
• if your partner is pregnant, you must use a condom whenever you have sex during your treatment with Xtandi and for three months after your treatment. If your partner is not pregnant but could become pregnant, you must use a condom and another form of birth control whenever you have sex during your treatment and for 3 months after your treatment.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking Xtandi.
• you should know that Xtandi may cause seizures. Do not drive a car or operate machinery until you know how this medication affects you.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Take the missed dose if you remember it later in the day. Skip the missed dose if it is almost time for your next day's dose. Do not take extra medicine to make up the missed dose.

Prostate Cancer

Treatment of metastatic castration-resistant prostate cancer previously treated with docetaxel-containing therapy.1 2 5 14

Administration

Oral Administration

Administer orally once daily without regard to meals.1

Swallow capsules whole; do not chew, dissolve, or open capsules.1

Dosage

Certain CYP-mediated interactions may affect dosage and administration.1 (See Interactions.)

Adults

Prostate Cancer Oral

160 mg once daily.1

In clinical trial, treatment could be continued until disease progression or unacceptable toxicity occurred.1 2

Dosage Modification for Toxicity Oral

If an intolerable adverse effect or grade 3 or greater toxicity occurs, interrupt therapy for 1 week or until symptoms improve to grade 2 or less; then may resume therapy with or without dosage reduction.1 If dosage reduction is necessary, reduce dosage to 120 or 80 mg daily.1

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): No initial dosage adjustment required.1

Severe hepatic impairment (Child-Pugh class C): Not studied.1

Renal Impairment

Mild to moderate renal impairment (Clcr 30–89 mL/minute): No initial dosage adjustment required.1

Severe renal impairment (Clcr <30 mL/minute) or end-stage renal disease: Not evaluated systematically.1

Geriatric Patients

No special dosage recommendations; most clinical trial participants were geriatric.1

Contraindications

• Women who are or may become pregnant.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.1 Contraindicated in women who are or may become pregnant.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1

Not known whether enzalutamide distributes into semen.1 15 During and for 3 months following discontinuance of enzalutamide therapy, men receiving the drug should use a condom during sexual encounters with pregnant women and should use a condom in conjunction with another effective contraceptive method during sexual encounters with women of childbearing potential.1

Seizure

Seizures reported;1 2 resolved following drug discontinuance.1 Safety of resuming therapy after resolution of a seizure not established.1

Safety not established in patients with predisposing factors for seizures (e.g., history of seizure, underlying brain injury with loss of consciousness, TIA within past 12 months, cerebrovascular accident, brain metastases, cerebral arteriovenous malformation, concomitant use of drugs that lower seizure threshold).1

Specific Populations

Pregnancy

Category X.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether distributed into milk; discontinue nursing or drug.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

No overall differences in safety and efficacy relative to younger adults; however, increased sensitivity cannot be ruled out.1

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B) did not substantially affect AUC of major active forms of the drug (enzalutamide plus N-desmethylenzalutamide).1

Not studied in patients with severe hepatic impairment (Child-Pugh class C).1

Renal Impairment

Mild or moderate renal impairment (Clcr 30–89 mL/minute) did not substantially affect clearance of enzalutamide.1

Not evaluated systematically in patients with severe renal impairment (Clcr <30 mL/minute) or end-stage renal disease.1

Common Adverse Effects

Asthenia/fatigue,1 2 5 back pain,1 diarrhea,1 2 arthralgia,1 hot flush,1 2 peripheral edema,1 musculoskeletal pain,1 2 headache,1 2 upper respiratory tract infection,1 muscular weakness,1 dizziness,1 insomnia,1 lower respiratory tract infection,1 spinal cord compression and cauda equina syndrome,1 hematuria,1 paresthesia,1 anxiety,1 hypertension.1

In the U.S.

• Xtandi

Available Dosage Forms:

• Capsule, Liquid Filled

Therapeutic Class: Antineoplastic Agent

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Take your medicine at the same time each day with or without food.

Swallow the capsule whole. Do not chew, dissolve, or open it.

If you are taking 2 cancer medicines, follow your doctor's instructions on when to take them.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For prostate cancer:
    • Adults—160 milligrams (mg) (four 40 mg capsules) once a day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Feeling tired or weak.
• Back pain.
• Not hungry.
• Hard stools (constipation).
• Muscle pain or weakness.
• Joint pain.
• Loose stools (diarrhea).
• Hot flashes.
• Signs of a common cold.
• Weight loss.
• Headache.
• Not able to sleep.
• Anxiety.
• Change in taste.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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

• Seizure [see Warnings and Precautions (5.1)] • Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions (5.2)]

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Three randomized clinical trials enrolled patients with metastatic prostate cancer that has progressed on androgen deprivation therapy (GnRH therapy or bilateral orchiectomy), a disease setting that is also defined as metastatic CRPC. Two trials were placebo-controlled (Studies 1 and 2), and one trial was bicalutamide-controlled (Study 3). In Studies 1 and 2, patients received Xtandi 160 mg or placebo orally once daily. In Study 3, patients received Xtandi 160 mg or bicalutamide 50 mg orally once daily. All patients continued androgen deprivation therapy. Patients were allowed, but not required, to take glucocorticoids.

The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the Xtandi-treated patients from the two randomized placebo-controlled clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.

Study 1: Xtandi versus Placebo in Metastatic CRPC Following Chemotherapy

Study 1 enrolled 1199 patients with metastatic CRPC who had previously received docetaxel. The median duration of treatment was 8.3 months with Xtandi and 3.0 months with placebo. During the trial, 48% of patients on the Xtandi arm and 46% of patients on the placebo arm received glucocorticoids.

Grade 3 and higher adverse reactions were reported among 47% of Xtandi-treated patients and 53% of placebo-treated patients. Discontinuations due to adverse events were reported for 16% of Xtandi-treated patients and 18% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was seizure, which occurred in 0.9% of the Xtandi-treated patients compared to none (0%) of the placebo-treated patients. Table 1 shows adverse reactions reported in Study 1 that occurred at a ≥ 2% higher frequency in the Xtandi arm compared to the placebo arm.

Table 1. Adverse Reactions in Study 1

	Xtandi N = 800		Placebo N = 399
	Grade 1-4a (%)	Grade 3-4 (%)	Grade 1-4 (%)	Grade 3-4 (%)
General Disorders
Asthenic Conditionsb	50.6	9.0	44.4	9.3
Peripheral Edema	15.4	1.0	13.3	0.8
Musculoskeletal And Connective Tissue Disorders
Back Pain	26.4	5.3	24.3	4.0
Arthralgia	20.5	2.5	17.3	1.8
Musculoskeletal Pain	15.0	1.3	11.5	0.3
Muscular Weakness	9.8	1.5	6.8	1.8
Musculoskeletal Stiffness	2.6	0.3	0.3	0.0
Gastrointestinal Disorders
Diarrhea	21.8	1.1	17.5	0.3
Vascular Disorders
Hot Flush	20.3	0.0	10.3	0.0
Hypertension	6.4	2.1	2.8	1.3
Nervous System Disorders
Headache	12.1	0.9	5.5	0.0
Dizzinessc	9.5	0.5	7.5	0.5
Spinal Cord Compression     and Cauda Equina Syndrome	7.4	6.6	4.5	3.8
Paresthesia	6.6	0.0	4.5	0.0
Mental Impairment Disordersd	4.3	0.3	1.8	0.0
Hypoesthesia	4.0	0.3	1.8	0.0
Infections And Infestations
Upper Respiratory Tract     Infectione	10.9	0.0	6.5	0.3
Lower Respiratory Tract And     Lung Infectionf	8.5	2.4	4.8	1.3
Psychiatric Disorders
Insomnia	8.8	0.0	6.0	0.5
Anxiety	6.5	0.3	4.0	0.0
Renal And Urinary Disorders
Hematuria	6.9	1.8	4.5	1.0
Pollakiuria	4.8	0.0	2.5	0.0
Injury, Poisoning And Procedural Complications
Fall	4.6	0.3	1.3	0.0
Non-pathologic Fractures	4.0	1.4	0.8	0.3
Skin And Subcutaneous Tissue Disorders
Pruritus	3.8	0.0	1.3	0.0
Dry Skin	3.5	0.0	1.3	0.0
Respiratory Disorders
Epistaxis	3.3	0.1	1.3	0.3
a    CTCAE v4 b    Includes asthenia and fatigue. c    Includes dizziness and vertigo. d    Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e    Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. f    Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Study 2: Xtandi versus Placebo in Chemotherapy-naïve Metastatic CRPC

Study 2 enrolled 1717 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy, of whom 1715 received at least one dose of study drug. The median duration of treatment was 17.5 months with Xtandi and 4.6 months with placebo. Grade 3-4 adverse reactions were reported in 44% of Xtandi-treated patients and 37% of placebo-treated patients. Discontinuations due to adverse events were reported for 6% of Xtandi-treated patients and 6% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was fatigue/asthenia, which occurred in 1% of patients on each treatment arm. Table 2 includes adverse reactions reported in Study 2 that occurred at a ≥ 2% higher frequency in the Xtandi arm compared to the placebo arm.

Table 2. Adverse Reactions in Study 2

	Xtandi N = 871		Placebo N = 844
	Grade 1-4a (%)	Grade 3-4 (%)	Grade 1-4 (%)	Grade 3-4 (%)
General Disorders
Asthenic Conditionsb	46.9	3.4	33.0	2.8
Peripheral Edema	11.5	0.2	8.2	0.4
Musculoskeletal And Connective Tissue Disorders
Back Pain	28.6	2.5	22.4	3.0
Arthralgia	21.4	1.6	16.1	1.1
Gastrointestinal Disorders
Constipation	23.2	0.7	17.3	0.4
Diarrhea	16.8	0.3	14.3	0.4
Vascular Disorders
Hot Flush	18.0	0.1	7.8	0.0
Hypertension	14.2	7.2	4.1	2.3
Nervous System Disorders
Dizzinessc	11.3	0.3	7.1	0.0
Headache	11.0	0.2	7.0	0.4
Dysgeusia	7.6	0.1	3.7	0.0
Mental Impairment Disordersd	5.7	0.0	1.3	0.1
Restless Legs Syndrome	2.1	0.1	0.4	0.0
Respiratory Disorders
Dyspneae	11.0	0.6	8.5	0.6
Infections And Infestations
Upper Respiratory Tract     Infectionf	16.4	0.0	10.5	0.0
Lower Respiratory Tract And     Lung Infectiong	7.9	1.5	4.7	1.1
Psychiatric Disorders
Insomnia	8.2	0.1	5.7	0.0
Renal And Urinary Disorders
Hematuria	8.8	1.3	5.8	1.3
Injury, Poisoning And Procedural Complications
Fall	12.7	1.6	5.3	0.7
Non-Pathological Fracture	8.8	2.1	3.0	1.1
Metabolism and Nutrition Disorders
Decreased Appetite	18.9	0.3	16.4	0.7
Investigations
Weight Decreased	12.4	0.8	8.5	0.2
Reproductive System and Breast disorders
Gynecomastia	3.4	0.0	1.4	0.0
a    CTCAE v4 b    Includes asthenia and fatigue. c    Includes dizziness and vertigo. d    Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e    Includes dyspnea, exertional dyspnea, and dyspnea at rest. f    Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. g    Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Study 3: Xtandi versus Bicalutamide in Chemotherapy-naïve Metastatic CRPC

Study 3 enrolled 375 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy, of whom 372 received at least one dose of study drug.  The median duration of treatment was 11.6 months with Xtandi and 5.8 months with bicalutamide. Discontinuations with an adverse event as the primary reason were reported for 7.6% of Xtandi-treated patients and 6.3% of bicalutamide-treated patients. The most common adverse reactions leading to treatment discontinuation were back pain and pathological fracture, which occurred in 3.8% of Xtandi-treated patients for each event and in 2.1% and 1.6% of bicalutamide-treated patients, respectively. Table 3 shows overall and common adverse reactions (≥ 10%) in Xtandi-treated patients.

Table 3. Adverse Reactions in Study 3

	Xtandi (N=183)		Bicalutamide (N=189)
	Grade 1-4 a (%)	Grade 3-4 (%)	Grade 1-4 a (%)	Grade 3-4 (%)
Overall	94.0	38.8	94.2	37.6
General Disorders
Asthenic Conditionsb	31.7	1.6	22.8	1.1
Musculoskeletal And Connective Tissue Disorders
Back Pain	19.1	2.7	18.0	1.6
Musculoskeletal Painc	16.4	1.1	14.3	0.5
Vascular Disorders
Hot Flush	14.8	0	11.1	0
Hypertension	14.2	7.1	7.4	4.2
Gastrointestinal Disorders
Nausea	14.2	0	17.5	0
Constipation	12.6	1.1	13.2	0.5
Diarrhea	11.5	0	9.0	1.1
Infections And Infestations
Upper Respiratory Tract Infectiond	12.0	0	6.3	0.5
Investigational
Weight Loss	10.9	0.5	7.9	0.5
a    CTCAE v 4 b    Including asthenia and fatigue. c    Including musculoskeletal pain and pain in extremity d    Including nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis

Laboratory Abnormalities

In the two randomized placebo-controlled clinical trials, Grade 1-4 neutropenia occurred in 15% of patients treated with Xtandi (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4). The incidence of Grade 1-4 thrombocytopenia was 6% of patients treated with Xtandi (0.3% Grade 3-4) and 5% of patients treated with placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with Xtandi (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with Xtandi (0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4).

Infections

In Study 1, 1% of patients treated with Xtandi compared to 0.3% of patients treated with placebo died from infections or sepsis. In Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls and Fall-related Injuries

In the two randomized placebo-controlled clinical trials, falls including fall-related injuries, occurred in 9% of patients treated with Xtandi compared to 4% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in patients treated with Xtandi and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension

In the two randomized placebo-controlled trials, hypertension was reported in 11% of patients receiving Xtandi and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm.

Post-Marketing Experience

The following additional adverse reactions have been identified during post approval use of Xtandi. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Body as a Whole: hypersensitivity (tongue edema, lip edema, and pharyngeal edema)

Gastrointestinal Disorders: vomiting

Neurological Disorders: posterior reversible encephalopathy syndrome (PRES)

Skin and Subcutaneous Tissue Disorders: rash

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Seizure

• Inform patients that Xtandi has been associated with an increased risk of seizure. Discuss conditions that may predispose to seizures and medications that may lower the seizure threshold. Advise patients of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Inform patients to contact their healthcare provider right away if they have loss of consciousness or seizure [see Warnings and Precautions (5.1)].

Posterior Reversible Encephalopathy Syndrome (PRES)

• Inform patients to contact their healthcare provider right away if they experience rapidly worsening symptoms possibly indicative of PRES such as seizure, headache, decreased alertness, confusion, reduced eyesight, or blurred vision [see Warnings and Precautions (5.2)].

Falls and Fall-related Injuries

• Inform patients that Xtandi is associated with an increased incidence of dizziness/vertigo, falls, and fall-related injuries [see Adverse Reactions (6.1)].

Hypertension

• Inform patients that Xtandi is associated with an increased incidence of hypertension [see Adverse Reactions (6.1)].

Infections

• Inform patients that Xtandi may be associated with an increased incidence of infections. Advise patients to immediately contact their healthcare provider if they develop signs and symptoms of infection [see Adverse Reactions (6.1)].

Dosing and Administration

• Inform patients receiving GnRH therapy that they need to maintain this treatment during the course of treatment with Xtandi. • Instruct patients to take their dose at the same time each day (once daily). Xtandi can be taken with or without food. Each capsule should be swallowed whole. Do not chew, dissolve, or open the capsules. • Inform patients that they should not interrupt, modify the dose, or stop Xtandi without first consulting their healthcare provider. • Inform patients that if they miss a dose, then they should take it as soon as they remember. If they forget to take the dose for the whole day, then they should take their normal dose the next day. They should not take more than their prescribed dose per day [see Dosage and Administration (2.1)].

Embryo-Fetal Toxicity

• Inform patients that Xtandi can be harmful to a developing fetus. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of Xtandi. Advise male patients to use a condom if having sex with a pregnant woman [see Use in Specific Populations (8.3)].

 

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

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

16K089-XTA-SPL

Rx Only
© 2017 Astellas Pharma US, Inc.

Xtandi® is a registered trademark of Astellas Pharma Inc. 

Xtandi® (ex TAN dee)
(enzalutamide)
capsules

What is Xtandi®?

Xtandi is a prescription medicine used to treat men with prostate cancer that no longer responds to a medical or surgical treatment that lowers testosterone and that has spread to other parts of the body.

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

Who should not take Xtandi?

Xtandi is not for use in women.

Do not take Xtandi if you are pregnant or may become pregnant. Xtandi can harm your unborn baby.

Before taking Xtandi, tell your healthcare provider about all your medical conditions, including if you:

• have a history of seizures, brain injury, stroke, or brain tumors • have a partner who is pregnant or may become pregnant. Men who are sexually active with a pregnant woman must use a condom during and for 3 months after treatment with Xtandi. If your sexual partner may become pregnant, a condom and another form of effective birth control must be used during and for 3 months after treatment. Talk with your healthcare provider if you have questions about birth control. See “Who should not take Xtandi?”

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Xtandi may affect the way other medicines work, and other medicines may affect how Xtandi works.

You should not start or stop any medicine before you talk with the healthcare provider that prescribed Xtandi.

Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Xtandi?

• Take Xtandi exactly as your healthcare provider tells you. • Take your prescribed dose of Xtandi 1 time a day, at the same time each day. • Your healthcare provider may change your dose if needed. • Do not change or stop taking your prescribed dose of Xtandi without talking with your healthcare provider first. • Xtandi can be taken with or without food. • Swallow Xtandi capsules whole. Do not chew, dissolve, or open the capsules. • If you miss a dose of Xtandi, take your prescribed dose as soon as you remember that day. If you miss your daily dose, take your prescribed dose at your regular time the next day. Do not take more than your prescribed dose of Xtandi in one day.

If you take too much Xtandi, call your healthcare provider or go to the nearest emergency room right away. You may have an increased risk of seizure if you take too much Xtandi.

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. Your healthcare provider will stop Xtandi if you have a seizure during treatment. • 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. Your healthcare provider will stop Xtandi if you develop PRES.

The most common side effects of Xtandi include:

• weakness or feeling more tired than usual • back pain • decreased appetite • constipation • joint pain • diarrhea • hot flashes • upper respiratory tract infection

• swelling in your hands, arms, legs, or feet • shortness of breath • muscle and bone pain • weight loss • headache • high blood pressure • dizziness • a feeling that you or things around you are moving or spinning (vertigo)

Xtandi may cause infections, falls and injuries from falls. Tell your healthcare provider if you have signs or symptoms of an infection or if you fall.

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

How should I store Xtandi?

• Store Xtandi between 68°F to 77°F (20°C to 25°C). • Keep Xtandi capsules dry and in a tightly closed container.

Keep Xtandi and all medicines out of the reach of children.

General information about the safe and effective use of Xtandi.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Xtandi for a condition for which it was not prescribed. Do not give Xtandi to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about Xtandi that is written for health professionals.

What are the ingredients in Xtandi?

Active ingredient: enzalutamide

Inactive ingredients: caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, black iron oxide

 

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

16K089-XTA-SPL

© 2017 Astellas Pharma US, Inc.

Xtandi® is a registered trademark of Astellas Pharma Inc. For more information go to www.Xtandi.com or call 1-800-727-7003.

 

This Patient Information has been approved by the U.S. Food and Drug Administration.                     Revised: 07/2017

Xtandi (enzalutamide) is an anti-androgen. It works in the body by preventing the actions of androgens (male hormones).

Xtandi is used to treat prostate cancer.

Xtandi may also be used for purposes not listed in this medication guide.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose could cause you to have a seizure.

Xtandi can increase your risk of having a seizure. This effect may be more likely if you also use certain other medicines that increase seizure risk. Tell your doctor if you are using an antibiotic, an antidepressant, asthma medication (a bronchodilator), birth control pills or hormone replacement, insulin or oral diabetes medicine, a steroid, or medicine to treat mental illness.

Many drugs can interact with enzalutamide. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Xtandi. Give a list of all your medicines to any healthcare provider who treats you.

Applies to enzalutamide: oral capsule

Nervous system

Very common (10% or more): Headache (up to 12.1%), dizziness/vertigo (up to 11.3%)
Common (1% to 10%): Spinal cord compression and cauda equina syndrome, paresthesia, mental impairment disorders, hypoesthesia, dysgeusia, restless legs syndrome
Uncommon (0.1% to 1%): Seizures
Postmarketing reports: Posterior reversible encephalopathy syndrome[Ref]

It is unknown how the drug may lower the seizure threshold; however, it may be related to the drug's ability to inhibit the activity of the GABA-gated chloride channel. The risk of seizure may be related to dose.

Mental impairment disorders included amnesia, memory impairment, cognitive disorder, and disturbance in attention.[Ref]

Cardiovascular

Very common (10% or more): Hot flush (up to 20.3%), peripheral edema (up to 15.4%), hypertension (up to 14.2%)[Ref]

Dermatologic

Common (1% to 10%): Pruritus, dry skin[Ref]

Endocrine

Common (1% to 10%): Gynecomastia[Ref]

Gastrointestinal

Very common (10% or more): Constipation (up to 23.2%), diarrhea (up to 21.8%)[Ref]

Genitourinary

Common (1% to 10%): Hematuria, pollakiuria[Ref]

Hematologic

Very common (10% or more): Neutropenia (15%)
Common (1% to 10%): Thrombocytopenia
Frequency not reported: Leukopenia[Ref]

Hepatic

Very common (10% or more): ALT elevations (10%)
Common (1% to 10%): Bilirubin elevations[Ref]

Metabolic

Very common (10% or more): Decreased appetite (up to 18.9%), decreased weight (up to 12.4%)[Ref]

Musculoskeletal

Very common (10% or more): Back pain (up to 28.6%), arthralgia (up to 21.4%), musculoskeletal pain (up to 15%)
Common (1% to 10%): Muscular weakness, musculoskeletal stiffness[Ref]

Other

Fall-related injuries included non-pathologic fractures, joint injuries, and hematomas.[Ref]

Very common (10% or more): Asthenia/fatigue (up to 50.6%), falls (up to 12.7%)
Common (1% to 10%): Fall-related injuries[Ref]

Psychiatric

Common (1% to 10%): Insomnia, anxiety, hallucinations[Ref]

Respiratory

Upper respiratory tract infection included nasopharyngitis, sinusitis, rhinitis, pharyngitis, and laryngitis. Lower respiratory tract and lung infection included pneumonia and bronchitis.[Ref]

Very common (10% or more): Upper respiratory tract infection (up to 16.4%), dyspnea (up to 11%)
Common (1% to 10%): Lower respiratory tract and lung infection, epistaxis[Ref]

Some side effects of Xtandi may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.