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Xtandi

Last reviewed on RxList: 8/18/2020
Xtandi Side Effects Center

What Is Xtandi?

Xtandi (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of prostate cancer in patients who have previously received Docefrez (docetaxel).

What Are Side Effects of Xtandi?

Side effects of Xtandi include:

Tell your doctor if you have serious side effects of Xtandi including severe low back pain, trouble walking or standing up, pain or weakness in your lower body, severe and worsening numbness or tingly feeling, sudden loss of bladder or bowel control, fever, cough with yellow or green mucus, stabbing chest pain, wheezing, shortness of breath, red or pink urine, or increased blood pressure (severe headache, blurred vision, buzzing in your ears, confusion, chest pain, uneven heartbeats).

Dosage for Xtandi

Xtandi is available in capsules of 40 mg. The recommended dosage of Xtandi is 160 mg (four 40 mg capsules) administered orally once daily. Swallow capsules whole. Xtandi can be taken with or without food.

What Drugs, Substances, or Supplements Interact with Xtandi?

Xtandi may interact with other drugs. Tell your doctor all prescription and OTC medications you are taking.

Xtandi During Pregnancy and Breastfeeding

Xtandi is not indicated for use in women and may cause fetal harm when administered to a pregnant woman. Consult your doctor before breastfeeding.

Additional Information

Xtandi (enzalutamide) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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 FDA at 1-800-FDA-1088.

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Xtandi Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using enzalutamide and call your doctor at once if you have:

  • a seizure (black-out or convulsions);
  • confusion, thinking problems, severe headache, buzzing in your ears, 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; or
  • signs of a lung infection--fever, cough with yellow or green mucus, stabbing chest pain, wheezing, feeling short of breath.

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

Common side effects may include:

  • headache, dizziness, spinning sensation;
  • feeling weak or tired;
  • loss of appetite, weight loss;
  • flushing (redness, hot feeling);
  • joint pain; or
  • high blood pressure.

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 FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Xtandi (Enzalutamide Capsules)

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Xtandi Professional Information

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]

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.

The data in WARNINGS and PRECAUTIONS reflect seven randomized, controlled trials [AFFIRM, PREVAIL, TERRAIN, PROSPER, ARCHES, Asian PREVAIL (NCT02294461), and STRIVE (NCT01664923)] that were pooled to conduct safety analyses in patients with CRPC (N=3509) or mCSPC (N= 572) treated with XTANDI. Patients received XTANDI 160 mg (N= 4081) or placebo orally once daily (N= 2472) or bicalutamide 50 mg orally once daily (N= 387). All patients continued androgen deprivation therapy (ADT). In these seven trials, the median duration of treatment was 13.8 months (range: <0.1 to 87.6) in the XTANDI group.

In four placebo-controlled trials (AFFIRM, PROSPER, PREVAIL, and ARCHES), the median duration of treatment was 14.3 months (range: <0.1 to 87.6) in the XTANDI group [see Clinical Studies]. In these four trials, the most common adverse reactions (≥ 10%) that occurred more frequently (≥ 2% over placebo) in the XTANDI-treated patients were asthenia/fatigue, back pain, hot flush, constipation, arthralgia, decreased appetite, diarrhea, and hypertension.

AFFIRM (NCT00974311): XTANDI Versus Placebo In Metastatic CRPC Following Chemotherapy

AFFIRM 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. Discontinuations due to adverse events were reported for 16% of XTANDI-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 AFFIRM that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

Table 1: Adverse Reactions in AFFIRM

XTANDI
(N = 800)
Placebo
(N = 399)
Grade 1-41 (%)Grade 3-4 (%)Grade 1-4 (%)Grade 3-4 (%)
General Disorders
Asthenic Conditions2519.0449.3
Peripheral Edema151.0130.8
Musculoskeletal and Connective Tissue Disorders
Back Pain265.3244.0
Arthralgia212.5171.8
Musculoskeletal Pain151.3120.3
Muscular Weakness9.81.56.81.8
Musculoskeletal Stiffness2.60.30.30.0
Gastrointestinal Disorders
Diarrhea221.1180.3
Vascular Disorders
Hot Flush200.0100.0
Hypertension6.42.12.81.3
Nervous System Disorders
Headache120.95.50.0
Dizziness39.50.57.50.5
Spinal Cord Compression and Cauda Equina Syndrome7.46.64.53.8
Paresthesia6.60.04.50.0
Mental Impairment Disorders44.30.31.80.0
Hypoesthesia4.00.31.80.0
Infections and Infestations
Upper Respiratory Tract Infection5110.06.50.3
Lower Respiratory Tract And Lung Infection68.52.44.81.3
Psychiatric Disorders
Insomnia8.80.06.00.5
Anxiety6.50.34.00.0
Renal and Urinary Disorders
Hematuria6.91.84.51.0
Pollakiuria4.80.02.50.0
Injury, Poisoning and Procedural Complications
Fall4.60.31.30.0
Non-pathologic Fractures4.01.40.80.3
Skin and Subcutaneous Tissue Disorders
Pruritus3.80.01.30.0
Dry Skin3.50.01.30.0
Respiratory Disorders
Epistaxis3.30.11.30.3
1CTCAE v4
2Includes asthenia and fatigue.
3Includes dizziness and vertigo.
4Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.
5Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.
6Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

PREVAIL (NCT01212991): XTANDI Versus Placebo In Chemotherapy-naive Metastatic CRPC

PREVAIL 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. 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 PREVAIL that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

Table 2: Adverse Reactions in PREVAIL

XTANDI
(N = 871)
Placebo
(N = 844)
Grade 1-41 (%)Grade 3-4 (%)Grade 1-4 (%)Grade 3-4 (%)
General Disorders
Asthenic Conditions2473.4332.8
Peripheral Edema120.28.20.4
Musculoskeletal and Connective Tissue Disorders
Back Pain292.5223.0
Arthralgia211.6161.1
Gastrointestinal Disorders
Constipation230.7170.4
Diarrhea170.3140.4
Vascular Disorders
Hot Flush180.17.80.0
Hypertension147.24.12.3
Nervous System Disorders
Dizziness3110.37.10.0
Headache110.27.00.4
Dysgeusia7.60.13.70.0
Mental Impairment Disorders45.70.01.30.1
Restless Legs Syndrome2.10.10.40.0
Respiratory Disorders
Dyspnea5110.68.50.6
Infections and Infestations
Upper Respiratory Tract Infection6160.0110.0
Lower Respiratory Tract And Lung Infection77.91.54.71.1
Psychiatric Disorders
Insomnia8.20.15.70.0
Renal and Urinary Disorders
Hematuria8.81.35.81.3
Injury, Poisoning and Procedural Complications
Fall131.65.30.7
Non-Pathological Fracture8.82.13.01.1
Metabolism and Nutrition Disorders
Decreased Appetite190.3160.7
Investigations
Weight Decreased120.88.50.2
Reproductive System and Breast Disorders
Gynecomastia3.40.01.40.0
1CTCAE v4
2Includes asthenia and fatigue.
3Includes dizziness and vertigo.
4Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.
5Includes dyspnea, exertional dyspnea, and dyspnea at rest.
6Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.
7Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

TERRAIN (NCT01288911): XTANDI Versus Bicalutamide In Chemotherapy-naive Metastatic CRPC

TERRAIN 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 TERRAIN

XTANDI
(N = 183)
Bicalutamide
(N = 189)
Grade 1-41 (%)Grade 3-4 (%)Grade 1-4 (%)Grade 3-4 (%)
Overall94399438
General Disorders
Asthenic Conditions2321.6231.1
Musculoskeletal and Connective Tissue Disorders
Back Pain192.7181.6
Musculoskeletal Pain3161.1140.5
Vascular Disorders
Hot Flush150110
Hypertension147.17.44.2
Gastrointestinal Disorders
Nausea140180
Constipation131.1130.5
Diarrhea1209.01.1
Infections and Infestations
Upper Respiratory Tract Infection41206.30.5
Investigational
Weight Loss110.57.90.5
1CTCAE v 4
2Including asthenia and fatigue.
3Including musculoskeletal pain and pain in extremity.
4Including nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.

PROSPER (NCT02003924): XTANDI Versus Placebo In Non-metastatic CRPC Patients

PROSPER enrolled 1401 patients with non-metastatic CRPC, of whom 1395 received at least one dose of study drug. Patients were randomized 2:1 and received either XTANDI at a dose of 160 mg once daily (N = 930) or placebo (N = 465). The median duration of treatment at the time of analysis was 18.4 months (range: 0.0 to 42 months) with XTANDI and 11.1 months (range: 0.0 to 43 months) with placebo.

Overall, 32 patients (3.4%) receiving XTANDI died from adverse events. The reasons for death with ≥ 2 patients included coronary artery disorders (n = 7), sudden death (n = 2), cardiac arrhythmias (n = 2), general physical health deterioration (n = 2), stroke (n = 2), and secondary malignancy (n = 5; one each of acute myeloid leukemia, brain neoplasm, mesothelioma, small cell lung cancer, and malignant neoplasm of unknown primary site). Three patients (0.6%) receiving placebo died from adverse events of cardiac arrest (n = 1), left ventricular failure (n = 1), and pancreatic carcinoma (n = 1). Grade 3 or higher adverse reactions were reported among 31% of XTANDI-treated patients and 23% of placebo-treated patients. Discontinuations with an adverse event as the primary reason were reported for 9.4% of XTANDI-treated patients and 6.0% of placebo-treated patients. Of these, the most common adverse event leading to treatment discontinuation was fatigue, which occurred in 1.6% of the XTANDI-treated patients compared to none of the placebo-treated patients. Table 4 shows adverse reactions reported in PROSPER that occurred at a ≥ 2% higher frequency in the XTANDI arm than in the placebo arm.

Table 4: Adverse Reactions in PROSPER

XTANDI
(N = 930)
Placebo
(N = 465)
Grade 1-41 (%)Grade 3-4 (%)Grade 1-4 (%)Grade 3-4 (%)
Metabolism and Nutrition Disorders
Decreased Appetite9.60.23.90.2
Nervous System Disorders
Dizziness2120.55.20
Headache9.10.24.50
Cognitive and Attention Disorders34.60.11.50
Vascular Disorders
Hot Flush130.17.70
Hypertension124.65.22.2
Gastrointestinal Disorders
Nausea110.38.60
Constipation9.10.26.90.4
General Disorders and Administration Site Conditions
Asthenic Conditions4404.0200.9
Investigations
Weight Decreased5.90.21.50
Injury, Poisoning and Procedural Complications
Fall111.34.10.6
Fractures59.82.04.91.7
Psychiatric Disorders
Anxiety2.80.20.40
1CTCAE v 4
2Includes dizziness and vertigo.
3Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.
4Includes asthenia and fatigue.
5Includes all osseous fractures from all sites.

ARCHES (NCT02677896): XTANDI Versus Placebo In Metastatic CSPC Patients

ARCHES randomized 1150 patients with mCSPC, of whom 1146 received at least one dose of study drug. All patients received either a gonadotropin-releasing hormone (GnRH) analogue concurrently or had bilateral orchiectomy. Patients received either XTANDI at a dose of 160 mg once daily (N=572) or placebo (N=574). The median duration of treatment was 12.8 months (range: 0.2 to 26.6 months) with XTANDI and 11.6 months (range: 0.2 to 24.6 months) with placebo.

Overall, 10 patients (1.7%) receiving XTANDI died from adverse events. The reasons for death in ≥ 2 patients included heart disease (n=3), sepsis (n=2) and pulmonary embolism (n=2). Eight patients (1.4%) receiving placebo died from adverse events. The reasons for death in ≥2 patients included heart disease (n=2) and sudden death (n=2). Grade 3 or higher adverse events were reported in 24% of patients treated with XTANDI. Permanent discontinuation due to adverse events as the primary reason was reported in 4.9% of XTANDI-treated patients and 3.7% of placebo-treated patients. The most common adverse events resulting in permanent discontinuation in XTANDI-treated patients were alanine aminotransferase increased, aspartate aminotransferase elevation, and seizure, each in 0.3%. The most common adverse events leading to permanent discontinuation in placebo-treated patients were arthralgia, and fatigue, each in 0.3%.

Dose reductions due to an adverse reaction occurred in 4.4% of patients who received XTANDI. Fatigue/asthenia was the most frequent adverse reaction requiring dose reduction in 2.1% of XTANDI-treated patients and 0.7% of placebo-treated patients.

Table 5 shows adverse reactions reported in ARCHES that occurred at a ≥ 2% higher frequency in the XTANDI arm than in the placebo arm.

Table 5: Adverse Reactions in ARCHES

XTANDI
(N = 572)
Placebo
(N = 574)
Grade 1-41 (%)Grade 3-4 (%)Grade 1-4 (%)Grade 3-4 (%)
Metabolism and Nutrition Disorders
Decreased Appetite4.90.22.60
Nervous System Disorders
Cognitive and Memory Impairment24.50.72.10
Restless Legs Syndrome2.400.30
Vascular Disorders
Hot Flush270.3220
Hypertension8.03.35.61.7
General Disorders and Administration Site Conditions
Asthenic conditions3241.7201.6
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal Pain6.30.24.00.2
Injury, Poisoning and Procedural Complications
Fractures46.51.04.21.0
1CTCAE v 4.03.
2Includes memory impairment, amnesia, cognitive disorder, dementia, disturbance in attention, transient global amnesia, dementia alzheimer's type, mental impairment, senile dementia and vascular dementia.
3Includes asthenia and fatigue.
4Includes Fracture related preferred terms under high level terms: fractures NEC; fractures and dislocations NEC; limb fractures and dislocations; pelvic fractures and dislocations; skull and brain therapeutic procedures; skull fractures, facial bone fractures and dislocations; spinal fractures and dislocations; thoracic cage fractures and dislocations.

Laboratory Abnormalities

Table 6 shows laboratory abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies.

Table 6: Laboratory Abnormalities

XTANDI
(N = 3173)
Placebo
(N = 2282)
Grade 1-4 (%)Grade 3-4 (%)Grade 1-4 (%)Grade 3-4 (%)
Hematology
Neutrophil count decreased200.9170.4
White blood cell decreased170.49.80.2
Chemistry
Hyperglycemia833.2753.1
Hypermagnesemia160.1130
Hyponatremia131.48.61.5
Hypercalcemia6.80.14.50

Hypertension

In the combined data from four randomized placebo-controlled clinical trials, hypertension was reported in 12% of patients receiving XTANDI and 5% of patients receiving placebo. 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 are 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 (edema of the face, tongue, lip, or pharynx)

Gastrointestinal Disorders: vomiting

Neurological Disorders: posterior reversible encephalopathy syndrome (PRES)

Skin and Subcutaneous Tissue Disorders: rash

Read the entire FDA prescribing information for Xtandi (Enzalutamide Capsules)

Related Resources for Xtandi

© Xtandi Patient Information is supplied by Cerner Multum, Inc. and Xtandi Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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