Xtandi Side Effects Center

Last updated on RxList: 6/6/2022
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

Stop taking enzalutamide and 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:

  • dizziness, spinning sensation;
  • a seizure (black-out 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; 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:

  • feeling weak or tired;
  • constipation, diarrhea;
  • loss of appetite;
  • flushing (redness, hot feeling);
  • back pain, 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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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: 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 1-4 1(%) Grade 3-4 (%) Grade 1-4 (%) Grade 3-4 (%)
General Disorders
Asthenic Conditions2 51 9.0 44 9.3
Peripheral Edema 15 1.0 13 0.8
Musculoskeletal and Connective Tissue Disorders
Back Pain 26 5.3 24 4.0
Arthralgia 21 2.5 17 1.8
Musculoskeletal Pain 15 1.3 12 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 22 1.1 18 0.3
Vascular Disorders
Hot Flush 20 0.0 10 0.0
Hypertension 6.4 2.1 2.8 1.3
Nervous System Disorders
Headache 12 0.9 5.5 0.0
Dizziness3 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 Disorders4 4.3 0.3 1.8 0.0
Hypoesthesia 4.0 0.3 1.8 0.0
Infections and Infestations
Upper Respiratory Tract Infection5 11 0.0 6.5 0.3
Lower Respiratory Tract And Lung Infection6 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
1. CTCAE v4
2. Includes asthenia and fatigue.
3. Includes dizziness and vertigo.
4. Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.
5. Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.
6. Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

PREVAIL: 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 Conditions2 47 3.4 33 2.8
Peripheral Edema 12 0.2 8.2 0.4
Musculoskeletal and Connective Tissue Disorders
Back Pain 29 2.5 22 3.0
Arthralgia 21 1.6 16 1.1
Gastrointestinal Disorders
Constipation 23 0.7 17 0.4
Diarrhea 17 0.3 14 0.4
Vascular Disorders
Hot Flush 18 0.1 7.8 0.0
Hypertension 14 7.2 4.1 2.3
Nervous System Disorders
Dizziness3 11 0.3 7.1 0.0
Headache 11 0.2 7.0 0.4
Dysgeusia 7.6 0.1 3.7 0.0
Mental Impairment Disorders4 5.7 0.0 1.3 0.1
Restless Legs Syndrome 2.1 0.1 0.4 0.0
Respiratory Disorders
Dyspnea5 11 0.6 8.5 0.6
Infections and Infestations
Upper Respiratory Tract Infection6 16 0.0 11 0.0
Lower Respiratory Tract And Lung Infection7 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 13 1.6 5.3 0.7
Non-Pathological Fracture 8.8 2.1 3.0 1.1
Metabolism and Nutrition Disorders
Decreased Appetite 19 0.3 16 0.7
Investigations
Weight Decreased 12 0.8 8.5 0.2
Reproductive System and Breast Disorders
Gynecomastia 3.4 0.0 1.4 0.0
1. CTCAE v4
2. Includes asthenia and fatigue.
3. Includes dizziness and vertigo.
4. Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.
5. Includes dyspnea, exertional dyspnea, and dyspnea at rest.
6. Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.
7. Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

TERRAIN: 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

XTANDI
(N = 183)
Bicalutamide
(N = 189)
Grade 1-41 (%) Grade 3-4 (%) Grade 1-4 (%) Grade 3-4 (%)
Overall 94 39 94 38
General Disorders
Asthenic Conditions2 32 1.6 23 1.1
Musculoskeletal and Connective Tissue Disorders
Back Pain 19 2.7 18 1.6
Musculoskeletal Pain3 16 1.1 14 0.5
Vascular Disorders
Hot Flush 15 0 11 0
Hypertension 14 7.1 7.4 4.2
Gastrointestinal Disorders
Nausea 14 0 18 0
Constipation 13 1.1 13 0.5
Diarrhea 12 0 9.0 1.1
Infections and Infestations
Upper Respiratory Tract Infection4 12 0 6.3 0.5
Investigational
Weight Loss 11 0.5 7.9 0.5
1. CTCAE v 4
2. Including asthenia and fatigue.
3. Including musculoskeletal pain and pain in extremity.
4. Including nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.

PROSPER: 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 Appetite 9.6 0.2 3.9 0.2
Nervous System Disorders
Dizziness2 12 0.5 5.2 0
Headache 9.1 0.2 4.5 0
Cognitive and Attention Disorders3 4.6 0.1 1.5 0
Vascular Disorders
Hot Flush 13 0.1 7.7 0
Hypertension 12 4.6 5.2 2.2
Gastrointestinal Disorders
Nausea 11 0.3 8.6 0
Constipation 9.1 0.2 6.9 0.4
General Disorders and Administration Site Conditions
Asthenic Conditions4 40 4.0 20 0.9
Investigations
Weight Decreased 5.9 0.2 1.5 0
Injury, Poisoning and Procedural Complications
Fall 11 1.3 4.1 0.6
Fractures5 9.8 2.0 4.9 1.7
Psychiatric Disorders
Anxiety 2.8 0.2 0.4 0
1. CTCAE v 4
2. Includes dizziness and vertigo.
3. Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.
4. Includes asthenia and fatigue.
5. Includes all osseous fractures from all sites.

ARCHES: 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 Appetite 4.9 0.2 2.6 0
Nervous System Disorders
Cognitive and Memory Impairment2 4.5 0.7 2.1 0
Restless Legs Syndrome 2.4 0 0.3 0
Vascular Disorders
Hot Flush 27 0.3 22 0
Hypertension 8.0 3.3 5.6 1.7
General Disorders and Administration Site Conditions
Asthenic conditions3 24 1.7 20 1.6
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal Pain 6.3 0.2 4.0 0.2
Injury, Poisoning and Procedural Complications
Fractures4 6.5 1.0 4.2 1.0
1. CTCAE v 4.03.
2. Includes memory impairment, amnesia, cognitive disorder, dementia, disturbance in attention, transient global amnesia, dementia alzheimer's type, mental impairment, senile dementia and vascular dementia.
3. Includes asthenia and fatigue.
4. Includes 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 decreased 20 0.9 17 0.4
White blood cell decreased 17 0.4 9.8 0.2
Chemistry
Hyperglycemia 83 3.2 75 3.1
Hypermagnesemia 16 0.1 13 0
Hyponatremia 13 1.4 8.6 1.5
Hypercalcemia 6.8 0.1 4.5 0

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.

Gastrointestinal Disorders: vomiting

Immune System Disorders: hypersensitivity (edema of the face, tongue, lip, or pharynx)

Neurological Disorders: posterior reversible encephalopathy syndrome (PRES), dysgeusia

Skin and Subcutaneous Tissue Disorders: rash, severe cutaneous adverse reactions (including Stevens-Johnson syndrome (SJS), erythema multiforme, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP))

DRUG INTERACTIONS

Effect Of Other Drugs On XTANDI

Strong CYP2C8 Inhibitors

The coadministration of XTANDI with gemfibrozil (a strong CYP2C8 inhibitor) increases plasma concentrations of enzalutamide plus N-desmethyl enzalutamide, which may increase the incidence and severity of adverse reactions of XTANDI. Avoid the coadministration of XTANDI with strong CYP2C8 inhibitors. If the coadministration of XTANDI with a strong CYP2C8 inhibitor cannot be avoided, reduce the dosage of XTANDI [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].

Strong CYP3A4 Inducers

The coadministration of XTANDI with rifampin (a strong CYP3A4 inducer and a moderate CYP2C8 inducer) decreases plasma concentrations of enzalutamide plus N-desmethyl enzalutamide, which may decrease the efficacy of XTANDI. Avoid the coadministration of XTANDI with strong CYP3A4 inducers. If the coadministration of XTANDI with a strong CYP3A4 inducer cannot be avoided, increase the dosage of XTANDI [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].

Effect Of XTANDI On Other Drugs

Certain CYP3A4, CYP2C9, Or CYP2C19 Substrates

XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer. The coadministration of XTANDI decreases the concentrations of certain CYP3A4, CYP2C9, or CYP2C19 substrates [see CLINICAL PHARMACOLOGY], which may reduce the efficacy of these substrates. Avoid the coadministration of XTANDI with certain CYP3A4, CYP2C9, or CYP2C19 substrates for which a minimal decrease in concentration may lead to therapeutic failure of the substrate. If the coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.

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

© 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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