XTANDI (enzalutamide) sponsored by Astellas Pharma Inc. and Pfizer Inc. 


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Indications & Usage

INDICATIONS AND USAGE

XTANDI is an androgen receptor inhibitor indicated for the treatment of patients with:

• castration-resistant prostate cancer.

• metastatic castration-sensitive prostate cancer. 


Please see Full Prescribing Information 

Dosage & Administration

DOSAGE AND ADMINISTRATION

XTANDI 160 mg (two 80 mg tablets or four 40 mg tablets or four 40 mg capsules) administered orally once daily. Swallow capsules or tablets whole. XTANDI can be taken with or without food.-  Tablets available 2021

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


Please see Full Prescribing Information for additional Dosing and Administration information

Dosage Forms and Strengths

DOSAGE FORMS AND STRENGTHS

Capsule: 40 mg

Tablet: 40 mg, 80 mg  - Available in 2021


Please see Full Prescribing Information for additional Dosage Forms and Strengths information

Warnings & Precautions

WARNINGS AND PRECAUTIONS

• Seizure occurred in 0.5% of patients receiving XTANDI. In patients with predisposing factors, seizures were reported in 2.2% of patients. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

• Posterior reversible encephalopathy syndrome (PRES): Discontinue XTANDI.

• Hypersensitivity: Discontinue XTANDI.

• Ischemic Heart Disease: Optimize management of cardiovascular risk factors. Discontinue XTANDI for Grade 3-4 events.

• Falls and Fractures occurred in 11% and 10% of patients receiving XTANDI, respectively. Evaluate patients for fracture and fall risk, and treat patients with bone-targeted agents according to established guidelines.

 • Embryo-Fetal Toxicity: XTANDI can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception.


Please see Full Prescribing Information for additional Warnings and Precautions information

Adverse Reactions

ADVERSE REACTIONS

The most common adverse reactions (≥ 10%) that occurred more frequently (≥ 2% over placebo) in the XTANDI-treated patients are asthenia/fatigue, back pain, hot flush, constipation, arthralgia, decreased appetite, diarrhea, and hypertension.


To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088   or www.fda.gov/medwatch.


 Please see Full Prescribing Information for additional Adverse Reactions information

Drug Interactions

DRUG INTERACTIONS

• Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI.

 If co-administration is necessary, reduce the dose of XTANDI.

• Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI.

If co-administration is necessary, increase the dose of XTANDI.

• Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring. 

CYP2C8, cytochrome P450 family 2 subfamily C member 8; CYP2C9, cytochrome P450 family 2 subfamily C member 9; CYP2C19, cytochrome P450 family 2 subfamily C member 19; CYP3A4, cytochrome P450 family 3 subfamily A member 4; INR, international normalized ratio



 Please see Full Prescribing Information for additional Drug Interactions information


© 2020 Astellas Pharma US, Inc. and Pfizer Inc. All Rights Reserved076-5771-PM  10/20

XTANDI, Astellas, and the flying star logo are registered trademarks of Astellas Pharma Inc.

XTANDI Support Solutions®, a component of Astellas Pharma Support SolutionsSM, is a registered trademark of Astellas Pharma US, Inc.




Please see Full Prescribing Information

INDICATIONS AND IMPORTANT SAFETY INFORMATION


 

Indications

XTANDI (enzalutamide) is indicated for the treatment of patients with:

·        castration-resistant prostate cancer (CRPC)

·        metastatic castration-sensitive prostate cancer (mCSPC)

 

Important Safety Information

 

Warnings and Precautions

Seizure occurred in 0.5% of patients receiving XTANDI in seven randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in seven randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of four randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4 ischemic events occurred in 1.4% of patients on XTANDI versus 0.7% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of four randomized, placebo-controlled clinical studies, falls occurred in 11% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 10% of patients treated with XTANDI and in 4% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

 

Adverse Reactions (ARs)

In the data from the four randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were asthenia/fatigue, back pain, hot flush, constipation, arthralgia, decreased appetite, diarrhea, and hypertension. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In AFFIRM, the placebo-controlled study of metastatic CRPC (mCRPC) patients who previously received docetaxel, Grade 3 and higher ARs were reported among 47% of XTANDI-treated patients. Discontinuations due to adverse events (AEs) were reported for 16% of XTANDI-treated patients. In PREVAIL, the placebo-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to AEs were reported for 6% of XTANDI-treated patients. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AE as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients.

In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher AEs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to AEs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

Lab Abnormalities: Lab 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 are neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, and hypercalcemia.

Hypertension: In the combined data from four randomized placebo-controlled clinical trials, hypertension was reported in 12% of XTANDI patients and 5% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.


Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

 

Please see Full Prescribing Information