Xtandi

XTANDI^® is indicated for the treatment of patients with:

• •castration-resistant prostate cancer (CRPC)
• •metastatic castration-sensitive prostate cancer (mCSPC)
• •non‑metastatic castration‑sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)

• •Take XTANDI 160 mg administered orally once daily with or without food. (
  2.1 Recommended Dosage

  The recommended dosage of XTANDI is 160 mg administered orally once daily with or without food

  [see Clinical Pharmacology]

  until disease progression or unacceptable toxicity.

  Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Do NOT chew, dissolve, or open the capsules. Do NOT cut, crush, or chew the tablets.

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

  Patients with nmCSPC with high-risk BCR may be treated with XTANDI with or without a GnRH analog. For patients who receive XTANDI with or without a GnRH analog, treatment can be suspended if PSA is undetectable (< 0.2 ng/mL) after 36 weeks of therapy. Reinitiate treatment when PSA has increased to ≥ 2.0 ng/mL for patients who had prior radical prostatectomy or ≥ 5.0 ng/mL for patients who had prior primary radiation therapy

  [see Clinical Studies]

  .
  )
• •Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. (
  2.1 Recommended Dosage

  The recommended dosage of XTANDI is 160 mg administered orally once daily with or without food

  [see Clinical Pharmacology]

  until disease progression or unacceptable toxicity.

  Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Do NOT chew, dissolve, or open the capsules. Do NOT cut, crush, or chew the tablets.

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

  Patients with nmCSPC with high-risk BCR may be treated with XTANDI with or without a GnRH analog. For patients who receive XTANDI with or without a GnRH analog, treatment can be suspended if PSA is undetectable (< 0.2 ng/mL) after 36 weeks of therapy. Reinitiate treatment when PSA has increased to ≥ 2.0 ng/mL for patients who had prior radical prostatectomy or ≥ 5.0 ng/mL for patients who had prior primary radiation therapy

  [see Clinical Studies]

  .
  ,
  5.7 Dysphagia or Choking

  Severe dysphagia or choking, including events that could be life-threatening requiring medical intervention or fatal, can occur due to XTANDI product size. Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Consider use of a smaller tablet size of XTANDI in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.
  )
• •Patients receiving XTANDI for castration-resistant prostate cancer, or metastatic castration sensitive prostate cancer should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. (
  2.1 Recommended Dosage

  The recommended dosage of XTANDI is 160 mg administered orally once daily with or without food

  [see Clinical Pharmacology]

  until disease progression or unacceptable toxicity.

  Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Do NOT chew, dissolve, or open the capsules. Do NOT cut, crush, or chew the tablets.

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

  Patients with nmCSPC with high-risk BCR may be treated with XTANDI with or without a GnRH analog. For patients who receive XTANDI with or without a GnRH analog, treatment can be suspended if PSA is undetectable (< 0.2 ng/mL) after 36 weeks of therapy. Reinitiate treatment when PSA has increased to ≥ 2.0 ng/mL for patients who had prior radical prostatectomy or ≥ 5.0 ng/mL for patients who had prior primary radiation therapy

  [see Clinical Studies]

  .
  )
• •Patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis may be treated with or without a GnRH analog. (
  2.1 Recommended Dosage

  The recommended dosage of XTANDI is 160 mg administered orally once daily with or without food

  [see Clinical Pharmacology]

  until disease progression or unacceptable toxicity.

  Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Do NOT chew, dissolve, or open the capsules. Do NOT cut, crush, or chew the tablets.

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

  Patients with nmCSPC with high-risk BCR may be treated with XTANDI with or without a GnRH analog. For patients who receive XTANDI with or without a GnRH analog, treatment can be suspended if PSA is undetectable (< 0.2 ng/mL) after 36 weeks of therapy. Reinitiate treatment when PSA has increased to ≥ 2.0 ng/mL for patients who had prior radical prostatectomy or ≥ 5.0 ng/mL for patients who had prior primary radiation therapy

  [see Clinical Studies]

  .
  )

XTANDI 40 mg capsules are white to off-white oblong soft gelatin capsules imprinted in black ink with ENZ.

XTANDI 40 mg tablets are yellow, round, film-coated and debossed with E 40.

XTANDI 80 mg tablets are yellow, oval, film-coated and debossed with E 80.

The safety and efficacy of XTANDI have not been established in females. Based on animal reproductive studies and mechanism of action, XTANDI can cause fetal harm and loss of pregnancy. There are no human data on the use of XTANDI in pregnant females. In animal reproduction studies, oral administration of enzalutamide in pregnant mice during organogenesis caused adverse developmental effects at doses lower than the maximum recommended human dose

In an embryo-fetal developmental toxicity study in mice, enzalutamide caused developmental toxicity when administered at oral doses of 10 or 30 mg/kg/day throughout the period of organogenesis (gestational days 6-15). Findings included embryo-fetal lethality (increased post-implantation loss and resorptions) and decreased anogenital distance at ≥ 10 mg/kg/day, and cleft palate and absent palatine bone at 30 mg/kg/day. Doses of 30 mg/kg/day caused maternal toxicity. The doses tested in mice (1, 10 and 30 mg/kg/day) resulted in systemic exposures (AUC) approximately 0.04, 0.4 and 1.1 times, respectively, the exposures in patients. Enzalutamide did not cause developmental toxicity in rabbits when administered throughout the period of organogenesis (gestational days 6-18) at dose levels up to 10 mg/kg/day (approximately 0.4 times the exposures in patients based on AUC).

In a pharmacokinetic study in pregnant rats with a single oral 30 mg/kg enzalutamide administration on gestation day 14, enzalutamide and/or its metabolites were present in the fetus at a C_max that was approximately 0.3 times the concentration found in maternal plasma and occurred 4 hours after administration.