Drug information of Darolutamide

Darolutamide


Darolutamide is used to treat prostate cancer that has not spread to other parts of your body.

Darolutamide is given after surgery or other treatments did not work or have stopped working.

Mechanism of effect

Darolutamide is a competitive androgen receptor inhibitor. In addition to androgen binding inhibition, darolutamide also inhibits androgen receptor translocation and androgen receptor-mediated transcription. Keto-darolutamide (active metabolite) has similar in vitro activity to darolutamide. Androgen receptor inhibition results in decreased proliferation of prostate tumor cells and increased apoptosis, leading to a decrease in tumor volume.

Pharmacokinetics

Distribution

119 L; darolutamide has low blood-brain barrier penetration (Fizazi 2019).

Metabolism

Primarily metabolized by CYP3A4, as well as by UGT1A9 and UGT1A1; active metabolite is keto-darolutamide.

Excretion

Urine: 63.4% (~7% as unchanged drug); feces: 32.4% (~30% as unchanged drug); Clearance: 116 mL/minute.

Time to Peak

~4 hours.

Half-Life Elimination

~20 hours (darolutamide and keto-darolutamide).

Protein Binding

Darolutamide: 92%; keto-darolutamide (active metabolite): 99.8%; primarily to serum albumin.

Drug indications

Prostate cancer, nonmetastatic, castration-resistant: Treatment of nonmetastatic castration-resistant prostate cancer.

Dosage

Adult

Prostate cancer, nonmetastatic, castration-resistant: Oral: 600 mg twice daily (in combination with a gonadotropin-releasing hormone analog [if had not received bilateral orchiectomy]); continue until disease progression or unacceptable toxicity .

Missed dose: If a dose is missed, administer as soon as possible prior to the next scheduled dose; do not take 2 doses at the same time to make up for a missed dose.

Administration

Oral: Administer with food. Swallow tablets whole.

Drug contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to darolutamide or any component of the formulation.

Side effects

Side effects requiring immediate medical attention

Along with its needed effects, darolutamide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking darolutamide:

Less common

  • Blood in the urine
  • painful or difficult urination

Rare

  • Blurred vision
  • dizziness
  • headache
  • nervousness
  • pounding in the ears
  • slow or fast heartbeat

Side effects not requiring immediate medical attention

Some side effects of darolutamide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Pain in the arms or legs
  • unusual tiredness or weakness

Less common

  • Chest pain
  • cough
  • fever or chills
  • rash
  • sneezing
  • sore throat
  • troubled breathing
  • tightness in the chest

Rare

  • Diarrhea

st. john's wort

Alerts

Before taking this medicine tell your doctor if you have ever had:

  • liver or kidney disease.

Although darolutamide is not for use by women, darolutamide can harm an unborn baby or cause a miscarriage if a woman is exposed to it during pregnancy.

Use effective birth control if your sex partner is able to get pregnant. Keep using birth control for at least 1 week after your last dose. Tell your doctor right away if a pregnancy occurs while you are using darolutamide.

This medicine may affect fertility (your ability to have children). However, it is important to use birth control to prevent pregnancy because darolutamide can harm an unborn baby.

Points of recommendation

 Take with food.

Swallow the tablet whole and do not crush, chew, or break it.

If you have not had surgery to lower the amount of testosterone in your body, your doctor may also prescribe a gonadotropin-releasing hormone (GnRH) medicine such as Eligard, Lupron, Trelstar, Zoladex, or Vantas. Keep using your GnRH as directed.

Safety and efficacy have not been established in patients younger than 18 years.  

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Keep the bottle tightly closed after initial opening.

Pregnancy level

HAVE NOT BEEN ESTABLISHED

Use is contraindicated.

AU TGA pregnancy category: D

US FDA pregnancy category: Not assigned.

Risk Summary: The safety and efficacy of this drug have not been established in females. Based on its mechanism of action, this drug can cause fetal harm and loss of pregnancy.

Comments:

-Advise male patients with female partners of reproductive potential to use effective contraception during therapy and for 1 week after.

-Based on animal studies, this drug may impair fertility in males of reproductive potential.

Breast feeding warning

Safety has not been established.

Excreted into human milk: Unknown

Excreted into animal milk: Data not available

Comments:

-The effects in the nursing infant are unknown.

-This drug is not indicated for use in female patients.

Drug forms

Nubeqa

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