Darolutamide – Uses, Dosage, Side Effects, Interaction

Use in Cancer

Darolutamide is approved to treat:

• Prostate cancer. It is used in adults whose cancer:
  • Has spread to other parts of the body and responds to treatment that lowers testosterone levels. It is used with docetaxel.
  • Has not spread to other parts of the body and no longer responds to treatment that lowers testosterone levels.

Darolutamide is also being studied in the treatment of other types of cancer.

Contraindications

• excessive fat in the blood
• a low seizure? threshold
• high blood pressure
• coronary artery disease?
• seizures
• pregnancy
• chronic kidney disease? stage 4 (severe?)
• Child-Pugh class B liver? impairment

Dosage?

Strengths: 300 mg

Prostate Cancer

• 600 mg orally 2 times a day
• Patients receiving this drug should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.
• For nonmetastatic castration-resistant prostate cancer (nmCRPC)

Renal? Dose Adjustments

• Mild? to moderate? renal impairment (CrCl 30 to 89 mL/min): No adjustment recommended.
• Severe renal impairment (CrCl 15 to 29 mL/min) who are not receiving hemodialysis: 300 mg orally 2 times a da
• End-stage? renal disease (CrCl 15 mL/min or less): Data not available

Liver Dose Adjustments

• Mild (Child-Pugh A) hepatic impairment: No adjustment recommended.
• Moderate (Child-Pugh B) hepatic impairment: 300 mg orally 2 times daily
• Severe (Child-Pugh C) hepatic impairment: Data not available

Dose Adjustments

• Grade 3 or greater toxicity or an intolerable adverse reaction: Withhold therapy or reduce to the dose to 300 mg 2 times a day until symptoms improve; then resume therapy at 600 mg orally 2 times a day.
• Dose reduction below 300 mg orally 2 times a day is not recommended.

Administration advice:

• This drug should be taken with food.
• Swallow tablets whole; do not divide, crush, or chew.
• If a dose is missed it should be taken as soon as it is remembered prior to the next scheduled dose; do not take 2 doses together to make up for a missed dose.

Side Effects

The Most Common

• extreme tiredness
• arm, leg, hand, or foot pain?
• arm, leg, hand, or foot pain
• rash?
• blood in urine?
• fever?, rapid and/or shallow breathing, or cough?
• chest pain? or feeling of pressure in the chest
• seizures
• severe ongoing nausea? or diarrhea?;
• painful or difficult urination;
• blood in your urine;
• severe headache?, blurred vision?, pounding in your neck or ears;
• slow heart rate?, weak pulse, fainting?, slow breathing (breathing may stop);
• signs of a blood clot in the lung–chest pain, sudden cough, wheezing?, rapid breathing, coughing up blood; or
• signs of a lung infection–fever, chills, cough with mucus, chest pain, shortness of breath.

More common

• Black, tarry stools
• bleeding gums
• blood in the urine
• bloody nose
• blurred vision
• coughing or spitting up blood
• difficulty in breathing or swallowing
• dizziness
• frequent urination
• headache
• increased menstrual flow or vaginal bleeding
• lower abdominal or stomach cramping
• nausea and vomiting
• nervousness
• nosebleeds
• painful urination
• paralysis
• pounding in the ears
• prolonged bleeding from cuts
• red or dark brown urine
• red or black, tarry stools
• slow, fast, or irregular heartbeat
• vomiting of blood or material that looks like coffee grounds
• unusual bleeding or bruising

Rare

• Blood in the urine
• chest pain or discomfort
• pain in the shoulders, arms, jaw, or neck
• painful or difficult urination
• seizures
• sweating
• trouble breathing
• Constipation
• decreased appetite
• increased weight
• pain in the arms or legs
• rash
• unusual tiredness or weakness
• Chest pain or tightness
• cough
• fever or chills
• muscle or bone pain
• sneezing
• sore throat

Drug Interaction

Pregnancy and Lactation

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Pregnancy

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. 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.

Lactation

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

References