Darolutamide is a prescription oral medication, sold under the brand name Nubeqa, used to treat specific forms of prostate cancer. As an antiandrogen, it is part of a treatment plan that targets the hormonal pathways fueling tumor growth in men.
Medical Uses of Darolutamide
Darolutamide is approved to treat two types of prostate cancer. The first is non-metastatic castration-resistant prostate cancer (nmCRPC). In this condition, the cancer has not spread to other parts of the body but continues to progress even when testosterone levels are very low, a state known as “castration-resistant.”
The medication is also used for metastatic hormone-sensitive prostate cancer (mHSPC), where the cancer has spread to other parts of the body. In this case, the cancer cells are “hormone-sensitive,” meaning their growth can be slowed by lowering testosterone levels. Darolutamide is often used in combination with other treatments, such as the chemotherapy drug docetaxel.
For both conditions, darolutamide is given to patients who are also receiving a gonadotropin-releasing hormone (GnRH) analog or have had a bilateral orchiectomy (surgical removal of the testicles). These treatments maintain low testosterone levels. The addition of darolutamide has been shown to extend metastasis-free survival in patients with nmCRPC.
How Darolutamide Works
Darolutamide is an androgen receptor inhibitor (ARI). Prostate cancer cells use male hormones, known as androgens like testosterone, to grow. These hormones act like a key, fitting into a specific lock on the surface of the cancer cell called an androgen receptor. When the key enters the lock, it signals the cell to grow and divide.
The primary function of darolutamide is to block this process by competitively inhibiting androgens from binding to these receptors. This action is like placing a block in the keyhole, preventing the key from entering and unlocking the door. By preventing androgens from attaching, darolutamide stops the signal that tells the cancer cell to proliferate.
This blockade inhibits the androgen receptor from moving into the cell’s nucleus, a process called nuclear translocation. It also prevents the receptor from interacting with the cell’s DNA to carry out gene-regulating functions. The result is a decrease in the growth of prostate cancer cells and a reduction in tumor size. Its main metabolite, keto-darolutamide, exhibits similar activity.
Administration and Dosage
Darolutamide comes as a 300 mg tablet. The recommended dosage is 600 mg (two tablets) taken twice daily, for a total daily dose of 1,200 mg. It is important to follow the specific instructions from a healthcare provider, as dosages can be adjusted.
The medication should always be taken with food. Consuming darolutamide with a meal increases its bioavailability, meaning the body can absorb and use the drug more effectively. This helps maintain a consistent concentration of the drug in the bloodstream.
If a dose is missed, the patient should take it as soon as they remember but should not take two doses at once to compensate. If a patient experiences serious side effects, a healthcare provider might interrupt therapy or reduce the dosage to 300 mg twice daily until symptoms improve.
Potential Side Effects and Risks
Patients taking darolutamide may experience a range of side effects. Common issues include:
- Fatigue or weakness
- Pain in the arms and legs
- Skin rash
- Constipation
- Reduced appetite
- Weight gain
- Changes in blood pressure
There are also more serious, though less common, risks. A serious risk is ischemic heart disease, where blood flow to the heart is reduced, which can lead to major cardiac events. Patients may also experience heart failure. Because of these risks, healthcare providers monitor for signs of heart problems and manage cardiovascular risk factors like high blood pressure and diabetes.
Other serious potential side effects include decreased neutrophils (a type of white blood cell) and changes in liver function tests. Although not observed in clinical trials, seizures are a possible risk, and caution is advised for patients with a history of seizure disorders. It is important for patients to report any side effects to their doctor.
Darolutamide can interact with other medications, increasing the risk of toxicities. Patients should inform their provider of all medications they take, including over-the-counter drugs and supplements. Because the drug can harm a developing fetus, effective contraception is recommended for male patients with female partners of reproductive potential during treatment and for one week after the final dose.