Enzalutamide

Prostate Cancer Treatment

Enzalutamide is primarily used to treat adult men with different stages of prostate cancer. It is often prescribed when the cancer is castration-resistant, meaning it continues to grow even after medical or surgical treatments are used to lower testosterone levels.

Specific Uses

This medication is approved for the following conditions:

• Castration-Resistant Prostate Cancer (CRPC): This includes cancer that has spread to other parts of the body (metastatic) and cancer that has not yet spread (non-metastatic) but is no longer responding to hormone therapy.
• Metastatic Castration-Sensitive Prostate Cancer (mCSPC): This refers to prostate cancer that has spread to other areas of the body but still responds to treatments that lower testosterone.
• Non-Metastatic Castration-Sensitive Prostate Cancer (nmCSPC): It is used for patients who have a high risk of the cancer returning (biochemical recurrence) after initial treatments like surgery or radiation, even if the cancer has not yet been detected in other parts of the body.

Enzalutamide may be used alone or in combination with other treatments, such as a gonadotropin-releasing hormone (GnRH) analog, or it may be used following a surgical procedure to lower testosterone.

Mechanism of Action

Prostate cancer cells often depend on male hormones, known as androgens (such as testosterone), to grow and multiply. Enzalutamide is classified as an androgen receptor inhibitor, which means it interferes with how these hormones interact with cancer cells.

The medication works by targeting the androgen signaling pathway in several specific ways:

• Blocking Attachment: It prevents androgens from binding to receptors on the cancer cells.
• Preventing Movement: It stops the androgen receptors from moving into the cell nucleus, where genetic information is stored.
• Inhibiting DNA Interaction: It prevents the receptors from binding with the cell DNA.

By disrupting these processes, enzalutamide cuts off the signals that tell prostate cancer cells to grow. This can help shrink tumors or slow the progression of the disease.

Common Side Effects

The most frequently reported side effects of enzalutamide include:

• Fatigue or physical weakness
• Hot flashes
• Joint, back, or muscle pain
• Headache
• Dizziness
• High blood pressure
• Diarrhea or constipation
• Decreased appetite and weight loss
• Swelling of the hands, arms, legs, or feet
• Cold-like symptoms or respiratory infections

Serious Side Effects

Contact a healthcare provider immediately if you experience any of the following serious symptoms:

• Seizures
• Sudden confusion, severe headache, or vision loss
• Chest pain or difficulty breathing
• Falls or bone fractures
• Blood in the urine or pain during urination
• Severe allergic reactions, including rash, itching, or swelling of the face and throat

Seizure Risk

Seizures have been reported in patients receiving enzalutamide. The risk may be higher for individuals with a history of seizures, brain injury, stroke, or brain tumors. If a seizure occurs during treatment, the medication is typically discontinued permanently.

Posterior Reversible Encephalopathy Syndrome (PRES)

PRES is a rare neurological disorder that has occurred in patients taking this medication. Symptoms can include headache, seizure, confusion, and vision changes. Diagnosis is usually confirmed through brain imaging, and the medication is stopped if PRES is identified.

Heart Disease

Ischemic heart disease, including heart attacks and blockages in the arteries, has been observed in clinical trials. This risk is generally higher in patients who already have cardiovascular risk factors such as high blood pressure, high cholesterol, or diabetes.

Falls and Fractures

Treatment with enzalutamide can increase the likelihood of falling and sustaining bone fractures. These events have occurred in patients both with and without a prior history of falls.

Hypersensitivity

Serious allergic reactions, known as hypersensitivity, have been reported. Symptoms may include swelling of the face, lips, tongue, or throat, which require immediate medical attention.

Reproductive Precautions

Enzalutamide can cause harm to a developing fetus. Male patients with female partners of reproductive potential should use effective contraception and condoms during treatment and for three months after the final dose. Male patients should also use a condom when having sex with a pregnant woman to prevent exposure to the medication.

Pregnancy Risks

Enzalutamide is not indicated for use in women. Research suggests that exposure to the drug during pregnancy can cause birth defects or the death of an unborn baby. Because the medication can be passed through semen, it is important to prevent exposure to female partners who are pregnant or may become pregnant.

Contraception Requirements

Men with female partners of reproductive potential should follow these precautions:

• Use a condom and another effective form of birth control during treatment.
• Continue using these methods for 3 months after the last dose of enzalutamide.
• If a partner becomes pregnant while the man is taking this medication, a healthcare provider should be notified immediately.

Breastfeeding

It is not known whether enzalutamide passes into breast milk or how it might affect a nursing infant. Since the drug is not approved for use in women, breastfeeding is not recommended while taking this medication.

Enzalutamide is provided as a solid medication for oral use. It is available in the following formats:

• Oral capsules
• Oral tablets

Patients should swallow the capsules or tablets whole. The medication should not be chewed, crushed, or opened before swallowing. It can be taken with or without food.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved enzalutamide in August 2012. Its initial indication was for the treatment of patients with metastatic castration-resistant prostate cancer who had previously received docetaxel chemotherapy. Over the following decade, the FDA expanded the approved uses to include patients who had not yet received chemotherapy and those with earlier stages of the disease.

Current Approved Indications

Enzalutamide is currently FDA-approved for the treatment of adult patients with:

• Castration-resistant prostate cancer (CRPC).
• Metastatic castration-sensitive prostate cancer (mCSPC).
• Non-metastatic castration-sensitive prostate cancer (nmCSPC) with high-risk biochemical recurrence (BCR).

Regulatory Safety Information

The FDA monitors the safety profile of enzalutamide through the FDA Adverse Event Reporting System (FAERS). In 2020, the FDA identified a potential signal of serious risk regarding ischemic heart disease associated with the use of this medication. Regulatory authorities use this information to determine if further action, such as updating the product labeling, is required.

As of the most recent updates, enzalutamide does not have a boxed warning, which is the FDA’s most serious type of warning. There is also no Risk Evaluation and Mitigation Strategy (REMS) program required for its distribution.

Insurance and Out-of-Pocket Costs

Enzalutamide is a specialty medication, and its cost is largely determined by the type of insurance coverage a patient has. Most Medicare Part D and commercial insurance plans include enzalutamide on their formularies, though it is often placed in a high-cost specialty tier. This means patients may be responsible for a significant coinsurance or copayment amount.

Financial Assistance Programs

Because of the high cost of treatment, there are several resources available to help manage expenses:

• Manufacturer Assistance: The drug manufacturer may offer co-pay cards for patients with commercial insurance to reduce out-of-pocket costs.
• Patient Assistance Programs: For patients without insurance or those who are underinsured, programs may provide the medication at little or no cost based on financial need.
• Charitable Foundations: Independent organizations sometimes offer grants to help patients cover the costs of prostate cancer medications.

It is important to work with a healthcare provider or a specialty pharmacy to explore these options. Specialty pharmacies often have dedicated staff to help navigate insurance approvals and identify financial aid opportunities.