A Comprehensive Guide to Enzalutamide: Uses, Side Effects, and Precautions

Enzalutamide isn't a drug you take for a cold or a headache. It’s a targeted therapy used when prostate cancer has spread and stopped responding to other treatments. If you or someone you care about has been prescribed enzalutamide, you’re likely looking for clear, no-fluff answers: How does it work? What side effects should you watch for? What should you avoid? This guide cuts through the noise and gives you what you need to know - based on current medical guidelines and real-world use.

What Is Enzalutamide and How Does It Work?

Enzalutamide is a type of hormone therapy, specifically an androgen receptor inhibitor. It’s used to treat advanced prostate cancer - cancer that has spread beyond the prostate gland and is no longer controlled by standard hormone treatments like leuprolide or goserelin.

Prostate cancer cells often grow in response to testosterone and other male hormones (androgens). Even when the testicles are removed or suppressed, some cancer cells still get signals from tiny amounts of androgens made elsewhere in the body. Enzalutamide blocks those signals at the source. It does three things:

• Prevents androgens from binding to receptors on cancer cells
• Stops the receptor from moving into the cell nucleus
• Blocks the receptor from interacting with DNA

This means cancer cells can’t get the signal to grow. In clinical trials, men taking enzalutamide lived longer and had slower disease progression compared to those on placebo. It’s approved for use in men with metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC).

Who Is Enzalutamide For?

Enzalutamide is not for everyone with prostate cancer. It’s specifically for men whose cancer has become resistant to treatments that lower testosterone. This usually happens after surgery or medical castration (like LHRH agonists) and after other hormone therapies like abiraterone or bicalutamide have stopped working.

Doctors test for two main conditions before prescribing it:

• Castration-resistant: Testosterone levels are below 50 ng/dL (the surgical or medical castration threshold), but cancer is still growing.
• Metastatic or non-metastatic: Whether the cancer has spread to bones, lymph nodes, or other organs (metastatic), or is still confined but rising in PSA levels (non-metastatic).

It’s not used for early-stage prostate cancer or for men who haven’t tried other hormone therapies first. It’s also not approved for women or children - and should never be taken by pregnant women, as it can cause serious harm to a developing fetus.

How Is Enzalutamide Taken?

Enzalutamide comes as a 40 mg capsule. The standard dose is four capsules once a day - that’s 160 mg total. You take it at the same time every day, with or without food. Swallow the capsules whole. Don’t crush, chew, or open them.

Most men take it continuously, as long as it’s working and side effects are manageable. Treatment doesn’t stop just because PSA levels drop - it continues until the cancer starts progressing again or side effects become too severe.

If you miss a dose, skip it and take your next dose at the regular time. Don’t double up. If you vomit after taking a dose, don’t take another one that day.

Enzalutamide is usually taken alongside ongoing androgen deprivation therapy (ADT), like injections or implants that keep testosterone low. It doesn’t replace ADT - it works with it.

Common Side Effects of Enzalutamide

Like all cancer treatments, enzalutamide has side effects. Not everyone gets them, and not all are serious. But you need to know what to watch for.

The most common side effects - affecting more than 1 in 10 men - include:

• Fatigue (feeling extremely tired, even after rest)
• Hot flashes
• Diarrhea
• Decreased appetite
• Joint pain or swelling
• High blood pressure
• Headache

Fatigue is the most reported issue. Many men say it hits harder than expected - not just a little tired, but a deep, bone-weary exhaustion that doesn’t go away with sleep. If fatigue interferes with daily life, talk to your doctor. It can sometimes be managed with light exercise, better sleep habits, or adjusting timing of doses.

Hot flashes are also very common. They feel like sudden waves of heat, often with sweating and flushing. Dress in layers, keep your room cool, and avoid triggers like spicy food or alcohol.

Serious Side Effects to Watch For

While most side effects are manageable, some can be dangerous. Seek medical help immediately if you experience:

• Seizures - This is rare but serious. Less than 1% of patients have seizures on enzalutamide, but the risk increases if you have a history of seizures, brain injury, stroke, or are taking other drugs that lower the seizure threshold.
• Sudden confusion, trouble speaking, or weakness on one side of the body - These could be signs of stroke.
• Severe dizziness or fainting - Could indicate low blood pressure or heart rhythm issues.
• Signs of liver problems - Yellowing of skin or eyes, dark urine, nausea, vomiting, or pain in the upper right abdomen.
• Severe diarrhea or dehydration - Can lead to kidney damage if untreated.

Enzalutamide can also raise blood pressure. Your doctor should check your blood pressure regularly - at least every 2 weeks for the first 3 months, then monthly. If it stays above 140/90, you may need blood pressure medication.

Drug Interactions to Avoid

Enzalutamide doesn’t play well with certain medications. It affects how your liver breaks down drugs, which can make some too strong or too weak.

Here are the key interactions:

• Strong CYP3A4 inducers: Drugs like rifampin, carbamazepine, or St. John’s wort can make enzalutamide less effective. Avoid them.
• Strong CYP3A4 inhibitors: Drugs like ketoconazole, clarithromycin, or grapefruit juice can increase enzalutamide levels in your blood, raising the risk of side effects.
• Anticoagulants like warfarin: Enzalutamide can lower the effect of warfarin, increasing clot risk. Your INR levels need close monitoring.
• Seizure medications: Enzalutamide can reduce levels of phenytoin, carbamazepine, and other antiseizure drugs, making them less effective.

Always tell your doctor and pharmacist about every medication, supplement, or herbal product you take - even over-the-counter ones like ibuprofen or melatonin.

Precautions Before Starting Treatment

Before you start enzalutamide, your doctor should review your full medical history. Here’s what matters most:

• History of seizures: If you’ve ever had a seizure, even one long ago, enzalutamide may not be safe for you. Your doctor might choose another option.
• Brain conditions: Stroke, brain tumors, or head injuries increase seizure risk.
• Liver disease: Enzalutamide is processed by the liver. If you have moderate to severe liver problems, your dose may need to be lowered or avoided.
• Heart problems: If you have heart failure or irregular heartbeat, your risk of complications from high blood pressure or electrolyte changes increases.
• Fracture risk: Men on long-term hormone therapy have higher risk of bone loss and fractures. Your doctor may recommend a bone density scan and prescribe calcium, vitamin D, or bisphosphonates.

Also, enzalutamide can cause dizziness or fatigue. Avoid driving or operating heavy machinery until you know how it affects you.

What Happens If It Stops Working?

Enzalutamide doesn’t cure prostate cancer - it controls it. Most men respond well for 12 to 24 months, sometimes longer. But eventually, cancer cells find a way around the block.

If your PSA starts rising again, or imaging shows new tumors, your doctor will look at other options:

• Chemotherapy like docetaxel or cabazitaxel
• Radium-223 (for bone metastases)
• PARP inhibitors if you have specific gene mutations (like BRCA)
• Clinical trials for newer hormone therapies

There’s no single next step - it depends on your cancer’s biology, your overall health, and what you’ve already tried. Your oncologist will use biomarker testing and imaging to guide the next decision.

Living With Enzalutamide: Tips for Daily Life

Managing side effects is key to staying on treatment. Here’s what helps real patients:

• Stay active: Even 20 minutes of walking daily reduces fatigue and improves mood.
• Hydrate: Drink water consistently. Dehydration worsens fatigue and dizziness.
• Track symptoms: Keep a simple log: tiredness level (1-10), bowel habits, blood pressure readings. Bring it to appointments.
• Use a pill organizer: Taking four capsules daily is easy to forget. A weekly box with alarms helps.
• Connect with others: Support groups - online or in person - help reduce isolation. Many men say talking to someone who’s been through it makes the biggest difference.

Also, don’t ignore emotional health. Depression and anxiety are common in men with advanced cancer. If you feel hopeless, withdrawn, or unable to enjoy things you used to, tell your care team. Counseling and antidepressants can help.

Final Thoughts: Is Enzalutamide Right for You?

Enzalutamide is a powerful tool in the fight against advanced prostate cancer. It extends life, delays symptoms, and gives men more time with their families. But it’s not without risks.

The best outcomes come when treatment is matched to the individual - not just the cancer stage, but also your overall health, other conditions, lifestyle, and personal goals. If you’re considering enzalutamide, ask your oncologist:

• What’s my chance of benefit based on my cancer’s characteristics?
• What are the alternatives, and how do they compare?
• How will we monitor for side effects?
• What should I do if something feels wrong?

There’s no perfect drug. But with the right information and support, enzalutamide can be a meaningful part of your journey.