Abiraterone (Zytiga) and enzalutamide (Xtandi) are two of the most widely used tablets for advanced prostate cancer. Both are hormone treatments, and both work by cutting off the cancer’s supply of testosterone. But they do it in different ways, they are taken differently, and their side effects are not the same. This guide explains how they compare, so you can have a better-informed talk with your cancer team.
Two ways to block testosterone
Most prostate cancers need male hormones (androgens), mainly testosterone, to grow. Standard hormone treatment (androgen deprivation therapy, or ADT) lowers the testosterone made by the testicles. But some testosterone is still made by the adrenal glands and by the cancer itself1. Abiraterone and enzalutamide go after that remaining supply from two different directions:
- Abiraterone makes less testosterone. It blocks an enzyme called CYP17, which the body needs to make androgens. This enzyme is found in the testicles, the adrenal glands and prostate tumour tissue13.
- Enzalutamide blocks what is left from working. It is an androgen receptor blocker: it stops testosterone from attaching to the cancer cells and switching on their growth signals23.
Neither one replaces standard hormone treatment. Men taking abiraterone should also have an injection to lower testosterone (a GnRH analogue) or have had both testicles removed. The same applies to enzalutamide in most situations, although men with one specific type of early, non-spread cancer may take enzalutamide with or without the injection12.
Who they are used for
Both are licensed in the US for prostate cancer that has spread, both when it still responds to standard hormone treatment (castration-sensitive) and when it has started to grow despite it (castration-resistant)12. Enzalutamide is also licensed for castration-resistant cancer that has not spread, and for men whose PSA rises again after surgery or radiotherapy and who are at high risk of the cancer spreading2. Which one your doctor suggests depends on your stage, your treatment so far, your other health conditions and your other medicines5.
Why abiraterone is taken with a steroid
This is one of the most common questions about abiraterone. Blocking the CYP17 enzyme has a knock-on effect: the adrenal glands can start making more of another type of hormone (mineralocorticoids). Too much of it raises blood pressure, lowers the potassium in your blood and makes your body hold on to fluid1.
That is why abiraterone is always taken with a low dose of a steroid, prednisone or prednisolone, which helps to reduce some of these side effects4. A few things to know:
- Take the steroid every day, exactly as prescribed1.
- Do not stop it suddenly or lower the dose yourself. Problems with the adrenal glands (adrenal insufficiency) have been reported when the steroid was stopped or reduced, or during an infection or other stress. Your doctor may raise the steroid dose before, during and after a stressful event such as an operation1.
Enzalutamide does not need a steroid.
How you take them
| Abiraterone (Zytiga) | Enzalutamide (Xtandi) | |
|---|---|---|
| Usual dose | 1,000 mg once a day (for example, four 250 mg tablets), with prednisone1 | 160 mg once a day2 |
| Food | Empty stomach: nothing to eat for 2 hours before and 1 hour after1 | With or without food2 |
| Swallowing | Whole, with water; do not crush or chew1 | Whole, with enough water; do not cut, crush or chew2 |
| Steroid needed | Yes1 | No2 |
The food rule for abiraterone matters. Food changes how much of the medicine gets into your body, which is why it must be taken on an empty stomach14. Many people find it easiest to take it at the same time every morning before breakfast, or late in the evening at least two hours after their last meal.
Enzalutamide capsules and tablets are fairly large. Choking has been reported, so if you find them hard to swallow, tell your team: smaller tablets may be an option2.
Side effects compared
Both medicines lower the effect of testosterone, so both can add to the side effects of hormone treatment, such as hot flushes, tiredness, loss of sex drive, erection problems and thinning bones3. Beyond that, each has its own pattern.
| Abiraterone (with prednisone) | Enzalutamide | |
|---|---|---|
| Most common side effects | Tiredness, joint pain, high blood pressure, nausea, swelling from fluid, low potassium, hot flushes, diarrhoea, vomiting, colds, cough, headache1 | Muscle and bone pain, tiredness, hot flushes, constipation, poor appetite, diarrhoea, high blood pressure, bleeding, falls, fractures, headache2 |
| Main warnings | High blood pressure, low potassium and fluid retention; adrenal problems; liver damage, which can be serious1 | Seizures (fits); a rare brain swelling condition called PRES; allergic reactions; heart disease; falls and broken bones2 |
| Who needs extra care | Men with heart disease; men with liver problems1 | Men who have had a seizure or have other risks for one; men at risk of falls or fractures2 |
Get medical help quickly if you notice any of these12:
- On abiraterone: dizziness, fast or irregular heartbeats, feeling faint, confusion, muscle weakness, or swelling in your legs or feet (signs of high blood pressure, low potassium or fluid build-up); yellowing of your skin or eyes, darker urine, or severe nausea or vomiting (signs of liver problems).
- On enzalutamide: a fit; a headache with confusion, drowsiness or problems with your sight; chest pain or discomfort, or shortness of breath.
If you have diabetes and take pioglitazone or repaglinide, abiraterone has been linked with very low blood sugar, so your sugar levels need checking1. For the effect of prostate cancer treatment on erections, see our guide to ED after prostate cancer treatment.
Interactions: enzalutamide affects many common medicines
This is one of the biggest practical differences between the two.
- Enzalutamide speeds up the breakdown of many other medicines, so they may not work as well. In studies it lowered the levels of medicines such as midazolam (a sedative), warfarin (a blood thinner) and omeprazole (a stomach acid medicine). Some medicines should be avoided with it, and others may need a dose change2. Some medicines, such as gemfibrozil (for cholesterol) and rifampicin (an antibiotic), also change the level of enzalutamide itself2. It can also make some blood tests for digoxin (a heart medicine) read falsely high2.
- Abiraterone should not be taken with strong “enzyme-inducing” medicines such as phenytoin, carbamazepine or rifampicin unless your doctor changes the dose. It can also raise the levels of some medicines broken down by an enzyme called CYP2D61. It is not recommended together with radium-223, a radiation treatment for bone spread, because of a higher risk of fractures and death1.
Before starting either one, give your team a full list of everything you take, including over-the-counter medicines and herbal products.
What if you switch from one to the other?
Because both medicines work on the same testosterone pathway, a cancer that has grown on one may not respond as well to the other. European guidelines say there is evidence of cross-resistance between abiraterone and enzalutamide, and that later treatments in general tend to help less than earlier ones5.
This was tested directly in a trial of men whose cancer had spread, who had already had docetaxel chemotherapy, and whose cancer had grown within a year on one of these two tablets. Switching to a different type of treatment, the chemotherapy cabazitaxel, kept the cancer under control for longer than switching to the other tablet6. That does not mean switching is never used, but it is why your team will look at the whole picture, including how long the first tablet worked, before choosing what comes next5. Other options can include chemotherapy, radiation-based medicines and, for cancers with certain gene changes, PARP inhibitors3. Our guide to when a cancer medicine stops working explains how these decisions are made.
Checks while you take them
- PSA blood tests. Your PSA is checked regularly. A rise can mean the cancer has started to grow again or become resistant to the treatment3. On its own, a change in PSA does not always tell you how well the treatment is working for you, so your team looks at scans and symptoms too1.
- On abiraterone: blood pressure, potassium and signs of fluid retention at least once a month, and liver blood tests before you start, every two weeks for the first three months, then monthly1.
- On enzalutamide: checks of your heart risk factors, such as blood pressure, cholesterol and blood sugar, and of your risk of falls and fractures2.
Pregnancy and contraception
Both medicines can harm an unborn baby. Men with a partner who could become pregnant should use effective contraception during treatment and for 3 weeks after the last dose of abiraterone, or 3 months after the last dose of enzalutamide12. Women who are or may become pregnant should not handle abiraterone tablets1.
Generic versions and cost
Generic abiraterone and enzalutamide contain the same active ingredients as Zytiga and Xtandi. If you are switching between brands, check the tablet strength, because the number of tablets you take each day depends on it. Our generic Zytiga and generic Xtandi pages explain the options, and our guide to what Zytiga costs compares prices.
We stock abiraterone, including Abirakast 250 mg, Abiraxen 250 mg and Zytiga 250 mg, and enzalutamide, including Enzamide 40 mg capsules. See all options on our abiraterone and enzalutamide pages, or browse our prostate cancer medicines. All need a prescription.
Frequently asked questions
Is Xtandi better than Zytiga?
Neither is simply better. They work in different ways and have different side effects and interactions. The right choice depends on your stage, your treatment so far, your other health conditions and your other medicines, so it is a decision to make with your cancer team.
Why do you take prednisone with abiraterone?
Abiraterone can make the adrenal glands produce extra hormones that raise blood pressure, lower potassium and cause fluid retention. A low-dose steroid helps to reduce these side effects. Do not stop the steroid without talking to your doctor.
Is abiraterone chemotherapy?
No. Abiraterone and enzalutamide are hormone treatments. They work by blocking testosterone, not by killing fast-dividing cells the way chemotherapy does. See our guide is it chemotherapy?
How long does abiraterone work?
It varies from person to person, and doctors cannot predict how long hormone treatment will keep a particular cancer under control. That is why your PSA is checked regularly, along with scans and symptoms.
Can you take abiraterone after enzalutamide?
Sometimes, but a cancer that has grown on one of these medicines may not respond as well to the other, because they work on the same pathway. Your team will weigh this against other options such as chemotherapy.
Sources & references
- US National Library of Medicine, DailyMed. Zytiga (abiraterone acetate) prescribing information.
- US National Library of Medicine, DailyMed. Xtandi (enzalutamide) prescribing information.
- National Cancer Institute. Hormone Therapy for Prostate Cancer. Reviewed 4 October 2024.
- Cancer Research UK. Abiraterone (Zytiga). Last reviewed 7 September 2023.
- European Association of Urology. EAU Guidelines on Prostate Cancer: Treatment.
- de Wit R, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381(26):2506-2518.
Related reading
- PARP inhibitors: olaparib vs niraparib
- Generic abiraterone guide
- How much does Zytiga cost?
- When a cancer medicine stops working
This content is for informational purposes only and is not medical advice. Cancer treatment decisions should be made with your oncologist, and you should not change or stop any medicine without talking to them. Used as prescribed by a licensed medical professional.
Babu S. Shetty is a licensed clinical pharmacist with 14 years of experience. He holds a B.Pharm and M.Pharm from Mohan Kumaramangalam Medical College. At OnlineMeds, he reviews medicine and health content to help ensure it is accurate, evidence-based, and easy to understand.