Vardenafil and Enzalutamide: Can They Be Taken Together?

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Key takeaways

• Enzalutamide significantly reduces vardenafil levels, so the ED medicine may not work effectively.
• The interaction is not usually dangerous but means vardenafil may not help with erectile dysfunction.
• Never stop cancer treatment to make ED medicine work—your prescriber can suggest alternatives.
• Non-oral ED treatments like vacuum devices or alprostadil are not affected by enzalutamide.
• Always discuss your complete medication list with your prescriber before starting ED treatment.

What is vardenafil and enzalutamide?

Vardenafil is a prescription medicine used to treat erectile dysfunction (ED) in adult men. It belongs to a group of medicines called PDE5 inhibitors, which work by relaxing blood vessels in the penis, allowing increased blood flow when you're sexually aroused [3][5]. Vardenafil is available in 5mg, 10mg and 20mg tablets, usually taken about 25–60 minutes before sexual activity, and its effects can last for several hours. Like all PDE5 inhibitors, vardenafil requires sexual stimulation to work and will not cause an automatic erection.

Enzalutamide (brand name Xtandi) is a prescription medicine used to treat prostate cancer. It works by blocking the effects of male hormones (androgens) that can fuel the growth of prostate cancer cells [12]. Enzalutamide is taken as a daily tablet, usually long-term, and is an important part of cancer treatment for many men. However, enzalutamide is a potent inducer of liver enzymes—specifically the CYP3A4 enzyme system—which means it speeds up the breakdown of many other medicines in the body, potentially making them less effective.

How do vardenafil and enzalutamide interact?

The interaction between vardenafil and enzalutamide occurs because enzalutamide significantly increases the activity of CYP3A4 enzymes in your liver. Vardenafil is broken down (metabolised) primarily by the CYP3A4 enzyme system, so when enzalutamide speeds up this process, vardenafil is cleared from your body much more quickly than usual [5][12]. This means the levels of vardenafil in your bloodstream may be too low to produce the desired effect, and the medicine may not work effectively for treating erectile dysfunction.

This type of interaction is called a pharmacokinetic interaction—it affects how much of the medicine reaches your bloodstream and how long it stays there. Unlike some dangerous drug interactions that cause serious side effects, this interaction primarily reduces the effectiveness of vardenafil rather than increasing the risk of harm. However, it's still important to discuss with your prescriber, as taking a medicine that doesn't work wastes both time and money, and leaves your ED untreated.

The enzyme-inducing effect of enzalutamide is potent and affects many medicines, not just vardenafil. It can take several weeks after starting enzalutamide for the full enzyme-inducing effect to develop, and it can persist for several weeks after stopping the medicine. Your prescriber will take this timing into account when planning your treatment.

Why this matters for erectile dysfunction treatment

Erectile dysfunction is common in men with prostate cancer, both as a result of the cancer itself and as a side effect of treatments including hormone therapy and surgery [1][2]. Many men understandably want to maintain their sexual function during cancer treatment. However, if you're taking enzalutamide, standard doses of vardenafil may simply not be effective enough to help with ED. Your prescriber needs to consider alternative treatment options that are not affected by enzalutamide's enzyme-inducing properties, ensuring you receive ED treatment that actually works.

At a glance

What your prescriber will check about vardenafil and enzalutamide

Before prescribing any erectile dysfunction treatment, your prescriber will review your complete medication list, including enzalutamide and any other cancer treatments you're taking. They will ask about the dose of enzalutamide, how long you've been taking it, and your overall health status. Because enzalutamide can interact with many medicines, your prescriber needs a full picture of your current treatment to make safe, effective recommendations [2][12].

Your prescriber will also assess whether erectile dysfunction treatment is appropriate for you at this stage of your cancer treatment. They'll check your cardiovascular health, blood pressure, and whether sexual activity is safe for you. Some men with advanced cancer or significant heart problems may be advised that sexual activity is not currently advisable, regardless of which ED medicine is considered [3][5].

If vardenafil is not suitable due to the interaction with enzalutamide, your prescriber will discuss alternative approaches. These might include other PDE5 inhibitors (though many are similarly affected by enzyme inducers), non-oral treatments such as vacuum devices, or discussing the timing of treatment with your oncology team. The goal is to find an approach that treats your erectile dysfunction effectively without compromising your cancer treatment.

Alternative ED treatments when taking enzalutamide

Because enzalutamide reduces the effectiveness of vardenafil and other oral ED medicines that are broken down by CYP3A4 enzymes, your prescriber may recommend alternative treatments. All PDE5 inhibitors—including sildenafil, tadalafil, vardenafil and avanafil—are metabolised by CYP3A4 to varying degrees, so enzalutamide can potentially affect all of them [3][4][5][6]. However, the extent of the interaction may differ, and your prescriber can advise on whether adjusting the dose or trying a different PDE5 inhibitor might be worthwhile.

Non-oral treatments for erectile dysfunction are not affected by enzalutamide because they don't rely on absorption through the digestive system or metabolism by liver enzymes. Options include vacuum erection devices (mechanical pumps that draw blood into the penis), alprostadil cream (Vitaros) applied to the tip of the penis, or alprostadil injections (Caverject) into the side of the penis [7]. While these approaches may seem less convenient than a tablet, they can be very effective and are not subject to drug interactions with enzalutamide.

It's also worth discussing the timing and duration of your enzalutamide treatment with your oncology team and prescriber together. In some cases, if enzalutamide is stopped or switched to a different treatment, oral ED medicines may become effective again after several weeks. However, you should never stop or change your cancer treatment without explicit advice from your oncologist—treating your cancer effectively is the priority.

What about other PDE5 inhibitors?

Sildenafil, tadalafil and avanafil are also metabolised by CYP3A4 enzymes and may be affected by enzalutamide, though the clinical significance can vary [3][4][6]. Some prescribers may try a higher dose of a PDE5 inhibitor or suggest tadalafil, which has a longer duration of action, to see if any benefit can be achieved. However, there is no guarantee that switching between PDE5 inhibitors will overcome the enzyme induction caused by enzalutamide. Your prescriber will assess your individual circumstances and may suggest a trial of an alternative if appropriate.

Practical advice if you're taking both medicines

If your prescriber decides to try vardenafil (or another PDE5 inhibitor) despite the interaction with enzalutamide, it's important to have realistic expectations. The medicine may not work as well as it would in someone not taking enzalutamide, and you may find that the effect is weaker or shorter-lasting than expected. Do not increase the dose on your own in an attempt to make it work better—always follow the prescribed dose and discuss any concerns with your prescriber [5].

Keep a record of how well the treatment works for you. If you find that vardenafil is not effective after trying it on several occasions, let your prescriber know so they can review your treatment plan. It's also important to continue taking enzalutamide exactly as prescribed by your oncologist—do not stop or reduce your cancer treatment in an attempt to make the ED medicine work better. Your cancer treatment must remain the priority.

Avoid taking vardenafil with grapefruit juice, as this can unpredictably affect medicine levels, and limit alcohol intake, as heavy drinking can worsen erectile dysfunction and increase the risk of side effects such as dizziness [5]. If you experience any side effects from vardenafil—such as headache, flushing, indigestion or dizziness—discuss these with your prescriber. Some side effects are common and mild, but persistent or severe symptoms should always be reported.

When to seek urgent help with vardenafil and enzalutamide

Although the interaction between vardenafil and enzalutamide primarily affects how well the ED medicine works rather than causing dangerous side effects, there are still important warning signs to watch for. If you take vardenafil and develop an erection that lasts longer than four hours (priapism), you must seek emergency medical help immediately by calling 999 or going to A&E. Priapism is rare but can cause permanent damage to the penis if not treated promptly [5].

Sudden loss of vision in one or both eyes, or sudden decrease or loss of hearing (which may be accompanied by ringing in the ears or dizziness), are rare but serious side effects of PDE5 inhibitors. Stop taking vardenafil and seek urgent medical attention if you experience either of these symptoms [5]. If you develop chest pain during or after sexual activity, do not continue—stop the activity, sit or lie down, and seek medical help. Never take nitrate medicines (such as GTN spray) for chest pain if you have taken vardenafil within the past 24 hours, as this combination can cause a dangerous drop in blood pressure [3][5].

If you experience any new or worsening symptoms while taking enzalutamide—such as seizures, confusion, severe fatigue, or signs of liver problems (yellowing of the skin or eyes, dark urine, severe nausea)—contact your oncology team or GP urgently. These are not related to the interaction with vardenafil but are important side effects of enzalutamide that need prompt assessment [12].

Reporting side effects and concerns

If you experience side effects from either vardenafil or enzalutamide, you can report them via the Yellow Card Scheme at yellowcard.mhra.gov.uk or by searching for 'Yellow Card' in the Google Play or Apple App Store. Reporting side effects helps improve the safety information available about medicines. You should also inform your prescriber and, in the case of enzalutamide, your oncology team about any side effects you experience.

When to get urgent help

• Erection lasting more than 4 hours—call 999 or go to A&E immediately
• Sudden loss of vision or hearing—stop vardenafil and seek urgent medical attention
• Chest pain during sex—stop activity, do not take nitrates if you've used vardenafil in the past 24 hours, seek help
• Seizures, confusion or severe fatigue while on enzalutamide—contact your oncology team or GP urgently
• Signs of liver problems (yellowing skin/eyes, dark urine)—contact your oncology team or GP urgently

Call 999 or go to A&E in an emergency, or contact NHS 111 for urgent advice.

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