Tadalafil and Apalutamide: Can They Be Taken Together?

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What Is Tadalafil and How Does It Work?

Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor licensed in the UK to treat erectile dysfunction and the urinary symptoms of benign prostatic hyperplasia [4]. It works by relaxing blood vessels in the penis, allowing increased blood flow when you are sexually aroused. Unlike some other ED treatments, tadalafil has a long duration of action—up to 36 hours—which is why it's sometimes called the 'weekend pill'.

Tadalafil is available as an on-demand treatment (usually 10mg or 20mg taken at least 30 minutes before sexual activity) or as a daily low-dose tablet (2.5mg or 5mg) [4]. The daily option can be helpful for men who want spontaneity or who also need treatment for urinary symptoms. Sexual stimulation is still needed for tadalafil to work; it does not cause an automatic erection.

Common brand names include Cialis, and generic versions are widely available at lower cost. At Cured Pharmacy, tadalafil is available after an online consultation reviewed by a UK prescriber, who will check your medical history and current medicines to ensure it is safe and suitable for you.

What Is Apalutamide and Why Is It Prescribed?

Apalutamide (brand name Erleada) is an androgen receptor inhibitor used to treat certain types of prostate cancer, including non-metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer [12]. It works by blocking the effects of male hormones (androgens) that can fuel the growth of prostate cancer cells.

Because apalutamide is a potent inducer of liver enzymes—specifically the CYP3A4 enzyme system—it speeds up the breakdown of many other medicines in the body [12]. This means that drugs processed by CYP3A4, including tadalafil, may be cleared from your system more quickly than usual, potentially reducing their effectiveness.

Men taking apalutamide are often managing complex health needs, and it is not uncommon for prostate cancer treatment to coincide with erectile dysfunction. However, the interaction between apalutamide and tadalafil must be carefully considered, and any ED treatment should only be started after discussion with your cancer specialist and prescriber.

How Apalutamide Affects Other Medicines

Apalutamide is classified as a strong CYP3A4 inducer, meaning it increases the activity of enzymes in the liver that break down many medicines [12]. When these enzymes work faster, the levels of affected drugs in your bloodstream drop, and their therapeutic effect may be reduced or lost altogether. This interaction is well-documented and applies to a wide range of medicines, not just tadalafil.

When to get urgent help

• Erection lasting more than 4 hours (priapism) – go to A&E immediately
• Sudden loss of vision in one or both eyes – stop tadalafil and seek urgent medical help
• Sudden decrease or loss of hearing, sometimes with ringing in the ears or dizziness – seek urgent advice
• Chest pain during or after sexual activity – call 999; do not take nitrates if you have used tadalafil in the last 48 hours
• Severe allergic reaction (swelling of face, lips, tongue, difficulty breathing) – call 999

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

How Do Tadalafil and Apalutamide Interact?

The interaction between tadalafil and apalutamide occurs because apalutamide induces the CYP3A4 enzyme, which is responsible for breaking down tadalafil in the liver [4][12]. When apalutamide is taken regularly, it speeds up this breakdown process, leading to lower levels of tadalafil in your blood. As a result, tadalafil may not work as well or may not work at all.

This is not a dangerous interaction in the sense that it does not cause a sudden drop in blood pressure or other acute harm, unlike the life-threatening interaction between tadalafil and nitrates. However, it is a clinically significant interaction because it can make tadalafil ineffective, meaning you may not get the benefit you are seeking for erectile dysfunction.

The British National Formulary notes that CYP3A4 inducers can reduce the efficacy of PDE5 inhibitors, and prescribers are advised to consider alternative treatments or adjust management accordingly [4]. If you are taking apalutamide and experiencing erectile dysfunction, your prescriber will need to discuss whether tadalafil is likely to be effective or whether another approach might be more suitable.

What Your Prescriber Will Check Before Treatment

Before prescribing tadalafil to someone taking apalutamide, a UK prescriber will review your full medication list, including all cancer treatments, to assess the likelihood of drug interactions [2]. They will also check your cardiovascular health, blood pressure, and any history of heart disease, stroke, or other conditions that might make PDE5 inhibitors unsuitable.

Your prescriber will discuss the potential for reduced effectiveness of tadalafil due to the enzyme-inducing effect of apalutamide. In some cases, they may suggest trying tadalafil to see if it provides any benefit, but they will also explain that the interaction may mean it does not work as expected. Alternatively, they may recommend a different treatment approach, such as alprostadil (a prescription treatment applied as a cream or injection) or a medical device like Eroxon gel [7].

It is essential to be open about all medicines you are taking, including over-the-counter products and supplements such as St John's wort, which is also a CYP3A4 inducer. Your cancer specialist should also be informed if you are considering or starting ED treatment, to ensure coordinated care.

Coordinating Care Between Specialists

If you are under the care of an oncologist or urologist for prostate cancer, any new treatment for erectile dysfunction should ideally be discussed with them as well as your GP or online prescriber. This ensures that all aspects of your health are considered and that your cancer treatment is not compromised. Good communication between healthcare professionals is key to safe and effective care.

At a glance

Practical Advice for Taking Tadalafil and Apalutamide

If your prescriber decides that a trial of tadalafil is appropriate despite the interaction, they may suggest starting with a higher dose or using the on-demand formulation to maximise the chance of some effect. However, there is no guarantee that tadalafil will work effectively while you are taking apalutamide, and you should have realistic expectations.

Do not stop or reduce your apalutamide without medical advice, as this is an important cancer treatment. Similarly, do not increase your tadalafil dose on your own in an attempt to overcome the interaction; higher doses increase the risk of side effects such as headache, flushing, indigestion, and dizziness, without necessarily improving effectiveness if the drug is being rapidly broken down.

If tadalafil does not work for you, speak to your prescriber about alternatives. Alprostadil cream (Vitaros) or alprostadil injections (Caverject) work by a different mechanism and are not affected by CYP3A4 inducers [7]. Eroxon, a topical gel that works through a physical cooling and warming effect, is another option that does not involve drug interactions. Vacuum erection devices and psychological support may also be helpful, depending on your circumstances.

Other Medicines and Considerations with Tadalafil

Beyond apalutamide, tadalafil has other important interactions that you must be aware of. Never take tadalafil with nitrates (such as GTN spray or isosorbide mononitrate), nicorandil, riociguat, or recreational drugs known as 'poppers' (amyl or alkyl nitrites), as the combination can cause a dangerous drop in blood pressure [4]. Do not take tadalafil alongside another PDE5 inhibitor such as sildenafil or vardenafil.

If you take alpha-blockers for prostate symptoms or high blood pressure (such as tamsulosin or doxazosin), there is a risk of dizziness or low blood pressure when combined with tadalafil. You should be stable on the alpha-blocker before starting tadalafil, and your prescriber will usually recommend the lowest effective dose of the ED treatment [4].

Potent CYP3A4 inhibitors—such as ritonavir, cobicistat (found in some HIV treatments), ketoconazole, itraconazole, and clarithromycin—have the opposite effect to apalutamide: they increase tadalafil levels and raise the risk of side effects. Your prescriber will adjust the dose accordingly [4]. Always declare every medicine, supplement, and herbal remedy you take during your consultation, and do not stop or change any prescribed treatment without professional advice.

Lifestyle Factors That Affect Tadalafil

Grapefruit juice can raise tadalafil levels and should be avoided. Heavy alcohol can worsen erectile dysfunction and add to the blood-pressure-lowering effect of tadalafil, increasing the risk of dizziness [4]. Smoking, lack of exercise, and poorly controlled diabetes or high blood pressure can all contribute to ED, so lifestyle changes may improve your response to treatment [1][2].

In summary

• Apalutamide can reduce tadalafil effectiveness by speeding up how your body breaks it down.
• The interaction is not dangerous but may mean tadalafil does not work as expected.
• Your prescriber will assess whether a trial is worthwhile or suggest alternatives like alprostadil.
• Never stop apalutamide or adjust tadalafil doses without medical advice.
• Inform both your cancer specialist and prescriber about all medicines you take.

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