Tadalafil and Methotrexate: Can They Be Taken Together?

Takes less than 2 minutes to complete 100% online

What Is Tadalafil and How Does It Work?

Tadalafil is a prescription medicine used to treat erectile dysfunction (ED) in 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 are sexually aroused [3][4]. Tadalafil does not cause an erection on its own—sexual stimulation is still needed.

Tadalafil is available in two forms: on-demand tablets (10mg or 20mg taken at least 30 minutes before sex, with effects lasting up to 36 hours) and daily low-dose tablets (2.5mg or 5mg taken once a day) [4]. The longer duration of action is why tadalafil is sometimes called 'the weekend pill'. It is the generic version of branded Cialis and is available at Cured Pharmacy following a consultation with a UK-registered prescriber.

Common side effects include headache, indigestion, back pain, muscle aches, flushing, and a blocked or runny nose [4]. Most side effects are mild and temporary. Tadalafil should not be taken with nitrates, nicorandil, riociguat, poppers, or another PDE5 inhibitor, as this combination can cause a dangerous drop in blood pressure.

What Is Methotrexate and Why Is It Prescribed?

Methotrexate is a disease-modifying anti-rheumatic drug (DMARD) commonly prescribed for autoimmune and inflammatory conditions such as rheumatoid arthritis, psoriasis, psoriatic arthritis, and Crohn's disease. It works by suppressing the overactive immune system that causes inflammation and joint damage. Methotrexate is usually taken once a week as tablets or an injection, alongside folic acid supplements to reduce side effects.

Because methotrexate affects the immune system and liver function, regular blood tests are required to monitor for potential side effects. Common side effects include nausea, mouth ulcers, fatigue, and increased risk of infection. Methotrexate can also interact with certain medicines, so it is important to tell your prescriber about all medications you take, including over-the-counter products and supplements.

Men taking methotrexate may experience erectile dysfunction due to the underlying inflammatory condition, fatigue, pain, or psychological factors such as stress and low mood. ED is not a direct side effect of methotrexate itself, but the conditions it treats—and their impact on overall health and wellbeing—can contribute to difficulties with erections [1][2].

When to get urgent help

• Erection lasting more than four hours (priapism)—go to A&E immediately
• Sudden loss of vision or hearing—stop tadalafil and seek urgent medical help
• Chest pain during or after sex—call 999; do not take nitrates if you have used tadalafil in the last 48 hours
• Severe dizziness, fainting, or very low blood pressure—seek same-day medical advice
• Allergic reaction (swelling of face, lips, tongue, or throat, difficulty breathing)—call 999

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

Is There an Interaction Between Tadalafil and Methotrexate?

No major direct interaction between tadalafil and methotrexate is commonly reported in clinical practice or drug interaction databases. Methotrexate does not significantly affect the way tadalafil is broken down in the body, and tadalafil does not interfere with methotrexate's mechanism of action. This means that, in most cases, the two medicines can be taken together without one reducing the effectiveness of the other or causing a dangerous reaction.

However, this does not mean tadalafil is automatically suitable for everyone taking methotrexate. Your prescriber will still need to review your full medical history, including your cardiovascular health, blood pressure, liver and kidney function, and any other medicines you take. Methotrexate is often prescribed for conditions associated with increased cardiovascular risk, such as rheumatoid arthritis, so a thorough assessment is essential [2].

During your online consultation at Cured Pharmacy, you will be asked about all your current medications, including methotrexate, to ensure tadalafil is safe and appropriate for you. Never stop or change your methotrexate dose without speaking to the doctor who prescribed it, as this could lead to a flare-up of your underlying condition.

How Tadalafil Is Processed in the Body

Tadalafil is broken down primarily by an enzyme in the liver called CYP3A4 [4]. Methotrexate does not significantly inhibit or induce this enzyme, which is why no major interaction occurs. However, other medicines that do affect CYP3A4—such as certain antibiotics (clarithromycin), antifungals (ketoconazole, itraconazole), or HIV medicines (ritonavir, cobicistat)—can raise tadalafil levels in the blood and require dose adjustments or avoidance [4]. Always declare every medicine you take during your consultation.

What Your Prescriber Checks Before Approving Tadalafil

When you request tadalafil through Cured Pharmacy, a UK-registered prescriber will review your online consultation answers to ensure the treatment is safe and suitable for you. They will check your cardiovascular health, blood pressure, and whether you have any conditions that make PDE5 inhibitors unsuitable, such as recent heart attack or stroke, unstable angina, severe heart failure, very low blood pressure, or a history of sudden vision loss (NAION) [3][4].

Your prescriber will also review all your current medicines, including methotrexate, to identify any interactions. If you take medicines that lower blood pressure (such as alpha-blockers like tamsulosin or doxazosin, or other antihypertensives), the prescriber will ensure you are stable on these treatments and may recommend starting tadalafil at a lower dose to minimise the risk of dizziness or fainting [4].

You will be asked about nitrates (GTN spray, isosorbide mononitrate or dinitrate), nicorandil, riociguat, and recreational drugs such as poppers (amyl or alkyl nitrites). Do not take tadalafil with any of these, as the combination can cause a dangerous drop in blood pressure. If you take potent CYP3A4 inhibitors, your prescriber will adjust the tadalafil dose or recommend an alternative treatment [4]. The consultation ensures that tadalafil and methotrexate, along with any other medicines you take, can be used together safely.

At a glance

Practical Advice for Taking Tadalafil and Methotrexate Together

If your prescriber approves tadalafil, take it exactly as directed. For on-demand tadalafil (10mg or 20mg), take one tablet at least 30 minutes before sexual activity; the effect can last up to 36 hours, so you do not need to rush [4]. For daily tadalafil (2.5mg or 5mg), take one tablet at the same time each day, regardless of when you plan to have sex. Sexual stimulation is still needed for tadalafil to work.

Continue taking your methotrexate exactly as prescribed by your rheumatologist or specialist. Do not skip doses or stop methotrexate because you are taking tadalafil, as this could cause your underlying condition to flare. Take methotrexate on the same day each week, and remember to take your folic acid on the other days as advised. Attend all scheduled blood tests to monitor your liver, kidneys, and blood counts.

Avoid drinking large amounts of alcohol, as heavy drinking can worsen erectile dysfunction and add to the blood-pressure-lowering effect of tadalafil, increasing the risk of dizziness [3][4]. Grapefruit juice can raise tadalafil levels in the blood, so it is best to avoid it. If you experience side effects such as severe headache, chest pain during sex, an erection lasting more than four hours, or sudden loss of vision or hearing, seek urgent medical help.

When to Speak to Your GP or Specialist

If you develop new or worsening erectile dysfunction while taking methotrexate, speak to your GP or specialist. ED can be an early warning sign of cardiovascular disease or diabetes, so it is important to have a full health check [1][2]. Your doctor can assess whether your ED is related to your underlying condition, medication, psychological factors, or a combination of these, and recommend appropriate treatment. Never stop methotrexate without medical advice.

Other ED Treatments Available at Cured Pharmacy

If tadalafil is not suitable for you, or if you would like to try a different PDE5 inhibitor, Cured Pharmacy offers several alternatives following an online consultation. Sildenafil (generic Viagra) is taken about one hour before sex and lasts for around four to six hours [3]. It is available in 25mg, 50mg, and 100mg strengths. Vardenafil (generic Levitra) is taken 25 to 60 minutes before sex and also lasts for several hours [5]. Avanafil (Spedra) has the fastest onset, working in as little as 15 to 30 minutes [6][11].

All PDE5 inhibitors work in a similar way and have similar interactions and contraindications. They should not be taken with nitrates, nicorandil, riociguat, poppers, or another PDE5 inhibitor. If you take methotrexate and have been assessed as suitable for one PDE5 inhibitor, you may also be suitable for others, depending on your preferences and how quickly you want the medicine to work.

Branded options such as Viagra and Cialis are also available if you prefer them. For men who cannot take PDE5 inhibitors, alternatives such as Vitaros (alprostadil cream applied to the tip of the penis) or Caverject (alprostadil injection) may be considered [7]. These require a prescription and specialist assessment. Your prescriber will discuss the best option for you during your consultation.

Pharmacy Medicines and Non-Prescription Options

Viagra Connect (sildenafil 50mg) and Cialis Together (tadalafil 10mg) are available from pharmacies without a prescription for men aged 18 and over, following a consultation with a pharmacist. Eroxon is a topical gel medical device that can be purchased without a prescription. However, if you take methotrexate or have an underlying health condition, it is safer to have a full consultation with a prescriber who can review your medical history and current medicines before recommending treatment.

In summary

• No major direct interaction between tadalafil and methotrexate is commonly reported in clinical practice.
• Your prescriber reviews your full medical history and all medicines during consultation to ensure safety.
• Continue taking methotrexate exactly as prescribed; do not stop or change your dose without medical advice.
• Tadalafil should not be taken with nitrates, nicorandil, riociguat, poppers, or another PDE5 inhibitor.
• If you develop new or worsening ED, speak to your GP as it can be an early sign of heart disease or diabetes.

Ready to Speak to a Pharmacist?

Start your journey to better health today.

• Reviewed by UK-based prescribers
• Takes under 3 minutes
• Discreet Packaging

Frequently Asked Questions