Tadalafil and Apomorphine Together: The Rationale and What Is Known

Combining two medicines that work in different ways is a familiar idea in medicine, from blood pressure to asthma. In erectile dysfunction, one combination that has drawn interest pairs tadalafil, which acts on blood vessels in the penis, with apomorphine, which acts on erection signals in the brain. Curekey is preparing a physician-prescribed dissolvable tablet that contains tadalafil 3 mg and apomorphine 1 mg. Before anyone weighs a treatment like this, it is worth being clear about why the two are combined, what is genuinely known, and what has not yet been studied.

Two different steps in the same process

An erection depends on a chain of events, and these two medicines act at different points in it.

• The brain starts the process. Arousal activates centers in the hypothalamus, which send signals through the spinal cord to the nerves of the penis. Apomorphine, a dopamine agonist, is thought to act on these central centers. Our apomorphine guide explains this in more detail.
• Blood vessels complete it. Those nerve signals release nitric oxide in the penis, which relaxes the smooth muscle so blood can flow in. Tadalafil, a PDE5 inhibitor, slows the breakdown of the messenger that keeps those vessels relaxed. Our tadalafil guide covers how that works and how long it lasts.

Tadalafil cannot create arousal, and apomorphine does not directly widen blood vessels. The idea behind combining them is that supporting both the starting signal and the blood-flow response might help men for whom one step alone is not enough.

Why a combination is proposed

The reasoning is pharmacological rather than proven:

• The two drugs act through separate pathways, so in principle their effects could add together.
• Pairing them could, in theory, allow lower doses of each, with the aim of fewer side effects than a higher dose of either alone.
• Some men do not respond fully to PDE5 inhibitors, and a medicine that acts centrally has been suggested as a possible addition for them.

These are reasonable hypotheses. They are not the same as evidence that the combination works better, and the next section sets out where things stand.

What the evidence shows, and what it does not

Being specific about the evidence matters, because it is thinner than for either medicine used alone at standard doses.

• No trial of this combination. We found no published clinical trial of tadalafil combined with apomorphine in men, at any dose.
• One related human study. A conference abstract described a small crossover study (43 men assessed) of sildenafil, a different PDE5 inhibitor, given with apomorphine under the tongue. The combination produced firm erections more often than sildenafil alone. It has not been published as a full peer-reviewed paper, and it did not use tadalafil.
• Animal work. A study in rabbits found apomorphine enhanced erections produced by sildenafil without a further drop in blood pressure. Animal findings do not reliably predict results in people.
• The apomorphine dose. Published ED trials of apomorphine used 2 mg or more. A 1 mg dose is below every dose studied, and there is no clinical evidence that 1 mg improves erections on its own.
• The tadalafil dose. Tadalafil is approved in 2.5, 5, 10 and 20 mg strengths. A 3 mg dose sits between the two approved once-daily doses of 2.5 mg and 5 mg, where the evidence for daily tadalafil is solid, but 3 mg itself has not been tested.

In plain terms: each ingredient has its own evidence at its own studied doses, and the combination at these doses has not been tested in a clinical trial. Results vary from person to person, and nobody can say from the current evidence how much each ingredient contributes in this product.

What compounding means

A combination like this is not sold as a commercially manufactured medicine. It is prepared by a licensed pharmacy as a compounded medication for an individual patient with a prescription.

• Not FDA-approved. Compounded medicines are not FDA-approved. The FDA does not review them for safety, effectiveness or quality before they are dispensed.
• How it is regulated. Pharmacies that compound for individual patients operate under section 503A of federal law and are overseen by state pharmacy boards. They use ingredients that are found in FDA-approved medicines.
• Not interchangeable with approved products. A compounded combination should not be described as equivalent to an approved tadalafil tablet. It is a different preparation with a different evidence base.

FDA's position is that compounded medicines are appropriate when an approved product does not meet a particular patient's needs, which is a judgment the prescribing physician makes.

Why a dissolvable tablet

The tablet is designed to dissolve in the mouth. There is a clear reason for this with apomorphine: when swallowed, most of it is broken down by the liver before it reaches the bloodstream, so less than 4% becomes available. Absorption through the lining of the mouth avoids much of that loss, which is why the apomorphine products studied for ED were tablets that dissolve under the tongue.

The same rationale does not carry over to tadalafil. It is well absorbed when swallowed, and we found no evidence that it is absorbed faster or more completely through the lining of the mouth. Any tadalafil that is swallowed is simply absorbed in the usual way. So the dissolvable format mainly reflects how apomorphine needs to be given. It is not a reason to expect faster results.

Follow the directions on your prescription label for how and when to take it, and ask your care team if anything is unclear.

Safety with both ingredients together

Each medicine has its own cautions, and some overlap:

• Nitrates and poppers are off limits. Tadalafil must never be combined with nitrate medicines such as nitroglycerin, or with recreational nitrites. Apomorphine adds to the blood-pressure drop from nitrates as well. If you ever have chest pain, tell emergency staff about this medicine, because nitrates should be avoided for at least 48 hours after a tadalafil dose.
• Blood pressure. Both ingredients can lower blood pressure. That matters if you take blood pressure medicines or alpha-blockers for prostate symptoms, or if you tend to feel faint when you stand up.
• Alcohol. Heavy drinking adds to the blood-pressure effect of both medicines and makes dizziness or fainting more likely. Keep alcohol moderate.
• Certain anti-nausea medicines. Ondansetron, granisetron and related 5-HT3 antagonists are contraindicated with apomorphine because the combination has caused severe drops in blood pressure and loss of consciousness. Tell any doctor or pharmacist who offers you an anti-nausea medicine that you take apomorphine.
• Heart health. Sexual activity is physical exertion. Men with recent heart attack or stroke, unstable angina or uncontrolled blood pressure may not be suitable for ED medicines until a doctor has assessed them.

The details are in our ED medication safety guide, and our side effects guide explains what is common and what is not.

Signs that need emergency care

Call emergency services or go to an emergency department if you have chest pain, faint and do not come to quickly, have an erection lasting more than four hours, or notice sudden loss of vision or hearing.

The physician's role

Whether a combination like this is suitable is a medical decision. A licensed physician reviews your medical history, heart health, blood pressure and current medicines, including any anti-nausea medicines or nitrates, before deciding whether to prescribe it. If it is not appropriate for you, the physician may suggest other options or recommend an in-person assessment.

The honest summary is that the combination rests on a sound idea, two ingredients with their own evidence at studied doses, and no trial yet of this pairing at these doses. That is worth knowing before you start, and worth discussing with the physician who reviews your case.

Sources

1. Tadalafil US prescribing information, DailyMed
2. Guillén V, et al. Apomorphine for the treatment of erectile dysfunction: systematic review and meta-analysis. Arch Sex Behav 2020
3. Is a sildenafil and apomorphine sublingual combination more effective than sublingual sildenafil? Value Health 2012 (abstract)
4. Potentiation of apomorphine effect on sildenafil-induced penile erection in rabbits (2004)
5. FDA. Compounding and the FDA: questions and answers
6. Tadalafil orodispersible films: bioequivalence in fed and fasted states. Pharmaceutics 2024
7. Apomorphine sublingual film prescribing information, FDA (2020)

Related reading

• How tadalafil works: the blood-flow ingredient, its long half-life and the once-daily trials.
• Apomorphine for erectile dysfunction: the central ingredient, its trials and its regulatory history.
• ED medication safety: nitrates, heart conditions and interactions in full.
• Side effects of ED medicines: what is common, what is rare and when to get help.
• Erectile dysfunction overview: causes, treatment approaches and when to see a doctor.

This article is for education only and is not a substitute for professional medical advice. Do not start, stop or change a medication without speaking to a licensed clinician. If you have chest pain, an erection lasting more than four hours, or sudden loss of vision or hearing, seek emergency care.