Tadalafil: what it is, how it works and what the evidence says

Tadalafil is, along with sildenafil, one of the most searched-for and worst-explained medicines in men's sexual health. Contradictory ideas circulate around it: that it is an aphrodisiac, that it helps you perform better in the gym, that you can buy it over the counter, that it makes no difference whether you take it with or without food. The reality is at once more boring and more interesting: it is a drug with a very specific mechanism, tightly defined authorised indications and a set of contraindications worth knowing before anything else. Here we explain what it is, what the Summary of Product Characteristics approved by the EMA and the AEMPS says, and what the European and American clinical guidelines actually support.

What it actually is and how it works

An erection is a vascular event. With sexual stimulation, nitric oxide is released in the erectile tissue of the penis, which triggers the production of cyclic GMP (cGMP), the molecule that relaxes the smooth muscle of the arteries and allows blood to flow in. The enzyme phosphodiesterase type 5 is responsible for breaking down that cGMP and returning things to baseline. Tadalafil is a selective, reversible inhibitor of that enzyme: it does not make cGMP, it simply slows its destruction.

From that follows the most important point, and the one most often misunderstood: without sexual stimulation there is no nitric oxide, without nitric oxide there is no cGMP, and without cGMP tadalafil has nothing to act on. The Summary of Product Characteristics states it explicitly: sexual stimulation is required. It is not a switch, it is an amplifier.

What it is authorised for in Spain

Cialis, the original tadalafil brand, holds a centralised authorisation from the European Medicines Agency, valid in Spain, for two indications in adult men: erectile dysfunction and the signs and symptoms of benign prostatic hyperplasia (BPH). The same Summary of Product Characteristics specifies that it is not indicated in women or in those under 18.

There is also a third route that tends to cause confusion: tadalafil 20 mg marketed as Adcirca and its generics is authorised for pulmonary arterial hypertension. It is a different indication, with a different brand and dosing, and with a different prescribing and reimbursement pathway. It is not the same product prescribed for erectile dysfunction, even though the active substance has the same name.

A note on the regimen

Tadalafil has an authorised low-dose daily regimen (2.5-5 mg) in addition to the classic on-demand regimen (10-20 mg), something the sildenafil Summary of Product Characteristics does not provide for. This does not mean one is better than the other, nor that anyone can simply choose: the regimen, the dose and its suitability depend on the individual case, on comorbidities and on concomitant medication, and that is exactly what a doctor assesses in consultation. We describe it here because it explains why tadalafil is perceived differently from other drugs in its family, not as a recommendation for use.

What the clinical guidelines say

The European Association of Urology (EAU) guidelines and the joint AUA/SMSNA guideline agree: PDE5 inhibitors are the first-line drug treatment for erectile dysfunction, with a strong recommendation based on multiple randomised controlled trials and meta-analyses. And they add a nuance worth underlining, because it dismantles much of the marketing: no PDE5 inhibitor has demonstrated clear superiority in efficacy over another. The differences between molecules lie in the pharmacokinetic profile, in the interaction with food and in the available regimens, not in one working and another not. If you want to compare it with the best-known molecule in the family, our guide on what sildenafil is and what the evidence says sets out the same framework.

There is another point in the European guidelines that rarely features in public conversation and that is probably the most relevant for long-term health: erectile dysfunction is a sentinel marker of cardiovascular disease and often precedes it by years. Erectile tissue has small-calibre arteries and suffers before the coronary arteries do. Translated: tadalafil treats the symptom, not the underlying cause. An erection that is starting to fail deserves a look at the whole picture (blood pressure, metabolism, sleep, smoking), not just a prescription. Conditions such as obstructive sleep apnoea or prediabetes are part of that map more often than people think.

In benign prostatic hyperplasia

The EAU guideline on non-neurogenic male lower urinary tract symptoms is fairly precise about the role of tadalafil in BPH: it improves symptoms, with no difference from alpha-blockers in the symptom score, but there are no data showing that it changes the progression of the disease, that is, that it prevents acute urinary retention or the need for surgery. That preventive benefit has only been demonstrated with 5-alpha-reductase inhibitors. It is an important distinction if someone expects the drug to change the course of the disease.

Contraindications and interactions: the non-negotiables

This is the part no article should bury at the end. Tadalafil is absolutely contraindicated alongside nitrates in any form (glyceryl trinitrate, isosorbide mononitrate) and alongside riociguat, because of the risk of severe hypotension. And one detail that is overlooked far too often: poppers, recreational amyl nitrite, are nitrates. The combination is dangerous, not a theoretical precaution.

• It requires caution or dose adjustment with alpha-blockers such as doxazosin and with potent CYP3A4 inhibitors such as ritonavir, ketoconazole or clarithromycin (Summary of Product Characteristics, section 4.5).
• It is contraindicated or not advised after a recent heart attack, in unstable angina, after a recent stroke, in hypotension, uncontrolled arrhythmia or unstable heart failure (Summary of Product Characteristics, sections 4.3 and 4.4).
• It is contraindicated in patients with a history of NAION, non-arteritic anterior ischaemic optic neuropathy, and must be stopped if there is sudden loss of vision. Sudden deafness and priapism lasting more than four hours are listed as warnings.
• The most common adverse reactions are headache, dyspepsia, back pain, myalgia, flushing and nasal congestion (Summary of Product Characteristics, section 4.8).

This list is for information only and does not replace reading the Summary of Product Characteristics or, above all, an assessment by a doctor who knows your medical history and your full medication list. That is precisely why tadalafil is a prescription-only medicine.

There is no over-the-counter version: the Spanish context

In Spain, tadalafil is a prescription-only medicine, and there is no PDE5 inhibitor dispensed without a prescription. This is a real difference from other countries: in the United Kingdom, sildenafil 50 mg is available without a prescription under pharmacist supervision. Not here. That is why any website offering tadalafil without a prescription is operating outside the law, and that is precisely the usual channel for counterfeit medicines: the AEMPS issues regular alerts about illegal products for erectile dysfunction, with compositions that do not match the label.

Myths worth dismantling

The first and most widespread: tadalafil does not act on libido. It is not an aphrodisiac and it does not produce an automatic erection without sexual stimulation. If the problem is desire rather than vascular mechanics, this drug does not address the cause; there it is worth looking elsewhere, including the hormonal axis, as we explain when discussing the real symptoms of low testosterone.

The second: it is not authorised for premature ejaculation or for female sexual dysfunction, and the available evidence in those uses is inconsistent or insufficient. The third: there are no trials supporting benefits in athletic performance, cardiovascular prevention, dementia prevention or cognitive enhancement. These are hypotheses born of observational or preclinical studies, and a hypothesis is not a result. The fourth, in the opposite direction: the association reported with melanoma or prostate cancer comes from observational studies with substantial confounding by sun exposure and socioeconomic status, and no causal relationship has been demonstrated.

In summary, and what you can do today

Tadalafil is an effective, well-characterised drug within a very specific territory: it amplifies a vascular response that needs stimulation to exist, it has two authorised indications in Spain and a list of contraindications that leaves no room for improvisation. What it is not: an aphrodisiac, a cognitive enhancer or something you buy without a prescription. And above all, difficulty with erections is usually a signal that deserves to be looked at in full, not simply covered up, and sometimes that look leads to the hormonal axis. For that part, what does exist in Spain today is male hormonal health treatment, with a prior assessment, a prescription from a registered doctor when appropriate and ongoing follow-up. If you think this may be your case, you can check whether you are eligible.