Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor licensed in the UK for erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension. Understanding whether tadalafil functions as a vasodilator is crucial for safe prescribing and managing potential drug interactions. This article examines tadalafil's mechanism of action, its vasodilatory properties, clinical applications aligned with NICE and MHRA guidance, and essential safety considerations. Healthcare professionals and patients will gain clarity on how tadalafil affects blood vessels and the implications for cardiovascular health and concurrent medication use.

What Is Tadalafil and How Does It Work?

Tadalafil is a prescription medication belonging to a class of drugs known as phosphodiesterase type 5 (PDE5) inhibitors. It is licensed in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) and is available under various brand names, including Cialis for erectile dysfunction and Adcirca for pulmonary arterial hypertension.

The primary mechanism of action involves the selective inhibition of the PDE5 enzyme, which is highly expressed in the corpus cavernosum of the penis and pulmonary vasculature. Under normal physiological conditions, sexual stimulation triggers the release of nitric oxide (NO) in the corpus cavernosum of the penis. Nitric oxide activates the enzyme guanylate cyclase, leading to increased levels of cyclic guanosine monophosphate (cGMP). This second messenger causes smooth muscle relaxation and increased blood flow to the penile tissues, facilitating an erection.

PDE5 normally breaks down cGMP, thereby limiting the duration and intensity of the erectile response. By inhibiting PDE5, tadalafil allows cGMP to accumulate, prolonging smooth muscle relaxation and enhancing blood flow. Importantly, tadalafil requires sexual stimulation to be effective — it does not cause spontaneous erections in the absence of appropriate physiological triggers.

Tadalafil is distinguished from other PDE5 inhibitors by its extended half-life of approximately 17.5 hours, which allows for a longer duration of action (up to 36 hours). This pharmacokinetic profile permits both on-demand and daily low-dose dosing regimens. The medication is absorbed relatively quickly, with peak plasma concentrations reached within 2 hours, and can be taken with or without food, as food does not have a clinically significant effect on its absorption.

Clinical Uses of Tadalafil in the UK

In the United Kingdom, tadalafil is licensed for several distinct clinical indications, each with specific dosing recommendations aligned with NICE guidance and MHRA approval.

Erectile Dysfunction (ED)

Tadalafil is widely prescribed for the treatment of erectile dysfunction in adult men. NICE Clinical Knowledge Summaries recommend PDE5 inhibitors as first-line pharmacological treatment following appropriate assessment and exclusion of underlying causes. The medication is available in two dosing strategies:

• On-demand dosing: 10 mg taken prior to anticipated sexual activity (may be increased to 20 mg or decreased to 5 mg based on efficacy and tolerability)

• Daily dosing: 5 mg taken once daily (may be reduced to 2.5 mg if not tolerated), regardless of timing of sexual activity

The daily regimen may be particularly suitable for men who anticipate sexual activity more than twice weekly or who prefer spontaneity without planning medication timing.

Benign Prostatic Hyperplasia (BPH)

Tadalafil 5 mg once daily is licensed for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. It is used as monotherapy; co-administration with alpha-blockers specifically for BPH is not recommended in the UK due to potential hypotension risk and limited efficacy data. If a patient is already stable on an alpha-blocker for another indication, tadalafil should be initiated at the lowest dose with blood pressure monitoring.

Pulmonary Arterial Hypertension (PAH)

Under the brand name Adcirca, tadalafil is indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) to improve exercise capacity. The typical dose is 40 mg once daily, and treatment is usually initiated and monitored by specialists in pulmonary hypertension centres.

Prescribing Considerations

In England, tadalafil for erectile dysfunction is not routinely available on NHS prescription except in specific circumstances outlined in the NHS Drug Tariff, including cases where ED results from specified medical conditions such as diabetes, prostate cancer treatment, or severe pelvic injury. These Selected List Scheme (SLS) restrictions may vary across UK nations. Many patients obtain tadalafil through private prescription or online regulated pharmacies.

Safety Considerations and Contraindications

Tadalafil is generally well-tolerated, but healthcare professionals must carefully assess patients before prescribing, considering both contraindications and situations requiring caution.

Contraindications

• Concurrent nitrate use: Tadalafil is absolutely contraindicated in patients taking any form of nitrate medication (including glyceryl trinitrate, isosorbide mononitrate, or recreational "poppers" containing alkyl nitrites). The combination can cause severe, potentially life-threatening hypotension. Nitrates must be avoided for at least 48 hours after the last dose of tadalafil.

• Guanylate cyclase stimulators: Concomitant use with riociguat is contraindicated due to risk of symptomatic hypotension.

• Recent cardiovascular events: Patients who have experienced myocardial infarction within the past 90 days, stroke within the past 6 months, serious arrhythmia within the last 6 months, or heart failure (NYHA class II or greater) within the last 6 months should not use tadalafil.

• Cardiovascular conditions: Including uncontrolled hypertension, hypotension (<90/50 mmHg), or unstable angina, especially angina occurring during sexual activity.

• Prior non-arteritic anterior ischaemic optic neuropathy (NAION): History of vision loss in one eye due to NAION.

• Severe hepatic impairment (Child-Pugh Class C)

• Hypersensitivity to tadalafil or any excipients

Cautions

• Hereditary degenerative retinal disorders, including retinitis pigmentosa

• Renal impairment: In moderate renal impairment, dose reduction may be needed; once-daily dosing is not recommended in severe renal impairment for ED

• Alpha-blockers: Avoid combination with doxazosin; for other alpha-blockers, ensure patient is stable on alpha-blocker therapy before initiating tadalafil, start with lowest dose, and monitor blood pressure

Common Adverse Effects

Patients should be counselled about potential side effects, which typically include:

• Headache (most common, affecting approximately 15% of users)

• Dyspepsia and gastro-oesophageal reflux

• Flushing

• Nasal congestion

• Back pain and myalgia (more common with tadalafil than other PDE5 inhibitors, possibly related to PDE11 inhibition)

• Visual disturbances (rare, but include changes in colour perception)

Serious Adverse Events Requiring Immediate Medical Attention

Patients must be advised to seek urgent medical care if they experience:

• Priapism: An erection lasting more than 4 hours requires emergency treatment to prevent permanent erectile tissue damage

• Sudden vision loss: May indicate non-arteritic anterior ischaemic optic neuropathy (NAION)

• Sudden hearing loss or tinnitus

• Chest pain during sexual activity

Drug Interactions

Beyond nitrates and riociguat, tadalafil interacts with potent CYP3A4 inhibitors (such as ritonavir, ketoconazole, and itraconazole), grapefruit juice, and other antihypertensive medications. Excessive alcohol consumption should be avoided due to increased risk of orthostatic hypotension. Patients should inform all healthcare providers about tadalafil use and report any suspected side effects via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

Is Tadalafil a Vasodilator?

Yes, tadalafil is classified as a vasodilator, though it is important to understand the specific mechanism and context of this vasodilatory action.

Tadalafil produces vasodilation through its inhibition of phosphodiesterase type 5, which leads to increased concentrations of cyclic GMP in vascular smooth muscle cells. This biochemical cascade results in smooth muscle relaxation and subsequent dilation of blood vessels. However, the vasodilatory effects of tadalafil are selective and tissue-specific rather than causing generalised systemic vasodilation.

Mechanism of Vasodilation

The vasodilatory properties of tadalafil are most pronounced in tissues with high PDE5 expression, including:

• Corpus cavernosum of the penis (primary site for erectile function)

• Pulmonary vasculature (basis for its use in pulmonary arterial hypertension)

• Systemic arterial smooth muscle (to a lesser extent, contributing to modest blood pressure reductions)

In the pulmonary circulation, tadalafil's vasodilatory action reduces pulmonary vascular resistance and pulmonary artery pressure, improving right ventricular function and exercise capacity in patients with PAH. This demonstrates that its vasodilatory effects extend beyond penile tissue.

Clinical Implications of Vasodilation

At recommended doses, tadalafil produces generally small and clinically insignificant reductions in systemic blood pressure in most patients. These changes are typically well-tolerated. However, in patients taking other vasodilators (particularly nitrates) or those with compromised cardiovascular reserve, the additive vasodilatory effects can lead to symptomatic hypotension, dizziness, or syncope.

Comparison with Other Vasodilators

While tadalafil is indeed a vasodilator, it differs from other vasodilatory medications in several important ways. Unlike direct-acting vasodilators such as hydralazine or calcium channel blockers, tadalafil's effects are dependent on the nitric oxide pathway and require endogenous NO production. This makes its action more physiologically regulated and less likely to cause reflex tachycardia or severe hypotension in most clinical scenarios.

Understanding tadalafil as a vasodilator is essential for safe prescribing, particularly when assessing cardiovascular risk and potential drug interactions. Healthcare professionals should always evaluate a patient's complete medication list and cardiovascular status before initiating treatment.

Frequently Asked Questions