Sildenafil (Viagra) and nitrates must never be taken together due to the risk of severe, life-threatening hypotension. This absolute contraindication exists because both medications affect blood vessel dilation through complementary mechanisms. Nitrates increase cyclic guanosine monophosphate (cGMP) production, whilst sildenafil prevents its breakdown, leading to excessive accumulation. The result is profound vasodilation and dangerously low blood pressure that can cause syncope, myocardial ischaemia, or inadequate organ perfusion. UK regulatory guidance from the MHRA and BNF strictly prohibits this combination, with nitrates contraindicated for at least 24 hours after sildenafil use.

Why Sildenafil and Nitrates Cannot Be Taken Together

Sildenafil, commonly known by the brand name Viagra, is a phosphodiesterase type 5 (PDE5) inhibitor used primarily to treat erectile dysfunction and pulmonary arterial hypertension. Nitrates are medications prescribed for angina (chest pain) and certain heart conditions. The concurrent use of sildenafil and nitrates is absolutely contraindicated due to the risk of severe, potentially life-threatening hypotension (dangerously low blood pressure).

The mechanism underlying this contraindication relates to how both drug classes affect vascular smooth muscle. Nitrates work by releasing nitric oxide, which activates the enzyme guanylate cyclase, leading to increased levels of cyclic guanosine monophosphate (cGMP). This causes blood vessels to dilate, reducing the workload on the heart. Sildenafil works by inhibiting PDE5, the enzyme responsible for breaking down cGMP. When sildenafil is present, cGMP levels remain elevated for longer periods, prolonging vasodilation.

When these two medications are combined, their effects are synergistic and marked. The nitrate increases cGMP production whilst sildenafil prevents its breakdown, resulting in excessive accumulation of cGMP. This leads to profound and sustained vasodilation throughout the body, causing blood pressure to drop precipitously. This hypotensive crisis can result in inadequate blood flow to vital organs, potentially causing syncope, myocardial ischaemia or infarction.

The Medicines and Healthcare products Regulatory Agency (MHRA) and the British National Formulary (BNF) clearly state this absolute contraindication. Nitrates must not be used within at least 24 hours of taking sildenafil. This contraindication also applies to other nitric oxide donors such as nicorandil and amyl nitrite ('poppers'). Healthcare professionals must screen all patients for nitrate use before prescribing sildenafil, and patients must inform emergency services of sildenafil use if presenting with chest pain, as this affects treatment options.

Risks of Combining Sildenafil with Nitrate Medications

The primary risk of combining sildenafil with nitrates is severe hypotension, which can manifest rapidly. Blood pressure may fall to dangerously low levels within minutes to hours of taking both medications, even if they are not taken simultaneously. Clinical studies have demonstrated significant blood pressure reductions when these drugs are combined.

Symptoms of this hypotensive reaction include:

• Dizziness and light-headedness, particularly when standing

• Fainting or syncope, which may result in falls and injury

• Severe headache due to cerebral vasodilation

• Rapid or irregular heartbeat (tachycardia) as the body attempts to compensate

• Chest pain or discomfort

• Blurred vision from reduced ocular perfusion

• Confusion or altered consciousness from cerebral hypoperfusion

The duration of risk extends beyond the immediate period after taking sildenafil. The drug has a half-life of approximately 4 hours, but its effects on the cardiovascular system can persist for up to 24 hours. This means that nitrates must not be used within at least 24 hours of taking sildenafil. Conversely, patients who regularly take nitrates must avoid sildenafil entirely.

In emergency situations, this contraindication creates a clinical dilemma. Patients experiencing acute coronary syndrome who have recently used sildenafil cannot safely receive nitrate therapy, which is an important option for symptom relief in angina. This may necessitate alternative management strategies.

If you experience chest pain after taking sildenafil:

• Call 999 immediately

• Do not take GTN spray or tablets within 24 hours of sildenafil use

• Inform the emergency services that you have taken sildenafil and when you took it

• Show them your medications if possible

Common Nitrate Medications to Avoid with Sildenafil

Patients prescribed sildenafil must be aware of all nitrate formulations, as the contraindication applies universally across different preparations and routes of administration. Glyceryl trinitrate (GTN) is perhaps the most commonly encountered nitrate, available in several forms:

• Sublingual tablets or spray used for acute angina relief

• Transdermal patches providing sustained nitrate delivery

• Modified-release tablets for angina prophylaxis

• Intravenous preparations used in hospital settings for acute coronary syndromes

Isosorbide mononitrate is another widely prescribed nitrate for angina prevention, typically given as 10–60 mg once or twice daily in standard or modified-release formulations. Isosorbide dinitrate serves a similar purpose and is equally contraindicated with sildenafil.

Nicorandil, a potassium channel activator with nitric oxide donor properties, is also contraindicated with sildenafil. Amyl nitrite and related alkyl nitrites, sometimes used recreationally as 'poppers', carry the same risks and must be strictly avoided. Some patients may not recognise these substances as nitrates, making education particularly important.

It is crucial to understand that this contraindication applies regardless of:

• The dose of either medication

• The formulation or route of administration

• Whether nitrate use is regular or occasional (e.g., PRN for angina)

• The timing - nitrates must not be used within at least 24 hours of taking sildenafil

Patients should carry a list of their medications and inform all healthcare providers, including emergency services, about sildenafil use. Pharmacists play a vital role in screening for potential interactions when dispensing either medication. The BNF and electronic prescribing systems flag this interaction, but patient awareness remains the ultimate safeguard against accidental co-administration.

Safe Alternatives for Erectile Dysfunction with Heart Conditions

Men with cardiovascular disease who require nitrate therapy are not without options for managing erectile dysfunction, though choices require careful consideration and specialist input. The first step involves comprehensive cardiovascular risk assessment by a GP or cardiologist to determine whether sexual activity itself is safe, as this represents moderate physical exertion equivalent to climbing two flights of stairs.

For patients whose cardiac condition is stable and well-controlled but who require nitrates, non-pharmacological approaches should be explored first:

• Vacuum erection devices (VEDs) are mechanical aids that create an erection through negative pressure, with a constriction ring maintaining tumescence. These may be available on NHS prescription depending on local commissioning and individual eligibility.

• Lifestyle modifications including smoking cessation, weight management, increased physical activity (as tolerated), and moderation of alcohol intake can improve erectile function.

• Psychological interventions such as psychosexual counselling or cognitive behavioural therapy may address anxiety or relationship factors contributing to erectile dysfunction.

When pharmacological treatment is appropriate, alternative PDE5 inhibitors are equally contraindicated with nitrates. Tadalafil (Cialis), vardenafil (Levitra), and avanafil (Spedra) all share the same mechanism of action and carry identical contraindications. There is no 'safer' PDE5 inhibitor for use with nitrates. PDE5 inhibitors must also not be used with riociguat (a soluble guanylate cyclase stimulator).

For carefully selected patients, intracavernosal or intraurethral alprostadil (prostaglandin E1) may be considered. These preparations work through a different mechanism—directly relaxing smooth muscle—and do not interact with nitrates. Alprostadil is available as:

• Caverject or Viridal injections administered directly into the corpus cavernosum

• MUSE intraurethral pellets inserted into the urethra

These options require proper training and carry their own risks, including priapism (prolonged erection) and local discomfort. If an erection lasts longer than 4 hours, this requires urgent medical attention at A&E. NICE guidance suggests these as second-line treatments when PDE5 inhibitors are contraindicated or ineffective.

Specialist referral to a cardiologist or urologist is strongly recommended for men with cardiac disease seeking erectile dysfunction treatment. In some cases, optimising cardiac management may allow discontinuation of nitrates, potentially permitting future PDE5 inhibitor use. However, this decision must never be made by patients independently—stopping nitrates without medical supervision could precipitate dangerous cardiac events.

If you experience any suspected side effects from medications, report them through the MHRA Yellow Card scheme.

Frequently Asked Questions