Sildenafil and amlodipine are frequently prescribed medications that can be taken together, but their combined use requires careful consideration due to a recognised pharmacodynamic interaction. Both drugs cause blood vessel relaxation through different mechanisms—sildenafil by inhibiting phosphodiesterase type 5 (PDE5) and amlodipine by blocking calcium channels. When used concurrently, their vasodilatory effects are additive, potentially leading to greater blood pressure reduction than either medication alone. Whilst this interaction is classified as moderate rather than severe and does not constitute an absolute contraindication, understanding how these medications interact is essential for safe and effective treatment. This article examines the nature of the sildenafil-amlodipine interaction, its clinical implications, and practical guidance for patients taking both medications.

Understanding Sildenafil and Amlodipine

Sildenafil and amlodipine are two commonly prescribed medications that work on different aspects of cardiovascular function, yet share overlapping effects on blood vessels. Understanding how each medication works is essential for recognising why their combined use requires careful consideration.

Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor primarily prescribed for erectile dysfunction and, as a separate formulation (Revatio), for pulmonary arterial hypertension at a dose of 20 mg three times daily. It works by inhibiting the enzyme PDE5, which leads to increased levels of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. This biochemical cascade causes relaxation of vascular smooth muscle, particularly in the corpus cavernosum of the penis, facilitating increased blood flow. The medication typically begins working within 30–60 minutes (though high-fat meals can delay onset) and its effects can last for approximately four hours. For erectile dysfunction, sildenafil should not be taken more than once daily. Common side effects include headache, facial flushing, nasal congestion, and indigestion, with visual disturbances being less common.

Amlodipine belongs to the calcium channel blocker class of antihypertensive medications. It works by blocking calcium ions from entering vascular smooth muscle cells and cardiac muscle cells through L-type calcium channels. This action causes relaxation of arterial smooth muscle, leading to vasodilation and reduced peripheral vascular resistance. Amlodipine is primarily prescribed for hypertension and angina pectoris. It has a long half-life of 30–50 hours, allowing once-daily dosing. Common adverse effects include peripheral oedema (ankle swelling), headache, dizziness, and flushing.

Both medications ultimately cause blood vessel relaxation through different mechanisms, which is the fundamental reason why their interaction warrants clinical attention and appropriate management by healthcare professionals. Sildenafil is contraindicated in patients with severe hypotension (blood pressure below 90/50 mmHg), in those taking nitrates or nitric oxide donors (including 'poppers'/amyl nitrite), and in patients taking riociguat.

Does Sildenafil Interact with Amlodipine?

Yes, sildenafil does interact with amlodipine, and this interaction is pharmacodynamic in nature—meaning both drugs produce similar effects on the cardiovascular system that can be additive when taken together. The British National Formulary (BNF) recognises this interaction, classifying it as moderate rather than severe.

The primary concern centres on the additive vasodilatory effects of both medications. When sildenafil and amlodipine are taken concurrently, the combined relaxation of blood vessels can lead to a more pronounced reduction in blood pressure than either medication would produce alone. This additive effect occurs because both drugs, despite their different mechanisms of action, ultimately result in smooth muscle relaxation within arterial walls.

Clinical studies, as documented in the sildenafil (Viagra) Summary of Product Characteristics, have demonstrated that co-administration of sildenafil with amlodipine can result in additional blood pressure lowering. Research has shown mean additional reductions in systolic blood pressure of approximately 8 mmHg and diastolic pressure reductions of around 7 mmHg when sildenafil is added to stable amlodipine therapy. Whilst these reductions are generally well-tolerated in most patients, they can occasionally cause symptomatic hypotension.

It is important to note that this interaction does not constitute an absolute contraindication. Many patients safely take both medications together under appropriate medical supervision. The interaction is predictable and manageable, but requires awareness from both prescribers and patients. The key consideration is whether the patient can tolerate the additional blood pressure lowering effect without experiencing problematic symptoms such as dizziness, light-headedness, or fainting.

Particular caution is needed when sildenafil is used alongside alpha-blockers (such as doxazosin), as this combination further increases the risk of symptomatic postural hypotension. Patients should be stable on alpha-blocker therapy before starting sildenafil, which should be initiated at the lowest dose (25 mg).

How This Interaction Affects Blood Pressure

The combined blood pressure-lowering effect of sildenafil and amlodipine occurs through complementary mechanisms that affect different points in the vascular regulation pathway. Understanding these mechanisms helps explain why some patients experience more pronounced effects than others.

Amlodipine's sustained effect on blood pressure is continuous throughout the day due to its long half-life. It maintains steady vasodilation by persistently blocking calcium channels in arterial smooth muscle. This creates a baseline level of reduced vascular resistance that is present regardless of the time of day.

Sildenafil's acute effect is more time-limited and pronounced. When taken, it rapidly increases cGMP levels, causing additional vasodilation that peaks within 1–2 hours of administration. Taking sildenafil with a high-fat meal can delay this peak effect. During this peak period, the combined vasodilatory effect is at its maximum. Patients are most likely to experience symptomatic blood pressure reduction during this window, particularly if they move from sitting to standing (orthostatic hypotension).

The clinical manifestations of this interaction vary considerably between individuals. Factors influencing the degree of blood pressure reduction include:

• Baseline blood pressure: Patients with well-controlled or lower blood pressure may be more susceptible to symptomatic hypotension

• Dose of both medications: Higher doses of either drug increase the likelihood of significant interaction

• Age: Older patients may have reduced baroreceptor sensitivity and be less able to compensate for blood pressure drops

• Hydration status: Dehydration can exacerbate hypotensive effects

• Concurrent medications: Other antihypertensives, alpha-blockers, or vasodilators can compound the effect

Most patients experience mild effects such as slight dizziness or light-headedness, which resolve as the body's compensatory mechanisms engage. However, in susceptible individuals, more significant hypotension can occur, potentially leading to falls or syncope.

Safety Guidance When Taking Both Medications

If you have been prescribed both sildenafil and amlodipine, there are several important safety measures to follow to minimise the risk of problematic blood pressure reduction whilst maintaining the therapeutic benefits of both medications.

Before taking sildenafil for the first time whilst on amlodipine, ensure your prescriber is aware of all your current medications. Your doctor should assess your baseline blood pressure and cardiovascular status to determine whether the combination is appropriate for you. Sildenafil is contraindicated in patients with severe hypotension (blood pressure below 90/50 mmHg).

Dosing considerations are particularly important. Your doctor may recommend:

• Starting with a lower dose of sildenafil (25 mg rather than 50 mg) to assess tolerance

• Taking sildenafil at times when you can rest if needed, avoiding situations requiring alertness immediately after dosing

• Maintaining consistent timing of amlodipine to predict when the combined effect will be greatest

• Not taking sildenafil more than once daily for erectile dysfunction

Practical safety measures include:

• Avoid sudden position changes: Rise slowly from sitting or lying positions, particularly within 2–3 hours of taking sildenafil

• Stay well-hydrated: Dehydration can worsen hypotensive effects

• Limit alcohol consumption: Alcohol is also a vasodilator and can compound blood pressure reduction

• Avoid hot environments: Saunas, hot baths, or very hot weather can enhance vasodilation

• Monitor for symptoms: Be alert to dizziness, light-headedness, blurred vision, or feeling faint

• Avoid grapefruit juice: This can increase sildenafil levels by inhibiting its metabolism

Do not adjust doses independently. If you experience troublesome side effects, contact your GP or prescriber rather than stopping or changing doses on your own. Both medications require careful dose management, and abrupt changes can have unintended consequences.

Patients should also be aware that sildenafil should never be taken with nitrate medications (such as glyceryl trinitrate for angina), nitric oxide donors (including 'poppers'/amyl nitrite), or riociguat, as these combinations can cause severe, potentially life-threatening hypotension. These are separate and more serious interactions than that with amlodipine. Caution is also needed with certain antibiotics and antifungals (e.g., erythromycin, clarithromycin, itraconazole) that can increase sildenafil levels.

When to Seek Medical Advice

Whilst most patients tolerate the combination of sildenafil and amlodipine without serious problems, certain symptoms warrant prompt medical attention. Knowing when to seek help is an essential aspect of safe medication use.

Seek immediate medical attention (call 999 or attend A&E) if you experience:

• Severe dizziness or fainting, particularly if accompanied by chest pain or difficulty breathing

• Chest pain or pressure that does not resolve quickly, especially if radiating to the arm, jaw, or back

• Prolonged erection (priapism) lasting more than four hours—this is a medical emergency requiring urgent treatment to prevent permanent damage

• Sudden vision loss or significant visual disturbances

• Symptoms of stroke, such as facial drooping, arm weakness, or speech difficulties

• Signs of severe allergic reaction such as swelling of the face, lips, tongue or throat, or difficulty breathing

• Blood pressure below 90/50 mmHg with symptoms such as confusion, weakness, or pale, clammy skin

Contact your GP or NHS 111 within 24 hours if you experience:

• Persistent dizziness or light-headedness that interferes with daily activities

• Recurrent episodes of feeling faint when standing

• Severe headaches that are unusual for you

• Significant ankle swelling that worsens or becomes uncomfortable

• Palpitations or irregular heartbeat

• Any side effects that concern you or affect your quality of life

Schedule a routine appointment with your GP if:

• You feel the current dose of either medication is not providing adequate benefit

• You wish to discuss alternative treatment options

• You are planning to start any new medications or supplements

• Your blood pressure readings at home are consistently low (systolic <100 mmHg)

Before taking sildenafil, ensure you have discussed your complete medical history with your prescriber, including any history of cardiovascular disease, stroke, liver or kidney impairment, or retinal disorders. Regular medication reviews, typically annually or when circumstances change, help ensure that your treatment remains appropriate and safe. Your pharmacist is also an excellent resource for advice about medication interactions and can provide guidance on the safe use of both sildenafil and amlodipine.

If you experience any suspected adverse reactions to either medication, you can report them through the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

Frequently Asked Questions