What are the contraindications for sildenafil (Viagra) in patients with cardiovascular disease, hypersensitivity, or other medical conditions?

Contraindications for Sildenafil

Sildenafil is absolutely contraindicated in patients taking any form of organic nitrates and in those with known hypersensitivity to the drug. 1

Absolute Contraindications

Concomitant Nitrate Use

• Any form of organic nitrate therapy (regular or intermittent) is an absolute contraindication to sildenafil use due to the risk of life-threatening hypotension. 2, 1
• The combination of sildenafil and nitrates synergistically potentiates vasodilation through the NO-cGMP pathway, causing profound and potentially fatal hypotension. 2, 3
• Patients must wait at least 24 hours after taking sildenafil (or vardenafil) before any nitrate can be safely administered. 2
• For tadalafil, the waiting period extends to 48 hours due to its longer half-life of 17.5 hours. 2, 4, 5
• This is a Class III (Harm) recommendation by the American Heart Association/American College of Cardiology, meaning the intervention should not be performed. 2, 5

Hypersensitivity

• Known hypersensitivity to sildenafil or any tablet component is an absolute contraindication. 1
• Hypersensitivity reactions including anaphylaxis, anaphylactic shock, and anaphylactoid reactions have been reported. 1

High-Risk Conditions Requiring Extreme Caution

Hemodynamically Unstable Cardiovascular Conditions

• Resting hypotension (BP <90/50 mmHg) represents a significant risk due to sildenafil's vasodilatory properties causing additional blood pressure reductions of approximately 10/7 mmHg. 1, 3
• Severe left ventricular outflow obstruction increases risk of adverse hemodynamic effects. 1
• Fluid depletion predisposes to profound hypotension, particularly in elderly patients. 2, 1
• Autonomic dysfunction impairs compensatory mechanisms for blood pressure regulation. 1

Recent Acute Coronary Events

• Sildenafil should be used with extreme caution in patients with recent (within 6 months) myocardial infarction, unstable angina, or life-threatening arrhythmias, as safety data in these populations are lacking. 6
• Sexual activity itself carries a small but finite risk of precipitating ischemia or infarction in unstable cardiac patients. 6, 7

Decompensated Heart Failure

• Patients with heart failure and tenuous blood pressure or volume status should not receive sildenafil due to risk of hemodynamic decompensation. 7
• While sildenafil may provide hemodynamic benefits in stable heart failure patients, it should not be given to those taking nitrates, which eliminates many symptomatic patients from consideration. 2

Special Populations and Conditions

Pulmonary Veno-Occlusive Disease (PVOD)

• Sildenafil administration is not recommended in patients with PVOD, as pulmonary vasodilators may significantly worsen cardiovascular status. 1
• If pulmonary edema develops during sildenafil therapy, consider the possibility of underlying PVOD. 1

Pediatric Patients

• Chronic use of sildenafil is not recommended in children due to increased mortality observed with increasing doses in long-term trials of pediatric pulmonary arterial hypertension. 1

Bleeding Disorders

• Safety is unknown in patients with active peptic ulceration or bleeding disorders. 1
• Epistaxis incidence was 13% in patients with pulmonary arterial hypertension secondary to connective tissue disease, and 9% in those on concomitant vitamin K antagonists. 1

Retinal Conditions

• Use with caution in patients with retinitis pigmentosa, particularly those with genetic disorders of retinal phosphodiesterases. 1
• Risk of non-arteritic anterior ischemic optic neuropathy (NAION) exists, particularly in patients with anatomic risk factors (crowded disc, age >50) or vascular risk factors (diabetes, hypertension, coronary disease, hyperlipidemia, smoking). 1

Drug Interactions Beyond Nitrates

CYP3A4 Inhibitors

• Medications that inhibit cytochrome P450 CYP3A4 (erythromycin, cimetidine) can increase systemic sildenafil exposure and prolong its half-life, requiring dose adjustment. 8, 6

Antihypertensive Medications

• While sildenafil can be used with standard antihypertensive agents (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium antagonists), blood pressure should be monitored as additive (not synergistic) effects may occur. 1, 3, 9
• The combination produces additive but not potentiating blood pressure decreases, unlike the synergistic effect seen with nitrates. 9

Clinical Decision Algorithm

Before prescribing sildenafil:

1. Verify the patient is not taking any form of nitrate therapy (short-acting, long-acting, or intermittent). 2, 1
2. Assess hemodynamic stability: Check resting blood pressure (must be ≥90/50 mmHg) and volume status. 1
3. Evaluate cardiac stability: Ensure no recent (<6 months) MI, unstable angina, or decompensated heart failure. 6
4. Screen for hypersensitivity history to sildenafil or related compounds. 1
5. Consider exercise stress testing in patients with known or suspected coronary disease to determine if they can safely achieve 3-5 metabolic equivalents without ischemia. 2, 8