What are the contraindications for Viagra (sildenafil) in patients, particularly older adults, with a history of myocardial infarction, stroke, or life-threatening arrhythmias, and those with impaired renal function or severe hepatic impairment?

Contraindications to Viagra (Sildenafil)

The absolute contraindication to Viagra is concurrent use with any form of organic nitrate therapy, as this combination causes life-threatening hypotension through synergistic potentiation of the NO-cGMP vasodilation pathway. 1, 2

Absolute Contraindications

• Nitrate therapy in any form (sublingual, oral, transdermal, topical ointments) is an absolute contraindication due to risk of profound hypotension, myocardial infarction, and death 3, 2, 1
• Patients must wait at least 24 hours after taking sildenafil before any nitrate can be safely administered 3, 2
• This is a Class III (Harm) recommendation by the ACC/AHA, meaning the intervention should never be performed 2, 4
• Known hypersensitivity to sildenafil or any tablet component, including anaphylactic reactions 1

Critical Drug Interactions Requiring Extreme Caution

• Tadalafil (Cialis) requires a 48-hour waiting period before nitrates can be given due to its longer half-life 3, 5, 4
• Alpha-blockers may cause symptomatic hypotension when combined with sildenafil; patients should be stable on alpha-blocker therapy before initiating sildenafil at the lowest dose 6
• Amlodipine causes an additional mean reduction of 8/7 mm Hg in blood pressure when combined with sildenafil 6
• Mixed alpha/beta blockers (carvedilol, labetalol) should be approached with similar caution as pure alpha-blockers 6

High-Risk Cardiovascular Conditions

• Active coronary ischemia with unstable angina requires extreme caution, as these patients often need nitrate therapy which would be contraindicated 7, 8
• Heart failure with tenuous blood pressure and volume status, particularly in fluid-depleted elderly patients who are predisposed to profound hypotension 2, 7
• Recent myocardial infarction, stroke, or life-threatening arrhythmias (within 6 months) - safety has not been established in these patients 6
• Uncontrolled hypertension or hypotension - safety data are insufficient 6

Special Populations Requiring Dose Adjustment

• Severe renal impairment (CrCl <30 mL/min) results in doubling of AUC and Cmax, with N-desmethyl metabolite levels increased by 200% 1
• Severe hepatic impairment (Child-Pugh class C) has not been studied; moderate impairment (Child-Pugh A/B) increases AUC by 84% and Cmax by 47% 1
• Elderly patients (≥65 years) have 84-107% higher plasma concentrations due to reduced clearance 1

Pre-Treatment Risk Stratification

• Patients with known or suspected coronary artery disease should undergo exercise stress testing to determine if they can safely achieve 3-5 metabolic equivalents without ischemia before prescribing sildenafil 2, 8
• This assessment determines whether the metabolic demands of sexual activity pose an increased risk of myocardial ischemia 8

Common Pitfalls to Avoid

• Never assume topical nitrates (like Nitro-BID ointment) are safer - all nitrate formulations carry the same absolute contraindication 5
• Always ask patients presenting with chest pain about recent PDE5 inhibitor use before administering nitroglycerin 5
• Do not assume that antihypertensive medications contraindicate sildenafil - the combination causes additive (not potentiating) blood pressure decreases that are generally well-tolerated 9, 6, 10
• Retinitis pigmentosa is listed as a condition where safety has not been established 6

Medications That Increase Sildenafil Exposure

• Potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) substantially increase sildenafil levels 1
• Mild/moderate CYP3A inhibitors reduce sildenafil clearance by approximately 30% 1
• Erythromycin and cimetidine may prolong sildenafil's half-life 8
• CYP3A4 inducers (like bosentan) cause a 3-fold increase in sildenafil clearance, substantially decreasing plasma levels 1