Which medications can cause hypotension when combined with sildenafil?

Medications That Cause Hypotension with Sildenafil

Nitrates and nicorandil are absolutely contraindicated with sildenafil due to the risk of profound, life-threatening hypotension, myocardial infarction, and death. 1, 2

Contraindicated Medications (Class III - Harm)

Organic Nitrates - ABSOLUTE CONTRAINDICATION

• All forms of nitrates are contraindicated with sildenafil, including:
  • Sublingual, oral, transdermal, or intravenous nitroglycerin 1
  • Isosorbide dinitrate and isosorbide mononitrate 2
  • Long-acting nitrate preparations 1
• Mechanism: Both drugs increase cGMP levels through different pathways, causing synergistic (not just additive) vasodilation that can result in profound systemic hypotension 1, 3, 4
• Critical timing requirements:
  • Patients must wait ≥24 hours after sildenafil (half-life ~4 hours) before taking any nitrate 1
  • For tadalafil, wait ≥48 hours due to its 17.5-hour half-life 1, 5
  • For vardenafil, the safe interval is not definitively established but blood pressure generally returns to baseline by 24 hours 1

Nicorandil - CONTRAINDICATED

• Nicorandil is contraindicated with sildenafil through the same cGMP mechanism as nitrates 1

Riociguat - CONTRAINDICATED

• Soluble guanylate cyclase stimulators (riociguat) are contraindicated due to hypotension risk 2

Medications Requiring Caution and Dose Adjustment

Alpha-Blockers - HIGH RISK

• Coadministration may lead to symptomatic hypotension in some individuals 6
• Management algorithm: 6
  • Patient must be stable on alpha-blocker therapy before initiating sildenafil
  • Start sildenafil at the lowest dose (25 mg)
  • Monitor for orthostatic hypotension and syncope
• Mixed alpha/beta blockers (carvedilol, labetalol) should be treated with the same caution as pure alpha-blockers 6

Calcium Channel Blockers - MODERATE RISK

• Amlodipine: Produces additive (not synergistic) blood pressure reductions 7, 6, 4
  • Mean additional reduction: 8 mmHg systolic and 7 mmHg diastolic 6, 4
  • Monitor for hypotension when coadministered 7
  • Does not require dose adjustment but requires clinical monitoring 4
• Other dihydropyridine CCBs: Similar additive effects expected 8

Other Antihypertensive Agents - LOW TO MODERATE RISK

• ACE inhibitors, ARBs, diuretics, and beta-blockers: Produce additive (not potentiating) blood pressure decreases 8, 3
• Clinical significance: Generally well-tolerated without increased adverse events 8, 3, 6
• Monitoring: Watch for excessive systemic hypotension, particularly in patients on multidrug antihypertensive regimens 1, 8

Drug Interactions Affecting Sildenafil Levels (Indirect Hypotension Risk)

CYP3A4 Inhibitors - Increase Sildenafil Levels

• HIV protease inhibitors (ritonavir, saquinavir): Markedly increase sildenafil levels, requiring dose adjustments 1
• Ketoconazole: Increases sildenafil levels; may not require dose adjustment for short courses 1
• Erythromycin: Increases sildenafil levels; may not require dose adjustment for short courses 1
• Cimetidine: Increases sildenafil levels; may not require dose adjustment 1
• Recommendation: Start with 25 mg sildenafil when using potent CYP3A4 inhibitors 9

CYP3A4 Inducers - Decrease Sildenafil Levels

• Bosentan: Sildenafil levels fall 50%; bosentan levels increase 50% 1
  • May not require dose adjustments of either drug 1
• Phenytoin: May decrease sildenafil levels 1

Common Pitfalls to Avoid

1. Never assume a patient is not taking nitrates: Specifically ask about sublingual nitroglycerin, nitrate patches, long-acting nitrates, and "as-needed" nitrate use before prescribing sildenafil 1

2. Do not overlook recreational nitrate use: Amyl nitrite ("poppers") is contraindicated with sildenafil 3

3. Baseline hypotension is a relative contraindication: Avoid sildenafil in patients with systolic BP <90 mmHg or >30 mmHg below baseline 1

4. Elderly patients and those with hepatic/renal impairment: Start with 25 mg dose due to increased systemic exposure 9

5. Post-myocardial infarction patients: The need for nitrate therapy must be weighed against phosphodiesterase-5 inhibitor use; if nitrates are essential, sildenafil should not be used 1, 5