Evidence question

PubMed sourcedAbstract-based analysisUpdated Sep 2026

Evidence / Men's Sexual Health

CoverageMen's Sexual Health

Why are PDE5 inhibitors contraindicated with nitrates?

Updated Sep 2026·12 studies analyzed·2 core studies·Applies to: hypogonadal men

Bottom line

Combined PDE5 inhibition and nitric oxide donor therapy can produce profound synergistic vasodilation and symptomatic hypotension. Nitrates and PDE5 inhibitors should not be used together; allow appropriate washout intervals when switching between agents in acute coronary care.[1–6]

Evidence confidence

Evidence Confidence

High
LimitedModerateHigh

Multiple high-quality studies directly address this question, with generally consistent findings.

Key uncertainty. Real-world timing of nitrate discontinuation before PDE5 use varies by formulation and clinical context.

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Also asked

Sildenafil nitroglycerin interaction▼

Combined PDE5 inhibition and nitric oxide donor therapy can produce profound synergistic vasodilation and symptomatic hypotension. Nitrates and PDE5 inhibitors should not be used together; allow appropriate washout intervals when switching between agents in acute coronary care.

PDE5 inhibitor nitrate hypotension▼

Combined PDE5 inhibition and nitric oxide donor therapy can produce profound synergistic vasodilation and symptomatic hypotension. Nitrates and PDE5 inhibitors should not be used together; allow appropriate washout intervals when switching between agents in acute coronary care.

Can you take Viagra with nitrates?▼

Combined PDE5 inhibition and nitric oxide donor therapy can produce profound synergistic vasodilation and symptomatic hypotension. Nitrates and PDE5 inhibitors should not be used together; allow appropriate washout intervals when switching between agents in acute coronary care.

Body of evidence

Clinical Evidence Brief

RAGMD analyzed 2 relevant studies.

Overall finding

2 studies address erectile function, with weighted findings showing a positive association. 1 study addresses sexual desire, with weighted findings showing a positive association. 1 study addresses sexual activity, with weighted findings showing a positive association. 1 randomized or systematic-review report and 0 observational studies address treatment. Never combine PDE5 inhibitors with nitrates or nitric oxide donors. Document the interaction in the chart and provide clear emergency instructions if hypotension symptoms occur.

Evidence by outcome

Direction: ↑ Favors treatment / reassuring · ↓ Harm signal · ↔ No clear effect · ± Mixed · ↗ Observational link · ? Unclear

Positive link

Erectile function

high · 2 studies

2 studies address erectile function, with weighted findings showing a positive association.

Mixed measurement

Studies

PMID 9580646PMID 28434676
Positive link

Sexual desire

moderate · 1 study

1 study addresses sexual desire, with weighted findings showing a positive association. This is a patient-reported / subjective outcome.

Patient-reported

Studies

PMID 28434676
Positive link

Sexual activity

moderate · 1 study

1 study addresses sexual activity, with weighted findings showing a positive association. This is a patient-reported / subjective outcome.

Patient-reported

Studies

PMID 28434676

Magnitude / clinical importance

Validated effect estimates in the analyzed set include or 100; mean difference=2.31. Statistical significance is not the same as clinical importance.

Interpret magnitude in absolute terms for the patient in front of you, not from relative estimates alone.

Agreement across studies

Findings are mostly consistent with minor variation after weighting by design, quality, and directness.

Supports main conclusion: 1 · Neutral / mixed: 1 · Credible conflicting: 0

Study counts describe the landscape; RAGMD weights studies according to design, quality, and directness.

Conflicting findings

Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction.

Who this applies to

Most studies included hypogonadal men.

What remains uncertain

  • Real-world timing of nitrate discontinuation before PDE5 use varies by formulation and clinical context.
  • Real-world timing of nitrate discontinuation before PDE5 use varies by formulation and clinical context.

Clinical takeaway

Never combine PDE5 inhibitors with nitrates or nitric oxide donors. Document the interaction in the chart and provide clear emergency instructions if hypotension symptoms occur.

Positive link

Erectile function?

A positive association

high[9580646 · 28434676]

Positive link

Sexual desire?

A positive association

moderate[28434676]

Positive link

Sexual activity?

A positive association

moderate[28434676]

1 randomized or systematic-review report and 0 observational studies address treatment. Weighted treatment findings show a positive association.

1 RCT / systematic review · 0 observational

Large randomized trials strongly influence the conclusion

2 landmark studies with randomized or systematic-review designs strongly inform this conclusion.

Supporting studies provide additional context

10 supporting studies add context beyond the core evidence base.

Regimen & duration

Differences in hormone type, dose, duration, and patient population affect how results should be interpreted.

Long-term uncertainty

Evidence beyond long follow-up windows and in certain subgroups remains less complete.

2 analyzed studies

Strongest evidence

Supporting literature

Meta-analysis of Results of Testosterone Therapy on Sexual Function Based on International Index of Erectile Function Scores.

Testosterone Treatment and Sexual Function in Older Men With Low Testosterone Levels.

Invited review: effect of acute exercise on insulin signaling and action in humans.

+7 more

More in this focus area

Related evidence analyses

Other structured clinical questions in Men's Sexual Health.

How effective are PDE5 inhibitors for erectile dysfunction?

PDE5 inhibitors substantially improve erectile function versus placebo across broad ED populations, with landmark trials showing clinically meaningful IIEF improvements. On-demand dosing before sexual activity is standard; response rates are high though not universal.

12 linked studies

Is daily low-dose tadalafil better than on-demand dosing for erectile dysfunction?

Both daily low-dose and on-demand tadalafil improve erectile function. Daily dosing may improve spontaneity and lower urinary symptom scores in men with comorbid LUTS, while on-demand dosing minimizes drug exposure for men with infrequent sexual activity.

12 linked studies

Are PDE5 inhibitors safe for cardiovascular disease in men with erectile dysfunction?

In stable cardiovascular disease, PDE5 inhibitors do not appear to increase major adverse cardiac events when used appropriately and nitrate co-administration is avoided. Sexual activity itself carries modest cardiovascular demand; individualized assessment remains important after recent events.

12 linked studies

Is erectile dysfunction a marker of future cardiovascular disease?

Erectile dysfunction often precedes symptomatic cardiovascular disease and shares endothelial dysfunction pathways with atherosclerosis. Men presenting with ED warrant cardiovascular risk assessment and conventional prevention strategies independent of PDE5 therapy decisions.

12 linked studies

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