We use essential cookies (authentication, your saved goals/stack) by default. With your permission we’ll also enable privacy-respecting analytics (Vercel Web Analytics, anonymous load-time metrics) and error-replay diagnostics (Sentry — DOM snapshots only when an error fires) so we can fix bugs faster. Learn more about cookies
Avanafil (PDE5 inhibitor)
The newest oral PDE5 inhibitor (Stendra; Spedra in the EU) for erectile dysfunction, FDA-approved in 2012. Same class and mechanism as sildenafil and tadalafil (PDE5 inhibition → ↑cGMP → nitric-oxide vasodilation), but engineered for fast onset (~15-30 minutes) and high PDE5 selectivity, which may mean fewer visual side effects. Robust phase-3 RCT evidence for ED, including diabetic ED and post-prostatectomy. A prescription drug, not a supplement.
Prescription medication — not a dietary supplement
Avanafil (Stendra) is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Avanafil (Stendra) doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from high-quality meta-analyses and randomised trials published 2010–2024.
Based on 34 studies · 11 meta-analyses · 13 RCTs
Confidence
High confidenceBy outcome
Avanafil has a strong, well-replicated phase-3 RCT and meta-analytic base for erectile dysfunction, including diabetic ED, plus systematic-review support for the PDE5-inhibitor class after radical prostatectomy and a clear pharmacological rationale for its fast onset and high PDE5 selectivity. The score sits in the moderate tier because this is a prescription drug with a single narrow approved indication and a serious nitrate contraindication — it is described for information and is not recommended as a supplement.
13 randomised trials
92% were about Avanafil (Stendra) in an audit of 13 of them
Every randomised or controlled trial of Avanafil (Stendra) indexed in PubMed, not a hand-picked subset. Meta-analyses and systematic reviews are deliberately excluded from this count: most of them cover many compounds at once, so counting them would inflate it.
PubMed · as of Sep 2026
No trials currently enrolling · 23 completed on ClinicalTrials.gov
7 of the completed trials have posted results
Registered trials show research momentum for Avanafil (Stendra), not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Nov 2026
Avanafil is an oral phosphodiesterase-5 (PDE5) inhibitor — the newest of its class, marketed as Stendra in the US and Spedra in Europe and FDA-approved in 2012 for erectile dysfunction.
Like sildenafil and tadalafil it blocks PDE5, raising cyclic GMP and prolonging nitric-oxide-mediated smooth-muscle relaxation and vasodilation in the penile (and broader) vasculature.
What distinguishes avanafil is its pharmacology: it was designed for rapid absorption and fast onset — often working in roughly 15-30 minutes — and for high selectivity for PDE5 over related phosphodiesterases.
In particular it has markedly less cross-reactivity with PDE6 (concentrated in the retina) than sildenafil, which is the rationale for potentially fewer visual disturbances, and reduced PDE1 activity, relevant to flushing and tachycardia. It is short-acting, suiting on-demand use.
The efficacy evidence is strong: the phase-3 REVIVE trial and a parallel REVIVE-Diabetes trial were double-blind, placebo-controlled randomized studies showing clinically meaningful improvement on the International Index of Erectile Function and on per-attempt success rates across a broad ED population including men with diabetes, and a 52-week open-label extension supported sustained efficacy and tolerability.
A systematic review and meta-analysis confirmed efficacy and a favorable tolerability profile relative to placebo, and systematic-review evidence for the PDE5-inhibitor class supports erectile-function recovery after nerve-sparing radical prostatectomy.
The common adverse effects are the familiar vasodilatory ones — headache, flushing, and nasal congestion — and they are generally mild and dose-related.
The critical safety boundary is identical to the rest of the class: avanafil is absolutely contraindicated with nitrates in any form, because the combination can cause severe, potentially fatal hypotension.
It requires caution with alpha-blockers and other antihypertensives and with strong CYP3A4 inhibitors (which raise its levels), and it carries the rare class risks of priapism, non-arteritic anterior ischemic optic neuropathy (NAION), and sudden hearing loss.
The score reflects strong, well-replicated efficacy for erectile dysfunction set against the fact that this is a prescription drug with a narrow approved indication and a serious nitrate contraindication — it is described for information, not as a recommendation.
Avanafil blocks PDE5, raising cyclic GMP and prolonging nitric-oxide-mediated vasodilation — the basis for its erectile effect.
Engineered for rapid absorption (onset ~15-30 min) and high selectivity for PDE5 over PDE6 (retinal) and PDE1, the rationale for fewer visual side effects and a fast time-to-effect.
Enhanced NO/cGMP signaling improves penile blood flow and supports endothelial smooth-muscle relaxation.
How Avanafil (Stendra) works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Absolute contraindication — dangerous hypotension.
Avoid until cleared by a clinician.
Use low starting doses and monitor blood pressure.
Discuss the rare risk of optic-nerve injury with a clinician before use.
Combined PDE5 inhibitor + nitrate causes severe, potentially fatal hypotension — an absolute contraindication.
Additive blood-pressure lowering — use caution and lower starting doses.
Raise avanafil levels (e.g. ritonavir, ketoconazole, clarithromycin); dose reduction or avoidance advised.
Tip: Vasodilatory; usually mild and transient.
Tip: Class/dose-related; typically self-limited.
Tip: Seek urgent care; avoid nitrates; An erection lasting 4 hours or longer is an emergency whether or not it hurts: go to an emergency department now. One approaching 3 to 4 hours, or a painful erection unrelated to arousal, needs urgent medical assessment now. Do not wait.
Avanafil (Stendra) has an evidence score of 3.6/10 — emerging evidence based on 34 indexed studies, including 1 meta-analysis. The newest oral PDE5 inhibitor (Stendra; Spedra in the EU) for erectile dysfunction, FDA-approved in 2012. Same class and mechanism as sildenafil and tadalafil (PDE5 inhibition → ↑cGMP → nitric-oxide vasodilation), but engineered for fast onset (~15-30 minutes) and high PDE5 selectivity, which may mean fewer visual side effects. Robust phase-3 RCT evidence for ED, including diabetic ED and post-prostatectomy. A prescription drug, not a supplement. Representative study: PMID 24589460.
Dosing for Avanafil (Stendra): Approved on-demand ED dosing is 50-200 mg taken roughly 15-30 minutes before activity (100 mg typical start; range 50-200 mg). It can be taken with or without food. Any use is clinician-directed; this is not a supplement regimen. Individual needs vary, so check the right dose for you with a healthcare provider.
Timing is flexible for Avanafil (Stendra) — consistent daily use matters more than the time of day. Rapidly absorbed with a fast onset (~15-30 minutes), so it is taken on-demand shortly before activity.
Avanafil (Stendra) should be used with caution — talk to a healthcare provider before taking it. Reported side effects include priapism / NAION (sudden vision loss) / sudden hearing loss / symptomatic hypotension, headache / flushing, nasal congestion. How often they occur is not established for all of them. Use caution if any of these apply to you: Concurrent nitrates (any form); Recent cardiovascular event / unstable angina; Severe hypotension.
Testosterone (TRT)
Too few graded studiesThe primary male androgen and a prescription medicine with US FDA-approved products for specified causes of male hypogonadism, and a Schedule III controlled substance in the US. For men with genuinely low testosterone, randomized trials show real benefits: the Testosterone Trials (TTrials) improved sexual function, mood, anemia and bone density in older hypogonadal men, and the large TRAVERSE trial found TRT non-inferior to placebo for major cardiac events. But those benefits were modest and indication-specific, NOT a longevity or anti-aging result. It is prescription-only in Germany and Austria. Non-medical, supraphysiologic and 'anti-aging' use is not established as safe or effective for longevity and carries serious harms — erythrocytosis, suppressed sperm production/fertility, cardiovascular and psychiatric risk. This is a harm-reduction reference, not a recommendation, and testosterone is NOT a dietary supplement.
Nicotinamide Riboside
Too few graded studiesA vitamin B3 precursor that reliably raises cellular NAD+ levels and is well tolerated — but human trials have so far shown mostly null or mixed results on the functional outcomes (muscle, metabolism, blood pressure, cognition) that elevation is meant to drive.
MitoQ
Too few graded studiesA mitochondria-targeted antioxidant — CoQ10 conjugated to a triphenylphosphonium (TPP+) cation so it accumulates several-hundred-fold inside mitochondria. Sold OTC as a supplement. Its best human signal is improved endothelial/vascular function in older adults (one small RCT); several trials are null (Parkinson's, exercise adaptation), and almost all outcomes are surrogate/biomarker, not hard clinical endpoints.
Yohimbine
Too few graded studiesThe purified alkaloid (not crude yohimbe bark) — an alpha-2 adrenoceptor antagonist with modest evidence for erectile dysfunction and fasted fat loss, but real anxiety and cardiovascular risks and supplement potency that may differ from the label.
Explore: Best supplements for Men's Health
Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 34 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
Tap node to isolate • Pinch to zoom • Tap edge for research