What it is
Avanafil is a PDE5-inhibitor tablet taken by mouth, for adult men with erectile dysfunction. It is the most recently approved of the PDE5-inhibitor tablets, authorised for use in the EU since 21 June 2013 under EMA marketing authorisation EMEA/H/C/002581 (branded Spedra). Sexual stimulation is still required for it to work.Active ingredient: avanafil. Available strengths: 50 / 100 / 200 mg, taken on demand.
How it works
Avanafil does nothing on its own. When a man is sexually aroused, nerves and the blood-vessel lining in the penis release a gas called nitric oxide, which activates guanylate cyclase to raise cyclic guanosine monophosphate (cGMP) in corpus cavernosum smooth muscle. Avanafil blocks the PDE5 enzyme that normally degrades cGMP, so the cGMP signal persists, keeping cavernosal smooth muscle relaxed and allowing blood to fill the erectile tissue. Because sexual stimulation is required to initiate the local release of nitric oxide, PDE5 inhibition has no effect in its absence. In vitro, avanafil is >100-fold more selective for PDE5 than for PDE6 (found in retinal photoreceptors) and >1,000-fold more selective than for PDE4, PDE8 and PDE10, which is the basis for its narrower side-effect profile relative to older PDE5 inhibitors. By comparison, sildenafil has only approximately 10-fold selectivity for PDE5 over PDE6, which is why visual disturbances are more common with sildenafil than with avanafil (NIH DailyMed, avanafil prescribing information, confirmed by web fetch). The EU product information states the usual dose is 100 mg, taken about 15 to 30 minutes before sex. After oral administration, avanafil reaches peak plasma concentration in approximately 30 to 45 minutes (tmax). A high-fat meal delays absorption, reducing peak concentration by about 39% and delaying tmax by approximately 1 hour (EMA SmPC — Spedra, confirmed by web fetch). The elimination half-life is approximately 5 hours, which is shorter than other PDE5 inhibitors such as tadalafil or sildenafil (EMA SmPC, confirmed by web fetch).Take it about 15–30 minutes before sexual activity
At most one dose in 24 hours.
The doctor starts from the dose that fits your case
50, 100 or 200 mg, on demand.
Never combine with nitrates
Nitrates and poppers are contraindicated — blood pressure can fall dangerously.
What the studies reported
The EMA’s Spedra EPAR product information (SmPC sections 4.2, 4.8 and 5.1) reports general-population success rates of approximately 47%, 58% and 59% for the 50, 100 and 200 mg doses, against approximately 28% on placebo. The randomised, double-blind, placebo-controlled trial behind this was published in the Journal of Sexual Medicine in 2012 (PMID 22248153), and is registered on ClinicalTrials.gov as the TA-301 avanafil Phase 3 trial (NCT00790751); a second registered trial is listed as NCT00809471. That trial (TA-301) randomised 646 subjects across multiple centres to avanafil 50, 100 or 200 mg or placebo for 12 weeks, with subjects instructed to take study medicine 30 minutes before sexual activity and no restrictions on food or alcohol intake. The co-primary endpoints were Sexual Encounter Profile questions 2 and 3 (SEP2, SEP3) and the erectile function domain of the International Index of Erectile Function (IIEF-EF). All three doses significantly favoured avanafil over placebo (P ≤ 0.001 on all co-primary endpoints). No drug-related serious adverse events were reported.The often-quoted 15-minute and 6-hour onset figures come from small subsets of attempts — 300 and 80 respectively — inside that 12-week trial, so they are much less precise than the trial’s overall 12-week results (PMID 22248153, confirmed by web fetch).
What has been reported
Who it is not suitable for
Contraindications explained by mechanism
Avanafil is contraindicated with nitrate medicines and nitric-oxide donors because both avanafil and nitrates independently stimulate the cGMP–nitric oxide pathway: avanafil by blocking cGMP breakdown, nitrates by supplying exogenous nitric oxide. The combined effect can cause a dangerous drop in blood pressure. The same interaction risk applies to amyl nitrite and butyl nitrite (“poppers”), which are also nitric-oxide donors. Other contraindications include men with serious cardiovascular conditions such as a recent heart attack, stroke, or unstable angina — because PDE5 inhibition causes mild systemic vasodilation, and the haemodynamic reserve needed to compensate is reduced in these settings.Population specifics
Avanafil has not been studied in pregnant or breastfeeding women (it is not indicated for women). The medicine is predominantly metabolised by CYP3A4; concomitant use of strong CYP3A4 inhibitors (such as ketoconazole, ritonavir, clarithromycin) significantly increases avanafil exposure and the EU product information recommends a maximum dose of 50 mg in these patients. No dose adjustment is needed in mild-to-moderate renal or hepatic impairment, but avanafil has not been studied in severe renal or severe hepatic impairment and is not recommended in those populations (EMA SmPC, confirmed by web fetch).How Hi-Doctor handles it
A licensed EU doctor reviews your questionnaire and, if avanafil or another treatment is appropriate, issues an electronic prescription valid at any EU pharmacy under Directive 2011/24/EU. Hi-Doctor does not sell or ship medications — the medicine itself is paid separately, at a pharmacy of your choice. See pricing for the consultation fee, and the Spedra (avanafil) guide for day-to-day dosing detail. If erectile dysfunction is the condition you’re exploring treatment for more broadly, see the erectile dysfunction overview.Start a consultation
Sexual health consultation
Answer the sexual health questionnaire and a registered doctor reviews it.
They decide whether treatment is appropriate, which one, and at what dose —
and declining is a normal outcome. See what it costs
and how the review works.