Description
Avanafil is the most recent of the four PDE5 inhibitors and was developed around two properties: rapid onset and high selectivity. The mechanism is the same as for sildenafil, tadalafil and vardenafil. Phosphodiesterase type 5 breaks down cyclic guanosine monophosphate in erectile tissue; inhibit it and cGMP persists longer, smooth muscle relaxes and arterial inflow rises. As with the whole class, the substance only amplifies an existing signalling chain, it does not start a new one. Without sexual stimulation nothing happens.
The difference lies in the kinetics. The review by Sanford gives a median time to peak plasma concentration of 30 to 45 minutes, markedly shorter than the older members. In that analysis, roughly two thirds of attempts made either before 15 minutes or more than six hours after dosing were successful, against around one quarter on placebo.
The randomized, double-blind multicenter study by Goldstein and colleagues examined 390 men with diabetes mellitus and erectile dysfunction, allocated to 100mg, 200mg or placebo. Both doses improved all three co-primary endpoints significantly versus placebo. The timing held here as well: successful intercourse was possible from 15 minutes and still more than six hours after dosing. Diabetes is not an arbitrary subgroup but one of the harder ones, because a vascular and a neurogenic component often coincide.
High selectivity for PDE5 over PDE6 and PDE11 is the second point. PDE6 sits in the retina and is responsible for the visual disturbances seen with sildenafil; PDE11 is associated with muscle pain. The adverse effects reported most often in the trials were headache, nasopharyngitis, flushing and sinus congestion.
In a research context avanafil is therefore the member of the class with the shortest lead time and the most tolerable profile, but a distinctly shorter window than tadalafil.
You can order Avanafil as oral tablets with 100mg or 200mg per tablet, 4 tablets per blister.
This information is for research and educational purposes only. No medical advice.
Risks & Safety
The better tolerability profile changes nothing about the contraindication that applies to the entire class.
- Nitrates are an absolute contraindication: Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate and the alkyl nitrites sold as poppers. Nitrates and PDE5 inhibitors act on the same signalling chain. Together they can drop blood pressure to life-threatening levels. The faster onset of avanafil makes this point more dangerous rather than less, because less time passes between dosing and effect.
- Alpha blockers and other antihypertensives: The effects add up. Relevant with tamsulosin and alfuzosin among others.
- Cardiovascular status: Sexual activity is exertion. With unstable angina, a recent heart attack or stroke, or severe heart failure, capacity to exert is the real question.
- Tolerability in the trials: In a pooled analysis of three trials, per Sanford, at most 2 percent of avanafil and placebo recipients discontinued because of adverse events. Across more than 52 weeks of continued use it was 2.8 percent, with no drug-related serious adverse events.
- Common adverse effects: Headache, nasopharyngitis, flushing and sinus congestion, as reported by Goldstein and colleagues.
- Visual disturbances and priapism: Not excluded despite the higher selectivity. Any sudden loss of vision and any erection lasting more than four hours is an emergency.
- CYP3A4: Avanafil is metabolised via CYP3A4. Strong inhibitors such as ketoconazole, itraconazole, clarithromycin or ritonavir raise exposure substantially.
This classification does not replace medical advice. Risk and responsibility for any actual use lie entirely with the buyer.
Studies
- Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind study in men with diabetes mellitus - Mayo Clinic Proceedings 2012, Goldstein et al: 390 men with diabetes mellitus, 100mg and 200mg improved all three co-primary endpoints significantly, with successful intercourse possible from 15 minutes and still beyond six hours after dosing.
- Avanafil: a review of its use in patients with erectile dysfunction - Drugs & Aging 2013, Sanford: review with a Tmax of 30 to 45 minutes, results of the 12-week trial of 50, 100 and 200mg, data after nerve-sparing radical prostatectomy and discontinuation rates across more than 52 weeks.
