Clock first, then the brand name
Class, in six lines
Brand loyalty is a weak way to pick among these three. The American Urological Association says the oral PDE5 inhibitors have no proven winner on efficacy. What does differ is the time-curve.
Sildenafil citrate peaks in about an hour on an empty stomach. Vardenafil is in the same short band. Tadalafil peaks later, near two hours, then lingers because its half-life sits near 17.5 hours.
Helion reads those curves against three locked strengths. Tadalafil 20 mg is the as-needed tablet on this site. Sildenafil 25 mg is the first tablet. Vardenafil 5 mg is the start after a QT pass.
Arousal is still required. None of the three manufactures desire. They slow the breakdown of cGMP after nitric oxide has already opened penile arteries. Sit still with a tablet and no stimulation, and the blood level can be perfect while nothing happens.
So the comparison is a timing problem. Match the clock to how a week actually looks. Then apply the hold that never bends: nitrates and riociguat close the class before onset even matters.
How long each tablet stays useful
| Parameter | Sildenafil 25 mg | Tadalafil 20 mg | Vardenafil 5 mg |
|---|---|---|---|
| Median Tmax, fasted | about 1 h (0.5-2 h) | about 2 h | about 0.5-1 h |
| Terminal half-life | about 4 h | about 17.5 h | about 4-5 h |
| Useful window | about 4 h, then fade | up to about 36 h | about 4-6 h |
| Helion lock | first tablet | as-needed dose | QT-screened start |
| Daily option | no | yes, 2.5 or 5 mg | no |
| Cleared mainly by | CYP3A4 | CYP3A4 | CYP3A4 |
Read half-life before you read marketing. Sildenafil and its N-desmethyl metabolite each clear with a terminal half-life of about four hours. That is why the useful stretch is one evening, then a steep fade.
Vardenafil lives on a similar short clock: peak near one hour, half-life about four to five hours, useful window a few hours. It is a same-night tablet, not a next-morning leftover.
Tadalafil is the outlier. Half-life near 17.5 hours supports a response window that trials measured out to about 36 hours after a single as-needed dose. Friday evening can still cover Saturday morning if arousal is there.
AUA guidance states the practical contrast plainly: sildenafil and vardenafil share a Tmax near one hour and a half-life near four hours. Tadalafil's Tmax is nearer two hours and its half-life nearer 18 hours. Those numbers, not brand loyalty, decide spontaneity.
Maximum frequency is once in 24 hours for all three. A second tablet the same night does not rescue a mistimed first dose. It only stacks exposure.
Avanafil exists as a fourth US option with a shorter labelled Tmax. Helion does not lock it. The three clocks below are the ones this site actually reads: 20 mg, 25 mg and 5 mg.
Blue tint, back ache, QT
Shared effects come from vasodilation: headache, flushing, a blocked nose, indigestion. Those do not pick a winner. Off-target enzymes do.
Sildenafil crosses onto PDE6 in the retina more than the others. A temporary blue or blue-green tint, or harsh bright light, is the usual story. It fades as the four-hour half-life clears the drug. Sudden vision loss in one eye is a different event and needs same-day care.
Tadalafil's fingerprint is delayed back or thigh ache, often 12-24 hours after a dose, usually gone within 48 hours. The accepted link is weak PDE11 activity in skeletal muscle. Harmless for most men. Annoying enough that some switch clocks.
Vardenafil is the most PDE5-selective of the three on paper. The price of that profile is a labelled QT caution. Congenital long QT, or a class IA or class III antiarrhythmic (quinidine, procainamide, amiodarone, sotalol), means pick another tablet. Details sit in who a 5 mg start actually fits.
A class observational signal also sits on NAION, a sudden optic-nerve event, when a PDE5 inhibitor was used in the prior five half-lives. The risk estimate is about twofold in those case-crossover studies. Crowded optic discs were already a risk. Sudden one-sided vision loss is still same-day care, not a tint to wait out.
The hold that ends the visit
Nitrates plus any PDE5 inhibitor are a categorical ban. Nitroglycerin, isosorbide mono- or dinitrate, and recreational nitrites (poppers) dump nitric oxide into the same cGMP path these tablets protect. Blood pressure can fall to a dangerous low.
Tadalafil is the riskiest of the three on this point, because the hold lasts longest. The Cialis label says that if nitroglycerin is medically necessary after a dose, at least 48 hours should pass, and even then only under monitored care. Daily tadalafil keeps a continuous level, so the hold is always on.
Sildenafil's label is stricter in a different way: after a dose, it is unknown when a nitrate can be given safely. Plasma is much lower at 24 hours, but that is not a green light. Vardenafil carries the same class ban.
Riociguat and other soluble guanylate cyclase stimulators are banned for the same mechanism. Alpha-blockers are a softer caution: they can add a pressure drop, so the start is low and the timing is planned. They are not an automatic class veto.
If chest pain starts after any of these tablets, the sentence that matters is the INN and the hour. Emergency staff can work around a known PDE5 dose. They cannot work around a silent one.
Matching a clock to a week
Occasional, planned sex and a stomach that can be kept light: the short clock is enough. Helion's first sildenafil tablet is 25 mg. If that dose is tolerated and weak, the prescriber can move the labelled ladder, not the patient.
A blue tint that bothers colour-critical work is a reason to leave sildenafil. Vardenafil 5 mg is the near-cousin if the QT screen is clean. Tadalafil 20 mg is the other exit if the week is messy and food will not be controlled.
Spontaneous sex across a weekend, or a man who will not watch a clock: tadalafil. The 20 mg as-needed tablet covers a long window. The 2.5 or 5 mg daily strip, covered in the schedule split, removes the window entirely once steady state lands.
Prostate symptoms riding with erections also point to daily tadalafil 5 mg, the only one of the three licensed for BPH signs. Sildenafil and vardenafil never earned that line.
Safety filters still override preference. Nitrate anywhere in the plan: none of them. Long QT or those rhythm drugs: not vardenafil. CrCl under 30 mL/min: daily tadalafil is the wrong habit.
Cost rarely ranks them now that all three are generic. Stocking still does. Sildenafil and tadalafil sit on more shelves. Vardenafil 5 mg can be the one a small pharmacy has to order. Fit first. Let supply break a tie, not a brand memory from 2005.
Dinner delays two of the three
A high-fat meal is the most common reason a short-acting tablet looks weak. The Viagra label is specific: mean Tmax stretches by 60 minutes and mean Cmax falls by 29% after a high-fat meal.
That is why a 25 mg sildenafil tablet taken with steak and cream sauce can still be climbing when the evening has already moved on. The molecule did not fail. Absorption did. The food-and-hour guide walks that delay in order.
Vardenafil's film-coated tablet may be taken with or without food, per label. Published PK still shows a high-fat breakfast can cut Cmax and push Tmax later, often by about an hour. Treat a heavy dinner as a delay, not as proof the 5 mg start is useless.
Tadalafil absorption does not move in a clinically relevant way with food. That is one reason men who refuse to plan dinner around a tablet land on the long clock. The 20 mg as-needed dose can follow the largest meal of the week.
None of the three is instant. Earliest trial onsets sit in the teens of minutes for a minority. Median useful onset is still closer to 30-60 minutes, longer if fat is in the way.
Switch after a fair trial, not after one night
Failing one PDE5 inhibitor, when it was actually used on its own clock, is a reason to try another before closing the class. AUA could not rank them. Men still feel them differently.
A single weak night after a fatty meal is data about dinner, not about the molecule. Repeat the same tablet with a clear stomach and real lead time before you change INN.
CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) raise levels across the class and force lower ceilings. Hand the full list over. Grapefruit juice is a small extra push, not a party trick.
Priapism past four hours is a class emergency. So is sudden hearing loss. Those two lines do not pick a winner among 20 mg, 25 mg and 5 mg. They close the night the same way on all three.
If the first clock was used on its own rules and still failed, change one axis only: food, INN, or daily versus as-needed. Changing all three at once teaches nothing.
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