01
Three clocks, one wall
Men do not walk in asking which phosphodiesterase type 5 inhibitor is strongest. They ask which tablet fits a Tuesday that was not planned, a dinner that will be heavy, or a nitrate spray already in a coat pocket. Those are clock questions. Strength questions come later, if they come at all.
Cialis, Viagra, and Levitra all block the same enzyme. Sexual stimulation still has to fire first. No nitric oxide, no cyclic GMP to protect, no erection from the tablet alone. That shared mechanism is why comparison pages so often collapse into one row of near-identical claims. It is also why the useful differences sit in timing, food, leftover drug, and one cardiac interval, not in a slogan about potency.
Myrto hangs three labelled options and leaves the rest of each ladder in the notes. Daily tadalafil 5 mg. Sildenafil anywhere from 25 mg to 100 mg. Vardenafil 2.5 mg as the smallest film-coated tablet, with the usual 10 mg start named so the lock is not mistaken for a typical first prescription. The tables below carry the numbers. The prose carries the judgment a clinic actually uses.
03
The 25-100 mg evening and the empty plate
Sildenafil is sold as 25 mg, 50 mg, and 100 mg. For most men the recommended start is 50 mg about one hour before sexual activity. The printed window is wider than the habit people remember: 30 minutes to 4 hours. The dose may rise to 100 mg or fall to 25 mg on effect and side effects. Once per day is the cap.
Fasted, peak plasma sits between 30 and 120 minutes, median 60. A high-fat meal delays that peak by about 60 minutes and cuts Cmax by about 29 percent. Total exposure holds up better than the peak does, which is why a late, softer evening is more common than a true blank. Still, a first 'failure' after steak and sauce is often a food problem, not a class failure.
Mean absolute bioavailability is 41 percent (range 25-63). Terminal half-life is about 4 hours for parent and the N-desmethyl metabolite. Protein binding is about 96 percent. Volume of distribution is about 105 L. CYP3A4 does the heavy lifting; CYP2C9 is the minor route. Age over 65, hepatic impairment, creatinine clearance under 30 mL/min, or a strong CYP3A4 inhibitor all push the conversation toward 25 mg first.
Sildenafil is about 10-fold more potent at PDE5 than at PDE6 in the retina. That gap is the usual explanation for a blue tint or light sensitivity for a few hours. It is also why retinitis pigmentosa sits in the caution pile. The evening clock is short. The visual leftover is short too. Neither is a reason to skip the nitrate question.
04
What a 5 mg morning actually keeps in plasma
Tadalafil for once-daily use starts at 2.5 mg on the Cialis label for erectile dysfunction alone. The dose may rise to 5 mg if the lower tablet is tolerated and still thin. For benign prostatic hyperplasia, and for ED plus BPH together, the recommended daily dose is 5 mg at about the same clock each day. That is the tablet this gallery hangs.
Median time to peak after a single swallow is 2 hours, with a spread from 30 minutes to 6 hours. The number that changes the week is the half-life: 17.5 hours in healthy adults. After a few mornings the trough stops collapsing. Steady plasma levels are in by about five days of once-daily use. From then on there is no 60-minute wait before an evening. The drug is already sitting there.
Food does not rewrite that clock. Cialis may be taken with or without a meal. Absolute oral bioavailability was never pinned with an intravenous comparator. About 94 percent of circulating tadalafil is protein-bound. Clearance runs through CYP3A4. Once-daily use is not recommended when creatinine clearance is under 30 mL/min or the man is on hemodialysis. With a strong CYP3A4 inhibitor the daily ceiling is 2.5 mg, not 5 mg.
The daily habit also covers urinary BPH symptoms on the same tablet. That dual label is unique among these three. It is the reason a man with both problems often leaves with 5 mg every morning rather than an evening diamond. It is not a reason to force a daily tablet on someone who has sex twice a month and no prostate complaint.
05
QT is a vardenafil walk, not a class walk
In 59 healthy men aged 45-60, vardenafil 10 mg and a supratherapeutic 80 mg dose produced QTc increases in the same band as moxifloxacin 400 mg. At one hour, Fridericia-corrected change versus placebo was 8 msec (90 percent CI 6-9) after 10 mg and 10 msec (8-11) after 80 mg. Heart rate rose by about 5-6 beats per minute. The study was not built for head-to-head statistical claims between doses.
A later study in 44 volunteers found a placebo-subtracted QTcF change of 5 msec after 10 mg. Gatifloxacin 400 mg gave 4 msec. Together they added to 9 msec. The label says the clinical impact of these changes is unknown. It also says men with congenital QT prolongation, or those on Class IA drugs (quinidine, procainamide) or Class III drugs (amiodarone, sotalol), should avoid vardenafil.
Sildenafil and tadalafil do not carry that same QT walk on their US labels. That is why a new antiarrhythmic, a family long-QT story, or an unexplained syncope should push the conversation off Levitra before anyone argues about 2.5 mg versus 10 mg. The walk is the first step. The tablet is the second.
06
Onset is three different waits
| Clock | Cialis 5 mg daily | Viagra 25-100 mg | Levitra 2.5 mg |
|---|---|---|---|
| What the label hangs | Once daily at about the same hour, no sex timer | As needed, about 1 hour before; 30 min to 4 hours allowed | Smallest labelled tablet; usual start is 10 mg about 60 min before |
| Onset in practice | No evening wait after about 5 days at steady level | Median peak at 60 min fasting | Median peak at 60 min fasting |
| Food | Taken with or without a meal | High-fat meal: Tmax later by ~60 min, Cmax down ~29% | High-fat meal: Cmax down 18-50% |
| Useful window | Background coverage once the plateau is in | About 4 hours of fading effect | About 4-5 hours of fading effect |
| Half-life | 17.5 hours | About 4 hours | About 4-5 hours |
| QT walk | No class QT warning of this kind | No class QT warning of this kind | Avoid congenital long QT and Class IA / III antiarrhythmics |
| Nitrate leftover | At least 48 hours after the last tablet if a nitrate is later judged necessary | Plasma much lower at 24 hours; safe nitrate timing still unknown | Added BP/HR effect gone by 24 hours in the NTG study; still contraindicated |
Daily tadalafil 5 mg has no pre-sex timer once the five-day plateau is in. The wait happens at the start of the prescription, not at 21:00 on a Friday. Until that plateau, a man who starts 5 mg on Thursday should not treat Thursday night as a fair trial of the daily card.
Sildenafil's wait is the one people already know from the 1998 launch: swallow, give it about an hour on an empty-enough stomach, then rely on stimulation. Some men notice an effect closer to 30 minutes. Some need the far end of the 4-hour window. One quiet evening after a heavy meal does not decide the drug.
Vardenafil's wait looks like sildenafil's on a clock face: about an hour, median peak at 60 minutes. The difference is not the minute mark. It is the QT walk that has to happen before that first swallow, and the food hit that can flatten the peak by as much as half. A 2.5 mg tablet taken after a rich dinner is a weak test of a cut dose.
07
Duration leftover: a weekend versus one evening
As-needed tadalafil 10 mg or 20 mg can still support intercourse out to 36 hours in the trials that set that claim. Daily 5 mg does not try to be a 36-hour spike. It tries to be a flat line so the 36-hour story is no longer the point. The leftover that matters on daily use is the 48-hour nitrate gap after the last morning, not a weekend nickname.
Sildenafil's useful window is shorter. One RigiScan time-course study still saw an effect at 4 hours, weaker than at 2 hours. Half-life about 4 hours matches that fade. Plan the evening, not the next afternoon.
Vardenafil's half-life is about 4-5 hours. The practical evening is in the same band as sildenafil. In a nitroglycerin timing study, extra blood-pressure and heart-rate effects after 20 mg were gone by 24 hours. That 24-hour mark is a residual-clock fact. It is not permission to add a nitrate. The contraindication stays absolute for all three.
08
Why 2.5 mg exists on the Levitra card
Vardenafil film-coated tablets come as 2.5 mg, 5 mg, 10 mg, and 20 mg. The usual recommended start is 10 mg about 60 minutes before activity, then 5 mg or 20 mg on response. This gallery still hangs 2.5 mg because that is the smallest labelled tablet and the dose the label reaches for when a strong CYP3A4 inhibitor is already on the list.
With ritonavir, no more than a single 2.5 mg tablet in 72 hours. With indinavir, saquinavir, atazanavir, clarithromycin, ketoconazole 400 mg daily, or itraconazole 400 mg daily, do not exceed 2.5 mg once daily. Ketoconazole 200 mg or erythromycin land on a 5 mg cap instead. Age 65 and over, or moderate hepatic impairment (Child-Pugh B), starts at 5 mg, not 2.5 mg. Severe hepatic impairment was not studied.
Absolute bioavailability is about 15 percent. Fasted Tmax is 30 minutes to 2 hours, median 60. Half-life is about 4-5 hours. A high-fat meal cut Cmax by 18 to 50 percent in the food studies. Most of an oral dose leaves in feces as metabolites (about 91-95 percent), little in urine. The 2.5 mg card is not a shy version of 10 mg for a first healthy start. It is a cut for a crowded medicine list.
09
Food delays two clocks, not three
Tadalafil's label is blunt: take it without regard to food. That is the practical reason a daily 5 mg tablet survives a late Copenhagen dinner. The meal does not have to be negotiated. The morning hour does.
Sildenafil's food effect is a rate problem. Tmax moves later by about an hour. Cmax falls by about 29 percent. AUC is less bruised than the peak. The tablet still works for many men after food. It works later and softer. That mismatch is the most common reason a first 50 mg evening is written off as 'Viagra does nothing.'
Vardenafil sits between those stories. High-fat meals cut Cmax by 18 to 50 percent depending on the study. The clock still wants about 60 minutes. A light plate is a better first walk than a cream sauce. None of this is a fasting religion. It is a way to give the first two or three evenings a fair peak.
10
Hang the card that fits the week
A man who wants the evening off the clock, who is intimate often enough that thirty mornings are not wasted, or who also needs BPH cover, is a daily 5 mg tadalafil candidate if kidneys, CYP3A4 drugs, and nitrates are clear. A man who wants a tablet only on planned nights, who can clear the plate, and who wants the longest-studied evening in the class, is a sildenafil 25-100 mg candidate. A man whose list forces a CYP3A4 cut, or who already failed a fair sildenafil trial, may be a vardenafil candidate only after the QT line is clean. 2.5 mg is the cut tablet, not the default first swallow for a healthy start.
Switching among the three is ordinary. An unfair first trial is also ordinary: wrong meal, no stimulation, one attempt, then a verdict. The daily-versus-evening tadalafil dispatch, the sildenafil timing dispatch, and the vardenafil first-walk dispatch each slow that verdict down.
What does not switch is the floor. Erectile difficulty can be the first public sign of vascular disease. A real cardiovascular look belongs before the first tablet, not after a second brand. And the nitrate hold stays hung on every card on this wall.