I take sotalol for atrial fibrillation. My pharmacist would not dispense vardenafil. Was that right?
Third by prescription volume against first by nothing in particular
A molecule with a large trial programme, a small market share and one distinctive warning.
Vardenafil film-coated tablets, US prescribing information
Film-coated strengths2.5, 5, 10 and 20 mg
Usual start10 mg, 60 minutes ahead
After titration5 to 20 mg, once daily maximum
Time to peak, fasted30 to 120 minutes, median 60
Terminal half-life4 to 5 hours, drug and M1
BioavailabilityAbout 15 percent
Absolute barCongenital long QT, class IA or III, nitrates
Dissolving tablet10 mg only, not interchangeable
Film-coated vardenafil comes in 2.5, 5, 10 and 20 mg. For most men the recommended starting dose is 10 mg taken as needed about 60 minutes before sexual activity, raised to a maximum of 20 mg or lowered to 5 mg on efficacy and side effects, once per day at most. Sexual stimulation is required, as it is throughout the class.
The dataset is larger than the prescribing volume suggests: film-coated and dissolving vardenafil together have been given to more than 17,000 men in the clinical programme, mean age 54.5, range 18 to 89.
Pharmacokinetically it is the awkward one. Absolute bioavailability is about 15 percent, well under sildenafil's 41 percent, and peak concentration after a 20 mg dose arrives between 30 minutes and 2 hours, median 60. Clearance is 56 litres an hour, terminal half-life 4 to 5 hours for vardenafil and its M1 metabolite, and elimination is 91 to 95 percent faecal.
Where it fits is narrower than either alternative, and saying so beats presenting three equivalent options. Sildenafil has the longest record and the lowest price. Tadalafil has the long window, the only daily regimen and the prostate indication. Vardenafil has speed comparable to sildenafil and a paragraph about heart rhythm the other two do not carry.
Ten milligrams against five: where the label starts and what pulls it down
The FDA start here is 10 mg. Anyone opening at 5 should be able to name why.
What moves the opening dose below 10 mg
- Age 65 and over: a 5 mg starting dose should be considered.
- Stable on an alpha-blocker: start at 5 mg, and 2.5 mg where certain CYP3A4 inhibitors are also present. The alpha-blocker dose must be settled first.
- Moderate hepatic impairment, Child-Pugh B: start at 5 mg with a ceiling of 10 mg.
- Severe hepatic impairment, Child-Pugh C: do not use. It has never been evaluated.
- Strong CYP3A4 inhibition: 2.5 mg, with an interval attached rather than a daily allowance.
Ten milligrams is the number for most men. Each circumstance listed above is a reason to open lower, and none of them is simply caution.
The exposure figures behind those lines explain the caution. In men aged 65 and over, mean peak concentration was 34 percent higher and mean exposure 52 percent higher than in men aged 18 to 45. In moderate hepatic impairment the same 10 mg dose produced 130 percent higher peak and 160 percent higher exposure; in mild impairment the rises were 22 and 17 percent, which is why Child-Pugh A needs no adjustment and Child-Pugh B does.
Starting too low without a reason is its own error, and the trial data prices it. In the North American study at three months, the per-patient rate of maintaining an erection to successful intercourse was 51 percent on 5 mg, 64 percent on 10 mg and 65 percent on 20 mg, against 32 percent on placebo. The gap between 5 and 10 is thirteen points. The gap between 10 and 20 is one. Mean baseline erectile function domain score in those trials was 11.8 out of 30, so these were men with meaningful disease rather than mild complaints.
Read the 10 to 20 mg step for what it is: worth trying in a non-responder, and not where the useful gain lives.
Men who arrive on this tablet against men who should not be offered it
A second or third choice for most men, and a first choice for almost nobody.
Almost nobody starts here. The typical arrival has tried sildenafil and disliked something about it, or wants a defined window rather than a long tail, or was switched after an inadequate response. The molecule also has trial evidence in two harder populations, which is worth knowing before anyone treats it as a leftover.
In men with diabetes, the per-patient rate of achieving an erection sufficient for penetration was 61 percent on 10 mg and 64 percent on 20 mg against 36 percent on placebo, and maintenance to successful intercourse was 49 and 54 percent against 23. After radical prostatectomy the same measures were 47 and 48 percent against 22, and 37 and 34 percent against 10. Those post-surgical figures are the lowest in the programme and still several times placebo. Set the expectation there rather than quoting general-population numbers to a man who has had his prostate removed.
The exclusions are firmer than the indications. Congenital long QT syndrome. Class IA or class III antiarrhythmics. Child-Pugh C liver disease. Nitrates or riociguat anywhere on the list. And the cardiac situations where sex itself is the load in question, which is a judgement about exercise tolerance.
Enzyme selectivity against the side-effect list
The selectivity numbers are the side-effect list before anyone has taken a tablet.
Vardenafil inhibits PDE5 more than 15-fold more strongly than PDE6, more than 130-fold more than PDE1, more than 300-fold more than PDE11, and more than 1,000-fold more than PDE2, 3, 4, 7, 8, 9 and 10. Those ratios are not trivia. Each one predicts a category of adverse effect, and the narrowest margin predicts the most talked-about one.
PDE6 sits in retinal rods and cones and does the work of phototransduction. Single doses across this class produce transient, dose-related impairment of blue and green colour discrimination, along with reduced electroretinogram b-wave amplitude, most evident an hour after dosing and still present at six. In 25 men given 40 mg, twice the maximum daily dose, visual acuity, intraocular pressure and fundoscopy were unchanged.
Which is the honest version of the visual story: a measurable, temporary shift in colour perception that most men never notice, and no structural effect. It is not a reason to stop the drug, and it is worth mentioning to anyone whose work depends on colour discrimination in the hours after a dose.
Sudden loss of vision or hearing is a different matter entirely and belongs in the same category as a four-hour erection: stop, and get assessed the same day.
A dissolving 10 mg against a swallowed 10 mg
Same number printed on the box, different amount of drug in the blood.
| Film-coated tablet | Orally disintegrating tablet | |
|---|---|---|
| Strengths | 2.5, 5, 10, 20 mg | 10 mg only, unscored |
| Taken | Swallowed, with or without food | Placed on the tongue, without liquid |
| Median time to peak, fasted | 60 minutes after 20 mg | 45 to 90 minutes |
| Exposure vs 10 mg film-coated | Reference | 21% to 29% higher |
| Dose adjustment | Four strengths | None, switch to film-coated |
The orally disintegrating tablet exists in one strength, 10 mg, and the label is unusually direct about it: it is not interchangeable with the 10 mg film-coated tablet, because it delivers higher systemic exposure. Anyone who needs a lower or a higher dose has to be on film-coated tablets, since the dissolving version is unscored and comes in nothing else.
The mechanism is straightforward. It disintegrates on the tongue within seconds and is taken without liquid, so part of the dose crosses the oral mucosa and the rest is swallowed. Against the 10 mg film-coated tablet, mean exposure ran 21 percent higher in elderly men and 29 percent higher in younger men, while peak concentration was lower, by 19 and 8 percent. Median time to peak, fasted, was 45 to 90 minutes.
Two traps follow. Two dissolving 10 mg tablets are no substitute for a 20 mg film-coated tablet, and were explicitly ruled out as one during the approval review. And a prescription reading simply vardenafil 10 mg is ambiguous between two products of different exposure, which is worth raising with the pharmacist.
Who it genuinely helps: men who cannot swallow tablets easily, and men who would rather dose without a visible glass of water. Both are real reasons to choose it, and neither makes the two 10 mg products the same tablet in different packaging.
Rhythm against erection: the one label in this class with a QT section
The QT question gets settled before the erectile one, and it is settled from the medicine list.
The study behind the warning was small and deliberately built. Fifty-nine healthy men aged 45 to 60 took vardenafil 10 mg, vardenafil 80 mg, placebo and moxifloxacin 400 mg in a randomised crossover design, with QT measured one hour after dosing because that approximates peak concentration. The 80 mg arm, four times the maximum recommended dose, reproduces the plasma levels seen when 5 mg meets ritonavir 600 mg twice daily. Therapeutic and supratherapeutic doses raised QTc by amounts similar to the moxifloxacin control.
A later postmarketing study in 44 volunteers gives the cleaner numbers. Single doses of 10 mg produced a placebo-subtracted mean QTcF change of 5 msec, 90 percent confidence interval 2 to 8. Gatifloxacin 400 mg produced 4 msec, interval 1 to 7. Together the change was additive at 9 msec, interval 6 to 11. Heart rate also rose 5 beats per minute on 10 mg.
Five milliseconds in isolation is a small number and the label says plainly that the clinical impact is unknown. The number that matters is the total, and that is why the restriction is written as it is: avoid the drug in congenital QT prolongation and in men taking class IA agents such as quinidine or procainamide, or class III agents such as amiodarone or sotalol.
In practice the list runs longer than the label's two classes. A man already carrying a QT-prolonging antipsychotic, a macrolide and a low potassium has no reason to start the one PDE5 inhibitor with an additive QT finding on file, when two alternatives are stocked in the same pharmacy.
Ceilings written as milligrams per interval rather than milligrams per dose
Most of these limits do not shrink the tablet. They put a waiting period around it.
Interaction limits as the label writes them
- Ritonavir: no more than 2.5 mg in any 72-hour period.
- Indinavir, saquinavir, atazanavir, clarithromycin, ketoconazole or itraconazole at 400 mg daily: no more than 2.5 mg in any 24-hour period.
- Ketoconazole or itraconazole at 200 mg daily, erythromycin: no more than 5 mg in any 24-hour period.
- Cobicistat and other strong CYP3A4 inhibitors: adjustment required, so check the agent.
- Nitrates in any form, including recreational nitrites, and riociguat: contraindicated at every dose.
Vardenafil is cleared predominantly by CYP3A4, with contributions from CYP3A5 and the CYP2C isoforms, which is where every limit above comes from.
The structure of those limits changes what the drug is. A 2.5 mg ceiling every 72 hours is not an on-demand prescription in any meaningful sense, and a man handed that instruction alongside ritonavir needs to understand it as a planned dose rather than a spare tablet in the drawer.
Alpha-blockers are additive rather than forbidden, which is why the starting dose drops to 5 mg and why the alpha-blocker dose has to be settled first.
One asymmetry deserves flagging, because people carry numbers between drugs in this class. Tadalafil's label carries a 48-hour figure before emergency nitrate use, derived from a dedicated nitroglycerin study. There is no equivalent number in the vardenafil label. A clinician facing chest pain in a man who took vardenafil that evening is working without a published interval, which is a good reason for the man to be able to say the drug name and the time.
A withdrawn brand against a generic that is still stocked
Levitra and Staxyn are gone as brands. Nothing about the molecule changed when they left.
Vardenafil arrived as Levitra in August 2003, in the same four film-coated strengths dispensed today, and later as the dissolving tablet marketed as Staxyn. Neither brand is on the United States market now. Generic film-coated vardenafil and generic dissolving vardenafil are.
That has consequences beyond price. No promotion means very few new starts, so the men on it tend to be men who arrived deliberately. It also means a lot of comparison writing still discusses the drug as though a branded product were being handed over, with brand-era prices attached to nothing.
Absence of marketing is no evidence of inferiority. The trial programme is substantial and the label is detailed, arguably more detailed on cardiac matters than its two competitors. The withdrawal was commercial: a third entrant in a class where the first had recognition and the second had a duration claim nobody could match.
Speed against duration: the trade this molecule makes
Fast on, fast off. That is the shape of the whole prescription.
Peak inside the first hour, half-life of 4 to 5 hours. That gives a defined window with a recognisable start and end, which some men prefer to a drug that is measurably present a day and a half later. It also means there is no weekend in a single tablet, and anyone who wants one is describing tadalafil, set out in the scheduling briefing.
The metabolite does not extend anything, which is worth knowing because people assume it might. M1 circulates at about 26 percent of the parent concentration and inhibits PDE5 at about 28 percent of the parent's potency, so it accounts for roughly 7 percent of total pharmacological activity. Effectively, what you take is what acts.
Against sildenafil the timing profile is close enough that speed is a weak reason to switch. The food rule is the sharper practical difference and it favours neither cleanly: two food-effect studies found high-fat meals cut peak concentration by somewhere between 18 and 50 percent, a range wide enough that the two studies disagreed. The label still permits dosing with or without food.
The speed argument buys predictability rather than pace.
What a fair trial of this drug looks like, and the point at which to stop
Four conditions make a trial fair. Most reported failures miss at least one of them.
An adequate trial has four conditions and men routinely meet two. The right dose, which for most people means 10 mg before anything is concluded. Sixty minutes ahead, not fifteen. No heavy fatty meal immediately beforehand, given that high-fat meals cut peak concentration by 18 to 50 percent in the food-effect studies. And arousal with continued stimulation.
Then several attempts, not one. Failure declared after a single evening is not a finding about the drug.
The escalation is short: 10 mg, then 20 mg, then the question changes from dose to diagnosis. Milligrams do not convert across this class, and a man who needed 100 mg of sildenafil is not thereby a 20 mg vardenafil candidate. The three labels sit side by side in the class comparison, and the sildenafil timing rules that catch people out are in the timing briefing.
There is also a reason to stop that has nothing to do with response. A new antiarrhythmic, a new antipsychotic, a potassium result that has drifted down, or a strong CYP3A4 inhibitor added by another prescriber all change the arithmetic on the QT paragraph after the prescription was written, and the man himself will notice nothing. This is one of the few drugs in ordinary use where the reason to stop turns up on a cardiology letter. Anyone whose response has faded rather than never existed should read why erections fail before asking for a larger tablet.
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What readers asked
Answered by Dr. Marc Vidal, MD · Internal medicine and clinical pharmacology
Vardenafil questions arrive from two directions: men who were switched onto it and want to know why, and men who read the QT warning and stopped. The replies below are general education and cannot account for a medicine list I have not seen.
It was, and I would have said the same. Sotalol is a class III antiarrhythmic, and the vardenafil label asks prescribers to avoid the drug in men taking class IA or class III agents, alongside anyone with congenital QT prolongation. The reason is additive: a 10 mg dose produced a mean QTcF increase of 5 msec on its own in the postmarketing study, and 9 msec when given with a quinolone that adds 4 msec by itself. Sotalol's whole mechanism is QT prolongation, so the sum is not a number anyone wants to test. What matters practically is that this restriction is specific to vardenafil rather than to the class. Sildenafil and tadalafil carry no equivalent paragraph, so there is a conversation to have with your own prescriber rather than a dead end.
My husband was given 5 mg. He is 68 and otherwise well. Why not the usual 10?
Age alone is the reason, and it is in the label. In the volunteer study, men aged 65 and over reached mean peak concentrations 34 percent higher and mean exposure 52 percent higher than men aged 18 to 45 on the same dose, so a 5 mg start should be considered in that age group. It is a starting point rather than a ceiling. Five milligrams gave a 51 percent rate of maintaining an erection to successful intercourse in the North American trial against 32 percent on placebo, and 10 mg gave 64 percent, so there is a real step available if 5 is not enough after several fair attempts. That step belongs to whoever knows his blood pressure and his medicine list.
The pharmacy gave me a tablet that melts on the tongue instead of my usual 10 mg. Same thing?
No, and this is one of the few genuinely important formulation differences in this class. The dissolving tablet is not interchangeable with the 10 mg film-coated tablet, because it delivers higher systemic exposure. In the manufacturer's comparison, mean exposure was 21 to 29 percent higher depending on age group. It also only exists as 10 mg, unscored, so there is no way to adjust down from it. Take it on the tongue without water and expect the peak somewhere between 45 and 90 minutes. If you have been managing well on film-coated 10 mg, ring the pharmacy and ask whether this was a deliberate substitution or a stocking decision, because it should have been a prescribing one.
Is this drug actually any faster than sildenafil, or is that marketing?
Largely marketing, at least as a reason to choose between them. Vardenafil peaks at a median of 60 minutes fasted with a range of 30 to 120, and sildenafil peaks at a median of 60 minutes with the same range. The half-lives are close too, 4 to 5 hours against about 4. If a man does better on one than the other, the explanation is more likely individual absorption than a class property, and absolute bioavailability is around 15 percent for vardenafil against 41 percent for sildenafil, with wide individual variation in both. Where the two genuinely differ is the QT paragraph and the interaction ceilings, not the clock.
Ten milligrams did not do much. Is 20 worth trying or should I change drug?
Worth trying, though the honest expectation is modest. In the North American trial, the per-patient rate of maintaining an erection to intercourse was 64 percent on 10 mg and 65 percent on 20 mg, so the gain from doubling is small in the aggregate even though individual men do respond to it. Before you do, check the four conditions that make a trial fair: 60 minutes ahead rather than fifteen, no heavy fatty meal immediately before, arousal and continued stimulation, and several attempts rather than one. High-fat meals cut the peak by anywhere from 18 to 50 percent in the food-effect studies. If 20 mg over several properly timed attempts does nothing, the useful next step is a look at the cause rather than another tablet in the same class.
He is on clarithromycin for a chest infection this week. Can he still use his 10 mg?
Not at 10 mg. Clarithromycin is a strong CYP3A4 inhibitor and vardenafil is cleared mainly by that enzyme, so the label caps him at 2.5 mg in any 24-hour period while he is on it. Notice that the limit is written as a dose and an interval rather than as a smaller tablet, which is the pattern throughout this section of the label: ritonavir is 2.5 mg per 72 hours, erythromycin and lower azole doses are 5 mg per 24 hours. The practical answer for a one-week antibiotic course is usually to wait it out. If he does want to take something during it, that is a prescriber's decision, and 2.5 mg tablets may not be what is in the house.
I noticed a blue-green tinge on colours for an hour or two. Should I stop?
Almost certainly not, though it is worth telling your prescriber it happened. What you are describing is the recognised PDE6 effect. Vardenafil is more than 15-fold more selective for PDE5 than for PDE6, which is the narrowest of its selectivity margins, and PDE6 is the enzyme doing phototransduction in retinal rods and cones. Formal testing across this drug class shows transient, dose-related impairment of blue and green discrimination, most evident about an hour after the dose and reduced but still detectable at six hours. In 25 men given 40 mg, twice the maximum daily dose, visual acuity, intraocular pressure and fundoscopic examination were unchanged. What is not in that category is sudden loss of vision or hearing, which means stop the drug and get seen the same day.
I had my prostate removed two years ago. Realistically, will this work?
Sometimes, and the trial numbers are worth having in front of you because they are the lowest in the programme. In the post-prostatectomy study, the rate of achieving an erection sufficient for penetration was 47 percent on 10 mg and 48 percent on 20 mg against 22 percent on placebo, and maintenance to successful intercourse was 37 and 34 percent against 10. So a real effect, roughly three to four times placebo, and well below what the same drug does in men with intact nerves. Whether nerve-sparing surgery was possible matters more than the dose does, and that is a question for your surgeon's operation note. A fair trial here means more attempts over more weeks than usual before drawing a conclusion, and a frank conversation about second-line options if it comes to that.
Why did his doctor pick this one when there are two better-known tablets?
Usually one of three reasons, and it is fair to ask which. A poor or unsatisfactory response to sildenafil is the commonest. A preference for a defined window rather than a drug that is measurably present a day and a half later is the second. The third is simply what a particular prescriber is comfortable with, and that is a legitimate answer as long as the QT question was asked first. What should not be part of the reasoning is that it is somehow stronger, because it is not: this class works by the same mechanism and the milligrams do not convert between molecules. The brand left the United States market some years ago and the generic remains, so the price should now look like a generic price. If it does not, that is worth checking too.
Read each reply as a general teaching point, not a plan built for the person who asked. Your own situation - notes, bloods, every medicine you take - belongs in front of a prescriber who can weigh all of it together.