You keep saying the gap over placebo matters more than the drug's own success rate. Why?
The 36-hour ad used 20 mg; Brock's 5 mg cell bought IIEF
Separate the invoice from the slogan. Cialis 5 mg PRN has a published as-needed receipt. The weekend clock that still lives on billboards is a different milligram.
Sexual-medicine marketing loves a round number of hours. Thirty-six is vivid. It is also a 20 mg timed-study claim, not a 5 mg as-needed domain score. If a page leads with the clock and never names Brock's 5 mg cell, you are reading an ad with a citation stuck on the end.
Trial cost, on this desk, means what the sponsor actually paid for in endpoints. For Cialis 5 mg PRN that payment is IIEF-EF change, SEP2 change, and SEP3 change against placebo over 12 weeks. Hours after a 20 mg swallow are a different line item. You can care about both. You cannot spend one as if it were the other.
This essay is not a second monograph. The tadalafil compound card already lists doses and holds. Here the job is narrower: show which named study produced the 5 mg as-needed numbers people should quote, and show which famous clock those numbers never purchased. Dose-point method on an evidence page means mark the receipt, then name the milligram the table actually tested.
If you came from the Bothell story of the 5 mg night chip, you already know daily was a later ask. This page asks a different question. Once those PRN numbers existed, what did 5 mg as needed actually buy - and what did reviews keep charging to the wrong account?
151 men, +4.6 points, SEP3 +22 - that is the 5 mg PRN receipt
Brock and colleagues pooled five 12-week, randomized, double-blind, placebo-controlled trials (April 1999 to April 2001, 74 centers, n = 1,112). Mean age 59 (range 22 to 82). Mild to severe ED, mixed etiologies. Fixed as-needed strengths: 2.5, 5, 10, or 20 mg, no food or alcohol restrictions in the protocol language. The 5 mg cell held 151 men. Placebo held 308.
Co-primaries were IIEF-EF change plus mean per-patient SEP2 and SEP3 yes rates. On Cialis 5 mg PRN, mean IIEF-EF rose from baseline by 4.6 points to an end-point 17.7, versus +0.6 to 15.1 on placebo (p < 0.001). SEP2 (penetration) end-point success was 57 percent, a +16 point change. SEP3 (completed intercourse) end-point success was 40 percent, a +22 point change. Placebo SEP3 sat at 31 percent (+6 from baseline).
GAQ improved-erection rate on 5 mg was 50 percent versus 35 percent on placebo. Intercourse-satisfaction and overall-satisfaction domains also moved at 5 mg (both p < 0.001 versus placebo). Discontinuation for adverse events in the 5 mg cell was 0.7 percent (one man) versus 1.3 percent on placebo. That is a tolerability voice, not a potency contest with 20 mg.
The 20 mg cell is the one screenshots love: +7.9 IIEF-EF, end-point 23.9, about 75 percent of attempts completed, 81 percent GAQ yes. Quote those bars as 20 mg. A review that pastes 75 percent next to a 5 mg PRN blister is not rounding. It is swapping invoices. Dose-response was numeric. 5 mg cleared the bar. It did not match the 20 mg peak. That is why most US starts are still 10 mg, with 5 mg as the labeled step-down.
Placebo already moved; subtract before you spend the claim
ED placebo arms run hot. Diary keeping, hope, and a scheduled visit lift SEP on their own. The drug effect is what remains after you subtract that background.
Always read the gap, not the raw drug percentage. A headline that shouts 40 percent SEP3 on 5 mg without the placebo 31 percent is a flyer, not a trial. Brock published both arms. Use both. The honest 5 mg PRN spend is a +22 point SEP3 change against a +6 point placebo change, and a +4.6 IIEF-EF change against +0.6.
IIEF-EF averages weeks of memory. SEP2 asks whether penetration happened. SEP3 asks whether intercourse finished. A man can pass SEP2 and fail SEP3. That pattern is the sustain complaint clinics already know. Regulators wanted both the questionnaire and the diary so a good week of mood could not carry a weak attempt record, and so a few lucky nights could not hide a flat IIEF.
Notice the 5 mg end-point IIEF-EF of 17.7. That is still in a mild-to-moderate band for many men, not a jump to the Cappelleri normal zone of 26 or greater that 59 percent of the 20 mg group reached. A complete review says that out loud. An ad does not. Trial cost includes the ceiling you did not buy.
Class tools are shared. Sildenafil trials used the same diaries. Differentiation at the desk is duration, food, back-pain rates, and the 48-hour versus roughly 24-hour nitrate spacing - not a secret IIEF champion. Cialis 5 mg PRN wins on a smaller as-needed peak, not on a unique questionnaire.
Nitrate users never sat in that 151
Published Cialis 5 mg PRN numbers look clean because the dangerous row never sat in the chair. Brock excluded men treated with nitrates, along with recent stroke or myocardial infarction, unstable angina, poorly controlled blood pressure, and failure after radical prostatectomy or pelvic surgery. The SEP column therefore cannot tell you how a man on isosorbide would have fared.
Sponsors answer expectation with randomization and locked endpoints. They answer the nitrate problem a cruder way: they do not enroll it. That is ethically correct. It is also why a review that reprints +4.6 IIEF points and forgets the door is incomplete. You can trust the placebo-adjusted gains inside the enrolled population. You cannot smuggle a chest-pain spray into that population with a smaller stamp.
Porst's timed 36-hour protocol used the same class door. So did the later once-daily packages. Interaction risk is mechanistic - shared cGMP rise, additive hypotension - plus dedicated blood-pressure work after tadalafil 5 to 20 mg plus a nitrate. It will never appear as a SEP cell you can subtract. Reviews that skip nitrates are not lying about IIEF. They are lying by omission about who the IIEF describes.
In those interaction studies, tadalafil potentiated nitrate hypotension at each measured time point through 24 hours. At 48 hours, most hemodynamic measures no longer showed the interaction; a few men still had greater blood-pressure lowering. After 48 hours the interaction was not detectable as a group effect. That curve is why the label says: if nitrate is medically necessary in a life-threatening situation after Cialis, wait at least 48 hours from the last dose, then give nitrate only with monitoring. That is not a home protocol. A 5 mg PRN swallow is still a last dose.
Porst's clock is a different invoice
Porst, Padma-Nathan, Giuliano, and colleagues randomized 348 men (mean age 57) in Europe and the US to tadalafil 20 mg (n = 175) or placebo (n = 173). Men were assigned to 4-week intervals that requested attempts at about 24 or 36 hours after the swallow. Primary outcome: successful intercourse to ejaculation on the SEP diary. Three hundred twenty-seven men finished (94 percent).
At 36 hours, 59.2 percent of attempts succeeded on tadalafil versus 28.3 percent on placebo. At 24 hours, 52.9 versus 29.1. Headache, flushing, dyspepsia, and myalgia were more common on drug. That is the 36-hour claim in numbers, not in advertising copy. Notice what is absent. No Cialis 5 mg PRN arm. No nitrate challenge. No 48-hour blood-pressure curve as a SEP endpoint.
Brock did report successful-intercourse rates at selected post-dose intervals for the 20 mg group - 73 to 80 percent of attempts between 30 minutes and 36 hours. Again: 20 mg. A Portland desk that counsels Cialis 5 mg PRN can say the molecule is long. It cannot honestly say the 5 mg cell purchased Porst's 59.2 percent at hour 36. That study never asked 5 mg that question.
Duration data get quoted as if they were a safety study. They are a timing study on a clean roster. Hours are not a hold. The 48-hour emergency sentence lives in pharmacology, not in a weekend slogan. If a review leads with 36 hours and never names the 5 mg IIEF receipt, the review failed the invoice test.
Headache 11 percent is the 5 mg PRN safety voice, not a slogan
Adverse-event tables are part of trial cost. A page that only prints IIEF is still spending half the receipt.
In Brock's 5 mg cell, headache occurred in 11 percent (versus 6 percent on placebo), dyspepsia in 5 percent (versus 2), back pain in 3 percent (versus 5 - not a 5 mg signal there), nasal congestion in 4 percent, myalgia in 1 percent, flushing in 3 percent. Events were mostly mild or moderate. The 20 mg cell was louder: headache 21 percent, dyspepsia 17 percent, back pain 9 percent, myalgia 7 percent.
That gradient is why a man who flushed on 10 or 20 mg is a candidate for Cialis 5 mg PRN, not a candidate for a speech about toughness. Back pain and myalgia in the class often show up 12 to 24 hours after a swallow and usually ease within 48 hours. Counsel it. Do not let it crowd out the nitrate door.
Brock tabulated blood pressure, vision complaints, and cardiac events, but the design never stress-tested a man who keeps nitroglycerin in a jacket. One tadalafil-treated patient (0.1 percent across all doses) reported abnormal color vision. Quoting Brock as proof that Cialis is heart-safe in nitrate users is a category error. The study never asked that question.
CYP3A4 is the other skipped row. Strong inhibitors raise tadalafil exposure. The labeled PRN maximum becomes 10 mg no more than once every 72 hours. Daily maximum becomes 2.5 mg. Trial efficacy tables were not built as interaction tables. The PI's dose-adjustment chapter is. Guanylate-cyclase stimulators share the nitrate logic: hard no.
How a Portland desk reads a 5 mg PRN table
Start with schedule. If the table says 5 mg and the methods say as needed before intercourse, you are in Brock's PRN cell. If the table says once daily for 24 weeks, you are in the 2008 package, and 5 mg there is a breakfast trough, not Cialis 5 mg PRN. Wrong schedule is the most common honest mistake I see on printouts.
Then subtract placebo. Then name the tool: IIEF-EF versus SEP2 versus SEP3 versus, later, IPSS. Then say who was absent: nitrate users, many post-prostatectomy failures, unstable coronary disease. A covering pharmacist does not need a cheer. They need those four lines.
Then refuse the clock swap. If the page in your hand leads with 36 hours, ask which milligram Porst used. If the answer is 20 mg, the clock is not the 5 mg receipt. You can still counsel that tadalafil lasts longer than sildenafil. You cannot paste 59.2 percent at hour 36 onto a 5 mg blister.
If your only question is whether a 5 mg as-needed strip wastes fewer swallows than a morning almond, leave this page for the Portland split on 5 mg PRN versus daily. IIEF will not price a blister. IPSS will not either.
Point: pay for the domain change you can name
| Named package | Milligram that paid | What a review must not steal |
|---|---|---|
| Brock 2002, 5 mg cell (n=151) | PRN 5 mg; +4.6 IIEF-EF; SEP3 +22 | 20 mg SEP3 ~75%; Porst 36-hour rates |
| Brock 2002, 20 mg cell (n=258) | PRN 20 mg; +7.9 IIEF-EF; ~75% SEP3 | A 5 mg blister; daily breakfast claims |
| Porst 2003 (n=348) | 20 mg timed 24/36 h SEP success | Any 5 mg PRN duration claim |
| Rajfer 2007 (n=287, 24 wk) | Daily 2.5 and 5 mg; IIEF and SEP | A 5 mg as-needed receipt |
| Nitrate PK studies (label) | BP after tadalafil 5-20 mg + nitrate | SEP diaries; a 5 mg PRN safety passport |
Commercial reviews love a single percentage. Cialis 5 mg PRN improved completed intercourse by 22 percentage points in Brock. That sentence is true and still incomplete. Add the placebo +6. Add the 12-week length. Add the closed nitrate door. Add the 20 mg clock that this cell did not buy. Then the sentence is a point.
Bing-style pages that skip nitrates are not a small omission. They are the omission that gets a man in trouble on a Monday chest-pain call. EMS needs the last-dose time. A Friday 5 mg is a last dose. There is no 36-hour charm that makes a spray safe.
Food is a secondary honesty check. Tadalafil absorption was not materially blunted by high-fat meals in the protocols reviewers cite, unlike sildenafil. That is a real administration win. It is not a safety win. Do not trade a clean plate for a forgotten nitrate history.
Point. Cialis 5 mg PRN works on IIEF and SEP in men who were allowed through the door. The trial cost is +4.6 domain points and a +22 SEP3 change, not a 36-hour ad filmed on 20 mg. Your job is to put the receipt and the door back on the printout before anyone treats a weekend slogan as a 5 mg result.
Reader mail
Reader questions on this article
Answered by Dr. Priya Raman, PharmD · Clinical pharmacology & drug safety
These threads asked what a 5 mg as-needed cell actually purchased. Answers stay general. Priya has not weighed you or seen your spray list.
Sexual-medicine placebo arms run hot. Diary keeping, hope, and a scheduled visit lift SEP on their own. The drug effect is what remains after you subtract that background. Brock's Cialis 5 mg PRN arm improved completed intercourse by 22 percentage points; placebo did 6. End-point SEP3 was 40 percent versus 31 percent. Quoting 40 without 31 is a flyer. I want both bars, the 12-week length, and the nitrate door on the same scrap of paper before I trust a review.
What is the practical difference between SEP2 and SEP3 on a 5 mg PRN chart?
SEP2 is penetration. SEP3 is completion. You can pass the first and fail the second. That is the sustain complaint. Brock reported both as co-primaries with IIEF-EF. On 5 mg as needed, SEP2 rose 16 points to 57 percent; SEP3 rose 22 points to 40 percent. I care more about SEP3 when a couple's goal is finished intercourse, and I still want IIEF for the weeks between attempts. Neither diary enrolled a nitrate user. Do not let a yes on SEP2 talk you into a spray.
My father is on isosorbide. His clinic quoted Brock's +4.6 IIEF points. Is that relevant?
The +4.6 is real for the enrolled 5 mg as-needed group versus +0.6 on placebo. It is not relevant as a safety passport. Isosorbide is an organic nitrate. The trial never randomized that pair. The PI contraindicates any tadalafil schedule with any nitrate form. Cialis 5 mg PRN is still a last dose with a 48-hour emergency gap, not a loophole because the stamp looks small. Cardiology owns the chest plan. I would not start tadalafil from a quoted domain score.
Did the 36-hour Porst study prove my 5 mg tablet still works Sunday after a Friday swallow?
Porst measured SEP success at 24 and 36 hours after 20 mg, on a nitrate-free roster. Brock's interval analysis of successful attempts out to 36 hours was also a 20 mg story. Cialis 5 mg PRN uses the same long half-life, so a next-day attempt is biologically plausible for some men. Plausible is not Porst's 59.2 percent. I will not paste a 20 mg timed study onto a 5 mg blister. And none of those hours make a nitrate safe the next morning.
Are the 5 mg PRN results just a weaker leftover from the 20 mg cell?
Weaker peak, same evidentiary bar. Brock's 20 mg IIEF gain of 7.9 points is not a reason to call the 5 mg gain of 4.6 a failure. Each arm had to beat its own placebo. I pick Cialis 5 mg PRN when 10 mg is too much flush or too much peak, and 10 or 20 mg when the 5 mg domain change is not enough. I do not rank them on a single IIEF leaderboard stolen from an ad. Neither package enrolled nitrates.
Why do some pages mix Rajfer's daily 5 mg numbers into a PRN review?
Because the stamp is identical and the schedule is not. Rajfer asked whether 5 mg every morning for 24 weeks beat placebo without a pre-sex bolus. Brock asked whether 5 mg before sex for 12 weeks beat placebo. Daily 5 mg is a trough. Cialis 5 mg PRN is a bolus. If a page will not name Brock versus Rajfer, will not subtract placebo, and will not mention nitrates, treat it as advertising. Ask for the citation. Then open the schedule row yourself.
If all PDE5 trials use IIEF and SEP, are the drugs interchangeable on evidence?
Efficacy tools cluster. Administration does not. Half-life, food, myalgia, and nitrate spacing differ. Tadalafil's 48-hour emergency gap is longer than the sildenafil habit because drug persists. Cialis 5 mg PRN still persists. I still want a full med list, including poppers, before anyone treats class tools as a free swap. Interchangeable questionnaires are not interchangeable holds.
Do these trials tell us anything useful about heart medicines besides nitrates?
They tabulate adverse events and exclusions. They do not replace an interaction review. Alpha-blockers need a stable dose first and a low PDE5 start if the pair is for ED, not a stacked BPH pair. Strong CYP3A4 inhibitors cap PRN tadalafil at 10 mg every 72 hours. Riociguat is a hard no. Efficacy trials prove SEP movement. The PI's interaction chapters prove the rest. Bring the full list to your own pharmacist.
I saw a review that said 75 percent success and nothing else. Which paper is that even from?
That raw figure is in the Brock 20 mg PRN neighborhood (SEP3 around 75 percent of attempts), not the 5 mg as-needed cell (end-point SEP3 40 percent, change +22 versus +6 on placebo). If a page will not name the milligram, will not subtract placebo, and will not mention nitrates, treat it as a 36-hour ad with a footnote. Ask for the citation. Then read the 5 mg receipt yourself.
General education from a clinician, not personal medical advice. Bring your own history to your own prescriber.
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