Cialis vs Vardenafil (Levitra/Staxyn): Switching Between Them

How Tadalafil and Vardenafil Work

Both drugs block phosphodiesterase type 5 (PDE5) in the corpus cavernosum, increasing cyclic GMP and allowing smooth-muscle relaxation during sexual arousal. The mechanism is identical at the enzyme level. What separates them is pharmacokinetics, tissue selectivity, and formulation options.

Tadalafil has a half-life of approximately 17.5 hours, giving it the longest activity window among PDE5 inhibitors 1. This extended duration earned it the informal label of "the weekend pill." Vardenafil, by contrast, reaches peak plasma concentration (Tmax) in about 60 minutes and clears with a half-life of 4 to 5 hours 2. That shorter window means vardenafil is strictly an on-demand medication. Tadalafil's pharmacokinetic profile also enables an FDA-approved daily regimen at 2.5 mg or 5 mg, which eliminates the need to time doses around sexual activity.

Both agents show selectivity for PDE5 over PDE6 (the retinal isoform), though vardenafil has slightly higher PDE6 affinity than tadalafil. Tadalafil, on the other hand, inhibits PDE11 to a greater degree, which may explain some of the myalgia and back pain reported with that drug. Neither difference is clinically dangerous, but they contribute to the distinct side-effect profiles discussed below.

Efficacy Comparison: What the Trials Show

No large, prospective, head-to-head trial has directly compared tadalafil to vardenafil. The evidence base consists of separate placebo-controlled trials and several crossover preference studies.

In the Brock et al. registration trial (N=1,112), tadalafil 20 mg improved the International Index of Erectile Function (IIEF) erectile-function domain score by a mean of 7.9 points over placebo (P<0.001), and 81% of intercourse attempts were successful at 36 hours post-dose 1. Porst et al. studied vardenafil in men with diabetes-associated ED (N=452) and found that vardenafil 20 mg improved IIEF-EF scores by 6.6 points versus placebo (P<0.001), with a 49% success rate on the Sexual Encounter Profile question 3 (SEP-3) compared to 23% for placebo 2. Direct numeric comparison across these trials is unreliable because the populations differed; diabetic ED is inherently harder to treat.

A 2006 meta-analysis published in the European Urology journal pooled 82 randomized controlled trials of all PDE5 inhibitors and concluded that tadalafil, vardenafil, and sildenafil produced statistically similar improvements in IIEF-EF scores when adjusted for baseline severity 3. The American Urological Association (AUA) 2018 guideline on ED states that no single PDE5 inhibitor is superior to another in overall efficacy and that drug selection should be guided by patient preference, dosing convenience, and side-effect tolerance 4.

Dosing and Formulations

Tadalafil is available in 2.5 mg, 5 mg, 10 mg, and 20 mg tablets. The on-demand starting dose is 10 mg taken at least 30 minutes before anticipated sexual activity, adjusted to 20 mg or down to 5 mg based on response and tolerability. The daily regimen uses 2.5 mg or 5 mg taken at the same time each day, regardless of sexual timing.

Vardenafil comes as film-coated tablets (5 mg, 10 mg, 20 mg) and the orally disintegrating tablet (ODT) Staxyn at 10 mg. The ODT dissolves on the tongue without water, which some men prefer for discretion or convenience. The standard starting dose is 10 mg taken 25 to 60 minutes before sexual activity, with a maximum of one dose per 24 hours. There is no approved daily-dosing regimen for vardenafil.

High-fat meals delay vardenafil absorption and reduce Cmax by roughly 18 to 50% depending on the formulation 5. Tadalafil absorption is not meaningfully affected by food, which gives it a practical advantage for men who prefer not to plan meals around dosing.

For men older than 65, vardenafil prescribing information recommends starting at 5 mg. Tadalafil does not carry a specific age-based dose reduction but does require adjustment for renal impairment: men with creatinine clearance 30 to 50 mL/min should not exceed 5 mg daily or 10 mg every 48 hours on demand 6.

Side-Effect Profiles

PDE5 inhibitors share class-wide side effects: headache, flushing, nasal congestion, and dyspepsia. The frequency and character of adverse events differ between the two drugs because of their distinct tissue selectivities.

Tadalafil's inhibition of PDE11 in skeletal muscle contributes to back pain and myalgia, reported in 5 to 6% of men taking 20 mg on demand 1. These symptoms typically appear 12 to 24 hours after dosing, are mild to moderate, and resolve within 48 hours. Vardenafil does not commonly cause back pain or myalgia, but its slightly higher PDE6 activity means visual disturbances (blue-tinged vision, increased brightness sensitivity) occur in about 2% of men on 20 mg, though this rate is lower than that reported with sildenafil 2.

Flushing rates are comparable: approximately 11% with tadalafil 20 mg and 11% with vardenafil 20 mg in registration trials. Dyspepsia is somewhat more common with tadalafil (8 to 11%) versus vardenafil (3 to 4%). Nasal congestion occurs at similar rates with both.

Vardenafil carries a QTc prolongation warning in its prescribing information. Men with congenital long QT syndrome or those taking Class IA or III antiarrhythmics (quinidine, procainamide, amiodarone, sotalol) should avoid vardenafil. Tadalafil does not carry this QTc warning, making it the safer choice in men with rhythm concerns.

Both drugs are absolutely contraindicated with nitrates. A minimum 48-hour washout is recommended after tadalafil (given its long half-life) before nitrate administration versus 24 hours after vardenafil 6.

How to Switch from Cialis to Vardenafil (or Vice Versa)

Switching between PDE5 inhibitors does not require a formal washout period. Stop taking the first drug and start the second at the next planned dose.

The practical steps differ slightly depending on direction. A man discontinuing daily tadalafil 5 mg can take vardenafil on demand the following day, since tadalafil's therapeutic window will have largely closed after 24 to 36 hours. Going the other direction is even simpler: vardenafil clears the system within 20 hours (roughly five half-lives), so daily tadalafil can begin the next day.

Three common reasons drive a switch:

1. Timing preference. Men who want spontaneity over a weekend or vacation often prefer tadalafil. Men who prefer a defined window with faster offset may prefer vardenafil.
2. Side-effect intolerance. Persistent myalgia or back pain on tadalafil is one of the top reasons men try vardenafil. Conversely, a man bothered by visual disturbances on vardenafil may tolerate tadalafil without that issue.
3. Concurrent BPH/LUTS. Tadalafil 5 mg daily is the only PDE5 inhibitor approved for both ED and benign prostatic hyperplasia 7. Men with significant urinary symptoms benefit from this dual indication.

A 2004 crossover study by Tolra et al. found that 62% of men who were dissatisfied with one PDE5 inhibitor achieved satisfactory erections after switching to another, and patient preference split roughly equally between tadalafil and vardenafil when both were tried 8. The AUA guideline specifically recommends trialing at least two PDE5 inhibitors at optimal doses before concluding a patient is a PDE5 non-responder 4.

Tadalafil Daily vs. Vardenafil On-Demand: Which Regimen Fits Whom

The daily tadalafil regimen (2.5 or 5 mg) maintains a steady-state plasma concentration after approximately 5 days of dosing. The advantage is continuous readiness: no planning required, no pill-taking visible to a partner, and stable drug levels that some men report improve endothelial function over time 9.

Vardenafil's on-demand model suits men who have intercourse fewer than twice per week and prefer not to take a daily medication. Its rapid onset (some data show effect as early as 15 minutes with the ODT) is a genuine clinical advantage for unplanned encounters within its activity window 10.

Cost is another variable. Generic tadalafil daily is often cheaper per month than branded Staxyn and comparable to generic vardenafil tablets, though pricing depends on insurance formulary and pharmacy. GoodRx data from May 2026 shows generic tadalafil 5 mg (30 tablets) averaging $15 to $40 at U.S. retail pharmacies, while generic vardenafil 20 mg (10 tablets) ranges from $25 to $60.

Dr. Arthur Burnett, Professor of Urology at Johns Hopkins and a principal investigator in multiple PDE5 trials, has stated: "The choice between PDE5 inhibitors is not about which drug is stronger. It is about matching the pharmacokinetic profile to the patient's lifestyle and sexual patterns" 4.

Drug Interactions and Contraindications

Both tadalafil and vardenafil are metabolized primarily by CYP3A4. Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) increase plasma levels of both drugs and require dose reduction. With vardenafil, the maximum dose drops to 5 mg per 24 hours when co-administered with a potent CYP3A4 inhibitor. For tadalafil, the recommendation is not to exceed 10 mg every 72 hours on demand, or to avoid the daily regimen altogether with strong inhibitors 6.

Alpha-blockers interact with both PDE5 inhibitors. Tadalafil should not be co-administered with doxazosin. With tamsulosin 0.4 mg (the most uroselective alpha-blocker), tadalafil can be given at any approved dose. Vardenafil should be initiated at 5 mg when combined with any alpha-blocker, and the alpha-blocker should be stable for at least 6 hours before vardenafil is taken.

Grapefruit juice and moderate CYP3A4 inhibitors (erythromycin, fluconazole, aprepitant, verapamil, diltiazem) may increase exposure to both drugs. The clinical significance is usually modest, but awareness prevents unexpected side effects at standard doses.

Special Populations: Diabetes, Post-Prostatectomy, and Cardiovascular Risk

Diabetic ED is common: roughly 52% of men with type 2 diabetes report some degree of erectile difficulty 11. Both drugs work in this population, though response rates are lower than in the general ED population. Porst et al. demonstrated that vardenafil 20 mg improved GAQ (Global Assessment Question) positive response to 57% versus 36% for placebo in men with diabetes 2. Tadalafil 20 mg produced GAQ positive responses of 64% in the Brock et al. mixed-population trial, though the diabetic subgroup had lower rates 1.

Post-radical-prostatectomy patients with intact nerve bundles respond to PDE5 inhibitors at lower rates overall (roughly 35 to 60% depending on nerve-sparing quality). Daily tadalafil 5 mg has been studied for penile rehabilitation after prostatectomy, with the REACTT trial (N=423) showing that daily tadalafil preserved penile length and improved spontaneous erection recovery at 9 months compared to on-demand use or placebo 12.

Regarding cardiovascular safety, the Princeton III Consensus Panel concluded that PDE5 inhibitor use is safe in men at low cardiovascular risk and can be considered in men at intermediate risk after exercise stress testing 13. Neither tadalafil nor vardenafil increases cardiovascular event rates in controlled trials. The QTc caveat for vardenafil remains the relevant distinction for men with arrhythmia history.

When Neither Drug Works: Next Steps

Approximately 30 to 35% of men with ED do not respond adequately to any oral PDE5 inhibitor 4. Before labeling a patient a non-responder, clinicians should confirm that the drug was taken correctly (adequate sexual stimulation, proper timing, avoidance of heavy meals with vardenafil) and that at least two different PDE5 inhibitors were tried at maximum tolerated doses.

If oral therapy fails, second-line options include intracavernosal injection (alprostadil, trimix), intraurethral suppositories (MUSE), vacuum erection devices, and low-intensity shockwave therapy (Li-SWT). Third-line treatment is penile prosthesis implantation, which carries satisfaction rates above 90% in published series 14.

The AUA guideline recommends shared decision-making at each stage, noting that patient and partner satisfaction varies as much with expectations and relationship factors as with physiological response 4. Men taking daily tadalafil 5 mg for combined ED and BPH who find ED response inadequate at that dose can trial on-demand vardenafil 10 to 20 mg on top of stopping the daily tadalafil, rather than escalating to injections prematurely.