Vardenafil Vs Tadalafil: Duration, Dosing, Side Effects, Cost

Vardenafil and tadalafil differ in potency, duration, onset, dosing, and approved uses. Vardenafil demonstrates higher potency at the molecular level and achieves a faster onset of action, usually within the first hour. Its effectiveness lasts for about 4–6 hours, making it suitable for short-term relief. Tadalafil, in contrast, shows a longer half-life and extended activity, with results lasting up to 36 hours. It reaches peak effect in about 2 hours and maintains efficacy regardless of food intake, while vardenafil absorption can be delayed by high-fat meals. Vardenafil is used only as an on-demand treatment for erectile dysfunction, while tadalafil offers both on-demand and daily dosing, and is approved for benign prostatic hyperplasia and pulmonary arterial hypertension. Side effect patterns mark another area of separation. Vardenafil is more often linked with visual disturbances due to PDE6 inhibition, while tadalafil is commonly associated with back pain and muscle aches from PDE11 inhibition. Both drugs share general effects such as headache, flushing, and nasal congestion, though these overlap less prominently than their distinguishing adverse events. Below is a table that provides a side-by-side comparison of vardenafil and tadalafil, summarising their key differences in potency, onset, duration, dosing, approved uses, side effects, and cost.

Aspect	Vardenafil	Tadalafil
Potency (IC₅₀)	0.089–0.89 nM (more potent)	1.8–9.4 nM (less potent)
Onset of Action	10–60 minutes (faster)	16–30 minutes (slower)
Duration of Effect	4–6 hours	Up to 36 hours
Bioavailability	~15%	~80%
Food Effect	Delayed and reduced absorption with high-fat meals	No significant effect
Dosing Regimen	5–20 mg on-demand, max once daily	10–20 mg on-demand or 2.5–5 mg daily
Approved Uses (FDA)	Erectile dysfunction only	Erectile dysfunction, benign prostatic hyperplasia, ED + BPH combination (Entadfi), pulmonary arterial hypertension
Side Effect Profile	Visual disturbances (2–4%), headache, flushing	Back pain (8–9%), myalgia (4–5%), headache, flushing
Drug Interactions	More sensitive to CYP3A4 inhibitors, contraindicated with nitrates and riociguat	Less sensitive to CYP3A4 inhibitors, contraindicated with nitrates and riociguat
Cost (Generic)	Generally lower	Often higher due to broader medical uses

What Is The Difference Between Vardenafil And Tadalafil?

Vardenafil and tadalafil differ in potency, selectivity, pharmacokinetics, clinical profiles, and side effects, even though both belong to the same class of PDE5 inhibitors. Vardenafil demonstrates greater potency and selectivity for PDE5 than tadalafil. According to the “European public assessment report (EPAR) for Levitra” published by European Medicines Agency, vardenafil achieves an IC₅₀ of 0.89 nM compared to tadalafil’s 9.4 nM.

The selectivity patterns for other phosphodiesterase isoforms also separate these agents. A study titled, “Current use of phosphodiesterase inhibitors in urology” shows that vardenafil has a selectivity ratio of 15 for PDE6, which explains its association with visual side effects. In contrast, A research titled, “Identification of Amino Acid Residues Responsible for the Selectivity of Tadalafil Binding to Two Closely Related Phosphodiesterases, PDE5 and PDE6”, indicates that tadalafil displays 200 fold higher affinity for PDE5 than PDE6, which reduces the likelihood of ocular disturbances compared to vardenafil.

Pharmacokinetic differences are significant between both the drugs. Tadalafil exhibits nearly 80% bioavailability, while vardenafil’s is around 15%. A pharmacokinetics study published in PMC reports that tadalafil reaches maximum plasma concentration in about 2 hours, whereas vardenafil peaks within 1 hour in fasting states. Elimination half-life adds to the contrast: the “Tadalafil in the treatment of erectile dysfunction” review confirms tadalafil’s half-life of 17.5–21.6 hours, extending its therapeutic effect to 36 hours, while vardenafil’s half-life is about 4 hours.

Food effects are another differentiator. Rajagopalan et al.’s clinical trial notes that a high-fat meal reduces vardenafil’s Cmax by 18% and delays absorption by up to 1 hour. Tadalafil, however, remains unaffected by fatty meals or alcohol due to its slower absorption and longer half-life.

Onset of action is faster with vardenafil. P J Wright’s, “Comparison of phosphodiesterase type 5 (PDE5) inhibitors”, comparison study indicates that 21% of men achieved successful intercourse within 10 minutes of taking vardenafil, while 16% did so with tadalafil within 16 minutes. However, tadalafil’s longer duration compensates for this slower onset.

Patient satisfaction also differs. A multinational observational study, “Therapeutic Effectiveness and Patient Satisfaction after 6 Months of Treatment with Tadalafil, Sildenafil, and Vardenafil: Results from the Erectile Dysfunction Observational Study (EDOS)”, of 8,047 patients shows that tadalafil achieved the highest rates of patient satisfaction and perceived effectiveness. Supporting this, the Korean preference study titled, “Comparison of the Efficacy, Safety and Patient Preference of the Phosphodiesterase Type 5 Inhibitors for the Patients with Erectile Dysfunction” reports that 35.4% of men preferred tadalafil, compared with 29.2% each for sildenafil and vardenafil.

Adverse events vary between the two drugs. Vardenafil’s inhibition of PDE6 contributes to visual side effects. Roessler et al.’s double-blind crossover study found temporary increases in color vision error scores and reduced retinal b-wave amplitudes in subjects taking vardenafil, which resolved within 24 hours. By contrast, tadalafil often causes musculoskeletal effects due to PDE11 inhibition. Seftel et al.’s three-part study reports back pain and myalgia in 9.4% of patients on 10 mg tadalafil and 8.3% on 20 mg.

These distinctions underline that vardenafil offers stronger potency and a faster onset, while tadalafil provides extended duration, higher patient preference, and fewer visual side effects. Both remain effective treatments for erectile dysfunction, but the clinical choice depends on patient needs, tolerability, and lifestyle considerations.

What Are The Medical Uses Of Vardenafil And Tadalafil?

Condition	Vardenafil	Tadalafil
Erectile Dysfunction (ED)	FDA-approved (2003)	FDA-approved
Benign Prostatic Hyperplasia (BPH)	Not approved	FDA-approved (improves IPSS, daily 5mg dose)
ED + BPH Combination	Not approved	FDA-approved (Entadfi with finasteride, 2021)
Pulmonary Arterial Hypertension (PAH)	Not approved (small investigational trials only)	FDA-approved (2009, 40mg daily, improves 6MWD, QoL, clinical outcomes)
High-Altitude Pulmonary Edema (HAPE)	No evidence	Off-label, preventive benefit shown in trials
Raynaud’s Phenomenon	Off-label, strong evidence (reduces attack severity, frequency, and duration)	Off-label, weaker evidence
Premature Ejaculation (PE)	Off-label, strong evidence (increases latency time, superior to sertraline)	Not effective
Combination with Finasteride	No indication	FDA-approved (Entadfi for BPH with enlarged prostate)

Vardenafil and tadalafil differ in the range of their medical uses, with tadalafil achieving broader FDA approvals while vardenafil remains limited to a narrower scope. Vardenafil is approved only for erectile dysfunction. The FDA authorized vardenafil in 2003 solely for treating erectile dysfunction, defined as difficulty or inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. In contrast, tadalafil holds multiple FDA-approved indications beyond erectile dysfunction. StatPearls confirms that tadalafil is approved not only for erectile dysfunction but also for benign prostatic hyperplasia, combined ED with BPH, and pulmonary arterial hypertension.

The efficacy of tadalafil in BPH has been established by strong clinical evidence. A BJUI international randomized, placebo-controlled trial of 511 men demonstrated that tadalafil 5mg once daily significantly improved International Prostate Symptom Score (IPSS) by -2.1 points compared to placebo (p=0.001), with improvements seen as early as one week. Cui et al.’s meta-analysis in Frontiers in Medicine further confirmed these findings, showing that tadalafil 5mg once daily led to significantly better IPSS scores than placebo across 15 randomized clinical trials.

Tadalafil is also FDA-approved for pulmonary arterial hypertension, while vardenafil has not achieved approval for this condition. The landmark study by Galiè et al., published in Circulation, randomized 405 patients with PAH to tadalafil or placebo and found that tadalafil 40mg once daily improved six-minute walk distance by 33 meters compared with placebo. Rosenzweig’s expert review in Expert Opinion on Pharmacotherapy confirmed that this pivotal trial supported FDA approval in 2009, showing improvements in exercise capacity, quality of life, and reduced time to clinical worsening. By contrast, vardenafil’s role in pulmonary hypertension remains investigational. Aizawa et al., in Hypertension Research, studied five patients treated with vardenafil for three months and reported a 20.7% reduction in pulmonary vascular resistance/systemic vascular resistance ratio and lower brain natriuretic peptide levels, but this evidence did not translate into FDA approval.

Differences also appear in off-label applications. Tadalafil has demonstrated preventive effects in high-altitude pulmonary edema. Maggiorini et al. conducted a randomized trial in 29 adults with HAPE history and found that only 1 of 8 tadalafil recipients developed HAPE compared to 7 of 9 placebo recipients (p=0.007). Tadalafil has also shown potential in Raynaud’s phenomenon, although not formally approved. Vardenafil, however, has stronger evidence for Raynaud’s management. Caglayan et al. carried out a double-blind crossover study in 53 patients, showing that vardenafil 10mg twice daily significantly reduced Raynaud Condition Score (p=0.03) and decreased both attack frequency and duration. A Frontiers in Cardiology systematic review by Lambova and Müller-Ladner supported these findings, suggesting vardenafil reduces severity, duration, and frequency of Raynaud attacks.

Another notable distinction is vardenafil’s evidence in premature ejaculation. Aversa et al.’s double-blind placebo-controlled study in 42 men showed vardenafil 10mg increased intravaginal ejaculatory latency time from 0.6±0.3 to 4.5±1.1 minutes (p<0.01). Mathers et al. compared vardenafil 10mg with sertraline 50mg in 49 men, finding vardenafil improved latency time to 5.01±3.69 minutes (p<0.001), showing superior efficacy over sertraline. Tadalafil, in contrast, is not strongly supported for premature ejaculation treatment.

Tadalafil also demonstrates unique benefit when combined with finasteride. Casabé et al.’s randomized trial of 695 men with BPH showed that tadalafil plus finasteride produced significantly greater improvements in IPSS compared to finasteride alone, with a -4.0 versus -2.3 point reduction at four weeks (p<0.001). This led to FDA approval of Entadfi in 2021 for BPH management in men with enlarged prostates.

These clinical distinctions emphasize that vardenafil’s approved use remains limited to erectile dysfunction, though it shows promising off-label utility in Raynaud’s phenomenon and premature ejaculation. Tadalafil, however, extends its therapeutic role far beyond erectile dysfunction, with robust FDA approvals for BPH, combined ED and BPH, and pulmonary arterial hypertension, supported by large randomized clinical trials and meta-analyses.

Which Is More Effective For Erectile Dysfunction: Vardenafil Or Tadalafil?

Tadalafil demonstrates superior overall effectiveness for erectile dysfunction compared to vardenafil, even though both drugs show comparable acute efficacy rates. The most comprehensive evidence comes from Yuan et al.’s network meta-analysis published in European Urology, which reviewed 118 randomized controlled trials with 31,195 patients. This analysis reported that tadalafil improved International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores by 1.49 points more than vardenafil (95% CI: 0.50–2.50), concluding that tadalafil was the most effective PDE5 inhibitor, followed by vardenafil.

Direct head-to-head trials confirm comparable short-term outcomes but highlight differences in long-term effectiveness. Park et al.’s Korean triple-crossover study of 113 men showed similar IIEF improvements with both vardenafil and tadalafil, with no statistically significant difference in efficacy scores. Yet, when patients were asked for preference after all treatment cycles, 35.4% chose tadalafil compared to 29.2% for vardenafil, suggesting higher overall satisfaction.

Pharmacological differences explain these clinical outcomes. Vardenafil demonstrates superior potency and faster onset. The RELY-II study showed that vardenafil 20mg achieved an 81% first-dose success rate for penetration and a 70% success rate for erection maintenance. Hellstrom et al. further confirmed that repeated attempts with vardenafil increased penetration success rates to 85–88%. In contrast, tadalafil’s strength lies in its duration. Salonia et al.’s crossover study in spinal cord injury patients demonstrated that tadalafil maintained normal sexual function for up to 24 hours after dosing, significantly outperforming sildenafil and highlighting its prolonged therapeutic window.

Real-world and observational studies reinforce tadalafil’s advantage in patient outcomes. The EDOS study, which included 8,047 patients across nine European countries, reported that men using tadalafil had numerically higher therapeutic effectiveness and greater satisfaction compared to those using sildenafil or vardenafil, especially in domains related to time flexibility and psychological confidence. Similarly, preference studies consistently favored tadalafil: a crossover trial with 181 patients found 73% preferred tadalafil over sildenafil, while another European study of 2,453 men reported that 82% chose tadalafil after testing both options. Although vardenafil maintained strong efficacy across diverse patient groups, as shown in Eardley et al.’s pooled analysis of 13 trials, it did not achieve the same levels of long-term preference or psychological benefit as tadalafil.

The cumulative evidence shows that while vardenafil may provide faster onset and high biochemical potency, tadalafil’s extended duration, higher patient satisfaction, and superior psychosocial outcomes make it more effective overall for erectile dysfunction. As Abdel Raheem and Kell emphasized, patients should ideally try different PDE5 inhibitors, but clinical data consistently position tadalafil as the more effective choice for most men.

How Does Vardenafil Work Compared To Tadalafil?

Vardenafil works with greater binding potency and faster onset, while tadalafil works with superior selectivity and longer duration. Corbin et al.’s binding study showed that vardenafil inhibits PDE5 with an IC₅₀ of 0.091 ± 0.031 nM compared to tadalafil’s 1.8 ± 0.40 nM, confirming stronger affinity. Wang et al.’s crystallographic analysis further revealed that vardenafil binding causes conformational changes in the H-loop and M-loop of PDE5 and displaces conserved zinc and magnesium ions, a mechanism not observed with tadalafil. These structural differences explain vardenafil’s 10- to 40-fold higher potency than sildenafil and its rapid onset of action.

All PDE5 inhibitors (PDE5i) for erectile dysfunction work by preventing the breakdown of cyclic guanosine monophosphate (cGMP) in penile tissue. This mechanism prolongs smooth muscle relaxation, increases blood flow, and enables natural erection during sexual stimulation. The shared pathway explains why vardenafil and tadalafil both improve erectile function, though their molecular interactions create distinct outcomes.

However, vardenafil’s potency is offset by weaker selectivity. Zhang et al.’s selectivity study showed vardenafil has only threefold selectivity for PDE5 over PDE6, the retinal enzyme, which accounts for dose-related visual side effects. Tadalafil avoids this by demonstrating more than 700-fold greater selectivity for PDE5 over PDE6, as confirmed by Carson et al.’s review, which explains its minimal visual disturbances. Instead, tadalafil cross-reacts with PDE11, as demonstrated in Şen et al.’s molecular dynamics study, which linked this interaction to skeletal muscle effects like back pain and myalgia.

These mechanistic differences explain their clinical profiles. Vardenafil’s stronger potency and faster onset translate to high first-dose success, but its PDE6 cross-reactivity can cause visual side effects. Tadalafil’s high selectivity and PDE11 interaction produce extended duration of action and higher satisfaction but carry risks of muscle-related discomfort. Both drugs inhibit PDE5 by stabilizing cGMP levels, yet their distinct molecular interactions and selectivity patterns shape their unique therapeutic outcomes.

Which Drug Works Faster: Vardenafil Or Tadalafil?

Vardenafil works faster than tadalafil. According to Montorsi et al.’s multicenter trial, vardenafil produced erections as early as 10–11 minutes after dosing, with 50–53% of men successful within 25 minutes (p < 0.0001). In contrast, Porst et al.’s tadalafil study showed the earliest significant response at 16–30 minutes, with 52% success at 30 minutes (p = 0.038). Real-world evidence from Capogrosso et al. confirmed that 34.5% of men using vardenafil ODT achieved satisfactory erections within 15 minutes. Carson’s clinical review further emphasizes that vardenafil demonstrates earlier and more reliable onset compared to tadalafil.

Which Lasts Longer: Vardenafil Or Tadalafil?

Tadalafil lasts much longer than vardenafil. Vardenafil has a terminal elimination half-life of about 4 hours, with most patients experiencing effective erections for up to 6 hours after taking the dose. According to Hellstrom et al. in Comparison of phosphodiesterase type 5 (PDE5) inhibitors, this limited duration reflects its shorter half-life. In contrast, tadalafil shows a mean elimination half-life of 17.5 hours, which extends to 21.6 hours in elderly men. Porst et al. in Tadalafil in the treatment of erectile dysfunction confirmed that this longer half-life allows tadalafil to remain effective for up to 36 hours. This extended therapeutic window makes tadalafil’s duration of action significantly greater than vardenafil’s.

What Is The Usual Dosage Of Vardenafil And Tadalafil?

Vardenafil and tadalafil differ in their usual dosage regimens. Vardenafil is generally prescribed at an initial dose of 10 mg taken orally about 60 minutes before sexual activity. The dose can be adjusted between 5 mg and 20 mg depending on individual response, but it should not be taken more than once per day. According to Roosler et al. in Vardenafil for the treatment of erectile dysfunction, these recommendations come from pivotal Phase III trials and the FDA-approved prescribing information. Tadalafil, on the other hand, offers both on-demand and daily dosing options. For on-demand use, the typical starting dose is 10 mg taken at least 30 minutes before sexual activity, which may be increased to 20 mg or reduced to 5 mg depending on tolerability. For once-daily dosing, tadalafil is prescribed in lower amounts, usually 2.5 mg to 5 mg taken at the same time each day without regard to sexual activity. StatPearls in Tadalafil in the treatment of erectile dysfunction confirms that both regimens are effective and included in product labeling. This distinction highlights that vardenafil is designed primarily for on-demand use, while tadalafil allows flexibility between on-demand and continuous daily dosing.

What Are The Side Effects Of Tadalafil And Vardenafil?

Tadalafil and vardenafil share several side effects, but they differ in drug-specific adverse events and in the incidence rates of common reactions. Tadalafil is more strongly associated with musculoskeletal effects. According to Seftel et al. in a three-part study, back pain occurred in 9.4% of patients on 10 mg tadalafil and 8.3% on 20 mg, compared with 3.7% on placebo, while myalgia was reported in 4.4% and 4.8% versus 2.3% on placebo. Vardenafil, in contrast, shows a higher rate of visual disturbances. Roessler et al. in a double-blind crossover study reported visual changes, such as color vision disturbances and photophobia, in 2–4% of patients compared with less than 1% on placebo, with these symptoms resolving within 24 hours.

Headache is frequent with both drugs, but incidence rates vary. According to Carson in a PDE5 review, vardenafil produced headache in 13–15% of patients compared with 6–7% on placebo, while Galiè et al. in the PAH trial showed that tadalafil caused headache in 15–17% of patients compared with 7–9% on placebo. Flushing also appears in both but occurs slightly more often with tadalafil. Galiè et al. reported flushing in 11–13% of tadalafil patients compared with 4–5% on placebo, while Carson found flushing in 9–11% of vardenafil patients compared with 3–4% on placebo.

Gastrointestinal events differ in their frequency. Dyspepsia was reported in 5–8% of tadalafil patients compared with 2–3% on placebo, according to Galiè et al., while Carson observed dyspepsia in 4–6% of vardenafil patients compared with 1–2% on placebo. Nasal congestion shows similar rates but remains consistently higher with both drugs compared to placebo. Galiè et al. reported 6–7% with tadalafil compared with 2–3% on placebo, and Carson found 5–6% with vardenafil compared with 2–3% on placebo. These findings confirm that while both tadalafil and vardenafil cause overlapping adverse events such as headache, flushing, dyspepsia, and nasal congestion, tadalafil uniquely predisposes to back pain and myalgia, whereas vardenafil produces more frequent visual disturbances.

Side Effect	Tadalafil (Occurrence)	Vardenafil (Occurrence)
Headache	15–17%	13–15%
Dyspepsia	5–8%	4–6%
Flushing	11–13%	9–11%
Nasal congestion	6–7%	5–6%
Back pain	8–9%	≈1–2%
Myalgia	4–5%	≈1–2%
Visual disturbances	<1%	2–4%

X-axis: Side effects (Headache, Dyspepsia, Flushing, Nasal congestion, Back pain, Myalgia, Visual disturbances).

Y-axis: % occurrence.

Bars: Two bars for each side effect → one for Tadalafil, one for Vardenafil.

Color coding: Different colors for each drug (e.g., blue for Tadalafil, green for Vardenafil).

What Are The Drug Interactions For Tadalafil And Vardenafil?

The drug interactions of tadalafil and vardenafil differ mainly in the extent of pharmacokinetic changes when combined with CYP3A4 inhibitors. Vardenafil shows a more pronounced increase in systemic exposure compared with tadalafil. According to the FDA label for Levitra, ketoconazole increased vardenafil’s AUC (area under the curve) four-fold, whereas the FDA label for Cialis reports only a 2.5-fold increase for tadalafil. This difference highlights that vardenafil is more sensitive to CYP3A4 inhibition than tadalafil.

Both drugs share the absolute contraindication with nitrates, as the combined use leads to profound hypotension. According to StatPearls: “PDE5 Inhibitors,” this interaction is clinically significant and potentially life-threatening. Both drugs also share the contraindication with riociguat. Phase I studies, as referenced in StatPearls: “PDE5 Inhibitors,” demonstrated that co-administration with riociguat results in severe hypotension.

The risk of low blood pressure when used with α-blockers has been documented for both drugs. A randomized placebo-controlled trial cited in StatPearls: “Tadalafil” reported that tadalafil 20 mg added to stable tamsulosin therapy caused transient orthostatic hypotension in 2% of patients, while the placebo caused none. Similar hemodynamic effects were observed for vardenafil, particularly with nonselective α-blockers, confirming comparable risks in this category.

Both tadalafil and vardenafil interact with CYP3A4 inducers, leading to reduced exposure and diminished efficacy. StatPearls: “PDE5 Inhibitors” confirms that rifampin and carbamazepine significantly lower plasma concentrations for both agents. Both drugs also interact with antihypertensive agents and vasodilators, producing additive reductions in blood pressure. A study referenced in StatPearls: “PDE5 Inhibitors” demonstrated that vardenafil 10 mg given with β-blockers caused an additional systolic blood-pressure decrease of 3 mmHg, though this effect was generally asymptomatic. Grapefruit juice also alters metabolism of both drugs through CYP3A4 inhibition in the gut, leading to increased plasma concentrations. As noted in StatPearls: “PDE5 Inhibitors,” grapefruit juice is contraindicated for both agents due to this interaction. Below is a comparative table of drug interactions for tadalafil and vardenafil.

Interacting Agent	Tadalafil Effect	Vardenafil Effect
Nitrates	Contraindicated – severe hypotension	Contraindicated – severe hypotension
Riociguat	Contraindicated – severe hypotension	Contraindicated – severe hypotension
α-Blockers	Risk of orthostatic hypotension (2% cases with tamsulosin + tadalafil 20 mg)	Risk of symptomatic hypotension with nonselective α-blockers
CYP3A4 Inhibitors	2.5-fold ↑ in AUC with ketoconazole	4-fold ↑ in AUC with ketoconazole
CYP3A4 Inducers	Reduced exposure and efficacy	Reduced exposure and efficacy
Antihypertensives	Additive BP lowering, asymptomatic mostly	Additive BP lowering, ~3 mmHg systolic ↓
Other Vasodilators	Additive hypotensive effect	Additive hypotensive effect
Grapefruit Juice	↑ Plasma concentration (contraindicated)	↑ Plasma concentration (contraindicated)

Do Vardenafil And Tadalafil Interact With Food And Alcohol?

Vardenafil and tadalafil differ in how they interact with food and alcohol. Vardenafil shows sensitivity to high-fat meals, while tadalafil does not. According to the study, “Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil” (2003), a high-fat breakfast reduced vardenafil’s peak plasma concentration by 18% and delayed the time to peak from one to two hours. In contrast, a study titled “Tadalafil in the treatment of erectile dysfunction” reported that food, including a high-fat meal, had no significant effect on tadalafil’s absorption or pharmacokinetics. This establishes that food alters vardenafil onset but does not affect tadalafil.

Alcohol shows another point of difference. Dräger et al., “ICSM report” (2005) observed that co-administration of vardenafil 20 mg with 0.6 g/kg alcohol did not change vardenafil’s pharmacokinetics or increase adverse events, though vasodilatory effects like headache and hypotension could worsen. For tadalafil, Porst et al. noted that 0.6 g/kg alcohol did not change pharmacokinetics either, yet 8% of subjects experienced additive orthostatic hypotension with tadalafil and alcohol, compared to none with tadalafil alone. This indicates that tadalafil has a greater risk of alcohol-induced blood pressure changes compared to vardenafil.

Vardenafil’s absorption is delayed by high-fat meals, while tadalafil is unaffected. Both drugs show stable pharmacokinetics with moderate alcohol, yet tadalafil is more likely to exacerbate hypotensive responses.

Factor	Vardenafil	Tadalafil
Effect of high-fat meal	Decreases Cₘₐₓ by 18% and delays Tₘₐₓ to 2 hrs	No significant effect on Cₘₐₓ or AUC
Effect of moderate-fat meal	No clinically significant effect	No effect
Effect of alcohol on pharmacokinetics	No significant change in Cₘₐₓ or AUC	No significant change in Cₘₐₓ or AUC
Clinical effect with alcohol	May worsen vasodilatory adverse effects	8% experienced additive orthostatic hypotension

What Are The Different Dosage Forms Of Vardenafil Or Tadalafil?

Vardenafil and tadalafil differ significantly in their available dosage forms. Vardenafil has a unique orodispersible tablet (ODT) formulation, whereas tadalafil has pediatric oral suspensions, chewable tablets, and fixed-dose combination capsules. According to Sanford’s comprehensive review, vardenafil ODT exists only in a 10 mg strength and disintegrates rapidly in the mouth without water, unlike tadalafil, which has no such formulation. In contrast, the European Medicines Agency documentation confirms that tadalafil suspension (2 mg/mL) is available for pediatric patients, which vardenafil does not provide. The FDA also approved CHEWTADZY, a chewable tadalafil tablet in 5 mg, 10 mg, and 20 mg strengths, requiring complete chewing before swallowing, a dosage form not present with vardenafil. StatPearls further reports that tadalafil has a fixed-dose combination capsule with finasteride 5 mg, while vardenafil has no approved combination formulation.

Both drugs share the common film-coated tablet dosage form. Vardenafil is available in 2.5 mg, 5 mg, 10 mg, and 20 mg tablets, as confirmed in its original formulation. Similarly, tadalafil is available in 2.5 mg, 5 mg, 10 mg, and 20 mg film-coated tablets, with strengths and color coding verified by the DailyMed database.

The pharmacokinetics of these formulations also differ. Sperling et al.’s pharmacokinetic study found that vardenafil ODT, when taken without water, shows 21–44% greater bioavailability than film-coated tablets. The POTENT I and POTENT II studies confirmed that despite differences in bioavailability, vardenafil ODT demonstrated identical efficacy to film-coated tablets. In contrast, Moledina et al.’s multicenter study of 154 children showed that tadalafil suspension was well tolerated, with 66.9% of patients requiring suspension due to inability to take tablets. Similarly, Behjati-Ardakani et al. reported in an Iranian pediatric study that tadalafil suspension was easily administered and tolerated in children as young as two months.

The novel formulations of vardenafil have been studied in experimental research. El-Nahas et al. demonstrated that vardenafil oral dispersible films achieved complete drug release within 10 minutes in simulated saliva conditions. Khalil et al. developed a nanosphere formulation showing reduced inter-subject variability compared to commercial tablets. For tadalafil, however, recent FDA approval of CHEWTADZY chewable tablets provided flexibility for patients preferring non-swallowable dosage forms.

McMahon et al. reported that patients preferred vardenafil ODT for its discrete administration without water, while pediatric studies emphasized the practical advantage of tadalafil suspension with a 90-day shelf life. These formulation-specific considerations show that while vardenafil innovations emphasize improved bioavailability and discreet use, tadalafil formulations address broader patient groups, including pediatric and benign prostatic hyperplasia populations.

Drug	Dosage Form	Strengths & Key Details
Vardenafil	Film-Coated Tablets	2.5 mg, 5 mg, 10 mg, 20 mg
	Orodispersible Tablets (ODT)	10 mg, disintegrates in mouth without water
	Oral Dispersible Films (ODF, experimental)	9–10 mg, complete release in 10 min
	Nanosphere Formulation (experimental)	Improved pharmacokinetics, reduced variability
Tadalafil	Film-Coated Tablets	2.5 mg, 5 mg, 10 mg, 20 mg
	Oral Suspension (Pediatric)	2 mg/mL, weight-based dosing
	Chewable Tablets (CHEWTADZY)	5 mg, 10 mg, 20 mg; chew before swallowing
	Combination Capsule	Finasteride 5 mg + Tadalafil 5 mg

How Much Does Vardenafil Cost Compared To Tadalafil?

Vardenafil is generally less expensive than tadalafil across most retail and online pharmacy sources. Vardenafil averages $40 per pill for film-coated tablets and $34 for orally disintegrating tablets, while tadalafil averages $50 for generics and $83 for brand-name Cialis. Brand-name pricing shows a similar pattern, with Levitra ranging from $63 to over $160 per pill and Cialis priced at around $83 per pill. Norum et al.’s study in the International Journal of Impotence Research highlights that while both vardenafil and tadalafil are costlier than sildenafil in terms of cost-effectiveness, vardenafil still carries a lower upfront per-pill expense than tadalafil.

Is Vardenafil Safer Than Tadalafil?

Vardenafil and tadalafil are equally safe and effective options to treat ED. Both the drugs differ in the type and frequency of adverse effects. Vardenafil is more likely to cause transient visual disturbances due to cross-reactivity with PDE6. According to Roessler et al. in Ocular side effects of Levitra, 2–4% of vardenafil patients reported changes in color vision and photophobia, compared to less than 1% with tadalafil. Tadalafil is more likely to cause musculoskeletal pain due to PDE11 inhibition. Seftel et al. in a three-part tadalafil study reported back pain or myalgia in 8–9% of tadalafil users, whereas Carson’s PDE5 review noted only 1–2% with vardenafil. Both drugs carry a risk of hypotension with nitrates or α-blockers, but incidence differs. StatPearls (PDE5 Inhibitors) states symptomatic hypotension was seen in 2% of tadalafil with tamsulosin versus less than 1% with vardenafil and similar agents. Vardenafil also requires dose reduction in moderate hepatic impairment, while tadalafil requires adjustments in severe renal impairment, as outlined in StatPearls (PDE5 Inhibitors). This means neither drug is universally safer, and safety depends on patient-specific comorbidities and side-effect tolerance.

Aspect	Vardenafil	Tadalafil
Visual disturbances	2–4% incidence (color vision changes, photophobia)	<1% incidence
Musculoskeletal pain	1–2% incidence	8–9% incidence (back pain, myalgia)
Hypotension with α-blockers	<1% symptomatic hypotension	~2% symptomatic hypotension
Dose adjustments	Needed in moderate hepatic impairment	Needed in severe renal impairment

Which Is More Powerful: Vardenafil Or Tadalafil?

Vardenafil demonstrates greater biochemical potency than tadalafil. Corbin et al. in Binding of tritiated sildenafil, tadalafil, or vardenafil reported an IC₅₀ of 0.091 nM for vardenafil compared to 1.8 nM for tadalafil, showing vardenafil is about 20 times more potent in vitro. This higher potency is also reflected in first-dose efficacy rates. A vardenafil first-dose study showed that vardenafil 20 mg achieved 81% first-dose success on SEP2 and 70% on SEP3. In contrast, tadalafil 20 mg achieved around 62% SEP2 and 55% SEP3, as summarized in a tadalafil clinical trials review. This indicates that vardenafil is more powerful both in laboratory inhibition assays and in initial clinical response.

Measure	Vardenafil	Tadalafil
PDE5 inhibition potency (IC₅₀)	0.091 nM	1.8 nM
SEP2 (penetration, first dose)	81% success at 20 mg	~62% success at 20 mg
SEP3 (maintenance, first dose)	70% success at 20 mg	~55% success at 20 mg

Can You Take Vardenafil And Tadalafil Together?

No, Vardenafil and tadalafil should never be taken together. Dual PDE5 inhibition can excessively increase cGMP levels, leading to unpredictable vasodilation and severe hypotension. According to StatPearls (PDE5 Inhibitors), additive inhibition creates a significant risk of dangerous blood pressure drops. Combining Vardenafil and Tadalafil together also provides no therapeutic advantage. No clinical study has demonstrated better outcomes when using two PDE5 inhibitors simultaneously, while risks of adverse events increase. Clinical guidelines, including those by the European Association of Urology, explicitly recommend against using more than one PDE5 inhibitor within 24 hours. This establishes that vardenafil and tadalafil must not be co-administered under any circumstance.

Which Is The Most Effective ED Medication?

Tadalafil is the most effective ED medication based on the largest network meta-analysis of 118 trials involving 31,195 participants. Yuan et al.’s systematic review ranked tadalafil highest in overall effectiveness, followed by vardenafil and sildenafil. This finding remained consistent even after adjusting for dosage variations. However, the most effective ED medication depends on individual health conditions and response. Tadalafil shows the best overall efficacy and patient satisfaction. Avanafil works the fastest and is best for quick results. Vardenafil is the most potent in terms of biochemical activity. Sildenafil has the longest clinical track record and proven safety. Each PDE5 inhibitor has one clear strength, but tadalafil is considered the best overall.

How Long Does Tadalafil Last Compared With Other ED Drugs?

Tadalafil lasts significantly longer than all other ED drugs, maintaining therapeutic effects for up to 36 hours. In contrast, sildenafil and vardenafil last 4-5 hours, while avanafil offers a 4-5 hour window with slight variation. Tadalafil’s mean terminal half-life of 17.5 hours is four times greater than other PDE5 inhibitors, which average about 4 hours. Tadlafil’s duration supports its reputation as “The Weekend Pill,” allowing more spontaneity without strict timing.

Which One Is More Effective: Tadalafil Or Sildenafil?

Tadalafil and sildenafil provide similar acute efficacy, but tadalafil proves more effective in long-term outcomes and patient satisfaction. Gong et al.’s meta-analysis of 16 trials showed no difference in IIEF-EF scores, yet tadalafil offered significant improvements in psychological measures like SEAR Confidence and Relationship scores. In direct patient preference studies, tadalafil vs sildenafil consistently favors tadalafil, with users appreciating its longer duration and reduced time pressure. A randomized, blinded, crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction (ED) in male spinal cord-injured (SCI) patients further confirmed that tadalafil sustained normal sexual function up to 24 hours post-dose, while sildenafil lasted only 4-6 hours.