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Sexual function

Sildenafil + Tadalafil (combo)

A combination of two PDE-5 inhibitors: the fast onset of sildenafil plus the long duration of tadalafil.

1 min read 8 sources

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White tablet bottle with the black TPD label on a white podium, next to two blue 3D molecule models in a bright lab, symbolic image for the combination of sildenafil and tadalafil
Components approved · sildenafil since 1998, tadalafil since 2002

Summary

At a glance

Sources checked on 26 Oct 2026

On the same enzyme
2 compounds

Sildenafil and tadalafil both inhibit PDE5, with direct binding according to ChEMBL8

Half-life of sildenafil
~4 hours

Peak level when fasted after 30 to 120 minutes, median 604

Half-life of tadalafil
17.5 hours

better than placebo up to 36 hours after intake according to the label5

Successful attempts on sildenafil
69 %

last 4 weeks of a 12-week trial, placebo 22%1

Improved erections on tadalafil
81 %

highest study dose, 5 trials with 1,112 men, placebo 35%2

  • The tablet combines two PDE-5 inhibitors. Both slow the same enzyme, which breaks down the vessel-relaxing messenger cGMP in the erectile tissue.18
  • The difference lies in the time course: sildenafil has a half-life of about 4 hours, tadalafil of 17.5 hours.45
  • Each component has large placebo-controlled trials: on sildenafil 69 instead of 22 percent of attempts succeeded, on tadalafil 81 instead of 35 percent reported improved erections.12
  • There is no dedicated approval trial for the fixed combination in one tablet. A small study tested daily tadalafil plus sildenafil as needed, side effects were not more frequent there than with tadalafil alone.36
  • Both compounds are approved according to ChEMBL, the fixed combination has not been tested as a product of its own. Everything here is the state of research, not a recommendation.78
Profile

Updated May 2026

Class
PDE-5 inhibitor combination
Composition
50mg sildenafil + 20mg tadalafil per tablet
Route
Oral

on demand

Duration
Fast onset + long window
Sizes
100tabs

1 size in the shop

Contents 12 sections
  1. At a glance
  2. What is the combo?
  3. How it works
  4. How to take it
  5. What the research shows
  6. Research status
  7. Safety and interactions
  8. Storage
  9. Related compounds
  10. FAQ
  11. Glossary
  12. Sources

What is the combo?

This tablet combines two PDE-5 inhibitors: 50mg sildenafil and 20mg tadalafil. The idea is to merge the strengths of both, the fast onset of sildenafil and the long duration of tadalafil.

In practice that means it kicks in quickly and then stays available over a long window. Both compounds work through the same mechanism.

Comparison

One enzyme, different time windows

The PDE-5 inhibitors in the TPD lexicon, as described there. Tap a card to open its entry.

Fast onset Sildenafil PDE5 Long time window Tadalafil PDE5 Highly selective Vardenafil (Levitra) PDE5 Very fast onset Avanafil (Stendra, Spedra) PDE5
Both in one tablet Sildenafil + Tadalafil (combo) PDE5

Simplified: all inhibit PDE5. They differ mainly in how fast they act and for how long. 78

How it works

Both components block the enzyme PDE-5 and so keep the vessel-relaxing messenger in the penis up for longer. Sildenafil gets the effect going fast, tadalafil holds it over many hours. Here too: it only amplifies the natural response and does not replace arousal.

Where it acts

Where the two compounds act

Tap a point or a card. Colour = PDE5, grey = observed in studies.

  1. Vessels in the erectile tissue

    Breakdown of cGMP slowed, the response to sexual stimulation is enhanced1

    PDE5
  2. Circulation

    Potentiates the blood-pressure-lowering effect of nitrates, so never together5

    Observed in trials
  3. Eye

    Visual disturbances, mostly a colour tinge, in 3 instead of 0 percent on sildenafil4

    Observed in trials
  4. Stomach

    Indigestion in 10 instead of 1 percent on tadalafil5

    Observed in trials
  5. Back and muscles

    Back pain in 6 instead of 3 percent on tadalafil5

    Observed in trials

Targets in the ChEMBL database8

Compound CHEMBL192 (Sildenafil), CHEMBL779 (Tadalafil): one recorded mechanism, Inhibitor, direct binding (both compounds).

Phosphodiesterase 5 (PDE5)
Gene
PDE5A
UniProt
O76074
ChEMBL
CHEMBL1827
Action
Inhibitor, direct binding (both compounds)
Translucent blue glass enzyme with branching extensions, one blue molecule sits in its pocket, a second docks below
Both compounds block the same enzyme, PDE5. Symbolic image.

How to take it

One tablet already contains both compounds in a fixed dose. It is taken as a single dose, about 30 to 60 minutes before.

  • At most once a day.
  • With some gap from fatty food, as that delays the sildenafil part.
  • Because two compounds come together, ease in carefully rather than combining with anything else right away.
White tablet bottle with the black TPD label, a few white tablets in front, a glass of water next to it on a bright table
Tablet with both compounds in a fixed amount. Symbolic image.

What the research shows

For the exact fixed combination there is no large dedicated approval study; the data base comes from the two individual compounds. Sildenafil (Goldstein, 1998) and tadalafil (Brock, 2002) are each very well evidenced. Their action principles and profiles are known from those studies.

The studies on both components are in the source block below.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Results of the single compounds12

Share in percent, each compound against its own placebo

Successful attempts1 Sildenafil, last 4 of 12 weeks, 329 men
Placebo (sildenafil trial) 22%
Sildenafil 69%
Improved erections2 Tadalafil, 5 trials over 12 weeks, 1,112 men
Placebo (tadalafil trials) 35%
Tadalafil, highest study dose 81%
Successful attempts (tadalafil)2 Placebo value not stated in the abstract
Tadalafil, highest study dose 75%

Two separate trial programmes with their own placebo, the bars cannot be read directly against each other. There are no such data for the combination in one tablet.

Half-life compared45

Hours until only half is left in the blood

Sildenafil4 active metabolite also about 4 hours
Sildenafil 4.0 h
Tadalafil5 peak level after 30 minutes to 6 hours, median 2
Tadalafil 17.5 h

Values from the US labels. A high-fat meal delays the absorption of sildenafil, for tadalafil food makes no difference according to the label.

Two curved glass vessel tubes with red blood cells, one short and one long, on a white lab bench
Short and long time window: the data come from the trials of the single compounds. Symbolic image.

Research status

Where the research stands

There is no completed trial of the fixed combination in one tablet. ClinicalTrials.gov lists 38 trials with both compounds, mostly as a comparison. Shown are the large ones on erectile dysfunction and the running trial on taking both together. As of 26 Oct 2026. 6

  1. Preclinical Principle: inhibit PDE5 in the erectile tissue so cGMP lasts longer
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 2 trials on components, 2 completed
  5. Approval sildenafil since 1998, tadalafil since 2002
3,138 participants in phase 3 Both components approved: ChEMBL lists sildenafil with first approval in 1998 and tadalafil in 2002. The fixed combination has no approval trial of its own.7
Show all 5 phase 3 and 4 trials on a timelineHide timeline 4 completed 1 running 0 with results
Phase 3
Phase 4

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.

Safety and interactions

The same hard rule applies as for the single substances, here even doubly: never combine with nitrates. Heart nitrates (e.g. nitroglycerin) and "poppers" (amyl nitrite) together with PDE-5 inhibitors can crash blood pressure dangerously. Through the tadalafil part the risk exists over an especially long window.

Caution with alpha-blockers and cardiovascular disease. With pre-existing conditions or other medication, clear it with a doctor first.

Tolerability

Frequency in the placebo-controlled trials

Out of 100 participants, how many had the event. Values from the US labels of the single compounds, there are no such data for the fixed combination.

4 of 100 Placebo
16 of 100 Compound (sildenafil or tadalafil)
Event PlaceboCompound (sildenafil or tadalafil)
Headache · Sildenafil4 4%16%
Headache · Tadalafil5 5%15%
Flushing · Sildenafil4 1%10%
Flushing · Tadalafil5 1%3%
Indigestion · Sildenafil4 2%7%
Indigestion · Tadalafil5 1%10%
Back pain · Tadalafil5 3%6%

Sildenafil: flexible-dose trials (734 versus 725). Tadalafil: highest study dose in eight trials (635 versus 476). Rarely an erection lasting over 4 hours and sudden loss of vision are described, both are an emergency.451

Storage

Store the tablets dry, at room temperature and protected from light, out of reach of children. Keep the original packaging closed and mind the expiry date.

Three white tablet bottles on a bright shelf next to a folded light blue towel
Dry, at room temperature and away from light. Symbolic image.

Related

Related compounds

Same targets, blends with Sildenafil + Tadalafil (combo) or a different path: all in the TPD lexicon.

Sildenafil + Tadalafil (combo)
Sildenafil Component, single entry in the lexicon Tadalafil Component, single entry in the lexicon Kamagra Oral Jelly (Sildenafil) Sildenafil as a gel in a sachet Vardenafil (Levitra) Another PDE-5 inhibitor Avanafil (Stendra, Spedra) Another PDE-5 inhibitor PT-141 Different path: acts centrally via melanocortin receptors

FAQ

Common questions about Sildenafil + Tadalafil (combo)

Short answers, each backed by the sources below.

Is the combination approved?

The two compounds are: ChEMBL lists sildenafil with first approval in 1998 and tadalafil in 2002. There is no dedicated approval trial for the fixed combination in one tablet, the data come from the trials of the single compounds. Everything here is the state of research, not a recommendation.78

Why two inhibitors for the same enzyme?

They act on the same target but differ in time course. Sildenafil reaches its peak level when fasted after 30 to 120 minutes and has a half-life of about 4 hours. Tadalafil has a half-life of 17.5 hours and worked better than placebo up to 36 hours after intake in trials. The combination aims to merge both.45

Are there studies on taking both together?

Only a few. In a study of 180 men one group took low-dose tadalafil daily plus sildenafil as needed, the other only tadalafil. In severe erectile dysfunction the combination did better, side effects occurred equally often. That is a different form than the fixed tablet. A larger trial with a planned 500 men runs until the end of 2026.36

What did the large sildenafil trial show?

In the dose-escalation trial (329 men, 12 weeks) 69 percent of attempts succeeded in the last four weeks, on placebo 22 percent. On average that was 5.9 instead of 1.5 successful attempts per month. Headache, flushing and indigestion were the most common side effects.1

And the tadalafil trials?

A pooled analysis of five placebo-controlled trials with 1,112 men over 12 weeks: at the highest study dose 81 percent reported improved erections, on placebo 35 percent. 75 percent of attempts succeeded, the erectile function score rose by 7.9 points on average.2

Why never together with nitrates?

Both labels state that PDE-5 inhibitors potentiate the blood-pressure-lowering effect of nitrates, so the combination is contraindicated. After tadalafil, according to the label, at least 48 hours should pass even in an emergency before a nitrate is given. Through the tadalafil part the risk therefore lasts a long time.45

Which side effects are described?

Most often headache: on sildenafil 16 instead of 4 percent, on tadalafil 15 instead of 5 percent. In addition flushing, indigestion, nasal congestion and with tadalafil back pain. Rarely an erection lasting over 4 hours and sudden loss of vision are described, then get medical help at once.45

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Alpha-blocker
Blood pressure and prostate drugs. Together with PDE-5 inhibitors blood pressure can fall more.
As needed
Taken only before the occasion instead of daily at fixed times.
cGMP
Cyclic guanosine monophosphate, a messenger that relaxes the smooth muscle of the vessels.
Dyspepsia
Indigestion such as a feeling of fullness or heartburn.
Erectile tissue
Tissue in the penis that fills with blood during an erection.
Half-life
Time after which only half of a substance is left in the blood.
Nitrates
Vessel-widening agents, for example for chest pain, plus poppers. With PDE-5 inhibitors blood pressure can drop dangerously.
PDE5
Phosphodiesterase 5, an enzyme in the erectile tissue that breaks down the messenger cGMP. A PDE-5 inhibitor slows this breakdown.
Placebo
Dummy preparation without active substance. Comparing against it shows what is due to the substance itself.
Priapism
Painful lasting erection over several hours, an emergency that can damage the tissue.

Evidence

Sources

Show all 8 sourcesHide sources 3 Studies1 Trial registry4 Database checked 26 Oct 2026

Studies

  1. Approval trials of sildenafil in erectile dysfunction

    Goldstein et al., New England Journal of Medicine, 1998

    DOI 10.1056/NEJM199805143382001 PMID 9580646
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. Pooled analysis of five placebo-controlled tadalafil trials

    Brock et al., Journal of Urology, 2002

    DOI 10.1016/S0022-5347(05)64442-4 PMID 12352386
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. Daily tadalafil plus sildenafil as needed versus tadalafil alone

    Cui et al., Andrologia, 2015

    DOI 10.1111/and.12216 PMID 24387078
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Trials with both compounds on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. US prescribing information for sildenafil

    DailyMed, U.S. National Library of Medicine (Stand 02.05.2023)

    Checked 26 Oct 2026 via DailyMed, openFDA
  2. US prescribing information for tadalafil

    DailyMed, U.S. National Library of Medicine (Stand 24.05.2024)

    Checked 26 Oct 2026 via DailyMed, openFDA
  3. Sildenafil: mechanism and approval in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL192, Mechanismus am Citrat CHEMBL1737)

    Checked 26 Oct 2026 via ChEMBL
  4. Tadalafil: mechanism and approval in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL779)

    Checked 26 Oct 2026 via ChEMBL

In the shop

Sildenafil + Tadalafil (combo) in the catalog

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