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Tadalafil in the treatment of erectile dysfunction
Open accessAbstract
Tadalafil in the treatment of erectile dysfunction Robert M Coward, Culley C CarsonDivision of Urologic Surgery, University of North Carolina, Chapel Hill, NC, USAAbstract: The treatment for erectile dysfunction (ED) was revolutionized with the development of phosphodiesterase type 5 (PDE5) inhibitors. Tadalafil (Cialis®; Eli Lilly and Company, Indianapolis, IN, USA) is the newest and most versatile PDE5 inhibitor in the clinical armamentarium for the treatment of ED. Its most unique characteristic is its long half-life of 17.5 hours, which lends itself to a longer therapeutic window with on-demand dosing and effective steady-state plasma concentrations with once-daily dosing. Clinical trials have proven its safety and efficacy with both dosing strategies for all severities and etiologies of ED, including difficult-to-treat ED. This thorough review will discuss ED, the physiology of penile erection and the role of PDE5, and all aspects of tadalafil, from its development, through its pharmacology, to its latest clinical studies and indications.Keywords: tadalafil, Cialis, PDE5 inhibitors, phosphodiesterase type 5, erectile dysfunction, penile erection
Overview
CoChat Summary
TL;DR
Tadalafil is a PDE5 inhibitor with a uniquely long half-life (17.5 hours in healthy men; 21.6 hours in elderly men) that is safe and effective for erectile dysfunction (ED) across severities and etiologies, using either on-demand or once-daily dosing. This narrative review summarizes its pharmacology, clinical trial efficacy, safety, drug interactions, and patient/partner preference data.
Key findings
- In an integrated analysis of 5 randomized trials (1112 men), tadalafil 10 mg and 20 mg increased IIEF-EF scores by 6.5 and 7.9 points versus 0.6 with placebo (p < 0.001); SEP-Q3 successful intercourse improved by 34% and 39% versus 6% with placebo (p < 0.001); GAQ improved erections in 81% with tadalafil 20 mg versus 35% with placebo (p < 0.001).
- A larger integrated analysis (original 1112 plus 1215 additional men) found IIEF-EF increases of 6.5 (10 mg) and 8.6 (20 mg) versus 0.9 with placebo (p < 0.001); SEP-Q3 success improved by 34% to 58% and 46% to 68% versus 8% to 31% with placebo (p < 0.001); GAQ improved erections in 71% and 84% versus 33% with placebo (p < 0.001).
- Once-daily tadalafil trials showed efficacy: in 268 men, IIEF-EF improved by 9.7 (5 mg) and 9.4 (10 mg) versus 0.9 with placebo (p < 0.001), with successful intercourse in 67.2% and 72.8% versus 36.7% (p < 0.001); in 287 men over 24 weeks, IIEF-EF improved by 6.0 (2.5 mg) and 7.0 (5 mg) versus 1.2 with placebo (p < 0.001).
- Tadalafil was preferred over sildenafil in multiple crossover studies: 90.5% of prior sildenafil users switched to tadalafil; 71% chose tadalafil versus 29% sildenafil in a 291-man study (p < 0.001); female partners preferred tadalafil in 79.2% versus 15.6% for sildenafil. Adverse events with tadalafil 20 mg included headache (15%), dyspepsia (8%), and back pain (5%), with 3.2% discontinuing treatment.
Methods
- Narrative review of tadalafil for ED, covering erectile physiology, PDE5 biology, tadalafil development, pharmacology, safety, drug interactions, efficacy, and patient preference.
- Data sources are published clinical trials, integrated analyses, randomized controlled trials, open-label extensions, crossover preference studies, and prescribing information; no new primary data are presented.
- Main analysis is qualitative synthesis of efficacy outcomes (IIEF-EF, SEP-Q2/Q3, GAQ, EDITS), pharmacokinetics, adverse events, and cardiovascular/α-blocker/nitrate interactions.
Limitations
- Stated in the paper: the 2-year once-daily GAQ data had a significant dropout rate and likely selection bias toward responders; the risks of tadalafil’s longer half-life have yet to be completely elucidated; the clinical significance of PDE11 inhibition is not fully understood; and it remains uncertain whether continuous or on-demand dosing is superior after bilateral nerve-sparing radical prostatectomy.
- Stated in the paper: further basic science and clinical research is needed to define tadalafil’s role in lower urinary tract symptoms secondary to benign prostatic hyperplasia.
- Evident from the text: as a narrative review, it does not report a systematic search strategy, formal risk-of-bias assessment, or meta-analysis, and it relies on selected published trials and prescribing information rather than independent primary data.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 Valid · 0 Not valid · 123 Not checked · 14 Own results and interpretations
In the paper
“This longer half-life provides a therapeutic window of 36 hours for tadalafil (Porst et al 2003).”
§ Tadalafil in the treatment of erectile dysfunction > Tadalafil pharmacology > Duration of action
What the sources say
- Not checked yetcites Porst et al 2003 source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Tadalafil is at least 9000 times more selective for PDE5 than most of the other families of PDEs, with the exception of PDE11 (Briganti et al 2005).”
§ Tadalafil in the treatment of erectile dysfunction > Tadalafil pharmacology > Phosphodiesterase selectivity
What the sources say
- Not checked yetcites Briganti et al 2005 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Tadalafil has the slowest absorption of the available PDE5 inhibitors with a mean of 2 hours to reach its maximum concentration, compared with about 50 minutes for sildenafil and vardenafil (Briganti et al 2005).”
§ Tadalafil in the treatment of erectile dysfunction > Tadalafil pharmacology > Dosing and absorption
What the sources say
- Not checked yetcites Briganti et al 2005 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“For this reason, tadalafil has less than 0.1% occurrence of vision abnormalities (Brock et al 2002; Carson et al 2004a).”
§ Tadalafil in the treatment of erectile dysfunction > Tadalafil pharmacology > Phosphodiesterase selectivity
What the sources say
- Not checked yetcites Brock et al 2002 source
- Not matchedcites Carson et al 2004a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Several recent studies have shown a significant treatment benefit from once-daily, low-dose tadalafil (McMahon 2004; McMahon 2005; Porst et al 2006; Rajfer et al 2007; Hatzichristou et al 2008; Porst et al 2008).”
§ Tadalafil in the treatment of erectile dysfunction > Efficacy
What the sources say
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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Citations
Cites
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Research works printed but not linked: 2
- Cappelleri JC Rosen RC Smith MD 1999 Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function Urology 54 346 51 10443736
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2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products
Borthwick, A. D. (2012) · Chemical Reviews · doi:10.1021/cr200398y · Cited by 908
Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions
Francis, S. H., Blount, M. A., & Corbin, J. D. (2011) · Physiological Reviews · doi:10.1152/physrev.00030.2010 · Cited by 639
Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction
Andersson, K. (2011) · Pharmacological Reviews · doi:10.1124/pr.111.004515 · Cited by 408
Natural Occurrence and Industrial Applications of d‐ Amino Acids: An Overview
Martínez‐Rodríguez, S., Martínez‐Gómez, A. I., Rodríguez‐Vico, F., Clemente-Jiménez, J. M., & Heras‐Vázquez, F. J. L. (2010) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900245 · Cited by 140
Bojarska, J., Mieczkowski, A., Ziora, Z. M., Skwarczyński, M., Tóth, I., Shalash, A. O., Parang, K., El-Mowafi, S. A., Mohammed, E. H. M., Elnagdy, S. M., et al. (2021) · Biomolecules · doi:10.3390/biom11101515 · Cited by 134
Metadata
- Authors
- Coward, R., & Carson, C.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Coward, Robert
- ORCID
- Coward, Robert
- Venue
- Therapeutics and Clinical Risk Management
- Publisher
- Informa UK Limited
- Published
- 2008-12
- Volume
- Volume 4
- Issue
- 6
- Pages
- 1315-1329
- ISSN
- 1176-6336 (ISSN-L)
- 1178-203X
- PMC
- PMC2643112
- OpenAlex
- W1901755736
- Semantic Scholar
- 116e28f80b505ef21c8b0180a949c26ffbb49751
- Cited by
- 138
- References
- 88
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 14 · 2023: 9 · 2022: 15 · 2021: 10 · 2020: 7 · 2019: 12 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 5 · 2013: 2 · 2012: 4
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Therapeutics and Clinical Risk Management (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Keywords
- tadalafil, erectile dysfunction, phosphodiesterase-5 inhibitors, phosphodiesterase 5, once-daily dosing, on-demand dosing, drug safety and efficacy
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