Tadalafil

Structural formula
General
Non-proprietary name	Tadalafil
other names	(6 R , 12a R ) -6- (1,3-Benzodioxol-5-yl) -2-methyl-1,2,3,4,6,7,12,12a-octahydropyrazino- [2 ', 1' : 6,1] pyrido [3,4- b ] indole-1,4-dione ( IUPAC )
Molecular formula	C 22 H 19 N 3 O 4
External identifiers / databases
CAS number 171596-29-5 EC number 687-782-2 ECHA InfoCard 100.214.024 PubChem 110635 DrugBank DB00820 Wikidata Q424156
Drug information
ATC code	G04 BE08
Drug class	PDE-5 inhibitors
Mechanism of action	Enzyme inhibition of phosphodiesterase 5
properties
Molar mass	389.40 g · mol -1
Physical state	firmly
Melting point	301-302 ° C
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302-312-332 P: ?
Toxicological data	2000 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tadalafil , ( trade name Cialis (EU, USA, CH), manufacturer: Lilly Pharma ) is a sexual enhancer first launched on the market at the end of 2002 (Germany) and end of 2003 (USA) and is used to treat erectile dysfunction , and since 2010 also for Treatment of pulmonary arterial hypertension and since 2012 for the treatment of benign prostate syndrome .

application

Tadalafil works similarly to sildenafil ( Viagra ), vardenafil, and avanafil in that it inhibits the enzyme phosphodiesterase-5 (PDE-5). PDE-5 is responsible for the fact that an erection is broken down so that the tissue of the erectile tissue does not die due to a permanent erection due to insufficient blood flow. By inhibiting PDE-5, sexual stimulation makes erections easier and lasts longer. However, these PDE-5 inhibitors cannot replace sexual stimulation. Erections do not affect the duration of PDE-5 inhibitors. During this time, depending on the man's constitution, several erections and ejaculations can occur. In addition, the active ingredient was given a new indication: Tadalafil has also been prescribed for the treatment of benign prostate syndrome since November 2012 .

In contrast to the other active ingredients, tadalafil can also be taken daily in the low 5 mg dose. This so-called constancy therapy, together with a long duration of action, ensures that the active ingredient remains in the body around the clock and that spontaneous sexual activity is also possible. In the case of the higher doses of 10 mg and 20 mg, daily intake over a longer period is not recommended.

Tadalafil has been approved under the brand name Adcirca since 2010 for the treatment of pulmonary arterial hypertension for once-daily intake. Previously, only Sildenafil (brand name Revatio ) was approved for it. The principle of the same mechanism of action and the longer half-life of tadalafil make this active ingredient appear more suitable, since the costs and the frequency of use can be reduced for the patient.

Pharmacokinetics

At 17.5 hours, tadalafil has a significantly longer half-life than sildenafil (Viagra), vardenafil or avanafil . While the effect lasts for 4 to 6 hours for sildenafil, 8 to 12 hours for vardenafil and 6 to 17 hours for avanafil, it can last up to 36 hours for tadalafil. The effects usually set in after an hour, but it can take up to six hours for an effect to be felt.

Interactions

The simultaneous intake of tadalafil with organic nitrites or NO donors (this also includes the trendy drug poppers ) is contraindicated . The combined effect on blood pressure threatens an acute, life-threatening drop in blood pressure. The long half-life of tadalafil must also be taken into account here. Accordingly, nitrates or other antihypertensive drugs should not be taken until 48 hours later after taking tadalafil.

Tadalafil can be taken with or without food. However, the effect can be delayed in the case of a difficult to digest or extremely high-fat meal.

Side effects

Cardiovascular side effects (low blood pressure) are seldom observed, and "in practice" apparently more frequent muscle pain, which can last for several days, but is not of a serious nature. There have been reports of sudden hearing loss , sometimes with tinnitus or dizziness . Common side effects include headaches , indigestion , nasal congestion and back pain . Occasional side effects can manifest themselves in the form of a dry throat, fatigue or even tachycardia . In rare cases, permanent erections occur .

Contraindications

Tadalafil must not be used in severe cardiovascular diseases ( heart failure , coronary heart disease , heart valve disease and myocardial infarction ), cardiac arrhythmias or severe cardiac insufficiency .

It should also be avoided in the case of low blood pressure with a systolic value below 90 mmHg, severe liver or kidney dysfunction or diseases of the eye retina.

Other Information

Tadalafil requires a prescription in Germany, Switzerland, Austria and some other countries , but is freely available in other countries. It has been approved in the EU since November 2002 and in the USA since 2003 .

The Cialis brand is particularly often advertised in unsolicited e-mails ( spam ) , along with other sexual enhancers. This is often not the original drug, but also counterfeit copycat products with other active ingredients and unpredictable modes of action. Taking such preparations can therefore be associated with considerable health risks.

On November 15, 2017, the patent for the active ingredient in Germany expired, so that generics are approved from then on. Although the advantages over sildenafil are obvious, there was no postponement.

Web links

• European Public Assessment Report (EPAR) and product information for Cialis on the European Medicines Agency website
• Cialis info page of Lilly Deutschland GmbH

literature

Articles on pharmacology

• Padma-Nathan, In: Am. J. of Cardiology ., 92 / 9A, 2003, pp. 19M-25
• Sperling, In: Herz ., 28/4, 2003, pp. 314-324

Article for use

• Review of the three most important drugs for the treatment of erectile dysfunction: Gresser U., Gleiter CH: Erectile dysfunction: Comparison of efficacy and side effects of the PDE-5 inhibitors Sildenafil, Vardenafil and Tadalafil review of the literature. In: Eur J Med Res (2002) 7: 435-446. PMID 12435622 .
• Curran et al., In: Drugs 63/20, 2003, pp. 2203-2212
• Kloner et al., In: Am. J. of Cardiology ., 92 / 9A, 2003, 47M-57

Individual evidence

1. ↑ ^{a b} Entry on Tadalafil in the DrugBank of the University of Alberta , accessed July 7, 2020.
2. ↑ There is not yet a harmonized classification for this substance . A labeling of (2R, 8R) -2- (2H-1,3-benzodioxol-5-yl) -6-methyl-3,6,17-triazatetracyclo [8.7.0.0 ^ { is shown, which is derived from a self-classification by the distributor 3,8} .0 ^ {11,16}] heptadeca-1 (10), 11 (16), 12,14-tetraene-4,7-dione in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on 7th July 2020.
3. ^ John Cook: 36-hour Erection Drug Cialis Gets US Approval . In: Seattle Post-Intelligencer , November 22, 2003, p. A1. Retrieved January 10, 2009. 
4. ↑ ABDA database | Drug Base: CIALIS 5 mg film-coated tablets: extended indication
5. ↑ Sven Siebenand: PDE-5 inhibitor Tadalafil: More than a sexual enhancer , Pharmazeutische Zeitung of December 11, 2012, accessed on July 28, 2020.
6. ↑ Instructions for use Cialis 5mg (PDF; 247 kB).
7. ↑ Instructions for use Cialis 20mg (PDF; 250 kB).
8. ↑ Tadalafil (Adcirca) for pulmonary hypertension (pulmonary hypertension), 2010 ( memento of November 10, 2014 in the Internet Archive ), medknowledge, accessed on September 16, 2014.
9. ^ Robert P. Frantz, Louise Durst, Charles D. Burger, Ronald J. Oudiz, Robert C. Bourge, Veronica Franco, Aaron B. Waxman, Susanne McDevitt, Susan Walker: Conversion From Sildenafil to Tadalafil: Results From the Sildenafil to Tadalafil in Pulmonary Arterial Hypertension (SITAR) Study . In: Journal of Cardiovascular Pharmacology and Therapeutics . 2014, doi : 10.1177 / 1074248414528066 .
10. ↑ Nazzareno Galiè, Hossein A. Ghofrani, Adam Torbicki, Robyn J. Barst, Lewis J. Rubin, David Badesch, Thomas Fleming, Tamiza Parpia, Gary Burgess, Angelo Branzi, Friedrich Grimminger, Marcin Kurzyna, and Gérald Simonneau, for the Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group: Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension . In: New England Journal of Medicine . tape 353 , no. 1 , 2005, p. 2148-2157 , doi : 10.1056 / NEJMoa050010 .
11. Jump up ↑ Nazzareno Galiè, Marius M. Hoeper, Marc Humbert, Adam Torbicki, Jean-Luc Vachiery, Joan Albert Barbera, Maurice Beghetti, Paul Corris, Sean Gaine, J. Simon Gibbs, Miguel Angel Gomez-Sanchez, Guillaume Jondeau, Walter Klepetko , Christian Opitz, Andrew Peacock, Lewis Rubin, Michael Zellweger, Gerald Simonneau: Guidelines for the diagnosis and treatment of pulmonary hypertension . The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). In: European Heart Journal . tape 30 , no. 20 , 2009, p. 2493-2537 , doi : 10.1093 / eurheartj / ehp297 .
12. ↑ Specialist information on Cialis , Lilly, February 2017.
13. ↑ Contraindications to taking Tadalafil. Retrieved August 29, 2017 . 
14. ↑ Tadalafil: Potency pill is waiting for Malta .
15. ↑ Tadalafil: Little competition for Sildenafil .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !