Tadalafil-SZ, 28 pcs., 5 mg, film-coated tablets

Between the May holidays, it became known that Rospotrebnadzor began to withdraw from circulation the dietary supplements Sealex Forte and Ali Caps, intended to strengthen male potency. The reason is the allegedly detected content of the substance tadalafil in the drugs. This substance was not indicated when registering dietary supplements, so they were considered counterfeit.

Previously, the same fate befell another dietary supplement for men - “Tongkat ali platinum” and “Tongkat ali platinum forte”, in which the pharmaceutical substance tadalafil was also allegedly found. As a result, Rospotrebnadzor banned state registration of these additives.

The main complaint about the drugs is the presence of an active substance that was not declared during registration, since there is nothing dangerous in tadalafil itself - it is contained in almost all dietary supplements for increasing a man’s sexual performance.

Thus, at the end of April 2015, the Association of Manufacturers of Biologically Active Food Additives (SRO NPP BAD), together with the Union of Professional Pharmaceutical Organizations and the Pharmacy Guild, made a test purchase and examined dietary supplements advertised as natural potency stimulants. For analysis, samples of six brands included in the top 10 in terms of sales volumes in Russia in 2014 were selected. The results of laboratory examination showed that they contained undeclared synthetic components of prescription drugs, and in the vast majority of cases it was tadalafil.

Tadalafil-SZ, 28 pcs., 5 mg, film-coated tablets

Effect of other drugs on tadalafil

Tadalafil is mainly metabolized with the participation of the CYP3A4 isoenzyme. A selective inhibitor of the CYP3A4 isoenzyme ketoconazole (400 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Cmax by 107% and Cmax by 22%. 15% relative to AUC and Cmax values ​​for tadalafil alone.

Ritonavir (200 mg twice daily), an inhibitor of CYP3A4, CYP2C9, CYP2C19 and CYP2D6, increases single-dose tadalafil exposure (AUC) by 124% without changing Cmax. Although specific interactions have not been studied, it can be assumed that other HIV protease inhibitors, such as saquinavir, as well as CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole and grapefruit juice, may increase tadalafil plasma concentrations. The role of transporters (including P-gp) in the distribution of tadalafil is unknown. The potential for drug interactions mediated by transporter inhibition exists.

A selective inducer of the CYP3A4 isoenzyme, rifampicin (at a dose of 600 mg/day), reduces single-dose tadalafil exposure (AUC) by 88% and Cmax by 46% relative to AUC and Cmax for tadalafil alone. It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) should also reduce tadalafil plasma concentrations.

Concomitant use of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the AUC of tadalafil.

An increase in gastric pH as a result of taking the H2-histamine receptor blocker nizatidine had no effect on the pharmacokinetics of tadalafil.

The safety and effectiveness of combining tadalafil with other treatments for erectile dysfunction or other PDE5 inhibitors has not been studied and the use of such combinations is not recommended.

Effect of tadalafil on other drugs

Tadalafil is known to enhance the hypotensive effect of nitrates. This occurs as a result of the additive effect of nitrates and tadalafil on the metabolism of nitric oxide (II) and cGMP. Therefore, the use of tadalafil while taking nitrates is contraindicated.

Tadalafil does not have a clinically significant effect on the clearance of drugs whose metabolism occurs with the participation of cytochrome P450.

Studies have confirmed that tadalafil does not inhibit or induce the isoenzymes CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP2E1.

Tadalafil does not have a clinically significant effect on the AUC of S- or R-warfarin. Tadalafil does not affect the effect of warfarin on PT.

Tadalafil does not potentiate the increase in the duration of bleeding caused by taking acetylsalicylic acid.

Tadalafil has systemic vasodilatory properties and may enhance the effect of antihypertensive drugs. Additionally, patients taking multiple antihypertensive agents and whose hypertension was poorly controlled experienced a slightly greater reduction in blood pressure. In the vast majority of patients, this decrease was not associated with hypotensive symptoms. Patients treated with antihypertensive drugs and taking tadalafil should be given appropriate clinical advice.

There was no significant reduction in blood pressure when healthy volunteers co-administered tadalafil and the selective alpha1A-blocker tamsulosin.

Concomitant use of tadalafil with doxazosin is contraindicated. When tadalafil was administered to healthy volunteers taking doxazosin (4–8 mg/day), an alpha1-blocker, an increase in the hypotensive effect of doxazosin was observed. Some patients experienced symptoms associated with decreased blood pressure, including syncope.

Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated because Riociguat enhances the hypotensive effect of PDE-5 inhibitors.

Drug interaction studies have not been conducted with tadalafil and 5-alpha reductase inhibitors; caution should be exercised when taking them simultaneously.

Tadalafil causes an increase in the bioavailability of ethinyl estradiol when taken orally. A similar increase in bioavailability can be expected with terbutaline, but the clinical implications have not been established.

Tadalafil did not affect the concentration of alcohol, nor did alcohol affect the concentration of tadalafil. At high doses of alcohol (0.7 g/kg), taking tadalafil did not cause a statistically significant decrease in mean blood pressure. Postural dizziness and orthostatic hypotension have been observed in some patients. When taking tadalafil in combination with lower doses of alcohol (0.6 g/kg), no decrease in blood pressure was observed, and dizziness occurred with the same frequency as when taking alcohol alone.

Tadalafil does not have a clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.

What is erectile dysfunction, what causes it and how common is it?

Erectile dysfunction (ED) can be defined as the inability of a man to achieve or maintain an erection sufficient to insert the penis into the vagina and perform satisfactory sexual intercourse.
The incidence of ED varies depending on age. If in the age group from 20 to 40 years it averages 3%, then in the age group from 40 to 60 years it occurs in 15 - 20% of men. Over the age of 70, erectile dysfunction can affect up to 30% of men. At any age, ED is not the norm, because... the ability to have a regular and satisfactory sex life is one of the essential functions of a man of any age. Erection disorders can be caused by two groups of reasons: psychological (psychogenic) and somatic (organic). Research over the past 20 years has shown that ED is quite rarely caused by purely psychological reasons (stress, depression, behavioral characteristics, etc.). At the same time, it became known that about 80% of all cases of erectile dysfunction are caused by some physical (somatic, organic) conditions. These include: diabetes mellitus, high blood pressure, high blood cholesterol and vascular atherosclerosis, renal and liver failure, thyroid diseases, hormonal disorders, consequences of operations on the prostate gland and rectum, trauma and diseases of the spinal cord and brain (stroke , Alzheimer's disease, etc.), consequences of pelvic injuries, Peyronie's disease. Erection disorders can also be caused by taking certain medications. Persistent erectile dysfunction can develop due to bad habits such as drinking alcohol, smoking and taking drugs.

What place do erection pills occupy among ED treatment methods?

Currently, there are 5 groups of methods for treating erectile dysfunction:

1. Psychotherapy and sex therapy, which is used only for so-called psychologically caused or psychogenic ED, less often as an auxiliary method for somatic or organic ED.
2. Taking tablets or Viagra tablets for an erection: Cialis, Levitra. It is used as a first choice (first line of therapy) for all forms of organic ED, regardless of its cause.
3. Injection pharmacotherapy or “erection on demand”. It is used as a second-line treatment for all forms of ED in cases where erection pills do not provide the desired effect or their use is contraindicated. Erection pills and injections of vasodilators into the penis can be used together as a combination treatment option for ED.
4. Vacuum erection therapy or the use of vacuum erectors of various models and modifications to obtain or maintain an erection. It is a type of second-line treatment for organic and, less commonly, psychogenic forms of ED. — 90% efficiency; — There is no need to use medications that have side effects; — Non-aggressive method of treatment; - Helps create an erection while maintaining all precautions.
5. Surgical methods of treatment: operations on the vessels of the penis and penile prosthesis. The first group of interventions is divided into operations on the veins (limiting venous outflow) and arteries (increasing arterial inflow) of the penis. Vein surgery can be used effectively in selected cases of ED, especially in combination with erection pills. Surgeries on arteries are ineffective and are used less and less. Penile prosthesis is the most effective and radical of all types of treatment for ED, the only method that provides a complete cure for organic ED. Surgical methods, as a rule, are used only in cases of organic ED when conservative therapy has failed.

So, erection pills are the first-line therapy, which most often begins in the treatment of any form of ED. Viagra, Cialis and Levitra are today the only tablet drugs available in the world that are truly effective in treating ED. The effectiveness of all other advertised tablets, as a rule, is invented (and absolutely not proven) by their manufacturers and is no different from a pacifier. All these domestic “impazs”, “golden skates”, foreign “veromaxes”, “superyochimbe extracts” and many others. other drugs are nothing more than means of making money based on people who trust primitive advertising.

How do erection pills work? How harmful are they? Is it possible to become addicted to erection pills? What are the side effects and contraindications? What are the known drug interactions?

Viagra, Cialis and Levitra have exactly the same mechanism of action and are selective (selective) inhibitors of the activity of the enzyme - phosphodiesterase type 5 (PDEס). This enzyme, in turn, inhibits the production of cyclic guanosine monophosphate (CGMP) in smooth muscle tissue, which is formed from guanosine monophosphate (GMP) under the influence of nitric oxide (NO). The main function of CGMP is to relax the smooth muscles of the cavernous (cavernous) bodies of the penis. When the action of PDE is inhibited, a significantly larger amount of CGMP accumulates in the corpora cavernosa, their smooth muscles relax much better and a significantly larger amount of blood rushes to the penis, which causes an erection.

Drugs in this group act selectively in the vascular tissue of the penis and are practically harmless. They do not cause lasting negative consequences with long-term and regular use. No addiction to erection pills develops. With the exception of purely psychological dependence. Having once tried an erection pill and felt its significantly better quality, feeling the lost voluptuousness, a man sometimes does not want to give up Viagra pills. This is similar to how a driver who has once driven a high-quality foreign car tends to never drive a Zhiguli again.

The main side effects of Viagra. Cialis and Levitra and their frequency are summarized in Table 1.

Table 1. Frequency of side effects of certain dosages (mg) of erection pills in %.

The frequency of side effects depends on the dose of the drug and individual sensitivity. It also depends on what you eat the day before using erection pills. On a full stomach, the frequency of side effects, as well as the effectiveness of the drugs, is lower.

An absolute contraindication to taking erection pills is their intolerance (allergy) and the simultaneous use of organic nitrates (Nitroglycerin, Sustak, Nitrong, Nitrosorbide, Erinit, etc.). When taking erection pills and organic nitrates simultaneously, a fatal decrease in blood pressure can occur. It is extremely undesirable and potentially dangerous to prescribe erection pills from the group of PDE inhibitors to patients with the following diagnoses:

• Coronary heart disease with frequent attacks of chest pain.
• Congestive heart failure and significant decrease in blood pressure.
• Significant decrease in cardiac output.
• Complex complex drug therapy for hypertension.
• Drug therapy that can slow down the removal of PDE inhibitors from the body.

The described cases of deaths associated with taking Viagra were most often caused by the combined use of this drug with organic nitrates.

Drugs such as ketoconazole and erythromycin inhibit the removal of PDE inhibitors from the body. Individuals taking these drugs should reduce their dose of erection pills or avoid taking them altogether. Significantly enhances the effectiveness of erection pills, especially in persons with hypogonadism or male menopause (andropause), the simultaneous use of male sex hormones (testosterone).