Effex sildenafil 50 mg 6 pcs. Evalar film-coated tablets

Review of the Evalar company[edit | edit code]

Logo and branded pharmacy Evalar
Evalar

is the largest company producing and selling dietary supplements. The company accounts for about 20% of the pharmaceutical market in Russia (2012)[1] Production areas and plantations of medicinal herbs with an area of ​​about 900 hectares are located in the Altai Territory. Headquarters - in Biysk. Has its own pharmacy network.

The company's main products are dietary supplements of various forms based on natural raw materials of plant, mineral and animal origin: tablets, capsules, tinctures, drops, water-soluble drinks in sachets, teas in filter bags, oils, cosmetics in tubes. The company is actively criticized for numerous violations of the law and unsubstantiated advertising claims. Most supplements from Evalar are considered useless or potentially harmful to health.

The company was created in 1991 as a result of conversion on the basis of the Federal Research and Production Center "Altai". The closed joint stock company was headed by Larisa Prokopyeva, a researcher and candidate of technical sciences. Hence the name of the company, which comes from the combination of the names of two women: Eva, the director of a Polish cosmetics company, and Lar, Larisa Prokopieva.

“Evalar”: Harassment and deception of consumers under the “roof” for 10 million?

The results of a journalistic investigation into the activities of the current owner of a well-known brand of medical drugs and dietary supplements, actively advertised on television and on the pages of news publications in Russia to this day, are a real shock.

Employees of The Moscow Post managed to find out details about the peculiarities of doing business by the Evalar company, whose products, as journalists found out, can cause irreparable harm to the health of Russians who use advertised dietary supplements. The owner of a successful business project under this brand is Larisa Prokopyeva, who was included in the top rating of the 20 most successful and influential business women in the Russian Federation published at the end of March this year. The main asset of the businesswoman was Evalar, which over the past decade has repeatedly become the object of appeals from consumers dissatisfied with the purchase of low-quality drugs. The number of complaints about dietary supplements produced by this pharmaceutical company increases every year, which resulted in orders issued by Rospotrebnadzor and Roszdravnadzor to exclude a number of drugs from sale. However, Ms. Prokopieva’s pharmaceutical business continues to flourish, and the business organized “on the bones” of a large military enterprise continues to expand. But first things first.

Money from deception

The basis for the claims against Evalar products sent to the Russian regulatory authorities was actually the persecution organized by the manufacturer and deception of consumers with drugs that do not meet the stated description. Thus, in 2008, during an inspection of the composition of goods sold in pharmacies organized by the Federal Antimonopoly Service, the agency identified the presence of mold in the dietary supplements produced by Evalar, and a few years earlier, antimonopoly officials accused the organization’s management of unfair competition. The reason for this was the purchase of exclusive rights to the trade name “Red Root”, which allowed the manufacturer to fraudulently increase its share in the Russian market.

This was not the end of FAS checks against Prokopieva’s company - in April 2009, the agency drew attention to the submission of false information as part of an advertising campaign for the drug “Transit”. The advertisements that never left television screens presented the advertised product as a medication with medicinal properties, while the product itself was an ordinary dietary supplement. In addition to “Transit,” the manufacturing company “created the wrong impression” of potential buyers in relation to two more of its products from the category of dietary supplements. However, the FAS claims did not teach Evalar’s ​​management the correct conduct of production activities - in 2011, the antimonopoly agency again applied administrative penalties against Evalar - the company was convicted of a new violation of the Law “On Advertising”.

This time, the old scheme of deceiving consumers was used - advertising of the product “Glycine Forte Evalar” “created the impression” of the presence of medicinal properties, which became the reason for imposing a fine of 100 thousand rubles on the manufacturer. However, Prokopieva’s company continued to “push its line” - at the end of the same year, the FAS ordered the company to stop publishing obviously false advertisements for two more dietary supplements - “AD minus” and “Insulin Forte Evalar”. The scheme remained the same - advertising blocks promoting dietary supplements talked about the miraculous properties of “medicines”, which the products of the pharmaceutical company are not. Already in February 2013, the manufacturing company received similar accusations from another department - this time Rospotrebnadzor issued a ban on inappropriate advertising.

Arsenic in dietary supplements

The investigation of three years ago in relation to “Evalar” biological additives made it possible to reveal the presence of a poison dangerous to human health in “harmless” biological additives - the local department of Rospotrebnadzor in the Sakhalin region, experts found arsenic in products under a name that did not go off the television screen. The composition used to bait mice was contained in “Blueberry forte with lutein”, presented by the manufacturer as “vitamins for the eyes”. The deadly balls did not become the “last straw” - a little later, regulatory authorities discovered a new danger for compatriots - ionizing radiation in other Evalar dietary supplements - the Milona-9 product, positioned by the pharmaceutical company as a “medicine for the heart and blood vessels.”

Do dietary supplements cure cancer?

Prokopieva’s brainchild was not limited to the use of deadly poison, mold and ionizing radiation in the production of additives - the main “trick” of the company from the very beginning of its penetration into the domestic Russian market was an open lie to consumers, who were simply “sold” products that did not correspond to the description. The speech of Duma deputy Anton Belyakov, who, during a State Duma meeting held in May 2013, caught the manufacturer under discussion in outright deception, received a loud response in the media. According to Belyakov, in the advertising of a number of drugs various tricks were used about the supposedly medicinal properties of the advertised dietary supplement. Thus, “Ovesol” acquired the property of “removing toxins and preventing the formation of stones.” Another product of the company, “Endocrinol,” as the advertising brochure states, “corrects hormone levels.”

The amazing properties of Prokopieva’s dietary supplements do not end there - for example, “Troichatka Evalar,” which has been on TV screens and advertising pages of print and online publications for a long time, supposedly “has a parasitogenic effect,” when research conducted by the regulator has proven that this is not the case. But the most “relish” was the supply of “Shiitake” to consumers - this dietary supplement, it turns out, provides “prevention of cancer”, in no way being a medicinal product. Trusting buyers “fell for” the loud statements of the manufacturer, increasing the profit of the owner of “Evalar” by tens of millions of rubles annually, without even suggesting outright deception and lies. Representatives of the company were unable to explain how dietary supplements can treat cancer.

Where it all began

The appearance of a very intrusive brand in Russia occurred under very strange circumstances - the current owner of a pharmaceutical business project, Larisa Prokopyeva, who was educated at the Altai Polytechnic Institute, almost immediately after successfully receiving her diploma in 1974, went to work at a budgetary institution at her place of residence - the Altai Chemical Research Institute technologies, after a short period of work in which she got a job as an employee of the Federal Research and Production Center “Altai”. The latter was engaged in activities in favor of the Ministry of Defense, and the newly created scientific director headed the technological group for the creation of cold gas compositions. Finally, in 1991, the trade name “Evalar” was registered, under which Mrs. Prokopyeva, who continues to be its owner to this day, began producing decorative cosmetics.

Special attention is deserved by the fact that “Evalar” was created on the basis of the Federal Research and Production Center “Altai”, which produced products for the defense department, and Larisa Aleksandrovna herself became the head of the enterprise that turned into a joint-stock company. In fact, a recent researcher seized control of a defense enterprise from the state, changing the profile of its activities. The first product of the newly minted businesswoman was chewing gum, after which the production lines were repurposed for the production of cosmetics. Even a superficial glance at the scheme for the formation of “Evalar” on the basis of the Federal Research and Production Center “Altai” shows that this is a typical example of a raider takeover, with the help of which Prokopieva gained control over the assets of the research and production center and its property and industrial complex.

Help from outside

It would be naive to assume that a Russian businesswoman managed to pull off a scam involving the illegal seizure of property and assets of a state production institution alone. People brought in from outside helped “master” the budget money that was used by the enterprising Russian woman to produce chewing gum and then cosmetics. An active assistant in this was a representative of the top management of the Polena company registered in Poland named Ewa Dambrowski, who “had a hand” in the name of the subsequently formed commercial enterprise. It is very simple to understand - the Evalar brand arose by adding two names and then cutting off the extra ending - Eva plus Larisa.

An example of successful activity for companions was the high-profile launch in Russia, which was going through difficult times, of campaigns to promote Herbalife and the MMM financial pyramid, which instantly turned into real “kings of advertising.” After abandoning the production of cosmetics and switching to the creation of pharmaceutical products, Eva and Larisa focused not on the quality of the drugs produced, but on their “correct” presentation to customers. Since 1996, advertisements for the products of their jointly organized enterprise have appeared in all federal media, including television. Thanks to this, the company managed to increase its profit indicator annually, doubling at once.

If in 1996 the revenue of the “Evalar” couple amounted to 17 million rubles, then a year later it was already 35 million, and by 2002 the volume of income to the organization’s “treasury” exceeded 138 million rubles. Such a rapid rise was explained by the constant increase in the advertising budget - up to 12-15% of all revenue was spent on scrolling videos on TV and in leading news publications. By the beginning of 2013, the marketing budget allocated for the manufacturer of dietary supplements under the Evalar brand had reached fantastic values ​​- promoting products through outright lies cost 2.5 billion rubles. Multi-billion dollar marketing expenses raised the company to 21st place in the top ranking of the largest Russian advertisers. The visual experience of “MMM” was not in vain - the businesswoman perfectly learned to make money from outright deception.

“Roof” for 10 million

Larisa Alexandrovna was helped to run such a successful business not only by an enterprising Polish woman, but also by her own son, current deputy of the Russian State Duma Alexander Prokopyev, who took a direct part in organizing transactions for the sale of his mother’s non-core assets. In addition to Evalar, the owner owned profitable media assets until mid-2015 - the television company Planeta Service and the weekly publication Poscriptum. A third of the share in the latter, according to data that has become available to journalists, will soon end up in the hands of Vladimir Poletaev, represented in the upper parliamentary chamber of the Russian Federation. The controlling stake of the Planeta-Service TV channel - 51% of the participation share - is being bought back by the co-owner of the organization Yuri Ilyinykh, who previously founded it.

Prokopieva's son Alexander acted as a mediator in both transactions, despite the legal ban on the ownership and management of commercial business assets for government officials. But this is only the tip of a huge iceberg, the “roof” for which the enterprising family organized with the help of United Russia, where Alexander Prokopyev is a member. The evidence is on the surface - 4 years ago, a pharmaceutical company controlled by Larisa Alexandrovna acted as the general sponsor of the United Russia faction, investing 10 million rubles in the party’s political campaign. This is how much it cost the businesswoman and her son, who once headed the strategic development department of Evalar CJSC, for the protection of their business by government officials. This is confirmed by the unhindered sale of dietary supplements under the guise of medicinal drugs with miraculous properties, which even numerous appeals to Rospotrebnadzor and Roszdravnadzor cannot prevent.

Blatant lies, consumer deception and illegal management of business assets by current government officials do not prevent the Prokopyev family from continuing their successful business activities. All attempts by deputies to “push through” the law on introducing a final ban on advertising of dietary supplements run into constant opposition from United Russia members, who agree only to the introduction of “half measures” - indicating in small, illegible font information that dietary supplements are not a medicine. This, as can be seen from the financial statements of the company formed by Larisa Prokopieva, does not help at all to stop deceiving Russians and stopping the persecution of consumers with the deadly “additives” contained in dietary supplements.

Large-scale corruption conspiracy, flagrant violations of laws and “protection protection” for an unscrupulous businesswoman should soon become the object of close attention of the relevant law enforcement agencies, however, “financial donations” in the amount of 10 million rubles to the treasury of “United Russia” still remain good financial support for a strong “ roofs.”

Evgeny Averin

STOP! EVALAR[edit | edit code]

Logo "Stop!
Evalar" (community of victims of dietary supplement products) dietary supplement fraud. Discussion on channel one

A STOP! group was created on the VKontakte social network. Evalar. Community members are actively discussing their experience of using dietary supplements from Evalar. The group was soon abandoned by its creator.

One of the creators of the sister site STOP! Evalar, who introduces herself as Elena Bergman, writes that she decided to create this project “having received her bitter experience from taking dietary supplements (dietary supplements) from and having listened to many negative reviews from her friends and colleagues.”

Other resources:

• stopevalar.ru
  was registered on December 19, 2012, is currently unavailable and is in the REGISTERED, NOT DELEGATED, UNVERIFIED state (closed in 2013).[2]
• stopevalar.net
  was launched on December 26, 2012, and is currently also unavailable, but delegated until the end of 2014 (possibly closed under pressure from the company).[3]

Judging by the reviews, most often the users of the group blame the company for pronounced side effects from the drugs and attempts to present dietary supplement products in advertising as medicinal (which, by the way, Rospotrebnadzor is actively fighting against).

She recently found herself at the center of a high-profile scandal when her Blueberry Forte product was found to contain arsenic in excess of the norm.[4] A message about this was published by the press services of several regional departments of Rospotrebnadzor. The company itself hastened to refute the information.

Appeal from Elena Bergman[edit | edit code]

From the archives of the site stopevalar.net

[5]

Hello, my name is Elena Bergman! Why did I decide to create the project “STOP!EVALAR?” The answer is simple - having received my bitter experience from taking Dietary Supplements (BAA) and having listened to many negative reviews from my friends and colleagues, I am tired of looking at how this unscrupulous company earns billions of rubles annually by deceiving us, ordinary people who naively believe in everything the nonsense that comes out from the main federal channels and radio stations every day and around the clock. The goal of our community site “STOP!EVALAR” is to stop deception as much as possible. Share with each other and report all similar incidents that happened to you and your loved ones. Report fraud, so we will let other visitors know about the dishonest company.

Why dietary supplements? If you ask, you might think that I am an employee of a competing company. No! I am against all Dietary Supplement companies and actively cooperate with communities advocating a ban on dietary supplements. The company, positioning itself as the No. 1 pharmaceutical company in Russia, is the largest giant in the production and advertising of its low-quality products! According to the results of a study by TNS Gallup Media for the first quarter of 2012, Evalar was in 10th place in the Top 50 advertisers and spent more on advertising in the country in the first three months of 2012 than Sberbank, Beeline, M- Video, Eldorado, Volkswagen, Coca-Cola and many other famous brands. The main federal channels and such well-known and authoritative media as “Radio Russia”, “Echo of Moscow” daily sell many hours of advertising time to scammers and swindlers who profit from the problems of the elderly and pensioners. Taking advantage of gullibility and the hope of improving their health, they defraud them of their last money, offering them under the guise of treating serious diseases - dietary supplements, the effect of which is zero, and sometimes even threatening to health and life!

Despite the fact that dietary supplements constantly violate the advertising law, the fines for them are very minor. What is a fine of 40 thousand or even 100 thousand rubles if the company has annual sales of almost 170 million dollars? The authorities and the law in our country do not want to restore order in this area, despite public opinion and the disgusting essence of this type of deception and falsification. But I hope that together with the community of deceived and injured “STOP!EVALAR” we will cope with this problem, we will not remain indifferent, and we will be heard!

List of products from Evalar[edit | edit code]

• Turboslim ( types
  : coffee, tea, express weight loss, alpha, drainage, day, calorie blocker, etc.)
• Green coffee (Tropicana Slim)
• Troychatka (for the treatment of parasitosis)
• Troychatka forte (prohibited)
• Blueberry forte (prohibited)
• Parity (for the genitourinary system)
• Chitosan
• Sabelnik
• Laminaria (sea kale)
• Omega forte
• Inulin forte
• Laura, cream
• Hair expert, spray lotion

• Ginkgo biloba
• Shitake (for the treatment of cancer)
• Ovesol (for liver cleansing)
• Red root (to increase male potency)
• BP minus (to normalize blood pressure)
• Dihydroquercetin (antioxidant)
• Atheroclephitis (to lower cholesterol)
• Qi-clim (for menopause)
• Fitolax (for constipation)
• Glycine forte (sedative)
• Motherwort forte

List of products on the official website dated February 27, 2014

• AquaMaster
• Atheroclephitis
• ZheKaTon
• Red root plus
• Ginkum
• Pantocrine Panthea, tablets or liquid extract for oral administration
• Sabelnik tincture
• PhytoTransit
• Transit Lax
• Qi-klim
• Evalar, elixir

Effex sildenafil 50 mg 6 pcs. Evalar film-coated tablets

pharmachologic effect

A treatment for erectile dysfunction is a PDE5 inhibitor.

Composition and release form Effex sildenafil 50 mg 6 pcs. Evalar film-coated tablets

Tablets - 1 tablet:

• Active component: Tribulus terrestris herb dry extract (35÷45: 1, extractant ethyl alcohol 70%) containing the sum of furostanol saponins in terms of protodioscin and dry matter 45% - 250.0 mg;
• Auxiliary components: Lactose - 228.0 mg, potato starch - 55.2 mg, microcrystalline cellulose - 50.8 mg, povidone K17 - 39.1 mg, crospovidone - 34.5 mg, talc - 20.7 mg, silicon dioxide colloidal - 6.9 mg, calcium stearate - 4.8 mg;
• Auxiliary components of the shell: Hypromellose (hydroxypropyl methylcellulose) - 15.17 mg, macrogol-400 (polyethylene glycol 400) - 4.55 mg, red iron oxide dye - 2.12 mg, titanium dioxide - 1.52 mg, polysorbate-80 - 0 .76 mg, black iron oxide dye - 0.58 mg, talc - 0.30 mg.

Film-coated tablets, 50 mg, 100 mg.

1 tablet per sachet (sachet) made of a film combined based on polymer films and aluminum foil.

15 tablets (for a dosage of 100 mg) in a blister pack made of polyvinyl chloride film and flexible packaging made on the basis of aluminum foil.

1, 2, 4, 10 sachets (sachets) or 1 blister pack together with instructions for use are placed in a cardboard pack.

Description of the dosage form

The tablets are round, biconvex, film-coated from pale orange with a pinkish tint to pale brown with a pinkish tint; On a cross section, the core is white to almost white.

Directions for use and doses

Inside.

The recommended dose for most adult patients is 50 mg of sildenafil approximately 1 hour before sexual activity.

Taking into account effectiveness and tolerability, the dose can be increased to 100 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of use is 1 time per day.

Elderly patients

No dose adjustment is required for EFFEX® Sildenafil.

Renal dysfunction

For patients with mild or moderate renal failure (creatinine clearance 30-80 ml/min), no dose adjustment is required.

Concomitant use with other drugs

To minimize the risk of postural hypotension in patients taking α-blockers, sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. The advisability of reducing the initial dose of sildenafil should also be considered.

Pharmacodynamics

Sildenafil is a powerful selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

The physiological mechanism of erection is the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. This, in turn, leads to an increase in cGMP levels, resulting in relaxation of the smooth muscle tissue of the corpus cavernosum and increased blood flow in the corpus cavernosum.

Sildenafil does not have a direct relaxing effect on the isolated corpus cavernosum, but enhances the relaxing effect of nitric oxide, causing inhibition of PDE5, which is responsible for the breakdown of cGMP in the corpus cavernosum.

The pharmacological effect is achieved only in the presence of sexual stimulation.

In vitro studies have shown that sildenafil is selective for PDE5. Its activity in relation to other known isoenzymes is much lower: PDE6 - 10 times, PDE1 - more than 80 times, PDE2, PDE4, PDE7-11 - more than 700 times. Sildenafil is 4000 times more active against PDE5 compared to PDE3, which is of great importance since PDE3 is one of the key enzymes in the regulation of myocardial contractility.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

The use of sildenafil in doses up to 100 mg led to a slight, short-term decrease in blood pressure. The hypotensive effect is associated with the vasodilating effect of sildenafil, which is associated with an increase in the level of cGMP in vascular smooth muscle cells.

In some patients, 1 hour after taking the drug at a dose of 100 mg, the Farnsworth-Munsell 100 test revealed a mild and transient impairment in the ability to distinguish shades of color (blue/green). After two hours, color perception was restored. Color vision impairment is caused by inhibition of PDE6, which is involved in light transmission in the retina. Sildenafil does not affect visual acuity, contrast perception, electroretinogram readings, intraocular pressure or pupil diameter.

Pharmacokinetics

Suction

After oral administration, it is quickly absorbed. The maximum concentration in blood plasma is achieved within 30-120 minutes (average 60 minutes) when taken orally on an empty stomach. Bioavailability varies from 25 to 63%. When taken in combination with fatty foods, the rate of absorption decreases: Cmax decreases by an average of 29%, and the time to reach maximum concentration (Tmax) increases by 60 minutes, but the degree of absorption does not significantly change (area under the concentration-time pharmacokinetic curve (AUC) decreases by 11%).

Distribution

The volume of distribution of sildenafil at steady state averages 105 liters. The plasma protein binding of sildenafil and its main circulating N-demethyl metabolite is approximately 96% and is independent of the total drug concentration. Less than 0.0002% of the dose (average 188 ng) was detected in semen 90 minutes after taking sildenafil.

Metabolism

Sildenafil is metabolized mainly in the liver under the influence of microsomal cytochrome P450 isoenzymes: CYP3A4 (major pathway) and CYP2C9 (minor pathway). The main circulating metabolite, resulting from N-demethylation of sildenafil, undergoes further metabolism. The selectivity of this metabolite for PDE is comparable to that of sildenafil, and its activity against PDE5 in vitro is about 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma is about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism; its terminal half-life is approximately 4 hours.

Removal

The total clearance of sildenafil is 41 l/hour, and the terminal half-life is 3-5 hours. After oral administration, sildenafil is excreted as metabolites, mainly by the intestines (approximately 80% of the oral dose) and, to a lesser extent, by the kidneys (approximately 13% of the oral dose).

Pharmacokinetics in special groups of patients

Elderly patients

In healthy elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of free sildenafil in plasma is approximately 40% higher than in young patients (18-45 years). Age does not have a clinically significant effect on the incidence of side effects.

Renal dysfunction

With mild (creatinine clearance (CL) 50-80 ml/min) and moderate (CL 30-49 ml/min) degrees of renal failure, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal failure (creatinine clearance ≤30 ml/min), the clearance of sildenafil is reduced, which leads to an approximately twofold increase in the area under the pharmacokinetic concentration-time curve (AUC (100%) and Cmax (88%) compared with those with normal renal function in patients of the same age group.

Liver dysfunction

In patients with liver cirrhosis (stages A and B according to the Child-Pugh classification), the clearance of sildenafil is reduced, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age groups. The pharmacokinetics of sildenafil in patients with severe liver dysfunction (Child-Pugh stage C) has not been studied.

Indications for use Effex sildenafil 50 mg 6 pcs. Evalar film-coated tablets

Treatment of erectile dysfunction, characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse.

EFFEX® Sildenafil is effective only with sexual stimulation.

Contraindications

Hypersensitivity to sildenafil or any other component of the drug.

Use in patients receiving continuous or intermittent nitric oxide donors, organic nitrates or nitrites in any form, since EFFEX ® Sildenafil enhances the hypotensive effect of nitrates.

The safety and effectiveness of EFFEX® Sildenafil when used in combination with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended.

Combined use with ritonavir.

Liver dysfunction.

Chronic renal failure of severe severity.

Severe heart failure, unstable angina, stroke or myocardial infarction within the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mmHg) or hypotension (BP

According to its registered indication, EFFEX® Sildenafil is not intended for use in children under 18 years of age.

According to its registered indication, EFFEX® Sildenafil is not intended for use in women.

Carefully

Anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease).

Diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia).

Diseases accompanied by bleeding.

Exacerbation of peptic ulcer of the stomach and duodenum.

Hereditary retinitis pigmentosa.

Application of Effex sildenafil 50 mg 6 pcs. Evalar film-coated tablets during pregnancy and breastfeeding

According to its registered indication, the drug is not intended for use in women.

special instructions

To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination. Erectile dysfunction treatments should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie's disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia).

During post-marketing studies, cases of prolonged erection and priapism have been reported. If an erection persists for more than 4 hours, you should immediately seek medical help. If treatment for priapism is not carried out immediately, it can lead to damage to the tissue of the penis and irreversible loss of potency.

Medicines intended to treat erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.

Sexual activity poses a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient for an examination of the condition of the cardiovascular system. Sexual activity is not advisable in patients with heart failure, unstable angina, stroke or myocardial infarction in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP

Cardiovascular complications

During post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported. ), which had a temporary association with the use of sildenafil. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors.

Hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. However, before prescribing sildenafil, the physician should carefully assess the risk of possible undesirable manifestations of the vasodilating effect in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.

Since the combined use of sildenafil and α-blockers may lead to symptomatic hypotension in some sensitive patients, sildenafil should be administered with caution to patients taking α-blockers. To minimize the risk of postural hypotension in patients taking α-blockers, sildenafil should be started only after hemodynamic stability has been achieved in these patients. The advisability of reducing the initial dose of sildenafil should also be considered. The physician should inform patients about what actions to take if symptoms of postural hypotension occur.

Visual impairment

In rare cases, non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and cause of vision loss or reduction, has been reported during post-marketing use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors, including decreased papilledema/disc ratio (“congestive disc”), age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. An observational study assessed whether recent use of the PDE5 inhibitor class of drugs was associated with acute onset of NPINSID. Results indicate an approximately 2-fold increase in the risk of NPINSID within 5 half-lives of PDE5 inhibitor use. According to the published literature, the annual incidence of NPINSID is 2.5 – 11.8 cases per 100,000 men aged ≥ 50 years in the general population. In case of sudden loss of vision, patients should be advised to stop sildenafil therapy and consult a doctor immediately. Individuals who have already had a case of NPIND have an increased risk of recurrent NPIND. Therefore, the physician should discuss this risk with such patients, as well as discuss with them the potential for adverse effects from PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in such patients and only in situations where the expected benefit outweighs the risk.

A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of retinal phosphodiesterases. There is no information on the safety of sildenafil in patients with retinitis pigmentosa, so the drug should be used with caution.

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. If there is a sudden deterioration in hearing or hearing loss while taking sildenafil, you should consult your doctor immediately.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro. There are no data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so sildenafil should be used with caution in these patients. The incidence of epistaxis in patients with pulmonary hypertension associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%) . Patients receiving sildenafil in combination with a vitamin K antagonist had a higher incidence of epistaxis (8.8%) than patients not receiving a vitamin K antagonist (1.7%).

Use in conjunction with other means of treating erectile dysfunction

The safety and effectiveness of sildenafil in combination with other PDE5 inhibitors or other drugs for the treatment of pulmonary hypertension containing sildenafil (for example, Revazio®) or other drugs for the treatment of erectile dysfunction have not been studied, and therefore the use of such combinations is not recommended.

Impact on the ability to drive vehicles and machinery

Since when taking sildenafil, it is possible to develop dizziness, decrease in blood pressure, develop chromatopsia, blurred vision, etc. side effects, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. You should also be careful about the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Overdose

When using the drug EFFEX® Sildenafil in doses exceeding the recommended ones, adverse events were similar to those noted above, but usually occurred more often.

Treatment is symptomatic. Hemodialysis does not accelerate the elimination of the drug, since sildenafil binds tightly to plasma proteins and is not excreted by the kidneys.

Side effects Effex sildenafil 50 mg 6 pcs. Evalar film-coated tablets

The most common side effects were headache and flushing.

Typically, the side effects of the drug EFFEX® Sildenafil are mild or moderate and are transient.

Fixed-dose studies have shown that the incidence of some adverse events increases with increasing dose.

The frequency of adverse reactions is presented according to the following classification: Very often ≥10%; Often ≥1% and

Cannot be determined based on available data

From the immune system: rarely - hypersensitivity reactions (including skin rash), allergic reactions.

From the organ of vision: often – blurred vision, blurred vision, cyanopsia; uncommon – eye pain, photophobia, photopsia, chromatopsia, redness of the eyes/scleral injections, changes in the brightness of light perception, mydriasis, conjunctivitis, hemorrhage in the eye tissue, cataracts, disruption of the lacrimal apparatus; rarely - swelling of the eyelids and adjacent tissues, a feeling of dryness in the eyes, the presence of rainbow circles in the field of view around the light source, increased eye fatigue, seeing objects in yellow (xanthopsia), seeing objects in red (erythropsia), conjunctival hyperemia, irritation of the mucous membrane membranes of the eyes, discomfort in the eyes; frequency unknown - non-arteritic anterior ischemic optic neuropathy (NAIOP), retinal vein occlusion, visual field defect, diplopia*, temporary loss of vision or decreased visual acuity, increased intraocular pressure, retinal edema, retinal vascular disease, vitreous detachment/vitreal traction.

On the part of the hearing organ: uncommon – sudden decrease or loss of hearing, tinnitus, ear pain.

From the cardiovascular system: often - “hot flashes”; uncommon – tachycardia, palpitations, decreased blood pressure, increased heart rate, unstable angina, atrioventricular block, myocardial ischemia, cerebral vascular thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram readings, cardiomyopathy; rarely – atrial fibrillation.

From the blood and lymphatic system: infrequently – anemia, leukopenia.

From the side of metabolism and nutrition: infrequently - a feeling of thirst, edema, gout, uncompensated diabetes mellitus, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

From the respiratory system: often – nasal congestion; uncommon – nosebleeds, rhinitis, asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased volume of sputum, increased cough; rarely - a feeling of tightness in the throat, dryness of the nasal mucosa, swelling of the nasal mucosa.

From the gastrointestinal tract: often – nausea, dyspepsia; uncommon – gastroesophageal reflux disease, vomiting, abdominal pain, dry oral mucosa, glossitis, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, abnormal liver function tests, rectal bleeding; rarely – hypoesthesia of the oral mucosa.

From the musculoskeletal system: often – back pain; uncommon – myalgia, pain in the limbs, arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.

From the genitourinary system: infrequently - cystitis, nocturia, breast enlargement, urinary incontinence, hematuria, ejaculation disorders, genital swelling, anorgasmia, hematospermia, damage to penile tissue; rarely - prolonged erection and/or priapism.

From the central and peripheral nervous system: very often – headache; often - dizziness; uncommon – drowsiness, migraine, ataxia, hypertonicity, neuralgia, neuropathy, paresthesia, tremor, vertigo, symptoms of depression, insomnia, unusual dreams, increased reflexes, hypoesthesia; rarely – convulsions*, repeated convulsions*, fainting.

From the skin and subcutaneous tissues: uncommon - skin rash, urticaria, herpes simplex, itching, increased sweating, skin ulceration, contact dermatitis, exfoliative dermatitis; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis.

Other: infrequently - feeling of heat, swelling of the face, photosensitivity reaction, shock, asthenia, increased fatigue, pain of various localizations, chills, accidental falls, pain in the chest, accidental injuries; rarely – irritability.

* Side effects identified during post-marketing studies.

Cardiovascular complications

During post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported ), which had a temporary association with the use of sildenafil. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors.

Visual impairment

In rare cases, non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and cause of vision loss or reduction, has been reported during post-marketing use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors, including decreased papilledema/disc ratio (“congestive disc”), age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. An observational study assessed whether recent use of the PDE5 inhibitor class of drugs was associated with acute onset of NPINSID. Results indicate an approximately 2-fold increase in the risk of NPINSID within 5 half-lives of PDE5 inhibitor use. According to the published literature, the annual incidence of NPINSID is 2.5-11.8 cases per 100,000 men aged ≥ 50 years in the general population. In case of sudden loss of vision, patients should be advised to stop sildenafil therapy and consult a doctor immediately. Individuals who have already had a case of NPIND have an increased risk of recurrent NPIND. Therefore, the physician should discuss this risk with such patients, as well as discuss with them the potential for adverse effects from PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in such patients and only in situations where the expected benefit outweighs the risk.

Drug interactions

The influence of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the influence of the cytochrome isoenzymes CYP3A4 (the main pathway) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, accordingly, increase the clearance of sildenafil.

A decrease in the clearance of sildenafil was noted with simultaneous use of inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine).

Cimetidine (800 mg), a nonspecific inhibitor of the cytochrome CYP3A4 isoenzyme, when taken together with sildenafil (50 mg), causes an increase in plasma sildenafil concentrations by 56%.

A single dose of 100 mg of sildenafil together with erythromycin (500 mg/day 2 times a day for 5 days), a moderate inhibitor of the cytochrome CYP3A4 isoenzyme, while achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%.

When taking sildenafil (single 100 mg) and saquinavir (1200 mg/day 3 times a day), an inhibitor of HIV protease and the cytochrome CYP3A4 isoenzyme, while achieving a constant concentration of saquinavir in the blood, the Cmax of sildenafil increased by 140%, and the AUC increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir.

Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, may cause more severe changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), an HIV protease inhibitor and a strong inhibitor of cytochrome P 450, while achieving a constant concentration of ritonavir in the blood leads to an increase in Cmax of sildenafil by 300% (4 times). times), and AUC by 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng/ml (after a single use of sildenafil alone - 5 ng/ml).

If sildenafil is used in recommended doses by patients simultaneously receiving strong inhibitors of the cytochrome CYP3A4 isoenzyme, then the Cmax of free sildenafil does not exceed 200 nM, and the drug is well tolerated.

A single dose of an antacid (magnesium hydroxide/aluminum hydroxide) does not affect the bioavailability of sildenafil.

In studies in healthy volunteers, co-administration of an endothelin receptor antagonist, bosentan (an inducer of CYP3A4 (moderate), CYP2C9 and possibly CYP2C19) at steady state (125 mg twice daily) and sildenafil at steady state (80 mg three times daily) per day) there was a decrease in AUC and Cmax of sildenafil by 62.6% and 52.4%, respectively. Sildenafil increased the AUC and Cmax of bosentan by 49.8% and 42%, respectively. It is assumed that the simultaneous use of sildenafil with strong inducers of the CYP3A4 isoenzyme, such as rifampicin, may lead to a large decrease in the concentration of sildenafil in the blood plasma.

Inhibitors of the cytochrome CYP2C9 isoenzyme (tolbutamide, warfarin), the cytochrome CYP2D6 isoenzyme (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACE inhibitors and calcium antagonists do not affect the pharmacokinetics of sildenafil.

Azithromycin (500 mg/day for 3 days) has no effect on the AUC, Cmax, Tmax, elimination rate constant and T ½ of sildenafil or its main circulating metabolite.

Effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of cytochrome P 450 isoenzymes – 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50>150 µmol). When sildenafil is taken at recommended doses, its Cmax is approximately 1 µmol, so it is unlikely that sildenafil could affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with long-term use of the latter and when they are prescribed for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

When taking the α-blocker doxazosin (4 mg and 8 mg) and sildenafil (50 mg and 100 mg) simultaneously in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional decrease in systolic/diastolic blood pressure in the supine position was 9/5 mm Hg Art. and 8/4 mm Hg. Art., respectively, and in a standing position - 11/4 mm Hg. Art. and 4/5 mm Hg. Art., respectively. Rare cases of symptomatic postural hypotension, manifested in the form of dizziness (without fainting), have been reported in such patients. In selected sensitive patients receiving α-blockers, concomitant use of sildenafil may lead to symptomatic hypotension.

There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the cytochrome CYP 2 C 9 isoenzyme.

Sildenafil (100 mg) has no effect on the pharmacokinetics of inhibitors

HIV protease, saquinavir and ritonavir, which are substrates of the cytochrome CYP3A4 isoenzyme, at their constant level in the blood.

Co-administration of sildenafil at steady state (80 mg three times daily) increased the AUC and Cmax of bosentan (125 mg twice daily) by 49.8% and 42%, respectively.

Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).

Sildenafil (50 mg) does not enhance the hypotensive effect of alcohol in healthy volunteers with a maximum blood alcohol concentration of 0.08% (80 mg/dL) on average.

In patients with arterial hypertension, no signs of interaction between sildenafil (100 mg) and amlodipine were detected. The average additional decrease in blood pressure in the supine position is 8 mm Hg. Art. (systolic) and 7 mm Hg. Art. (diastolic).

The use of sildenafil in combination with antihypertensive drugs does not lead to additional side effects.