Sildenafil heals or has a temporary effect. Sealex sildenafil - instructions for use

For any man very great importance has a quality of sex life. And if it does not suit him, a man may be susceptible to depression. However, today there are a huge number of tools designed to combat sexual impotence. These funds can be used both "on demand" and systematically.

Among all the variety of available options, a drug called Sildenafil attracts special attention. It is this agent that is used as an active active ingredient in.

Interestingly, the unique properties of Sildnefil were discovered by chance. Initially, this substance was planned to be used to treat diseases. of cardio-vascular system... However, numerous studies have identified a unique side effect. All men who took Sildenafil for the treatment of heart disease reported the occurrence of spontaneous erections. As a result, this substance was no longer used to treat heart disease. It became popular as one of the most effective means to eliminate erectile dysfunction.

What is Sildenafil

Before evaluating the effectiveness of Sildenafil, you should understand the main characteristics of this drug. First, Sildenafil is a potent substance that helps increase blood flow to the penis. Due to this, the amount of cGMP in the blood increases and, therefore, an erection is strengthened.

Secondly, the duration of action of this substance is 4-5 hours. Given these indicators, Sildenafil is usually used "on demand". But for a long-term effect, tablets based on the substance Tadalafil are used. The duration of the effective action of this substance can reach one and a half days.

Thirdly, the effectiveness of Sildenafil largely depends on the reasons. If they were caused by psychological factors, then this tool will get rid of uncertainty. Thus, a man will be able to solve his problems and enjoy regular sex thanks to a persistent and long-lasting erection. If the problems with potency are due to the age factor, then any remedy of this kind can guarantee only a temporary effect.

Mechanism of action

Sildenafil, like other inhibitors of phosphodiesterase-5, promotes the activation of nitric oxide, which allows you to increase blood flow to the penis. When using such a tool, it is always worth remembering that an erection will never occur on its own. It appears only in case of sexual arousal. In simple words if there is no desire, then this remedy will be ineffective.

Tablets based on this active ingredient will also be ineffective in case of physiological disorders of the penis. Taking such pills is not recommended with the simultaneous use of alcohol or nitrate-containing drugs.

How to take Sildenafil correctly

The effectiveness of this remedy also depends on the correct application. The recommended dosage for healthy men is 100 milligrams.

Men who suffer from kidney or liver disease are advised to start taking this remedy with 25 milligrams. To achieve an effective result, it is better to take the drug one hour before the intended sexual intercourse.

When taking Sildenafil, it is worth remembering that in no case should you exceed the maximum permissible daily dose (100 mg). Otherwise, there is a risk of very unpleasant side effects.

Contraindications

Taking Sildenafil has several contraindications, due to which the action of this substance may be ineffective. The main contraindications include:

• Reception of funds for the treatment of angina pectoris. Such funds include isoket, kardiket and nitrosorbide. The effect of taking Sildenafil will also not be observed with the parallel use of nitric oxide donors. Moreover, the combination of the above drugs can lead to significant negative consequences... Most often, such a consequence is a catastrophic drop in blood pressure.
• Hypersensitivity to sildenafil. This problem can manifest itself in the appearance of an allergic skin rash, swelling, shortness of breath and itching.
• Low or high blood pressure.
• Physiological deformities of the genital organs.
• Having had a stroke or myocardial infarction within the past 6 months.

Another contraindication is that Sildenafil-based tablets are strictly prohibited for use by children or adolescents under the age of 18. In addition, tablets based on this substance are categorically not recommended for absolutely healthy men. Experiments like this can lead to the opposite effect.

Will Sildenafil be effective for women?

Not only men, but also women have problems with a regular sex life. Therefore, the use of tablets based on Sildenafil is also relevant for women. Reception of such funds contributes to:

• increased libido and sensitivity;
• reduction of excitation time;
• increased vaginal hydration and sensitivity in erogenous zones;
• improving blood circulation in the genitals;
• an increase in the duration of orgasm and endurance during intercourse.

It should be added that PDE-5 inhibitors such as Sildenafil contribute to a complex effect on women. They not only increase arousal, but also stimulate sexual attraction to a partner. Reception of such funds allows you to forget about such a problem as vaginal dryness and frigidity.

In general, Salednafil can have both temporary and long-term effects. In any case, drugs of this type allow you to forget about problems and enjoy a full sexual intercourse. You can buy these at the online pharmacy website.

G.04.B.E Drugs for the treatment of erectile dysfunction

G.04.B.E.03 Sildenafil

Recently, men are increasingly faced with various violations of potency. They often develop erectile dysfunction, which significantly affects the quality of their sexual life. Sildenafil will help to cope with such problems. Such a medicine helps to eliminate any changes in erection and restore self-confidence to a man.

Sildenafil is available in the form of tablets, which are coated with a blue film. They have a round shape and small bulges on the sides. The inside of the product is white. This drug is available as citrate.

The tablets also include additional ingredients that enhance the effect. These include microcrystalline cellulose and lactose monohydrate. In addition, the remedy includes povilone and croscarmellose. This medicine also contains magnesium stearate in small amounts.

Mechanism of action

By the principle of action, sildenafil can be classified as a special enzyme inhibitor. It is called cGMP-specific phosphodiesterase type 5. In an abbreviated form, the name of this substance is PDE-5.

By its action, the drug is included in the category of vasodilator drugs, or vasodilators. The tablets help to eliminate erectile dysfunction, which is manifested in the inability to obtain or maintain sufficient penis firmness required for normal intercourse.

This means that the use of this remedy helps to restore the response of the man's body to arousal. But the action of the remedy is possible only if there is sufficient stimulation.

The action of the drug is achieved by influencing the natural enzymes that are involved in the realization of arousal and ensuring a state of erection for the penis. The fact is that after arousal, a lot of nitric oxide is produced in the body. This substance leads to vasodilation, after which blood circulation in the cavernous zones of the penis increases.

However, this component of the agent does not have an independent effect on the vessels. This process requires the activation of a secondary process called cyclic guanosine monophosphate. Sildenafil helps to inhibit the activity of an enzyme that destroys the molecule of a given substance.

Thanks to this, it is possible to prolong the result obtained from the secondary intermediary. As a result, the vessels remain in an expanded state for a longer time, and the penis retains its erect position.

At the same time, the drug itself does not provoke blood flow to the organs of the reproductive system. It only increases arousal, which is accompanied by the ingress of certain components into the blood. This means that sildenafil helps build and prolong arousal. If the man does not receive appropriate stimulation, the drug will not work.

It should be remembered that an enzyme called PDE-5 is found not only in the penis - it is also found in the pulmonary vessels. Therefore, the use of a medicine can provoke the expansion of the vessels of this organ and reduce the pressure in them. Thanks to this, the drug becomes effective in pulmonary hypertension.

In men who suffer from this disease, this remedy relaxes the pulmonary vessels the most. It affects the rest of the arteries and veins only to a small extent.

Thanks to the use of drugs for the treatment of pulmonary hypertension, the quality of human life is significantly improved. So, this drug reduces shortness of breath and reduces the manifestations of respiratory failure. In addition, it contributes to a slight decrease in blood pressure, but this can be called a transient condition. After the completion of the action of the tool, this indicator usually returns to its original state.

Features of using the product for women

This substance is often used to combat sexual dysfunctions in women. The drug helps to stimulate arousal even during menopause or after surgery to remove the uterus.

• increase libido;
• prolong orgasm;
• eliminate frigidity;
• restore blood circulation in the pelvic organs;
• increase the release of vaginal lubrication;
• increase sensuality;
• reduce the amount of time it takes to achieve sexual arousal;
• increase libido in older women;
• increase stamina during sex.

Tablets have a complex effect on a woman's body. Thanks to the use of this tool, there is a desire for sexual intimacy, blood circulation in the pelvic organs increases, and erogenous zones acquire great sensitivity.

This effect allows you to get an orgasm during each intercourse. In addition, taking pills makes it possible to increase the amount of vaginal lubrication, and therefore they are recommended for those women who suffer from vaginal dryness.

However, he is able to provoke unwanted side effects. So, after taking this remedy, there is a risk of headaches, nausea, dizziness. The woman may lose clarity of vision or nasal breathing. Photophobia also often develops.

It is important to remember that the drug has a negative effect on uterine fibroids. Therefore, the question of its use must be decided by a gynecologist.

Clinical researches

This drug is highly popular, and therefore scientists have conducted a lot of studies that allow us to study its effects on the body. As a result, it was possible to establish that an increase in dosage led to a significant drop in systolic pressure. This effect was observed with the use of more than 100 mg of the active ingredient.

After using the product, problems were noticed with the identification of some colors - most often green and blue. Such reactions usually appear one hour after the use of the 100 mg product. These sensations are unexpressed and disappear completely after a couple of hours.

Pharmacokinetics

The drug is absorbed quickly enough. The bioavailability indicator of the product is 41%. The maximum blood level of the drug is reached 1 hour after consumption on an empty stomach. If the patient has taken alcohol or ate a fatty dish before this, the absorption of the drug will slow down.

The tablets bind to the protein components of the blood and evenly enter the tissues of the body. After which the agent is metabolized by liver enzymes. The elimination of the main metabolites takes about 4 hours. At the same time, they mainly leave the body with feces - about 80%, while only 13% leaves with urine.

Indications and application features

Sildenafil instructions to which must be strictly followed, it is recommended to take people with erectile dysfunction. In addition, the drug is often prescribed for pulmonary hypertension.

So, to eliminate erectile dysfunction, sildenafil must be taken orally. It is recommended to do this 1 hour before the planned sex. It is recommended to use 50 mg of the drug at a time.

However, this dosage can be adjusted upward or downward. This means that the doctor can prescribe from 25 to 100 mg of the drug. It depends on the characteristics of the organism and the severity of the pathology. The body's response to treatment is also important. It is forbidden to use these tablets more than 1 time per day.

In gerontology, the amount of the active ingredient should be 25 mg, provided that a person has nephrotic diseases or liver pathologies.

With the development of pulmonary hypertension, it is recommended to take 20 mg of the drug three times a day. This should be done at regular intervals of 6-8 hours. Moreover, it is not at all necessary that the use of the drug coincides with the intake of food.

If a person has a history of kidney dysfunction, the dosage of the active substance remains unchanged. However, this is true only for situations where the agent does not have a negative effect on the patient's body. Otherwise, the volume of the drug should be no more than 40 mg.

Contraindications

It is important to bear in mind that the use of sildenafil is not always permissible. The main contraindications to the use of this remedy include the following:

1. High sensitivity to the active ingredient of the drug and other components of the drug.
2. Use in people who are forced to constantly or periodically use nitric oxide donors. Also, do not combine this product with organic nitrates or different types of nitrites. The fact is that this drug provokes an increase in the hypotensive effect of nitrates. The effectiveness and harmlessness of combining this remedy with other drugs has not been studied, therefore, any combination should be treated with extreme caution.
3. Age under 18. The indications for use of the agent registered in the instructions include this limitation.
4. Female.
5. Lack of lactase, lactose intolerance.
6. Combination with ritonavir.

These tablets should be used with caution in case of anatomical deformities of the penis. These can include angulation or Peyronie's disease. Also included in this category is cavernous fibrosis.

In addition, you should consult your doctor if you have pathologies that predispose to the appearance of priapism. This group includes leukemia, myeloma, thrombocythemia. It is not recommended to take the drug uncontrollably for sickle-cell anemia. In such a situation, the doctor can choose safer analogues of the medicinal substance.

Also contraindications include pathologies that are accompanied by bleeding. Do not drink the remedy during an exacerbation of peptic ulcer disease. Also prohibitions include a hereditary form of pigmentary rhinitis.

The group of restrictions also includes pathologies of the cardiovascular system. Sildenafil is prescribed with great care in case of heart failure and the development of an unstable form of angina pectoris. A prohibition on taking it is a heart attack and a stroke, which have occurred within the last 6 months. Also, do not drink the drug with severe forms of hypertension and hypotension. Limitations include arrhythmia, which poses a danger to human life.

Another threatening combination is the use of sildenafil with episodes of ischemic neuropathy of the optic nerve. In such a situation, it is worth contacting a doctor who will select harmless analogues of this remedy.

Side effects

Side effects after using this substance are extremely rare.

However, some people suffer from the unpleasant consequences of taking it:

1. The nervous system can react to the intake of this remedy with headaches, rush of blood to the face area, vision problems, dizziness.
2. Respiratory system - after using this drug, the patient may experience a violation of nasal breathing.
3. Digestive system - a person may suffer from diarrhea and dyspeptic symptoms.
4. Genitourinary system - sometimes the use of sildenafil ends with the development of urinary tract infections.
5. Skin - the patient may develop rashes after using the product.
6. Other side effects - this category includes back pain, the development of arthralgia, and respiratory infections. In addition, some patients develop flu-like syndrome.

In people who took 100 mg of sildenafil, dyspeptic disorders and various visual impairments were most common. In patients who exceeded the recommended dosage, the likelihood of side effects increased.

special instructions

Before starting to use a medicinal product, important restrictions must be taken into account when choosing a dosage. So, in nephropathology and hepatopathology, the maximum allowable daily volume is 25 mg. The same requirement is also true for the gerontological group.

You should also be careful in such cases:

• anatomical defects of the penis;
• priapism and pathologies that contribute to its appearance;
• a tendency to develop bleeding.

Clinical trials have not revealed the effect of this drug on psychomotor reactions. It has no effect on mindfulness and memory.

Different categories of patients

These pills can have different effects on different categories of people:

1. Aged people. Scientists conducted studies among patients over 65 years old. Their condition remained normal. After that, it was possible to establish that the men managed to achieve positive results after using this tool.

After using the drug, the clearance began to decrease. When compared with younger patients, the elderly had an increase in the level of the agent that was present in the blood plasma by 40%. However, there were no significant side effects.

1. People with impaired kidney function. Patients with moderate to mild kidney disease can safely use sildenafil. A single use of the drug in the amount of 50 mg will not provoke significant changes in the body. Scientists have carried out special studies that have revealed this feature.

The clearance of the drug decreases if a person takes this drug for complex pathologies. In this case, all indicators are almost doubled in comparison with healthy people.

1. Patients with liver disorders. The excretion of sildenafil is reduced with problems in the functioning of the liver. Cirrhosis plays a special role in this issue, with stages A and B. Also, all indicators increase in comparison with those that were present in a healthy patient of the same age. It is important to note that studies have not been conducted in people with complex liver pathologies.

Overdose

According to the results of clinical trials, it was found that the use of an increased volume of sildenafil provokes more serious side effects.

• feeling of heat;
• digestive disorders;
• redness of the skin of the face;
• headache;
• violation of nasal breathing;
• decrease in pressure;
• vision problems.

If these manifestations occur, you should immediately consult a doctor who will select symptomatic therapy.

It is important to note that dialysis does not produce the desired results. This is due to the rapid binding of the drug to the protein components of the plasma.

Interaction with other drugs

The combination of this medicinal substance with other agents that affect the CYP3A4 enzyme provokes an extension of the period of its action. These include tetracycline, erythromycin, etc.

If you combine these tablets with antacids - for example, Almagel or Gastal, no special effect will follow.

Also, the following drugs do not affect the effectiveness of sildenafil:

• tolbutamide and warfarin;
• azithromycin;
• antihypertensive drugs - for example, amlodipine or diroton;
• diuretic drugs.

Moreover, this agent leads to an increase in the effect obtained from the use of nitroglycerin, nitroprusside and other donors of nitric oxide. Therefore, these drugs are not recommended to be combined.

The use of sildenafil with adrenergic blockers is fraught with a severe drop in pressure, which may be accompanied by symptoms of dizziness. If you combine this remedy with aspirin, there is a risk of increased bleeding.

Storage conditions

This product can be stored for a maximum of 5 years after manufacture. Moreover, the temperature cannot exceed 30 degrees. It is important to protect the medicinal substance from direct sunlight. Do not leave it in high humidity conditions. In addition, it is important to store the product in a place that is out of the reach of children.

Analogs

Analogs of this remedy include medicinal substances that have a similar effect, but contain other components.

Currently, such analogues of this medication can be distinguished:

• cialis;
• levitra;
• impaza;
• vuka-vuka;
• tribestan;
• laveron;
• viardot.

Sildenafil is an effective remedy that treats common erectile dysfunction and helps to significantly improve the quality of sex. In order to prevent the development of dangerous complications, you need to carefully study the instructions for use of this drug. If you have any contraindications, it is better to consult a doctor who will select effective and harmless analogues of this remedy.

Drawing conclusions

Did you misfire? Judging by the fact that you are reading this article, victory is not on your side.

And of course you know firsthand that a violation of potency is:

• Low self-esteem
• Women remember your every failure, tell their girlfriends and your friends
• Disease of the prostate
• Development of depression that negatively affects your health

Now answer the question: DOES IT SUIT YOU? How can this be tolerated? Do you remember that feeling when you look at a naked woman and cannot do anything? Enough - it's time to get rid of problems with potency, once and for all! Do you agree?

We studied a huge amount of materials and, most importantly, tested most of the potency remedies in practice. So, it turned out that a 100% working drug without any side effects is Predstanol. This drug consists of natural ingredients that completely exclude chemistry.

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Sildenafil is a drug for the treatment of erectile dysfunction, belonging to the group of phosphodiesterase type 5 inhibitors (PDE-5). Provides a stable and full-fledged erection, sufficient for sexual intercourse. Sildenafil is the active ingredient of the legendary Viagra, but in Russia it is also produced under its “maiden name” (read: under the international non-proprietary name). Sildenafil was synthesized in 1998 and became the first truly effective and safe tablet drug for the treatment of such a common disease today as erectile dysfunction. To understand the mechanism of action of sildenafil, it is necessary to delve a little into the biochemical "jungle". First of all, it should be noted what an important role in the functioning of the cardiovascular system is played by the endothelial relaxing factor, also known as nitric oxide (NO). Formed in the vascular endothelium, NO penetrates into the smooth muscle tissue, where it "wakes up" ... no, not Herzen, but the enzyme guanylate cyclase. As a result, the cellular concentration of cyclic guanosine monophosphate (abbreviated as cGMP) increases sharply, which, in turn, prevents the penetration of calcium ions into cells, which entails a decrease in vascular tone. But there is also a negative character here - the enzyme phosphodiesterase (PDE). It destroys cGMP, which limits the vasodilating effect of NO. To date, it has been established that PDE-5 is the most active in this regard. Thus, suppression of its activity enhances the effects of NO. Now you need to figure out what lies at the heart of the development of an erection. The condition for its occurrence is the relaxation of the smooth muscle "corset" of the arteries that carry blood to the cavernous bodies of the penis. This relaxation "organizes" the NO released by the endothelial cells. Sildenafil potentiates the effects of the latter by removing natural barriers to the blood flow to the glans penis. The clinical efficacy of sildenafil has been demonstrated in a number of large randomized trials.

In one of them, after 12 weeks, a clear improvement in erection was noted in 76% of patients taking sildenafil versus 22% who were satisfied with placebo. The high efficacy of the drug was observed in representatives of different age groups: even in people over 65, the drug worked in 69% of cases. One of the risk factors for erectile dysfunction is arterial hypertension. Sildenafil has a weak hypotensive effect, but its administration by hypertensive patients "sitting" on antihypertensive drugs does not potentiate the effect of the latter, therefore such persons can fight erectile dysfunction on a general basis. Another key risk factor for erectile dysfunction is smoking, which has not been shown to affect the effectiveness of sildenafil in clinical trials. The drug has another truly miraculous property: in patients suffering from psychogenic erectile dysfunction, it not only improves erection, but also helps to eliminate depression. A separate conversation is about persons who have developed erectile dysfunction against the background of diabetes mellitus. In this category of patients, it is most difficult to obtain a therapeutic response to pharmacotherapy. The effectiveness of sildenafil in such cases depends on the severity of the diabetes mellitus and the presence of complications. However, even in such difficult conditions, the drug showed itself from the best side: for example, in one of the clinical studies, an improvement in erection was noted in 69% of patients taking sildenafil (in fairness, it should be noted that these were patients without complications). Thus, sildenafil is definitely a "working" drug: its effectiveness does not decrease over time, which makes possible long-term pharmacotherapy. Side effects of the drug are usually mild and appear only at the beginning of treatment.

Pharmacology

Sildenafil is a potent selective inhibitor of cycloguanosine monophosphate (cGMP) -specific phosphodiesterase type 5 (PDE5).

Mechanism of action

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

Sildenafil does not have a direct relaxing effect on the isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting PDE5, which is responsible for the breakdown of cGMP.

Sildenafil is selective for PDE5 in vitro, its activity for PDE5 is superior to that for other known phosphodiesterase isoenzymes: PDE6 - 10 times; PDE1 - more than 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. Sildenafil is 4000 times more selective for PDE5 than PDEZ, which is of great importance, since PDEZ is one of the key enzymes in the regulation of myocardial contractility.

Sexual stimulation is a prerequisite for the effectiveness of sildenafil.

Clinical data

Cardiological examinations

The use of sildenafil in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in systolic pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg. Art., and diastolic pressure - 5.3 mm Hg. Art. A more pronounced, but also transient effect on blood pressure was observed in patients taking nitrates.

In a study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis of at least one coronary artery), the systolic and diastolic pressure at rest decreased by 7% and 6%, accordingly, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not interfere with blood flow in stenotic coronary arteries, and also led to an increase (by about 13%) in adenosine-induced coronary flow in both stenotic and intact coronary arteries.

In a double-blind, placebo-controlled study, 144 patients with erectile dysfunction and stable angina pectoris taking antianginal drugs (other than nitrates) did physical exercise until the angina symptoms subsided. The duration of the exercise was significantly longer (19.9 seconds; 0.9 - 38.9 seconds) in patients taking sildenafil in a single dose of 100 mg compared with patients receiving placebo.

A randomized, double-blind, placebo-controlled study investigated the effect of varying the dose of sildenafil (up to 100 mg) in men (n = 568) with erectile dysfunction and hypertension taking more than two antihypertensive drugs. Sildenafil improved erection in 71% of men compared with 18% in the placebo group. The incidence of adverse effects was comparable to that in other patient groups, as well as in those taking more than three antihypertensive drugs.

Research on visual impairment

In some patients, 1 hour after taking sildenafil at a dose of 100 mg, using the Farnsworth-Munsel 100 test, a mild and transient impairment of the ability to distinguish shades of color (blue / green) was revealed. These changes were absent 2 hours after taking the drug. It is believed that color vision impairment is caused by inhibition of PDE6, which is involved in the transmission of light in the retina. Sildenafil had no effect on visual acuity, contrast perception, electro-retinogram, intraocular pressure, or pupil diameter.

In a placebo-controlled crossover study of patients with proven early-age macular degeneration (n = 9), sildenafil at a single dose of 100 mg was well tolerated. There were no clinically significant changes in vision assessed by special visual tests (visual acuity, Amsler grating, color perception, color transmission modeling, Humphrey perimeter and photostress).

Efficiency

The efficacy and safety of sildenafil was evaluated in 21 randomized, double-blind, placebo-controlled studies lasting up to 6 months in 3000 patients aged 19 to 87, with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The efficacy of the drug was assessed globally using an erection diary, an international erectile function index (a validated questionnaire on the state of sexual function) and a partner survey.

The efficacy of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory intercourse, has been demonstrated in all studies and has been confirmed in long-term studies of 1 year duration. In studies using a fixed dose, the ratio of patients reporting that therapy improved their erection was 62% (sildenafil dose 25 mg), 74% (dose sildenafil 50 mg) and 82% (dose sildenafil 100 mg) compared to 25% in the placebo group. The analysis of the international index of erectile function showed that, in addition to improving erection, treatment with sildenafil also increased the quality of orgasm, made it possible to achieve satisfaction from intercourse and overall satisfaction.

According to pooled data, among the patients who reported improved erections with sildenafil treatment were 59% of diabetic patients, 43% of patients undergoing radical Irostatectomy and 83% of patients with spinal cord injuries (versus 16%, 15% and 12% in the placebo group, respectively). ).

Pharmacokinetics

Suction

After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages about 40% (from 25% to 63%). In vitro, sildenafil at a concentration of about 1.7 ng / ml (3.5 nM) inhibits human PDE5 activity by 50%. After a single dose of sildenafil at a dose of 100 mg, the average C max of free sildenafil in the blood plasma of men is about 18 ng / ml (38 nM). C max when taking sildenafil inside on an empty stomach is achieved on average within 60 minutes (from 30 minutes to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: C max decreases by an average of 29%, and TC max increases by 60 minutes, but the degree of absorption does not change significantly (the 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 connection of sildenafil and its main circulating N-demethyl metabolite with blood plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the sildenafil dose (average 188 ng) was found in semen 90 minutes after taking the drug.

Metabolism

Sildenafil is metabolized mainly in the liver by the action of the cytochrome CYP3A4 isoenzyme (main pathway) and the cytochrome CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite resulting from N-demethylation of sildenafil is further metabolized. The selectivity of this metabolite in relation to PDE is comparable to that of sildenafil, and its activity in relation to PDE5 in vitro is about 50% of that of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism; T 1/2 is about 4 hours.

Withdrawal

The total clearance of sildenafil is 41 l / h, and the final T 1/2 is 3-5 hours. After oral administration, as well as after intravenous administration, sildenafil is excreted as metabolites, mainly by the intestines (about 80% of the oral dose) and, to a lesser extent, by the kidneys (about 13% of the oral dose).

Pharmacokinetics in special patient groups

Elderly patients

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

Renal dysfunction

With mild (creatinine clearance (CC) 50-80 ml / min) and moderate (CC 30-49 ml / min) degree of renal failure, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal failure (CC< 30 мл/мин) клиренс силденафила снижается, что приводит к примерно двукратному увеличению значения AUC (100 %) и C max (88 %) по сравнению с таковыми показателями при нормальной функции почек у пациентов той же возрастной группы.

Liver dysfunction

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

Release form

Film-coated tablets of blue color, round, biconvex; at the break - white or almost white.

Excipients: microcrystalline cellulose 50 mg, lactose monohydrate 61.5 mg, croscarmellose sodium 7.5 mg, povidone 4.5 mg, magnesium stearate 1.5 mg.

The composition of the film shell: Opadray II (polyvinyl alcohol, partially hydrolyzed 2 mg, titanium dioxide 1.145 mg, macrogol 1.01 mg, talc 0.74 mg, aluminum varnish based on brilliant blue 0.096 mg, iron oxide (II) yellow 0.0085 mg, iron oxide (II ) black 0.0005 mg).

1 PC. - contour cell packaging (1) - cardboard packs.
2 pcs. - contour cell packaging (1) - cardboard packs.
4 things. - contour cell packaging (1) - cardboard packs.
10 pieces. - contour cell packaging (1) - cardboard packs.
20 pcs. - polymer cans (1) - cardboard packs.
20 pcs. - polymer bottles (1) - cardboard packs.

Dosage

The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Taking into account the effectiveness and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of use is once a day.

Renal dysfunction

< 30 мл/мин) - дозу силденафила следует снизить до 25 мг.

Liver dysfunction

Combined use with other drugs

When used together with ritonavir, the maximum single dose of Sildenafil should not exceed 25 mg, and the frequency of use should be 1 time per 48 hours.

When used together with inhibitors of the cytochrome CYP3A4 isoenzyme (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Sildenafil should be 25 mg. To minimize the risk of postural hypotension in patients taking alpha-blockers, Sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. Consideration should also be given to reducing the initial dose of sildenafil.

Elderly patients

No dose adjustment of Sildenafil is required.

Overdose

With a single dose of the drug Sildenafil in a dose of up to 800 mg, adverse events were comparable to those when the drug was taken at lower doses, but they were more common.

Treatment is symptomatic. Hemodialysis does not accelerate the clearance of sildenafil, since the latter actively binds to plasma proteins and is not excreted by the kidneys.

Interaction

The effect of other drugs on the pharmacokinetics of sildenafil

Sildenafil metabolism occurs mainly under the action of cytochrome isoenzymes CYP3A4 (main pathway) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, respectively, increase the clearance of sildenafil. A decrease in the clearance of sildenafil was noted with the 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 concentration of sildenafil by 56%. A single dose of 100 mg of sildenafil together with erythromycin (500 mg / day 2 times a day for 5 days), a specific inhibitor of the cytochrome CYP3A4 isoenzyme, against the background of reaching a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%.

With the combined administration of sildenafil (100 mg once) and saquinavir (1200 mg / day 3 times a day), an inhibitor of HIV protease and cytochrome CYP3A4 isoenzyme, against the background of reaching a constant concentration of saquinavir in the blood, the C max 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, can cause stronger changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P450, against the background of reaching a constant concentration of ritonavir in the blood leads to an increase in the C max of sildenafil by 300% (in 4 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 one sildenafil - 5 ng / ml), which is consistent with information about the pronounced effect of ritonavir on the pharmacokinetics of various substrates of cytochrome P 450. Sildenafil has no effect on the pharmacokinetics of ritonavir. The concomitant use of sildenafil with ritonavir is not recommended. If sildenafil is taken in recommended doses by patients receiving simultaneously strong inhibitors of the cytochrome CYP3A4 isoenzyme, then the C max 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.

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

Azithromycin (500 mg / day for 3 days) has no effect on AUC, C max T max, elimination rate constant and T1 / 2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other medicines

Sildenafil is a weak inhibitor of cytochrome P 450 isoenzymes -1A2, 2C9, 2C19, 2D6, 2E1 and ZA4 (IC 50> 150 μmol). When sildenafil is taken in recommended doses, its C max is about 1 μmol, therefore it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter and with their appointment for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

With the simultaneous administration of the α-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional decrease in systolic / diastolic blood pressure in the supine position was 7 / 7 mmHg Art., 9/5 mm Hg. and 8/4 mm Hg, respectively, and in the standing position - 6/6 mm Hg, 11/4 mm Hg. and 4/5 mm Hg, respectively. Reported rare cases of the development of symptomatic postural hypotension in such patients, manifested in the form of dizziness (without fainting). In some sensitive patients receiving α-blockers, the simultaneous use of sildenafil can lead to symptomatic hypotension.

Signs of significant interaction with tolbutamide (250 mg) or warfarioma (40 mg), which are metabolized by the cytochrome CYP2C9 isoenzyme, have not been identified.

Sildenafil (100 mg) has no effect on the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome CYP3A4 isoenzyme, at a constant level in the blood. 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% on average (80 mg / dL).

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

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

Side effects

Typically, the side effects of Sildenafil are mild to moderate and transient.

In studies using a fixed dose, it has been shown that the frequency

When using the drug Sildenafil in doses higher than recommended, adverse events were similar to those noted above, but usually more common.

General disorders: facial edema, photosensitivity reactions, shock, asthenia, pain, chills, abdominal pain, chest pain.

Allergic reactions: hypersensitivity reactions (including skin rash), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Central and peripheral nervous system disorders: drowsiness, insomnia, hypesthesia, paresthesia, ataxia, neuralgia, neuropathy, tremor, depression, unusual dreams, decreased reflexes, stroke, transient ischemic attack, convulsions, incl. recurrent.

Violations of the cardiovascular system: tachycardia, increase or decrease in blood pressure, myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina pectoris, AV block, cerebrovascular thrombosis, heart failure, ECG disorders, cardiomyopathy, sudden death, fainting.

Respiratory disorders: epistaxis, asthma, shortness of breath, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum production, increased cough.

Gastrointestinal disorders: vomiting, nausea, dryness of the oral mucosa, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, rectal bleeding, gingivitis.

Disturbances from the organ of vision: eye pain, redness of the eyes / scleral injections, conjunctival damage, impaired lacrimation, anterior ischemic optic neuropathy, retinal vascular occlusion, visual field defects, mydriasis, cataracts, eye pain.

Hearing disorders: vertigo, tinnitus, ear pain, deafness.

Blood and lymphatic system disorders: anemia, leukopenia.

Metabolic and nutritional disorders: thirst, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.

Musculoskeletal disorders: arthritis, arthrosis, myalgia, tendon rupture, tendovaginitis, bone pain, myasthenia gravis, synovitis.

Skin and subcutaneous tissue disorders: urticaria, herpes simplex, itching, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

Violations of the genitourinary system: cystitis, nocturia, frequent urination, gynecomastia, urinary incontinence, ejaculation disorders, genital edema, anorgasmia.

Reproductive system disorders: prolonged erection and / or priapism.

Indications

• treatment of erectile dysfunction, characterized by the inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.

Sildenafil is only effective for sexual stimulation.

Contraindications

• hypersensitivity to sildenafil or to any other component of the drug;
• use in patients receiving continuously or intermittently donors of nitric oxide, organic nitrates or nitrites in any form, since sildenafil enhances the hypotensive effect of nitrates (see the section "Interaction with other medicinal products") Safety and efficacy of Sildenafil when used together with other drugs treatment of erectile dysfunction has not been studied, therefore the use of such combinations is not recommended (see section "Special instructions");
• according to a registered indication, Sildenafil is not intended for use in children under 18 years of age;
• according to a registered indication, Sildenafil is not intended for use in women;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• concomitant use of sildenafil with ritonavir is not recommended.

With caution: anatomical deformity 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 gastric ulcer and duodenal ulcer.

Hereditary retinitis pigmentosa.

Heart failure, unstable angina, myocardial infarction, stroke or life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg) or hypotension (BP< 90/50 мм рт.ст.).

In patients with episodes of development of anterior non-arteritis ischemic neuropathy of the optic nerve (in history).

Application features

Application during pregnancy and lactation

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

Application for violations of liver function

Since the elimination of sildenafil is impaired in patients with liver damage (in particular, with cirrhosis), the dose of Sildenafil should be reduced to 25 mg.

Application for impaired renal function

With mild to moderate renal failure (CC 30-80 ml / min), dose adjustment is not required, with severe renal failure (CC< 30 мл/мин) - дозу силденафила следует снизить до 25 мг.

Application in children

special instructions

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

Drugs intended for the treatment of 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, therefore, before starting any therapy for erectile dysfunction, the doctor should refer the patient to an examination of the state of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina pectoris, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg) or hypotension (BP< 90/50 мм рт. ст.). В клинических исследованиях показано отсутствие различий в частоте развития инфаркта миокарда (1,1 на 100 человек в год) или частоте смертности от сердечно-сосудистых заболеваний (0,3 на 100 человек в год) у пациентов, получавших препарат Силденафил, по сравнению с пациентами, получавшими плацебо.

Cardiovascular complications

During the post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as serious cardiovascular complications (including myocardial infarction, unstable angina pectoris, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported. ) who had a temporary connection 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 were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct connection between the observed undesirable phenomena and the indicated or other factors.

Hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in LD, which is not clinically significant and does not lead to any consequences in most patients. However, before prescribing the drug Sildenafil, the physician should carefully assess the risk of possible undesirable manifestations of vasodilating action 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 systemic atrophy, manifested by severe dysregulation of blood pressure by the autonomic nervous system.

Since the combined use of sildenafil and α-blockers can lead to symptomatic hypotension in some sensitive patients, the drug Sildenafil should be used with caution in patients taking α-blockers. To minimize the risk of postural hypotension in patients taking α-blockers, Sildenafil should be started only after stabilization of hemodynamic parameters in these patients is achieved. You should also consider the feasibility of reducing the initial dose of the drug Sildenafil. The physician should advise patients of what action to take if symptoms of postural hypotension occur.

Visual impairment

Rare cases of the development of anterior non-arteritic ischemic neuropathy of the optic nerve as a cause of deterioration or loss of vision were noted against the background of the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as excavation (deepening) of the optic disc, age over 50, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia, and smoking. A causal relationship between the intake of PDE5 inhibitors and the development of anterior non-arteritis ischemic neuropathy of the optic nerve was not revealed. The doctor should inform the patient about the increased risk of developing anterior non-arteritis ischemic neuropathy of the optic nerve, if this condition has already been noted. In the event of a sudden loss of vision, patients should immediately receive the necessary medical attention. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of the functions of retinal phosphodiesterases. There is no information on the safety of using the drug Sildenafil in patients with retinitis pigmentosa, therefore, sildenafil should be used with caution.

Hearing impairment

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

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 the use of sildenafil in patients with a tendency to bleeding or exacerbation of gastric ulcer and duodenal ulcer, so the drug Sildenafil should be used with caution in these patients. The incidence of nosebleeds in patients with PH 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%). In patients receiving sildenafil in combination with a vitamin K antagonist, the incidence of nosebleeds was higher (8.8%) than in patients not taking a vitamin K antagonist (1.7%).

Application in conjunction with other drugs for the treatment of erectile dysfunction.

The safety and efficacy of the drug Sildenafil in conjunction with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended.

Influence on the ability to drive vehicles and use mechanisms

While taking sildenafil, there was no negative effect on the ability to drive a car or other technical means.

However, since when taking sildenafil, a decrease in blood pressure is possible, the development of chromatopsia, blurred vision, etc. side effects, you should be attentive to the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Description of the dosage form

Pills: covered with a blue film sheath, round, biconvex. At the break - white or almost white.

pharmachologic effect

Pharmacodynamics

Sildenafil is a potent selective inhibitor of cGMP-specific PDE-5.

Mechanism of action

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

Sildenafil does not have a direct relaxing effect on the isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting PDE-5, which is responsible for the breakdown of cGMP.

Sildenafil is selective for PDE-5 in vitro, its activity in relation to PDE-5 exceeds the activity in relation to other known isoenzymes of PDE: PDE-6 - 10 times; PDE-1 - more than 80 times; PDE-2, PDE-4, PDE-7-PDE-11 - more than 700 times. Sildenafil is 4000 times more selective for PDE-5 compared to PDE-3, which is of great importance, since PDE-3 is one of the key enzymes in the regulation of myocardial contractility.

Sexual stimulation is a prerequisite for the effectiveness of sildenafil.

Clinical data

Cardiological research. The use of sildenafil in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in systolic blood pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg. Art. , and DBP - 5.3 mm Hg. Art. A more pronounced, but also transient effect on blood pressure was observed in patients taking nitrates (see "Contraindications", "Interaction").

In a study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis of at least one coronary artery), SBP and DBP at rest decreased by 7 and 6%, respectively, and pulmonary SBP decreased by 9%. Sildenafil did not affect cardiac output and did not interfere with blood flow in stenotic coronary arteries, and also led to an increase (by about 13%) in adenosin-induced coronary flow in both stenotic and intact coronary arteries.

In a double-blind, placebo-controlled study, 144 patients with erectile dysfunction and stable angina, taking antianginal drugs (other than nitrates), did physical exercise until the angina symptoms subsided. The duration of the exercise was significantly longer (19.9 s; 0.9-38.9 s) in patients taking sildenafil in a single dose of 100 mg, compared with patients receiving placebo.

A randomized, double-blind, placebo-controlled study investigated the effect of varying the dose of sildenafil (up to 100 mg) in men (n = 568) with erectile dysfunction and hypertension taking more than two antihypertensive drugs. Sildenafil improved erection in 71% of men compared with 18% in the placebo group. The incidence of adverse effects was comparable to that in other patient groups, as well as in those taking more than three antihypertensive drugs.

Research on visual impairment. In some patients, 1 hour after taking sildenafil at a dose of 100 mg using the Farnsworth-Munsell 100 test, a mild and transient impairment of the ability to distinguish shades of color (blue / green) was revealed. These changes were absent 2 hours after taking the drug. It is believed that color vision impairment is caused by inhibition of PDE-6, which is involved in the transmission of light in the retina. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, IOP, or pupil diameter.

In a placebo-controlled crossover study of patients with proven early age macular degeneration (n = 9), sildenafil at a single dose of 100 mg was well tolerated. There were no clinically significant changes in vision, assessed by special visual tests (visual acuity, Amsler grating, color perception, modeling of color passage, Humphrey perimeter and photostress).

Efficiency

The efficacy and safety of sildenafil was evaluated in 21 randomized, double-blind, placebo-controlled studies lasting up to 6 months in 3000 patients aged 19 to 87 years, with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The efficacy of the drug was assessed globally using an erection diary, an international erectile function index (a validated questionnaire on the state of sexual function) and a partner survey.

The efficacy of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory intercourse, has been demonstrated in all studies conducted and confirmed in long-term studies of 1 year duration. In studies using a fixed dose, the ratio of patients reporting that therapy improved their erection was 62% (dose of sildenafil - 25 mg), 74% (dose of sildenafil - 50 mg) and 82% (dose of sildenafil - 100 mg) versus 25% in the placebo group. The analysis of the international index of erectile function showed that, in addition to improving erection, treatment with sildenafil also increased the quality of orgasm, made it possible to achieve satisfaction from intercourse and overall satisfaction.

According to pooled data, 59% of patients with diabetes mellitus, 43% of patients undergoing radical prostatectomy, and 83% of patients with spinal cord injuries were among the patients who reported improved erections with sildenafil treatment (versus 16, 15 and 12% in the placebo group, respectively). ...

Pharmacokinetics

Suction. After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro sildenafil at a concentration of about 1.7 ng / ml (3.5 nmol) inhibits human PDE-5 activity by 50%. After a single dose of sildenafil at a dose of 100 mg, the average C max of free sildenafil in the blood plasma of men is about 18 ng / ml (38 nmol) and is achieved when sildenafil is taken orally on an empty stomach for an average of 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: C max decreases by an average of 29%, and T max increases by 60 minutes, but the degree of absorption does not change significantly (AUC decreases by 11%).

Distribution. The V ss of sildenafil averages 105 liters. The connection of sildenafil and its main circulating N-demethyl metabolite with blood plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the sildenafil dose (average 188 ng) was found in semen 90 minutes after taking the drug.

Metabolism. Sildenafil is metabolized mainly in the liver by the action of the CYP3A4 isoenzyme (main pathway) and the CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite resulting from N-demethylation of sildenafil is further metabolized. The selectivity of this metabolite in relation to PDE is comparable to that of sildenafil, and its activity in relation to PDE-5 in vitro accounts for about 50% of the activity of sildenafil.

The concentration of the metabolite in the blood plasma of healthy volunteers is about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism; T 1/2 - about 4 hours

Excretion. The total clearance of sildenafil is 41 l / h, and the final T 1/2 is 3-5 hours.After oral administration, as well as after intravenous administration, sildenafil is excreted as metabolites, mainly by the intestines (about 80% of the oral dose) and to a lesser extent by the kidneys (about 13% of the oral dose).

Special patient groups

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

Renal dysfunction. With mild (Cl creatinine - 50-80 ml / min) and moderate (Cl creatinine - 30-49 ml / min) degree of renal failure, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal failure (Cl creatinine ≤30 ml / min), the clearance of sildenafil decreases, which leads to an approximately twofold increase in the AUC (100%) and C max (88%) values ​​compared with those with normal renal function in patients of the same age. groups.

Liver dysfunction. In patients with liver cirrhosis (stages A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase in the AUC (84%) and C max (47%) values ​​compared with those with normal liver function in patients of the same age group. The pharmacokinetics of sildenafil in patients with severely impaired liver function (stage C according to the Child-Pugh classification) has not been studied.

Indications of the drug Sildenafil-SZ

Treatment of erectile dysfunction, characterized by an inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.

Sildenafil is only effective for sexual stimulation.

Contraindications

hypersensitivity to sildenafil or any other component of the drug;

use in patients receiving continuously or intermittently donors of nitric oxide, organic nitrates or nitrites in any form, since sildenafil enhances the hypotensive effect of nitrates (see "Interaction");

lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

according to a registered indication, Sildenafil-SZ is not intended for use in women;

according to a registered indication, Sildenafil-SZ is not intended for use in children under 18 years of age.

The safety and efficacy of the drug Sildenafil-SZ when used together with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see "Special instructions"); the simultaneous use of sildenafil with ritonavir is not recommended (see "Dosage and Administration", "Interaction").

Carefully: anatomical deformity of the penis (angulation, cavernous fibrosis or Peyronie's disease) (see "Special instructions"); diseases that predispose to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia - see "Special instructions"); diseases accompanied by bleeding; exacerbation of gastric ulcer and duodenal ulcer; hereditary retinitis pigmentosa (see "Special instructions"); heart failure, unstable angina, myocardial infarction, stroke or life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg) or hypotension (BP<90/50 мм рт. ст. ) (см. «Особые указания»); пациенты с эпизодами развития неартериитной передней ишемической невропатии зрительного нерва (НПИНЗН) (в анамнезе).

Application during pregnancy and lactation

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

Side effects

The most common side effects were headache and hot flashes.

Typically, the side effects of Sildenafil-SZ are mild to moderate and transient.

Studies using a fixed dose 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 - ≥1 / 10%; often - from ≥1 to<10%; нечасто — от ≥0,1 до <1%; редко — от ≥0,01 до <0,1%; очень редко — <0,01%; частота неизвестна — невозможно определить на основе имеющихся данных.

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

On the part of the organ of vision: often - blurred vision, blurred vision, cyanopsia; infrequently - eye pain, photophobia, photopsia, chromatopsia, redness of the eyes / injection of sclera, change in the brightness of light perception, mydriasis, conjunctivitis, hemorrhage in the eye tissue, cataract, disruption of the lacrimal apparatus; rarely - swelling of the eyelids and adjacent tissues, a feeling of dryness in the eyes, the presence of iridescent circles in the field of vision around the light source, increased eye fatigue, seeing objects in yellow color (xanthopsia), seeing objects in red (erythropsia), conjunctival hyperemia, mucosal irritation membranes of the eyes, discomfort in the eyes; frequency unknown - NPINZN, retinal vein occlusion, visual field defect, diplopia *, temporary loss of vision or decreased visual acuity, increased IOP, retinal edema, retinal vascular disease, vitreous detachment / vitreous traction.

On the part of the organ of hearing: infrequently - sudden hearing loss or loss, tinnitus, ringing in the ears, ear pain.

From the CCC side: often hot flashes; infrequently - tachycardia, palpitations, decreased or increased blood pressure, increased heart rate, unstable angina pectoris, AV blockade, myocardial infarction, cerebral thrombosis, cardiac arrest, heart failure, abnormal ECG readings, cardiomyopathy; rarely - atrial fibrillation, sudden cardiac death *, ventricular arrhythmia *.

On the part of 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; infrequently - epistaxis, rhinitis, asthma, dyspnoea, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum volume, increased cough; rarely - a feeling of tightness in the throat, dryness of the nasal mucosa, edema of the nasal mucosa.

From the gastrointestinal tract: often - nausea, dyspepsia; infrequently - GERD, vomiting, abdominal pain, dryness of the oral mucosa, glossitis, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, abnormal liver function tests, rectal bleeding; rarely - hypesthesia of the oral mucosa.

From the side of the musculoskeletal system: often - back pain; infrequently - myalgia, pain in the extremities, arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.

From the genitourinary system: infrequently - cystitis, nocturia, breast enlargement, urinary incontinence, hematuria, ejaculation disorder, genital edema, anorgasmia, hematospermia, damage to the tissues of the penis; rarely - prolonged erection and / or priapism, bleeding from the penis.

From the side of the central and peripheral nervous system: very often - headache; often - dizziness; infrequently - drowsiness, migraine, ataxia, hypertonicity, neuralgia, neuropathy, paresthesia, tremor, vertigo, symptoms of depression, insomnia, unusual dreams, increased reflexes, hypesthesia; rarely - convulsions *, repeated convulsions *, fainting, cerebrovascular accident, transient ischemic attack.

On the part of the skin and subcutaneous tissues: infrequently - skin rash, urticaria, herpes simplex, pruritus, increased sweating, skin ulceration, contact dermatitis, exfoliative dermatitis; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis.

Others: infrequently - a feeling of heat, swelling of the face, photosensitivity reaction, shock, asthenia, fatigue, pain of various localization, chills, accidental falls, chest pain, accidental injuries; rarely - irritability.

During the post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina pectoris, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, hypertension and hypotension) were reported that had a temporary relationship 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 were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct connection between the observed undesirable phenomena and the indicated or other factors.

Visual impairment

In rare cases, during the post-registration use of all PDE-5 inhibitors, incl. sildenafil, have reported NPINZN, a rare disease and cause of decreased or loss of vision. Most of these patients had risk factors, in particular, a decrease in the ratio of the diameters of the excavation and the optic nerve head (stagnant disc), age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking.

An observational study assessed whether recent use of drugs of the PDE5 inhibitor class is associated with acute onset of NPINZN. The results indicate an approximately twofold increase in the risk of NPINZN within five T 1/2 after PDE-5 inhibitor administration. According to the published literature, the annual incidence of NPINZN 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 discontinue sildenafil therapy and consult a doctor immediately. Individuals who have already had a case of NPINZN have an increased risk of recurrence of NPINZN. Therefore, the physician should discuss this risk with these patients, and also discuss with them the potential chance of adverse effects of PDE5 inhibitors. PDE-5 inhibitors, incl. sildenafil, in these patients should be used with caution and only in situations where the expected benefit outweighs the risk. When using the drug Sildenafil-SZ in doses higher than recommended, adverse events were similar to those noted above, but usually more common.

* Side effects identified during post-marketing research.

Interaction

The effect of other drugs on the pharmacokinetics of sildenafil

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

A decrease in the clearance of sildenafil was noted with the simultaneous use of inhibitors of the isoenzyme CYP3A4 (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the isoenzyme CYP3A4, when taken together with sildenafil (50 mg), causes an increase in plasma concentration of sildenafil by 56%.

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

With the combined administration of sildenafil (once 100 mg) and saquinavir (1200 mg / day 3 times a day), an inhibitor of HIV protease and cytochrome CYP3A4 isoenzyme, against the background of reaching a constant concentration of saquinavir in the blood, the C max of sildenafil increased by 140%, and the AUC increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir.

Stronger inhibitors of the isoenzyme CYP3A4, such as ketoconazole and itraconazole, can cause more pronounced changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P450, against the background of reaching a constant concentration of ritonavir in the blood leads to an increase in the C max of sildenafil by 300% (4 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 one sildenafil - 5 ng / ml), which is consistent with the information on the pronounced effect of ritonavir on the pharmacokinetics of various substrates of cytochrome P450.

Sildenafil has no effect on the pharmacokinetics of ritonavir. The concomitant use of sildenafil with ritonavir is not recommended.

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

Inhibitors of the isoenzyme CYP2C9 (tolbutamide, warfarin), isoenzyme CYP2D6(SSRIs, 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 AUC, C max, T max, elimination rate constant and T 1/2 of sildenafil or its main circulating metabolite.

The effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC 50> 150 μmol). When sildenafil is taken in recommended doses, its C max is about 1 μmol, therefore it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter and with their appointment for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

With the simultaneous administration of the α-adrenergic blocker doxazosin (4 and 8 mg) and sildenafil (25, 50 and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional decrease in SBP / DBP in the supine position was 7/7, 9 / 5 and 8/4 mm Hg. Art. respectively, and in the standing position - 6/6 mm, 11/4 and 4/5 mm Hg. Art. respectively. Reported rare cases of the development of symptomatic postural hypotension in such patients, manifested in the form of dizziness (without fainting). In some sensitive patients receiving α-blockers, the simultaneous use of sildenafil can lead to symptomatic hypotension.

Signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the isoenzyme CYP2C9, have not been identified.

Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the CYP3A4 isoenzyme, at a constant level in the blood.

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

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

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

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

Method of administration and dosage

Inside. The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Taking into account the effectiveness and tolerability, the dose can be increased to 100 mg or reduced to 25 mg.

Renal dysfunction. With mild to moderate renal failure (Cl creatinine 30-80 ml / min), dose adjustment is not required, with severe renal failure (Cl creatinine<30 мл/мин) дозу силденафила следует снизить до 25 мг.

Liver dysfunction. Since the elimination of sildenafil is impaired in patients with liver damage (in particular, with cirrhosis), the dose of Sildenafil-SZ should be reduced to 25 mg.

Joint use with other drugs. When used together with ritonavir, the maximum single dose of Sildenafil-SZ should not exceed 25 mg, and the frequency of use should be 1 time per 48 hours (see Interaction).

When used together with inhibitors of the isoenzyme CYP3A4 (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Sildenafil-SZ should be 25 mg (see "Interaction").

To minimize the risk of postural hypotension in patients taking α-blockers, Sildenafil-SZ should be taken only after hemodynamic stabilization in these patients has been achieved. You should also consider the feasibility of reducing the initial dose of sildenafil (see "Special instructions" and "Interaction").

Elderly patients. No dose adjustment of Sildenafil-SZ is required.

Overdose

With a single dose of Sildenafil-SZ at a dose of up to 800 mg, adverse events were comparable to those when the drug was taken at lower doses, but they were more common.

Treatment: symptomatic. Hemodialysis does not accelerate the clearance of sildenafil, because the latter actively binds to plasma proteins and is not excreted by the kidneys.

special instructions

To diagnose erectile dysfunction, determine their possible causes and choose an adequate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination. Erectile dysfunction treatments should be used with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, Peyronie's disease) or risk factors for priapism (SCA, multiple myeloma, leukemia) (see Contraindications, Carefully).

Drugs intended for the treatment of 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, therefore, before starting any therapy for erectile dysfunction, the doctor should refer the patient to an examination of the state of the CVS.

Sexual activity is undesirable in patients with heart failure, unstable angina pectoris, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg) or hypotension (BP<90/50 мм рт. ст. ) (см. «Противопоказания», Carefully). Clinical studies have shown no differences in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of mortality from cardiovascular diseases (0.3 per 100 people per year) in patients treated with Sildenafil-SZ, compared to with patients receiving placebo.

Cardiovascular complications

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

Hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not clinically significant and does not lead to any consequences in most patients. Nevertheless, before prescribing the drug Sildenafil-SZ, the doctor should carefully assess the risk of possible undesirable manifestations of vasodilating action 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 systemic atrophy, manifested by severe impairment of blood pressure regulation by the autonomic nervous system.

Since the combined use of sildenafil and α-blockers can lead to symptomatic hypotension in some sensitive patients, the drug Sildenafil-SZ should be used with caution in patients taking α-blockers (see "Interaction"). To minimize the risk of postural hypotension in patients taking α-blockers, the drug Sildenafil-SZ should be started only after stabilization of hemodynamic parameters in these patients. You should also consider the feasibility of reducing the initial dose of the drug Sildenafil-SZ (see "Dosage and Administration"). The physician should advise patients of what action to take if symptoms of postural hypotension occur.

Visual impairment

There have been rare cases of NPINZN development as a cause of deterioration or loss of vision with the use of all PDE-5 inhibitors, including sildenafil. Most of these patients had risk factors such as excavation (deepening) of the optic nerve head, age over 50 years, diabetes mellitus, arterial hypertension, coronary heart disease, hyperlipidemia, and smoking. A causal relationship between the intake of PDE-5 inhibitors and the development of NPINZN has not been identified. The doctor should inform the patient about the increased risk of developing NPINZN, if this condition has already been noted in him. In the event of a sudden loss of vision, patients should immediately receive the necessary medical attention. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of the retinal PDE functions. There is no information about the safety of using the drug Sildenafil-SZ in patients with retinitis pigmentosa, therefore, sildenafil should be used with caution (see "Contraindications", Carefully).

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden hearing impairment or loss associated with the use of all PDE-5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden hearing impairment or loss. A causal relationship between the use of PDE5 inhibitors and sudden hearing impairment or hearing loss has not been established. In case of sudden deterioration or loss of hearing while taking sildenafil, you should immediately consult your doctor.

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 the use of sildenafil in patients with a tendency to bleeding or exacerbation of gastric ulcer and duodenal ulcer, therefore the drug Sildenafil-SZ should be used in these patients with caution (see "Contraindications", Carefully). The incidence of nosebleeds 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%, placebo - 2.4%). %). In patients receiving sildenafil in combination with a vitamin K antagonist, the incidence of nosebleeds was higher (8.8%) than in patients not taking a vitamin K antagonist (1.7%).

Use in conjunction with other drugs for the treatment of erectile dysfunction. The safety and efficacy of Sildenafil-SZ together with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see "Contraindications").

Influence on the ability to drive vehicles and work with mechanisms. While taking the drug Sildenafil-SZ, no negative effect on the ability to drive a car or other technical means was observed. However, since when taking sildenafil, a decrease in blood pressure is possible, the development of chromatopsia, blurred vision, etc. side effects, you should be attentive to the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

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