Sluggish precio de sildenafil tablets. The most powerful formula - Sildenafil with Dapoxetine! Interaction with drugs

Sildenafil (sildenafil)

Composition and form of release of the drug

Film-coated tablets white or almost white, round, biconvex; in cross section, the nucleus is white or almost white.

Excipients: microcrystalline cellulose, calcium hydrogen phosphate anhydrous, croscarmellose sodium, magnesium stearate.

film sheath: [hypromellose; talc; titanium dioxide; macrogol 4000 (polyethylene glycol 4000)] or [dry film coating mix containing hypromellose, talc, titanium dioxide, macrogol 4000 (polyethylene glycol 4000)].

15 pcs. - cellular contour packings (6) - packs of cardboard.
90 pcs. - high-density polyethylene cans (1) - cardboard packs.

pharmachologic effect

Selective inhibitor of cycloguanosine monophosphate (cGMP)-specific PDE5. PDE5, which is responsible for the breakdown of cGMP, is found not only in the cavernous body of the penis, but also in the vessels of the lungs.

Restores impaired erectile function and provides a natural response to sexual arousal. Sildenafil does not have a direct relaxing effect on the corpus cavernosum, but actively enhances the relaxing effect of nitric oxide on this tissue. During sexual arousal, local release of NO under the influence of sildenafil leads to inhibition of PDE5 and an increase in the level of cGMP in the cavernous body, as a result of which smooth muscles relax and blood flow in the cavernous body increases.

Being a PDE5 inhibitor, sildenafil increases the content of cGMP in the smooth muscle cells of the pulmonary vessels and causes them to relax. In patients with pulmonary hypertension, sildenafil leads to vasodilation of the lungs and, to a lesser extent, other vessels.

Sildenafil is selective for PDE5 in vitro. Its activity against PDE5 exceeds activity against other known PDE isoenzymes: PDE6, which is involved in the transmission of a light signal in the retina of the eye - 10 times; PDE1 - 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. The activity of sildenafil against PDE5 is more than 4000 times greater than its activity against PDE3, a cAMP-specific PDE involved in cardiac contraction.

Sildenafil can cause mild and transient impairment of color discrimination (blue/green). The proposed mechanism of color vision impairment is the inhibition of PDE6, which is involved in the process of light transmission in the retina. In vitro studies have shown that the effect of sildenafil on PDE6 is 10 times inferior to its activity against PDE5.

Pharmacokinetics

Sildenafil is rapidly absorbed after oral administration. Absolute bioavailability averages 40% (25-63%). After a single oral dose of 100 mg C max is 18 ng / ml and is achieved when taken on an empty stomach for 30-120 minutes. When taking sildenafil in combination with fatty foods, the rate of absorption decreases; T max increases by 60 minutes, and C max decreases by an average of 29%. V d of sildenafil in the equilibrium state averages 105 liters. Sildenafil and its major circulating N-desmethyl metabolite are approximately 96% protein bound. Protein binding is independent of the total concentration of sildenafil. Less than 0.0002% of the dose (mean 188 ng) was detected in semen 90 minutes after taking sildenafil.

Sildenafil is metabolized mainly by the action of microsomal liver isoenzymes CYP3A4 (the main route) and CYP2C9.

The main circulating metabolite, which is formed as a result of N-desmethylation of sildenafil, undergoes further metabolism. In terms of selectivity of action on PDE, the metabolite is comparable to sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil itself. The plasma concentration of the metabolite is approximately 40% of that of sildenafil. The N-desmethylmetabolite undergoes further metabolism; its terminal T 1/2 is about 4 hours.

The total clearance of sildenafil from the body is 41 l / h, and T 1/2 in the terminal phase is 3-5 hours. After oral administration, sildenafil is excreted as metabolites mainly in the feces (approximately 80% of the dose) and to a lesser extent in the urine (approximately 13% of the dose).

In elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of free active substance in plasma is approximately 40% higher than its concentration in young (18-45 years) patients.

special instructions

Before you start taking sildenafil for the treatment of erectile dysfunction, you should conduct an examination of the cardiovascular system.

Caution should be used in patients with anatomical deformity of the penis (eg, angulation, cavernous fibrosis, or Peyronie's disease) and people with diseases that predispose to the development of priapism (such as sickle cell anemia, multiple myeloma, or leukemia).

Should not be used in patients for whom sexual activity is undesirable.

Use with caution in patients with a tendency to bleeding, with peptic ulcer of the stomach and duodenum in the acute phase, with hereditary retinitis pigmentosa.

Sildenafil is not used in patients under the age of 18 years.

Influence on the ability to drive vehicles and control mechanisms

Sildenafil does not affect the ability to drive vehicles and control mechanisms.

Application in childhood

Sildenafil is not used in patients under the age of 18 years.

For impaired renal function

For impaired renal function, the dose is 25 mg.

For impaired liver function

For violations of liver function, the dose is 25 mg.

Use in the elderly

For elderly patients over the age of 65, the dose is 25 mg.

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 a man's self-confidence.

Sildenafil is produced 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 is white. This drug is produced in the form of citrate.

Tablets also include additional ingredients that enhance the effect. These include microcrystalline cellulose and lactose monohydrate. In addition, the remedy includes pavilon and croscarmellose. In a small amount, this medicine also contains magnesium stearate.

Mechanism of action

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

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

This means that the use of this tool helps to restore the response of the male body to arousal. But the effect 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 implementation of excitation and providing an erection for the penis. The fact is that after excitation, a lot of nitric oxide is produced in the body. This substance leads to vasodilation, after which blood circulation in the cavernous areas of the penis increases.

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

Thanks to this, it is possible to extend 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 the excitement, which is accompanied by the entry 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 must be remembered that an enzyme called PDE-5 is not only found in the penis - it is also found in the pulmonary vessels. Therefore, the use of the drug 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 most of all relaxes the pulmonary vessels. 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 state. After the end 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 dysfunction in women. The drug helps to stimulate excitement even during menopause or after surgery to remove the uterus.

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

Pills have a complex effect on the woman's body. Through the use of this tool, there is a desire for sexual intimacy, blood circulation in the pelvic organs increases, and erogenous zones become more sensitive.

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

However, it can cause unwanted side effects. So, after taking this remedy, there is a risk of developing headaches, nausea, dizziness. The woman may lose 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 the gynecologist.

Clinical researches

This drug is very popular, and therefore scientists have conducted a number of studies that allow us to study its effect 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 when using more than 100 mg of the active ingredient.

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

Pharmacokinetics

The drug is rapidly absorbed. The bioavailability index of the agent is 41%. The maximum level of the drug in the blood is reached 1 hour after ingestion on an empty stomach. If the patient has previously taken alcohol or ate a fatty meal, 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 that, the drug is metabolized by liver enzymes. It takes about 4 hours to remove the main metabolites. At the same time, they mainly leave the body with feces - approximately 80%, while only 13% leaves with urine.

Indications and application features

Sildenafil instructions to which must be strictly observed, 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. For 1 time, it is recommended to use 50 mg of the drug.

However, this dosage can be adjusted upwards or downwards. This means that the doctor may 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 the 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 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 data on violations in the functioning of the kidneys, 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 consider 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 donators. 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 safety of combining this drug with other drugs has not been studied, therefore, any combination should be treated with extreme caution.
3. Age up to 18 years. The indications for the use of the agent registered in the instructions include this limitation.
4. Female.
5. Lactase deficiency, lactose intolerance.
6. Combination with ritonavir.

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

In addition, you should consult a 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 with sickle cell form of anemia. In such a situation, the doctor can choose safer analogues of the drug.

Also contraindications include pathologies that are accompanied by bleeding. Do not drink the remedy during an exacerbation of peptic ulcer. 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 for heart failure and the development of an unstable form of angina pectoris. The ban on its reception is a heart attack and stroke that have occurred within the last 6 months. Also, do not drink the drug with severe forms of hypertension and hypotension. The limitations should also include arrhythmia, which poses a danger to human life.

Another threatening combination is taking sildenafil with episodes of ischemic optic neuropathy. In such a situation, you should consult 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 effects of taking it:

1. The nervous system can react to taking this drug with headaches, flushing of the face, vision problems, dizziness.
2. Respiratory system - the patient after using this remedy 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. Integuments - the patient may develop rashes after using the product.
6. Other side effects - this category includes pain in the back, the development of arthralgia, respiratory infections. In addition, some patients develop a flu-like syndrome.

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

special instructions

Before starting the use of a medicinal product, important limitations should be considered when choosing a dosage. So, with nephropathology and hepatopathology, the maximum allowable daily volume is 25 mg. The same requirement is 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;
• tendency to bleed.

Clinical trials did not reveal the effect of this drug on psychomotor reactions. It does not affect attention 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 of age. Their condition remained normal. After that, it was possible to establish that men managed to achieve positive results after using this remedy.

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

1. People with kidney disorders. Patients with moderate or mild kidney disease can safely use sildenafil. A single use of the drug in a volume of 50 mg will not provoke significant changes in the body. Scientists conducted special studies that revealed this feature.

The clearance of the drug is reduced if a person takes this remedy for complex pathologies. In this case, all indicators increase almost twice 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 matter, with stages A and B. Also, all indicators increase compared to 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.

• sensation of heat;
• digestive disorders;
• redness of the skin of the face;
• headaches;
• violation of nasal breathing;
• pressure reduction;
• 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 give 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 drugs that affect the CYP3A4 enzyme provokes a prolongation 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 agents do not affect the effectiveness of sildenafil:

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

At the same time, this agent leads to an increase in the effect obtained from the use of nitroglycerin, nitroprusside and other nitric oxide donators. 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. In this case, 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.

Analogues

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

Currently, it is possible to distinguish such analogues of this medication:

• cialis;
• levitra;
• impase;
• wuka-wuka;
• tribestane;
• laveron;
• viardot.

Sildenafil is an effective remedy that copes with common erectile dysfunction and helps to significantly improve the quality of sex. 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 have a 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
• prostate disease
• Developing depression that negatively affects your health

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

We have studied a huge amount of materials and, most importantly, tested most of the means for potency 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.

ATTENTION! STOCK! You can try the drug is free order by clicking the link or by filling out the form below.

Sildenafil: instructions for use and reviews

Latin name: Sildenafil

ATX code: G04BE03

Active substance: sildenafil (sildenafil)

Manufacturer: Actavis LTD (Malta), CJSC Severnaya Zvezda (Russia), CJSC Vertes St. Petersburg (Russia), Sandoz (Russia)

Description and photo update: 26.10.2018

Sildenafil is a drug for the treatment of erectile dysfunction.

Release form and composition

Sildenafil dosage form - film-coated tablets (25/50/100 mg): diamond-shaped, biconvex, blue on the outside and white or almost white on the break, engraved "I" on this side and "35" (for tablets 25 mg) , "36" (for 50 mg tablets) and "58" (for 100 mg tablets).

Composition of 1 tablet 25/50/100 mg:

• active substance: sildenafil citrate - 35.12 / 70.24 / 140.48 mg (in terms of sildenafil - 25/50/100 mg);
• auxiliary components: microcrystalline cellulose, anhydrous calcium hydrogen phosphate, sodium croscarmellose, magnesium stearate, opadra II blue (lactose monohydrate, hypromellose HPMC 2910, titanium dioxide, triacetin, blue / indigo carmine dye), opadra transparent (hypromellose HPMC 2910, triacetin).

Pharmacological properties

Pharmacodynamics

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

The mechanism of erection is associated with the release of nitric oxide in the cavernous body, which leads to an increase in the level of cGMP, relaxation of the smooth muscle tissue of the corpora cavernosa, and an increase in blood flow.

The action of the drug is due to an increase in the effect of nitric oxide due to the inhibition of phosphodiesterase 5 (PDE5), which is responsible for the breakdown of cGMP.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

Pharmacokinetics

The drug is rapidly absorbed when taken orally. Its bioavailability is about 40%. In vitro, sildenafil at a concentration of about 1.7 ng / ml (3.5 nM) inhibits human PDE5 activity by 50%. With a single dose of the drug on an empty stomach at a dose of 100 mg, the maximum concentration of free sildenafil is reached in 30-120 minutes and is 18 ng / ml (38 nM). Taking the drug together with fatty foods reduces the rate of its absorption.

The volume of distribution averages 105 liters. Communication with plasma proteins is about 96%. The main metabolism of sildenafil occurs in the liver. Its half-life is 3-5 hours. Excretion of the drug occurs mainly by the intestines, to a lesser extent - by the kidneys.

Indications for use

According to the instructions, Sildenafil is indicated for the treatment of erectile dysfunction, in particular with the inability to achieve and maintain an erection sufficient for sexual intercourse.

Contraindications

Absolute contraindications:

• arterial hypotension;
• conditions in which sexual activity is undesirable;
• condition after a recent myocardial infarction or cerebrovascular accident (during the last 6 months);
• degenerative diseases of the retina (hereditary), including pigmentary rhinitis;
• severe liver failure;
• female;
• increased sensitivity to the components of the drug;
• age up to 18 years.

Relative contraindications:

• anatomical deformation of the penis;
• conditions accompanied by bleeding;
• diseases that contribute to the development of priapism, such as sickle cell anemia, leukemia, multiple myeloma, thrombocythemia;
• peptic ulcer in the acute stage;
• arrhythmia, arterial hypertension, heart failure, obstructive diseases of the outflow department of the left ventricle of the heart, such as aortic stenosis, hypertrophic obstructive cardiomyopathy;
• episodes of development of anterior non-arteritic ischemic neuropathy of the optic nerve in history.

Instructions for use Sildenafil: method and dosage

Sildenafil tablets are recommended to be taken 1 hour before sexual activity, the usual recommended dose is 50 mg, if necessary and depending on the tolerability of the drug, it can be increased to 100 mg or reduced to 25 mg.

Side effects

• nervous system: headache, dizziness, hypesthesia, drowsiness, stroke, fainting, transient ischemic attack, convulsions (including recurrent);
• cardiovascular system: hot flashes, palpitations, tachycardia, decrease or increase in blood pressure (BP), myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina pectoris, sudden death;
• organ of vision: impaired vision and color perception, conjunctival damage, lacrimation disorder, anterior ischemic optic neuropathy, retinal vascular occlusion, visual field defects;
• organ of hearing: vertigo, tinnitus, epistaxis;
• gastrointestinal tract (GIT): dyspepsia, nausea, vomiting, dryness of the oral mucosa;
• allergic reactions: skin rash, Stevens-Johnson syndrome, Lyell's syndrome;
• genital organs: hematospermia, bleeding from the penis, priapism, prolonged erection;
• musculoskeletal system: myalgia;
• other: chest pain, fatigue.

Overdose

Overdose leads to an increase in the frequency and severity of side effects.

special instructions

Before using Sildenafil, it is recommended to conduct a medical examination aimed at identifying the causes of erectile dysfunction, as well as conditions in which sexual activity poses a certain risk, such as diseases of the cardiovascular system. The risk of undesirable effects of the vasodilating effect of the drug should be carefully assessed, especially in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with a rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.

When taking PDE5 inhibitors, there were cases of the development of anterior ischemic-optic neuropathy of non-arterial origin. Risk factors are excavation of the optic nerve head, age over 50 years, diabetes mellitus, coronary heart disease, arterial hypertension, hyperlipidemia, and smoking.

Sildenafil tablets should be used with caution in active peptic ulcers and internal bleeding.

According to some studies, there are cases of sudden decrease or loss of hearing, observed mainly in patients with risk factors for their development. A causal relationship of these phenomena with the use of PDE5 inhibitors has not been established, however, in the event of a sudden decrease or loss of hearing, it is recommended to stop taking the drug and consult a doctor.

It is also necessary to immediately consult a doctor in case of maintaining an erection for more than 4 hours, as this can lead to damage to the tissues of the penis and irreversible loss of potency.

Influence on the ability to drive vehicles and complex mechanisms

In connection with the possible development of undesirable effects of the drug, such as blurred vision, dizziness, etc., care should be taken when driving vehicles and other mechanisms that require quick psychomotor reactions.

For impaired renal function

In severe renal failure with creatinine clearance< 30 мл/мин рекомендовано снижение дозы препарата до 25 мг.

In violation of liver function

drug interaction

The effect of drugs on the pharmacokinetics of sildenafil:

• inhibitors of CYP3A4 and CYP2C9 isoenzymes: reduce its clearance;
• inducers of CYP3A4 and CYP2C9 isoenzymes: increase its clearance;
• cimetidine (800 mg) + 50 mg of sildenafil: increases the concentration of the latter in plasma by 56%;
• erythromycin (500 mg / day 2 times for 5 days) + 100 mg of sildenafil: the area under the curve of sildenafil increases by 182%;
• saquinavir (1200 mg / day 3 times) + 100 mg sildenafil: its area under the curve increases by 210%, and the maximum concentration by 140%;
• ritonavir: leads to an increase in the maximum concentration of sildenafil by 4 times, and the area under the curve by 11 times, and therefore the maximum recommended dose of Sildenafil is 25 mg 1 time in 48 hours;
• bosentan: the area under the curve is reduced by 62.6%, and the maximum concentration by 52.4%.

Tolbutamide, warfarin, selective serotonin reuptake inhibitors, tricyclic antidepressants, thiazide and thiazide-like diuretics, ACE inhibitors, calcium antagonists, azithromycin do not affect the pharmacokinetics of the drug.

The effect of sildenafil on other drugs:

• nitrates and nitric oxide donators: enhances their hypotensive effect, and therefore combined use is contraindicated;
• doxazosin (alpha-blocker): in rare cases, symptomatic postural hypotension may develop, in patients with hypersensitivity there is a risk of developing symptomatic hypotension;
• bosentan: its area under the curve increases by 49.8%, and the maximum concentration by 42%.

There was no clinically significant interaction of sildenafil with tolbutamide, warfarin, HIV protease inhibitors, saquinavir, ritonavir, acetylsalicylic acid, amlodipine, antihypertensive drugs.

Taking the drug together with beta-blockers is possible only after achieving stable hemodynamics, which reduces the risk of developing postural hypotension. The advisability of reducing the initial dose of Sildenafil should also be considered.

Analogues

Analogues of Sildenafil are Viagra, Vigrande, Vizarsin, Dynamico.

Terms and conditions of storage

Store at a temperature not exceeding 25 °C. Keep away from children.

Shelf life - 3 years.

The combination of a sexual intercourse prolongator and an erection enhancer allows a man to achieve the highest quality sex. Sildenafil with Dapoxetine is one such combination. The first substance is part of the well-known Viagra and provides a strong erection. The second is, perhaps, the only really working remedy against premature ejaculation.

How it works

Sildenafil affects the blood flow in the cavernous bodies of the penis. This is achieved by blocking the work of one enzyme (phosphodiesterase 5), which leads to increased release of nitric oxide, a powerful compound that relaxes the vascular wall and increases blood flow. This enzyme is found only in the cavernous bodies of the penis, but enzymes close to it in structure (phosphodiesterase 1, 2, 3, 4) are present in platelets, myocardium, retina, and skeletal muscles. The slight effect of Sildenafil on these enzymes causes the possibility of side effects.

Dapoxetine acts at the level of ejaculation centers in the brain. It has the ability to increase the concentration of serotonin, a compound necessary for the transmission of information between nerve cells. This leads to an increase in the frequency and strength of inhibitory impulses from the ejaculation centers of the brain to similar centers in the spinal cord. As a result, ejaculation occurs later and sexual intercourse lasts longer.

Sildenafil and Dapoxetine tablets: indications for use

The combination of these two active substances should be used in case of simultaneous erectile dysfunction and premature ejaculation. This condition can develop if:

• The age of the man is over 45 years;
• Past injuries of the pelvic area (bone fractures, bruises, muscle and tendon ruptures, prostate injuries);
• Postponed injuries of the spine (only if sensitivity is preserved in the genital area);
• Atherosclerosis (deposition of cholesterol on the wall of blood vessels) of the iliac arteries;
• All kinds of psychological complexes, injuries associated with the genitals or intimacy.

Also, the combination of Dapoxetine and Sildenafil is suitable for healthy men who want to achieve high-quality and long-lasting sex.

Contraindications

The combination of Sildenafil with Dapoxetine should not be used in case of:

• Allergy or hypersensitivity to these substances;
• Deformation of the penis;
• Blood pressure above 140/90 mm. rt. Art. or below 100/70 mm. rt. Art.;
• Cardiac pathology (pain in the region of the heart, shortness of breath during physical exertion, interruptions in rhythmic work, violation of the structure of the valvular apparatus, myocardial infarction);
• Taking medication for high blood pressure;
• Reception of nitrates (nitroglycerin, isosorbide dinitrate, nitrospray, etc.);
• Taking antidepressants in the last two weeks, or within a week after using these drugs;
• Liver pathology (hepatitis, cirrhosis, liver failure);
• Kidney pathology (glomerulonephritis, renal failure);
• Any mental illness;
• Age under 18 or over 65.

Possible side effects

Most often, adverse reactions develop as a result of taking medications despite contraindications, their combination with alcohol. Less often - in connection with the individual characteristics of the organism. Side effects of the combination of Sildenafil with Dapoxetine include:

• Changes in blood pressure;
• Interruptions in the work of the heart, palpitations, pain behind the sternum of a burning, pressing nature;
• restlessness, insomnia;
• dizziness, headache, nausea;
• Change in the normal perception of colors (blue-green);
• Nasal congestion.

In the case of a combination of drugs with any psychotropic substances or alcohol, paradoxical reactions may develop in the form of a lack of erection, premature ejaculation.

Mode of application

All combined preparations containing Sildenafil with Dapoxetine are available in the form of film-coated tablets. When taken orally, they should not be divided or chewed - this can lead to the destruction of part of the active substance in the acidic environment of the stomach. The tablet should be taken with a moderate amount of water.

The effect gradually develops after 60-90 minutes and lasts about 4-5 hours. After it ends, the strength of the erection and the duration of sexual intercourse return to their original values.

Sildenafil + Dapoxetine = Super P-Force

One common combination product containing these active ingredients is Super P-Force. The medicine is produced by the Indian company Sunrise Remedies, which specializes in the production of drugs to improve the quality of sexual life. It contains 100 mg of sildenafil and 60 mg of dapoxetine. Super P-Force is sold in blisters of 4 tablets, costing from 330 to 720 rubles. You can buy medicine both in pharmacy chains and order online.

The drug has collected a lot of positive feedback from men who have tested it on themselves. The development of side effects is most often associated with non-compliance with the rules for taking the drug, or individual intolerance.

Sildenafil + Dapoxetine - where can I buy?

In addition to Super P-Force, there are several more drugs with a similar composition and dosage: Cenforce-D, Super Kamagra. They differ from each other by the manufacturer and by a slight price fluctuation. Extra Super P-Force contains 100 mg of Sildenafil and 100 mg of Dapoxetine. You can buy any of these drugs in pharmacy chains, or order via the Internet.

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 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 "wilds". 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 the 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, inhibition of its activity enhances the effects of NO. Now you need to figure out what underlies 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" NO secreted by endothelial cells. Sildenafil potentiates the effects of the latter by removing natural barriers to 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 content with placebo. The high efficacy of the drug was observed in representatives of different age groups: even in people over 65 years old, the drug worked in 69% of cases. One of the risk factors for erectile dysfunction is arterial hypertension. Sildenafil has a weak antihypertensive effect, however, its use by hypertensive patients who are "sitting" on antihypertensive drugs does not potentiate the effect of the latter, so such individuals can fight erectile dysfunction on a common basis. Another key risk factor for erectile dysfunction is smoking, which has not been shown in clinical trials to affect the effectiveness of sildenafil. 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 diabetes and the presence of complications. However, even in such difficult conditions, the drug showed its 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 clearly a "working" drug: its effectiveness does not decrease over time, which makes long-term pharmacotherapy possible. Side effects of the drug, as a rule, are 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 cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, subsequent relaxation of the smooth muscle tissue of the cavernous body 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) through the inhibition of PDE5, which is responsible for the breakdown of cGMP.

Sildenafil is selective for PDE5 in vitro, its activity against PDE5 exceeds activity against 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 the utmost importance, since PDEZ is one of the key enzymes in the regulation of myocardial contractility.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

Clinical Data

Cardiac 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 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 noted in patients taking nitrates.

In a study of the hemodynamic effect of sildenafil at 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), systolic and diastolic pressure at rest decreased by 7% and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not impair blood flow in stenotic coronary arteries, and also led to an increase (by approximately 13%) of 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 who were taking antianginal drugs (except nitrates) performed physical exercise until the severity of angina symptoms improved. The duration of the exercise was significantly longer (19.9 seconds; 0.9 - 38.9 seconds) in patients taking sildenafil at a single dose of 100 mg compared with patients receiving placebo.

In a randomized, double-blind, placebo-controlled study, the effect of changing the dose of sildenafil (up to 100 mg) was studied in men (n = 568) with erectile dysfunction and arterial hypertension taking more than two antihypertensive drugs. Sildenafil improved erections in 71% of men compared to 18% in the placebo group. The frequency of adverse effects was comparable to that in other groups of patients, as well as in individuals 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 slight and transient impairment in the ability to distinguish shades of color (blue / green) was detected. 2 hours after taking the drug, these changes were absent. It is believed that the violation of color vision is caused by inhibition of PDE6, which is involved in the process of light transmission 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-related macular degeneration (n = 9), sildenafil at a single dose of 100 mg was well tolerated. There were no clinically significant visual changes assessed by specific visual tests (visual acuity, Amsler grating, color perception, color flow simulation, Humphrey perimeter, and photostress).

Efficiency

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

The effectiveness of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory intercourse, has been demonstrated in all studies conducted and has been confirmed in long-term studies lasting 1 year. In fixed dose studies, the ratio of patients reporting that the therapy improved their erections was: 62% (sildenafil 25 mg dose), 74% (sildenafil 50 mg dose) and 82% (sildenafil 100 mg dose) compared to 25% in the placebo group. An 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 sexual intercourse and overall satisfaction.

According to the pooled data, among patients reporting improvement in erection with sildenafil treatment, there were 59% of patients with diabetes, 43% of patients undergoing radical irostatectomy and 83% of patients with spinal cord injuries (vs. 16%, 15% and 12% in the placebo group, respectively). ).

Pharmacokinetics

Suction

Sildenafil is rapidly absorbed after oral administration. 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 Cmax of free sildenafil in the blood plasma of men is about 18 ng / ml (38 nM). C max when taking sildenafil orally 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 in the equilibrium state averages 105 liters. The relationship of sildenafil and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of sildenafil (mean 188 ng) was found in semen 90 minutes after taking the drug.

Metabolism

Sildenafil is metabolized mainly in the liver by the cytochrome CYP3A4 isoenzyme (major pathway) and the cytochrome CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite resulting from the N-demethylation of sildenafil undergoes further metabolism. The selectivity of this metabolite for PDE is comparable to that of sildenafil, and its activity for 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.

breeding

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 groups of patients

Elderly patients

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

Kidney 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 (CK< 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 cirrhosis of the liver (stages A and B according to the Child-Pyo 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 hepatic impairment (Child-Pyo grade C) has not been studied.

Release form

Blue film-coated tablets, 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: Opadry 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. - cellular contour packings (1) - packs of cardboard.
2 pcs. - cellular contour packings (1) - packs of cardboard.
4 things. - cellular contour packings (1) - packs of cardboard.
10 pieces. - cellular contour packings (1) - packs of cardboard.
20 pcs. - polymer cans (1) - packs of cardboard.
20 pcs. - polymer bottles (1) - cardboard packs.

Dosage

The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Based on efficacy and tolerability, the dose may 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.

Kidney dysfunction

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

Liver dysfunction

Joint use with other drugs

When combined with ritonavir, the maximum single dose of Sildenafil should not exceed 25 mg, and the frequency of use should not exceed 1 time in 48 hours.

When combined 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 α-adrepoblockers, Sildenafil should only be started after hemodynamic stabilization has been achieved in these patients. Consideration should also be given to reducing the initial dose of sildenafil.

Elderly patients

Dose adjustment of Sildenafil is not required.

Overdose

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

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

Interaction

Effect of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of cytochrome isoenzymes CYP3A4 (the 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 non-specific inhibitor of the cytochrome CYP3A4 isoenzyme, when co-administered 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 isoenzyme CYP3A4, against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%.

When co-administered sildenafil (100 mg once) and saquinavir (1200 mg/day 3 times a day), an inhibitor of HIV protease and cytochrome isoenzyme CYP3A4, against the background of achieving a constant concentration of saquinavir in the blood, Cmax of sildenafil increased by 140%, and AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir.

Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, can also cause stronger changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (once 100 mg) and ritonavir (500 mg 2 times a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P450, against the background of achieving a constant concentration of ritonavir in the blood, leads to an increase in Cmax 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 application of one sildenafil - 5 ng / ml), which is consistent with information about the pronounced effect of ritonavir on the pharmacokinetics of various cytochrome P 450 substrates. Sildenafil does not affect the pharmacokinetics of ritonavir. Co-administration of sildenafil with ritonavir is not recommended. If sildenafil is taken at the recommended doses by patients receiving simultaneously strong inhibitors of the cytochrome CYP3A4 isoenzyme, then 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.

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 AUC, C max T max, excretion rate constant and T1 / 2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other medicinal products

Sildenafil is a weak inhibitor of cytochrome P 450 -1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 isoenzymes (IC 50 >150 µmol). When taking sildenafil at recommended doses, its C max is about 1 μmol, so it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with long-term 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 donators is contraindicated.

While taking 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. Rare cases have been reported in these patients of symptomatic postural hypotension, manifested in the form of dizziness (without syncope). In selected 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 cytochrome CYP2C9 isoenzyme, have not been identified.

Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome isoenzyme CYP3A4, 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 increase 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, there were no signs of the interaction of sildenafil (100 mg) with 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 agents does not lead to additional side effects.

Side effects

Usually, the side effects of the drug Sildenafil are mild or moderate and are transient.

Fixed-dose studies have shown that the frequency

Organs and organ systems	Side effects	Sildenafil, %	Placebo, %
Most common side effects (> 1/10)
Nervous system	Headache	16	4
The cardiovascular system	Vasodilation ("flushing" of blood to the skin of the face)	10	1
Common side effects (> 1/100 and< 1/10)
Nervous system	Dizziness	2	1
Organ of vision	Visual disturbances (blurred vision, impaired color vision)	2,5	0,4
	Chromatopsia (mild and transient, mainly changes in color perception)	1,1	0,03
The cardiovascular system	Cardiopalmus	1,0	0,2
Respiratory system	Rhinitis (stuffy nose)	4	2
Digestive system	Dyspepsia	7	2
	Diarrhea	3	1
urinary system	Urinary tract infections	3	2
Skin and subcutaneous tissue	Rash	2	1

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

General condition disorders: swelling of the face, 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).

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

Cardiovascular disorders: tachycardia, increased or decreased blood pressure, myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina, AV block, cerebral thrombosis, heart failure, ECG abnormalities, cardiomyopathy, sudden death, syncope.

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.

On the part of the organ of vision: eye pain, eye redness / scleral injections, conjunctival damage, lacrimation disorder, 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.

Genitourinary system disorders: cystitis, nocturia, frequent urination, gynecomastia, urinary incontinence, ejaculation disorder, genital edema, anorgasmia.

Reproductive system disorders: prolonged erection and / or priapism.

Indications

• 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 with sexual stimulation.

Contraindications

• hypersensitivity to sildenafil or to any other component of the drug;
• use in patients receiving continuously or intermittently nitric oxide donators, organic nitrates or nitrites in any form, since sildenafil enhances the hypotensive effect of nitrates (see the section "Interaction with other drugs") Safety and efficacy of the drug Sildenafil when used together with other drugs treatment of erectile dysfunction has not been studied, so the use of such combinations is not recommended (see section "Special Instructions");
• according to the registered indication, the drug Sildenafil is not intended for use in children under 18 years of age;
• according to the registered indication, the drug 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 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.

Heart failure, unstable angina, past 6 months of myocardial infarction, stroke, or life-threatening arrhythmias, hypertension (BP > 170/100 mmHg) or hypotension (BP< 90/50 мм рт.ст.).

In patients with episodes of anterior non-arteritic ischemic optic neuropathy (history).

Application features

Use 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 excretion 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 violations of kidney function

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

Use in children

Contraindicated in children under 18 years of age.

special instructions

To diagnose erectile dysfunction, determine their possible causes and select adequate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination. Treatments for erectile dysfunction 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 developing 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 a cardiovascular examination. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mmHg), 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

Serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported during post-marketing use of sildenafil for the treatment of erectile dysfunction. ), which had a temporal 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 were observed shortly after sexual activity, and some of them were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish the existence of a direct relationship between the observed adverse events and these or other factors.

hypotension

Sildenafil has a systemic vasodilatory 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 Sildenafil, the physician should carefully assess the risk of possible adverse vasodilatory effects in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in rare multiple system atrophy syndrome, manifested by severe dysregulation of blood pressure from the autonomic nervous system.

Since the combined use of sildenafil and α-blockers can lead to symptomatic hypotension in some susceptible patients, Sildenafil should be used with caution in patients taking α-blockers. To minimize the risk of postural hypotension in patients taking a-blockers, Sildenafil should only be started after stabilization of hemodynamic parameters in these patients. Consideration should also be given to reducing the initial dose of Sildenafil. The physician should inform patients about what actions to take if symptoms of postural hypotension appear.

Visual disturbances

Rare cases of the development of anterior non-arteritic ischemic optic neuropathy have been noted as a cause of deterioration or loss of vision during 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 years, diabetes mellitus, arterial hypertension, coronary heart disease, hyperlipidemia, and smoking. A causal relationship between the use of PDE5 inhibitors and the development of anterior non-arteritic ischemic optic neuropathy has not been identified. The physician should inform the patient about the increased risk of developing anterior non-arteritic ischemic optic neuropathy, if this condition has already been noted in him. In case of sudden loss of vision, patients should receive the necessary medical attention immediately. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of the functions of retinal phosphodiesterases. There are no data on the safety of Sildenafil in patients with retinitis pigmentosa, so Sildenafil should be used with caution.

Hearing disorders

Some post-marketing and clinical studies report 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 worsening or loss of hearing. A causal relationship between the use of PDE5 inhibitors and sudden hearing impairment or hearing loss has not been established. In the event of a sudden deterioration in hearing 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. Data on the safety of the use of sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers are not available, so Sildenafil should be used with caution in these patients. The incidence of epistaxis in patients with PH associated with diffuse connective tissue disease 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 taking a vitamin K antagonist (1.7%).

Use in conjunction with other means of treating erectile dysfunction.

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

Influence on the ability to drive vehicles and control mechanisms

Against the background of taking sildenafil, 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, the development of chromatopsia, blurred vision, etc. is possible. side effects, you should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosing regimen.