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Preparation for the treatment of erectile dysfunction. FDE-5 inhibitor

Active substance

Release form, composition and packaging

Auxiliary substances: microcrystalline cellulose - 50 mg, monohydrate lactose (milk sugar) - 61.5 mg, sodium crossarmellosis (oxelose) - 7.5 mg, (polyvinylpyrrolidone medium olecular) - 4.5 mg, magnesium stearate - 1.5 mg.

The composition of the shell: Padray II (polyvinyl alcohol, partially hydrolyzed - 2 mg, titanium dioxide (E171) - 1.145 mg, macrogol (polyethylene glycol 3350) - 1.01 mg, talc - 0.74 mg, aluminum varnish based on diamond blue - 0.096 mg, iron oxide (II) Yellow (E172) - 0.0085 mg, iron oxide (II) black (E172) - 0.0005 mg).

Tablets covered with film shell Blue, round, double bobble; At the breakfast - white or almost white.

Auxiliary substances: microcrystalline cellulose - 54 mg, lactose monohydrate (sugar milk) - 74 mg, sodium crossarmellosis (oxelose) - 10 mg, povidone (polyvinylpyrrolidone medium olecular) - 10 mg, magnesium stearate - 2 mg.

The composition of the shell: Oddrauli II (polyvinyl alcohol, partially hydrolyzed - 2.4 mg, titanium dioxide (E171) - 1.374 mg, macrogol (polyethylene glycol 3350) - 1.212 mg, talc - 0.888 mg, aluminum varnish based on diamond blue - 0.1152 mg, iron oxide (II) Yellow (E172) - 0.0102 mg, iron oxide (II) black (E172) - 0.0006 mg).

1 PC. - Packaging cell contour (1) - packs cardboard.
2 pcs. - Packaging cell contour (1) - packs cardboard.
4 things. - Packaging cell contour (1) - packs cardboard.
7 pcs. - Packaging cell contour (1) - packs cardboard.
7 pcs. - Packaging cell contour (2) - packs cardboard.
8 pcs. - Packaging cell contour (1) - packs cardboard.
10 pieces. - Packaging cell contour (1) - packs cardboard.
10 pieces. - Packaging cell contour (2) - packs cardboard.
20 pcs. - Polymeric banks (1) - packs cardboard.
20 pcs. - Polymer bottles (1) - packs cardboard.

Tablets covered with film shell Blue, round, double bobble; At the breakfast - white or almost white.

Auxiliary substances: microcrystalline cellulose - 83.5 mg, lactose monohydrate (sugar milk) - 83.5 mg, sodium crossarmellosis (oxelose) - 15 mg, povidone (polyvinylpyrrolidone medium olecular) - 15 mg, magnesium stearate - 3 mg.

The composition of the shell: Oddray II (polyvinyl alcohol, partially hydrolyzed - 3.6 mg, titanium dioxide (E171) - 2.061 mg, macrogol (polyethylene glycol 3350) - 1.818 mg, Talc - 1.332 mg, aluminum varnish based on diamond blue - 0.1728 mg, iron oxide (II) Yellow (E172) - 0.0153 mg, iron oxide (II) black (E172) - 0.0009 mg).

pharmachologic effect

Sildenafil - powerful selective inhibitor Cyclooguanosin monophosphate (CGMF) -Ecificial phosphodiesterase 5th type (FDE5).

Mechanism of action

The implementation of the physiological mechanism of the erection is associated with the release of nitrogen oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of CGMF, subsequent relaxing of the smooth muscle tissue of the cavernous body and an increase in blood flow.

Sildenafil does not have a direct relaxing effect on an isolated cavernous human body, but enhances the nitrogen oxide effect (NO) by means of PDE5 inhibiting, which is responsible for the decay of the CGMF.

Sildenafil is selective with respect to PDE5 in vitro, its activity against PDE5 is active in relation to other known phosphodiesterase isoenzymes: FDE6 - 10 times; FDE1 - more than 80 times; FDE2, PDE4, FDE7-FDE11 - more than 700 times. Sildenafil is 4000 times more selective in relation to PDE5 compared with PDE3, which is essential, since PDE3 is one of the key enzymes of the regulation of myocardium.

The prerequisite for the effectiveness of Sildenafil is sexual stimulation.

Clinical data

Cardiology research

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

In the study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe IBS (more than 70% of patients were stenosis, at least one coronary artery), systolic and diastolic pressure at rest decreased by 7% and 6%, Accordingly, the pulmonary systolic pressure decreased by 9%. Sildenafil did not affect the release and did not violate the bloodstream in stenozed coronary arteries, and also led to an increase (approximately 13%) adenosine-induced coronary flux in both swollen and intact coronary arteries.

In a double-blind placebo-controlled study of 144 patients with erectile dysfunction and stable anginataking antichangal drugs (except nitrates) performed physical exercises Until that moment when the severity of the symptoms of the angina region decreased. The duration of the exercise was reliably more (19.9 seconds; 0.9-38.9 seconds) in patients who took Sildenafil in a single dose of 100 mg compared with patients receiving placebo.

In a randomized double-blind placebo-controlled study, the effect of a dose of siltenafil (up to 100 mg) in men (n \u003d 568) was studied with erectile dysfunction and arterial hypertension taking more than two. Sildenafil improved the erection in 71% of men compared with 18% in the placebo group. The frequency of adverse effects was comparable to such in other groups of patients, as well as persons hosting more than three antihypertensive drugs.

Studies of visual disorders

In some patients after 1 hour after taking sildenafil at a dose of 100 mg using a Farnsworth-Munsel test, a lightweight and transient ability to distinguish the shades of color (blue / green). After 2 hours after taking the drug, these changes were absent. It is believed that color vision violation is caused by the PDE6 inhibition, which is involved in the process of transmission of light in the retina. Sildenafil did not affect the visual sharpness, the perception of contrast, the electric sinograph, intraocular pressure or pupil diameter.

In a placebo-controlled cross-study study of patients with proven early aging macular degeneration (n \u003d 9), Sildenafil in a single dose of 100 mg was moved well. No clinically significant changes were revealed, estimated on special visual tests (visual acuity, amateur grille, color perception, color modeling, hamphrey perimeter and photostost).

Efficiency

The efficacy and safety of Sildenafil was evaluated in 21 randomized double-blind placebo-controlled studies by a duration of up to 6 months in 3,000 patients aged from 19 to 87 years, with erectile dysfunction of various etiology (organic, psychogenic or mixed). The effectiveness of the drug was evaluated globally using the erection diary, the international index of the erectile function (validated questionnaire on the state of the sexual function) and the partner survey.

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

According to the generalized data, among patients who reported an improvement in erection in sildenafil treatment were 59% of diabetes patients, 43% of patients undergoing radical prostatectomy and 83% of patients with spinal cord damage (versus 16%, 15% and 12% in the placebo group, respectively).

Pharmacokinetics

Suction

After taking inside, Sildenafil is quickly absorbed. Absolute bioavailability on average is about 40% (from 25% to 63%). In vitro Sildenafil at a concentration of about 1.7 ng / ml (3.5 nm) suppresses the activity of the FDE5 person by 50%. After a single reception of sildenafil in a dose of 100 mg, the average C Max of free sildenafil in the blood of men is about 18 ng / ml (38 nm). C MAX When taking sildenafil inside an empty stomach is reached on average for 60 minutes (from 30 minutes to 120 minutes). When taking combination with fatty food, the suction rate decreases: C MAX decreases by an average of 29%, and TC MAX increases by 60 minutes, but the degree of absorption does not significantly change (AUC decreases by 11%).

Distribution

V D Sildenafil in equilibrium state It averages 105 liters. The binding of sildenafil and its main circulating N-demethyl metabolite with blood plasma proteins is about 96% and does not depend on the overall concentration of the drug. Less than 0.0002% of Sildenafil dose (on average 188 ng) was found in sperm 90 minutes after taking the drug.

Metabolism

Sildenafil is metabolized mainly in the liver under the action of the Cyp3a4 cytochrome (main way) and the Cyp2C9 cytochrome (mining path) isoenzyme. The main circulating active metabolite formed as a result of n-demethylation of sildenafil is subjected to further metabolism. The selectivity of the action of this metabolite against PDE is comparable to such silildenafil, and its activity against PDE5 in vitro is about 50% of Sildenafil activity. The concentration of metabolite in the blood plasma of healthy volunteers was about 40% of Sildenafil concentration. N-demethyl metabolite is subjected to further metabolism; T 1/2 is about 4 hours.

Election

General clearance of sildenafil is 41 l / h, and the final T 1/2 - 3-5 hours after intake, as well as after in / in administration, sildenafil is derived in the form of metabolites, mainly in the intestine (about 80% oral dose) and, to a lesser extent, the kidneys (about 13% oral dose).

Pharmacokinetics in special groups of patients

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

With a light (QC 50-80 ml / min) and moderate (QC 30-49 ml / min), the degree of renal failure pharmacokinetics of sildenafil after one-time intake in a dose of 50 mg does not change. With severe renal failure (QK ≤30 ml / min), Sildenafil clearance decreases, which leads to an approximately two-time increase in the AUC value (100%) and C Max (88%) compared to those indicators with the normal function of the kidneys in the patients of the same age group .

In patients with cirrhosis of the liver (stage A and B according to the childcreational classification), siltenafil clearance decreases, which leads to an increase in the value of AUC (84%) and with MAs (47%) compared to those in the normal liver function in patients the same age group. Sildenafil's pharmacokinetics in patients with severe liver function (stage with Child-Pugh classification) has not been studied.

Indications

- Treatment of erection violations characterized by the inability to achieve or preserve the erection of a penis sufficient for a satisfactory sexual intercourse.

Sildenafil is effective only with sexual stimulation.

Contraindications

- application in patients receiving constantly or with interruptions donators nitrogen oxide, organic nitrates or nitrites in any forms, since Sildenafil enhances the hypotensive effect of nitrates;

- According to a registered indication, the drug is not intended for use in children and adolescents under the age of 18;

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

- lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

— increased sensitivity to Sildenafil or to any other component of the drug.

The safety and efficacy of the preparation of Sildenafil-SZ, with joint use with other means of treatment, the erection disorders were not studied, therefore the use of such combinations is not recommended.

Carefully:

- anatomical deformation of the penis (argument, cavernous fibrosis or Peyroni disease);

- diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocytemia);

- diseases accompanied by bleeding;

- exacerbation of ulcerative diseases of the stomach and duodenum;

- hereditary pigment retinit;

- cardiac insufficiency, unstable angina, transferred in the last 6 months of myocardial infarction, stroke or life-degraded arrhythmias, arterial hypertension (Hell\u003e 170/100 mm Hg) or hypotension (hell<90/50 мм рт.ст.);

- in patients with episodes of the development of the anterior non-idiotic corporate neuropathy of the optic nerve (a history).

Dosage

The drug is taken inward.

The recommended dose for most adult patients is 50 mg about 1 hour before sexual activity. Taking into account the effectiveness and tolerance of the dose can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended multiplicity of application is 1 time / day.

For renal failure light and medium degree (KK 30-80 ml / min) Dose correction is not required when renal failure of severe (QC<30 мл/мин) Dose Sildenafil should be reduced to 25 mg.

Since the removal of sildenafil is disturbed from patients with liver damage (in particular, with cirrhosis), Dose of the drug Sildenafil-SZ should be reduced to 25 mg.

Correction of the dose of the drug Sildenafil-SZ y elderly patients not required.

Sharing with other medicines

When co-use with ritonavir, the maximum one-time dose of the preparation of Sildenafil-SZ should not exceed 25 mg, and the multiplicity of application is 1 time in 48 hours.

When co-use with CYP3A4 cytochrome inhibitors (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Sildenafil-SZ drug should be 25 mg.

To minimize the risk of developing postural hypotension in patients taking alpha-adrenoblockers, taking the drug Sildenafil-SZ should be started only after achieving the stabilization of hemodynamics in these patients. It should also be considered the feasibility of reducing the initial dose of Sildenafil.

Side effects

The most frequent side effects were headache and "riding".

Usually, the side effects of the Sildenafil-SZ drug are weakly or moderately pronounced and are transient.

In studies using a fixed dose, it is shown that the frequency of some unwanted phenomena increases with increasing dose.

The frequency of unwanted 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 - the reaction of increased sensitivity (including skin rash), allergic reactions.

From the hematopopitation system: Infrequently anemia, leukopenia.

From the metabolism and nutrition: Infrequently - feeling of thirst, swelling, gout, noncompensated diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

From the body of the vision: Often - blurred vision, impairment of vision, cyanopsy; infrequently - eye pain, photophobia, photopsy, chromatopsy, redness of eyes / injection Scler, change in the brightness of light perception, mydriasis, conjunctivitis, hemorrhage in the fabric of the eye, cataract, disruption of the lacrimal apparatus; Rarely - swelling of the eyelids and adjacent fabrics, the feeling of dryness in the eyes, the presence of rainbow circles in sight around the light source, increased fatigue, vision of objects in yellow (xantopsy), vision of objects in red (erythropsy), hyperemia conjunctiva, mucous membrane Eye shells, discomfort in the eyes; The frequency is unknown - the non-analytic front ischemic neuropathy of the optic nerve, the occlusion of the retinal veins, the defect of the fields of view, diplopia *, temporary loss of vision or reduction of visual acuity, an increase in intraocular pressure, retinal edema, retinal vessel disease, a vitreous body delay / vitreal traction.

From the side of the hearing organ: Infrequently - a sudden decline or loss of hearing, noise in the ears, ringing in the ears, pain in the ears.

From the nervous system: Very often - headache; Often - dizziness; infrequently drowsiness, migraine, ataxia, hypertonus, neuralgia, neuropathy, paresthesia, tremor, vertigo, symptoms of depression, insomnia, unusual dreams, raising reflexes, hyptestesia; Rarely - cramps *, repeated cramps *, fainting, violation of cerebral circulation, transient ischemic attack.

From the side of the cardiovascular system: Often - "rings"; infrequently - tachycardia, feeling of heartbeat, decreased or increased blood pressure, increase in heart rate, unstable angina, AV blockade, myocardial infarction, brain vessel thrombosis, heart stop, heart failure, deviations in ECG testimony, cardiomyopathy; Rarely - atrial fibrillation, sudden heartfelt death *, ventricular arrhythmia *.

From the respiratory system: Often - nasal congestion; infrequent - nasal bleeding, rhinitis, asthma, dysnae, laryngitis, pharyngitis, sinusitis, bronchitis, increasing the volume of discharge wet, cough strengthening; Rarely - a sense of constraint in the throat, dryness of the mucous membrane of the nasal cavity, the swelling of the mucous membrane of the nasal cavity.

From the digestive system: often - nausea, dyspepsia; Infrequently - gastroesophageal reflux disease, vomiting, pain in the abdomen, dry oral mucosa, glossite, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, deviation of hepatic functional tests from the norm, rectal bleeding; Rarely - hysthesis of the oral mucosa.

On the side of the musculoskeletal system: Often - pain in the back; Infrequently - Malgia, pain in the limbs, arthritis, arthrosis, tendon gap, thaosinite, pain in the bones, miastic, synovit.

From the urinary system: Infrequently - cystitis, Nicturia, urinary incontinence, hematuria.

From the side of the genital organs and breasts: Infrequently - an increase in the mammary glands, a violation of ejaculation, hematmost, anorgasmia edema, hematospermia, damage to the penis tissues; Rarely - long-term erection and / or priapism, bleeding from the penis.

From the side of the skin and subcutaneous fabrics: infrequently - skin rash, urticaria, simple herpes, skin itching, increased sweating, skin ulceration, contact dermatitis, exfoliative dermatitis; The frequency is unknown - Stevens-Johnson syndrome, toxic epidermal necroliz.

Others: Infrequently - the feeling of heat, swelling of the face, the reaction of photosensitivity, shock, asthenia, increased fatigue, pain of various location, chills, random batuals, pain in the chest area, random injuries; Rarely irritability.

* Side effects identified during postmarketing research.

During the post-marketing application of sildenafil for the treatment of erectile dysfunction, such undesirable phenomena were reported as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden heartfelt death, ventricular arrhythmia, hemorrhagic stroke, hypertension and hypotension) that had Temporary connection with the use of sildenafil. Most of these patients, but not all of them, had the risk factors for cardiovascular complications. Many of these undesirable phenomena were observed shortly after sexual activity, and some of them were noted after receiving sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct connection between the noted undesirable phenomena and the specified or other factors.

Visible violations

In rare cases during the post-registration application of all FDE5 inhibitors, incl. Sildenafil, reported the non-successive front corporate neuropathy of the optic nerve (NPNZN) - a rare disease and the reason for the decline 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 disk of the optic nerve ("stagnant disk"), age over 50 years old, diabetes mellitus, hypertension, IBS, hyperlipidemia and smoking. The observational study was assessed whether the recent use of PDE5 inhibitors class with acute NPIZN inhibitors is connected. The results indicate an approximately two-time increase in the risk of NPINZN within 5 half-life after the use of the FDE5 inhibitor. According to published literary data, the annual frequency of the occurrence of the NPNZN is 2.5-11.8 cases per 100,000 men aged ≥50 years in the overall population. It should be recommended to patients in the event of a sudden loss of vision to stop therapy with sildenafil and immediately consult with the doctor. Persons who have already had a NPINZN case have an increased risk of recurrence of NPSNN. Therefore, a doctor should discuss this risk with such patients, as well as discuss with them a potential chance of adverse effects of FDE5 inhibitors. FDE5 inhibitors, incl. Sildenafil, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.

When using the Sildenafil-SZ drug in doses, exceeding the recommended, undesirable phenomena were similar to those noted above, but usually met more often.

Overdose

Symptoms: With a single reception of the preparation of Sildenafil-SZ in a dose of up to 800 mg, unwanted phenomena were comparable to those in the reception of the drug at lower doses, but they met more often.

Treatment: Conducting symptomatic therapy. Hemodialysis does not speed up Sildenafil clearance, because The latter actively binds to plasma proteins and is not excreted by the kidneys.

Medicinal interaction

Effect of other drugs for pharmacokinetics Sildenafil

Siltenafil metabolism occurs mainly under the action of Cytochrome CYP3A4 (main way) and CYP2C9, so inhibitors of these isoenzymes can reduce silildenafil clearance, and inductors, respectively, increase the Cleigh Sildenafil. The decrease in Sildenafil's clearance was noted while using the CYP3A4 cytochrome of cytochrome inhibitors (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the cytochrome CYP3A4 isoenzyme, with a joint admission with sildenafil (50 mg) causes an increase in the concentration of Sildenafil in a plasma by 56%. Solidenafil's single reception at a dose of 100 mg together with erythromycin (500 mg 2 times / day for 5 days), a specific inhibitor of Cytochrome CYP3A4, against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase in Sildenafil AUC by 182%.

With a joint admission of siltenafil (once 100 mg) and saquinavir (1200 mg / day 3 times / day), the CYP3A4 HIV protease inhibitor and the Cyp3a4 isoenzyme, against the background of achieving a constant concentration of Sqquinavir in the blood C Max Sildenafil ruling at 140%, and AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of Saquinavir.

The stronger inhibitors of the Cyp3a4 cytochrome isoenzyme, such as ketoconazole and itraconazole, can cause stronger changes in sildenafil pharmacokinetics.

The simultaneous use of sildenafil (once 100 mg) and ritonavir (500 mg 2 times / day), an inhibitor of HIV protease and a strong cytochrome P450 inhibitor, against the background of achieving a constant concentration of ritonavir in the blood leads to an increase in C Max Siltenafil by 300% (in 4 times), a AUC is 1000% (11 times). After 24 hours, the siltenafil concentration in the blood plasma is about 200 ng / ml (after one-time application of one sildenafil - 5 ng / ml), which is consistent with the information on the pronounced effect of ritonavir on pharmacokinetics of various substrates of cytochrome P450. Sildenafil does not affect the pharmacokinetics of Ritonavir. Combined use of sildenafil with ritonavir is not recommended.

An antacid single reception (hydroxide hydroxide / aluminum magnesium) does not affect the bioavailability of sildenafil.

Cyp2C9 cytochrome inhibitors (Tolbatamide, Warfarine), Cytochrome Cyp2D6 (selective serotonin reverse seizure inhibitors, tricyclic antidepressants), thiazide and thiazid-like diuretics, ACE inhibitors and calcium antagonists do not affect the pharmacokinetics of Sildenafil.

Azithromycin (500 mg / day for 3 days) does not affect the AUC, C Max, T Mach, the constant of the removal speed and T 1/2 of Sildenafil or its main circulating metabolite.

Effect of Sildenafil on Other Medicines

Sildenafil is a weak inhibitor of cytochrome P450 -1A2, 2C9, 2C19, 2D6, 2D6, 2E1, and 3A4 (IR 50\u003e 150 μmol). When taking sildenafil in the recommended doses, it C Max is about 1 μmol, so it is unlikely that Sildenafil may affect the clien substrates of these isoenzymes.

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

With simultaneous reception of the Alfa-adrenobloclocker of doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) in patients with a benign prostate gland hyperplasia with stable hemodynamics, the average additional decrease in systolic / diastolic blood pressure in the position lying on the back was 7 / 7 mm RT. 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. There are rare cases of development in such patients with symptomatic postural hypotension, which manifested in the form of dizziness (without fainting). In individual sensitive patients receiving alpha-adrenoblays, the simultaneous use of sildenafil can lead to symptomatic hypotension.

Signs of significant interaction with tolbatamide (250 mg) or warfarine (40 mg), which are metabolized by the Cyp2C9 cytochrome is not detected.

Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, Savinavira and ritonavir, which are substrates of the Cyp3a4 cytochrome isoenzyme, with their constant level in the blood.

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

Sildenafil (50 mg) does not enhances the hypotensive effect of ethanol in healthy volunteers at the maximum concentration of ethanol in the blood, on average 0.08% (80 mg / dl).

In patients with the arterial hypertension of signs of the interaction of sildenafil (100 mg) with amlodipine, was not identified. Average additional decrease in blood pressure in the lying position is 8 mm Hg. (systolic) and 7 mm Hg. (diastolic).

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

special instructions

To diagnose disorders of the erection, determining their possible causes and choice of adequate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination. The means of treatment of erectile dysfunction should be used with caution in patients with the anatomical deformation of the penis (profile, cavernous fibrosis, Peyroni disease), or in patients with the risk factors for reconciliation (sickle cell anemia, multiple myeloma, leukemia).

Preparations intended for the treatment of erection violations should not be prescribed to men for whom sexual activity is undesirable.

Sexual activity represents a certain risk in the presence of heart disease, so before the start of any therapy about the disorders of the erection, the doctor should be directed to the patient to examine the state of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina, transferred in the last 6 months of myocardial infarction or stroke, life-degraded arrhythmias, arterial hypertension (Hell\u003e 170/100 mm Hg. Art.) Or hypotension (hell<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-СЗ, по сравнению с пациентами, получавшими плацебо.

Cardiovascular complications

During the post-paying application of Sildenafil for the treatment of erectile dysfunction, such undesirable phenomena was reported as serious cardiovascular complications (including myocardial infarction, unstable angina, sudden heartfelt death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension ) who had temporary connection with Sildenafil. Most of these patients, but not all of them, had the risk factors for cardiovascular complications. Many of these undesirable phenomena were observed shortly after sexual activity, and some of them were noted after receiving sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct connection between the noted undesirable phenomena and the specified or other factors.

Hypotension

Sildenafil has a systemic vazodilative effect, leading to a transit reduction of blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. Nevertheless, before the prescriptions of the drug Sildenafil-SZ, the doctor must carefully assess the risk of possible unwanted 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 output tract of the left ventricle (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with rarely encountered multiple systemic atrophy syndrome, manifested by a severe violation of the regulation of blood pressure from the vegetative nervous system.

Since the joint use of sildenafil and alpha-adrenoblockers can lead to symptomatic hypotension in individual sensitive patients, the Sildenafil-SZ drug should be prescribed with caution to be patients receiving alpha-adrenoblays. To minimize the risk of developing postural hypotension in patients taking alpha-adrenoblays, the reception of the Sildenafil-SZ drug should be started only after achieving the stabilization of hemodynamic indicators in these patients. It should also be considered the feasibility of reducing the initial dose of the drug Sildenafil-SZ. The doctor must inform patients about what actions should be taken in the event of the emergence of symptoms of postural hypotension.

Visible violations

Rare cases of the development of the anterior non-idiotic corporate neuropathy of the optic nerve were noted, as the causes of deterioration or loss of vision against the background of the use of all FDE5 inhibitors, including Sildenafil. Most of these patients had risk factors, such as excavation (deepening) of the optic nerve disk, age older than 50 years, diabetes, arterial hypertension, CHA, hyperlipidemia and smoking. The causal relationship between the intake of PDE5 inhibitors and the development of the anterior non-idiotic corporate neuropathy of the optic nerve was not revealed. The doctor should inform the patient about increasing the risk of developing anterior non-idiotic corporate neuropathy of the optic nerve, if this state has already been noted. In the case of a sudden loss of vision, patients should immediately provide the necessary medical care. A small number of patients with hereditary pigment retinitis have genetically deterministic violations of the function of the phosphodiesterase of the retina. Information on the safety of the use of the drug Sildenafil-SZ in patients with pigment retinitis are absent, so sildenafil should be used with caution.

Disturbances

In some postmarketing and clinical studies, there are cases of sudden deterioration or hearing loss related to the use of all FDE5 inhibitors, including Sildenafil. Most of these patients had risk factors for sudden deterioration or hearing loss. The causal relationship between the use of PDE5 inhibitors and a sudden worsening of hearing or hearing loss is not established. In the case of a sudden deterioration of hearing or loss of hearing against the background of Sildenafil, immediately consult with the doctor.

Bleeding

Sildenafil enhances the anti-aggregative effect of nitroprusside sodium, Donator nitrogen oxide, in vitro thrombocyte. Data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of ulcerative diseases of the stomach and duodenum is absent, therefore the drug Sildenafil-SZ in these patients should be used with caution. The frequency of nasal bleeding in patients with LG associated with diffuse tissue diseases was higher (Sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (siltenafil 3%, placebo 2.4%). In patients who received sildenafil in combination with vitamin K antagonist, the frequency of nasal bleeding was higher (8.8%) than in patients who did not accept vitamin K antagonist (1.7%).

Application with other means of treating erection violations.

The safety and efficacy of the use of the drug Sildenafil-SZ together with other means of treatment of disorders of the erection was not studied, therefore the use of such combinations is not recommended.

Impact on the ability to driving vehicles and control mechanisms

Against the background of receiving sildenafil any negative impact on the ability to control the car or other technical means was not observed.

However, since when taking Sildenafil, decreased blood pressure, the development of chromatopia, blurred vision and other side effects, should be carefully referred to the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosing mode.

Pregnancy and lactation

Since the removal of sildenafil is broken in patients with liver damage (in particular, with cirrhosis), the dose of sildenafil-SZ drug should be reduced to 25 mg.

Application in old age

Correction of the dose of the drug Sildenafil-SZ in elderly patients is not required.

Conditions of vacation from pharmacies

The drug is released by the prescription.

Terms and Storage Terms

The drug should be stored in an inaccessible for children protected from light place at a temperature not higher than 25 ° C. Shelf life - 3 years.

In other other factors, an approximate assessment of differences in therapeutic dosages between Vardenafil and Sildenafil can be made on the basis of the differences between their biochemical power (approximately 10 times greater varyenafil) and bioavailability (approximately 3.3 times greater than Sildenafil). In accordance with this calculation, the therapeutic dose of vardenafil should be three times less than Sildenafil. This generally reflects the real relationship between the greatest recommended dose of vardenafil (20 mg) and. A small difference may be associated with the existence of unknown pharmacokinetic factors.

All three drugs have close values \u200b\u200bof T, which are in the range of 0.25-1.5 hours. The absorption of sildenafil and vardenafil is significantly slowed down in cases of their use after taking oily food. Tadalafil, on the contrary, absorbed pretty slowly and does not depend on the meal and alcohol.

The value with vardenafil is significantly lower than in two other PDE-5 inhibitors.

One of the most notable differences between the PDE-5 inhibitors is that Tadalafil significantly exceeds the same indicators of two other drugs. The causes of this difference can be slowed down the metabolism of the drug in the liver and, possibly, other, unknown factors currently. Enlarged half-life provides new therapeutic capabilities for patients for whom the spontaneity of sexual activity is important in the absence of strict time frames. In addition, a long period of action of this drug may be important in the treatment of chronic diseases under which the use of PDE-5 inhibitors is possible. On the other hand, in part of the patients, the preparation time coincides with the duration of side effects.

In the conclusion of this section it should be noted that the existence of three high-selective and effective PDE-5, Sildenafil inhibitors, Tadalafil, and the treatment of ED is an outstanding result of many years of research and clinical trials. Although all three drugs are comparable by their ability to inhibit FDE-5 and selectivity in inhibiting precisely this form of the enzyme, the differences in the strength of action, interaction with food and alcohol, semi-exploration periods and other characteristics make certain drugs more suitable in certain clinical situations. Currently, several research groups are developing new drugs capable of selectively inhibit FDE-5 and having their own structural and pharmacokinetic features. The appearance on the market of these drugs will make the therapeutic arsenal of the Andrologist's doctor even more diverse and even more will increase the number of patients satisfied with the treatment of ED.

Sildenafil 50 mg is a potency controller. The drug is used regardless of sexuality for lifting libido. In clinical practice, medication is used not only for the treatment of erectile dysfunction, but also of pulmonary hypertension due to the vasodilatory action on the endothelium of vessels in a small circulation circle. The medication is produced in a convenient form of tablet form and is designed for one-time application per day.

Other names and classification

ATH code: G04BE03.

International non-proprietary title

Sildenafil.

Trade names

Vertex;
Dynamic;
Vizarsin;
Revacio;
Sildenafil-C3;
Tornatis.

Registration number

Composition and dosage forms

The drug is produced in tablet form. The kernel of each tablet consists of an active ingredient - 50 mg of sildenafil citrate.

To facilitate absorption and increasing bioavailability in the process of production, auxiliary ingredients are added to the preparation:

microcrystalline cellulose;
sodium croskarmellosis;
dehydrated calcium hydrophosphate;
magnesium stearate.

A mixture of components gives a round-shaped tablet white. The units of the drug are covered on top of the film shell soluble in the intestine. The film is based on talc, titanium dioxide, polyethylene glycol 4000, hypimleloose. Tablets are contained by 15 pieces in contour cellular packs. Blisters are placed in a cardboard pack of 6 pieces. In addition, tablets are produced in polyethylene banks of 90 pieces.

Pharmacological group

The drug refers to potency regulators overwhelming the effect of phosphodiesterase-5 (FDE-5).

pharmachologic effect

The synthetic drug selectively blocks cyclic guanosine monophosphate (CGMF), located in PDE-5.

Phosphodiesterase is located in the cavernous body of the sexual organ in men and pulmonary vessels. As a result of the achievement of the therapeutic effect, an erectile function is restored, a natural physiological response to psychological excitement of a sexual nature is improved.

The active ingredient does not have a direct relaxing effect on the cavernous bodies in the genital organ.

Sildenafil enhances the relaxation of the cavernous bodies of nitrogen oxide on soft tissues. During the sexual stimulation with the enhanced production of nitrogen oxide, the FDE-5 is observed and an increase in the concentration of CGMF. Due to the achievement of the therapeutic effect, there is a relaxation of smooth muscles and an increase in the blood supply to the cavernous body.

Sildenafil is an inhibitor inhibitor, which helps to strengthen the ejaculation of the erected penis. In addition, the chemical compound has a vasodilatory effect on pulmonary vessels. Thanks to this effect, hypertension is reduced in a small circulation circle.

After use, the tablet is cleaved under the enzymatic effect of the estrase of the small intestine, sildenafil is released and diffuses into local blood flow.

Bioavailability varies depending on individual characteristics from 25% to 63%. With a single reception, the maximum values \u200b\u200bof the active substance in the blood plasma are fixed within 0.5-2 hours. The drug substance is transformed in hepatocytes with the formation of N-desmethyl metabolite.

Together with the product of metabolism Sildenafil binds to plasma proteins by 95-96%.

The half-life is 3-5 hours. The drug leaves the body with urine (13%) in the form of metabolites, 80% - along with the carte masses.

Indications for the use of Sildenafil 50 mg

The drug is used in clinical practice for the treatment of impotence caused by dysfunction of the muscles of the sexual organ, or to raise libido. The drug is suitable for both men and women, has the same effect, regardless of the patient's sexuality.

In rare cases, the drug is prescribed for the treatment of pulmonary hypertension in the composition of comprehensive therapy.

For men

The drug is used to restore the potency necessary to perform a satisfactory sexual intercourse, and is prescribed for the treatment of erectile dysfunction of various genes.

In the first case, to achieve a rack erection, it is necessary to take tablets per hour before sexual contact. It is recommended to take 25-100 mg per day depending on the individual needs and reactions of the body.

For women

The drug helps strengthen sexual activity and sexual attraction in women during the climax or restore the libido after conducting surgery for resection (removal) of the uterus. The drug positively affects the reproductive system of women, increases the sensitivity of the internal and external genital organs.

The medicine reduces the time to achieve natural excitation, increases the secretion of vaginal lubrication.

Drug toolic can be used in combating frigidity.

Method of application and dosage Sildenafil 50 mg

For the treatment of high pressure in pulmonary arteries, the drug is taken 2 times a day with an interval between receptions of 6-8 hours. A single dosage is 25 mg. The maximum allowable dosage per day is 60 mg. With poor tolerability, the drug is taken once in a daily dose - 25 mg per day.

For the treatment of erectile dysfunction, it is necessary to take 50 mg per hour before the estimated sexual proximity.

One-time dosage will be enough for sexual stimulation both at easy and at a running stage of erectile dysfunction. In some cases, with good tolerability, a dosage is allowed to 100 mg per day. Maximum dose - 0.1 g per day.

How much does it work?

The time of achievement and duration of the therapeutic effect depends on the individual characteristics of the patient's body. Basically from the speed of general metabolism. The average duration of the preparation is 4 hours, the maximum is 12 hours.

How long can you apply?

For the effective treatment of penis dysfunction, the Andrologists recommend taking a medicine within 2 months. At the same time, after one-time application, it is necessary to take a break before the next reception in 24-48 hours.

special instructions

Before the start of drug therapy, it is necessary to undergo a medical examination on identifying the pathology of the cardiovascular system. In the presence of congenital heart disease, unstable angina drug intake is not recommended.

Precautionary measures must be observed and undergo regular examination in the attending physician to patients with anatomical deformation of the genital organ:

angulation;
peyroni syndrome;
cavernous fibrosis.

It should be taken with caution to take the drug with an erection, which is accompanied by painful sensations due to the development of pathological processes. Priapism can develop due to malignant neoplasms and sickle-cell anemia. People prone to the development of bleeding or stratum ulcerative lesion of the stomach and duodenum is required, consultation with the doctor before taking the drug.

In old age

When violations of the liver function

With violations of the kidney function

Side effects of Sildenafil 50 mg

In the presence of increased sensitivity to chemical compounds included in the medication, the development of angioedema edema, skin itching, anaphylactic shock, skin rashes, the appearance of erythema is possible.

Disorders in the gastrointestinal tract are accompanied by asthenia, abdominal pains, nausea and vomiting.

In the oppression of the central nervous system, the patient may feel the headache, tides blood to face, loss of orientation in space. In rare cases, insomnia is developing.

Disorders of the musculoskeletal system arising from the reception of sildenafil are characterized by pain in the joints and muscles, an increase in the tone of the muscles of the skeletal muscles.

Breathing disorders are accompanied by nasal mortgage, inflammatory processes in the appropriate and otolonic sinuses, infectious diseases.

In some cases, violation of vision is accompanied by a decrease in acute, inflammation of the conjunctivation of the eyes. In men, there is a risk of developing changes in color perception, blurring objects.

The occurrence of flu-like syndrome, the emergence of infectious inflammatory diseases.

A vasodilatory effect of the drug may appear.

There is a risk of developing infections of the genitourinary system and disorders of the prostate gland. In exceptional cases, priapism can develop.

Impact on the ability to control vehicles and other mechanisms

The drug does not cause dependence, is not reflected in the peripheral and central nervous system. Therefore, during the treatment period, sidenafil is allowed to manage complex mechanisms, driving or other activities in which it is necessary to have a developed small motorcycle, the reaction rate and being concentrated.

Contraindications

The drug is strictly forbidden to be taken when treating nitrogen oxide or nitrates. Due to the possible development of anaphylactic shock, it is contraindicated to take the drug with increased susceptibility to active and auxiliary drugs.

Overdose

increasing body temperature;
sharp drop in blood pressure;
nasal congestion;
headache and dizziness;
flushed face;
impairment;
digestion disorder.

The severity of symptoms manifests itself depending on the exceeding the maximum allowable dosage. When signs of overdose, it is necessary to stop the reception of the drug and drink 10 tablets of activated carbon. If symptoms do not pass, you need to seek medical attention.

Interaction and compatibility

With the simultaneous purpose of the Blockers of the CYP3A4 isoenzyme decreases the clien's cylinder siltenafil. With this combination, the serum level of sildenafil in the blood is increased.

A similar increase in the concentration of the active substance is observed while simultaneously use:

Ritonavir;
Indinavir;
Saquinavir;
Ketoconazole;
Itraconazole.

Sildenafil is able to strengthen the antihypertensive effect of nitrates.

In post-marketing practice it was reported on the emergence of symptoms of diabetic chadomyolysis (acute muscle tissue necrosis) after a single application of sildenafil against the background of drug therapy simvastatin.

With alcohol

Sildenafil is a synthetic agent that does not combine with alcohol and ethanol-containing drugs. Parallel taking alcoholic beverages against the background of drug therapy is able to cause a pronounced dizziness with a loss of orientation in space, a heavy arterial hypotension, the oppression of breathing and cardiac rhythm. Collapse can begin in the body.

Conditions and shelf life

Manufacturer

CJSC North Star, Russia.

Conditions of vacation from pharmacies

Medicinal in free sale.

Price in the cities of Ukraine and Russia

The average cost of the potency regulator is about 163 UAH, while the price range in pharmacies of Russia is from 73 to 576 rubles. Generics are more expensive than the original drug.

Analogs

In the absence of a positive reaction of the body to receive the drug, you can go to another drug:

Viagra;
Dynamic;
Maxigra;
Sildenafil "Northern Star";
Erexezil;
Cialis.

Quickly about drugs. Sildenafil

Viagra with prostatitis

With sexual dysfunction and weak erection, Sildenafil preparation is often used. Its action is based on stimulating blood circulation in the organs of the small pelvis, due to which the potency increases, the time of sexual intercourse is prolonged.

Sildenafila has many analogues, ranging from all the well-known Viagra. How often can the drug "Sildenafil", reviews, instructions and the price of this means are considered in detail in our article.

Composition and description of the drug

The main active substance of the drug is Sildenafil citrate. According to Sildenafil, the dosage is 25, 50 and 100 mg. In addition, there are auxiliary substances: cellulose microcrystalline, aluminum hydroxide, magnesium stearate, sodium crossarmellos and dyes.

Dosage form

Sildenafil is produced in the form of two-screwed tablets covered with a shell. The shell color varies from pale blue to blue, a pearl and marble effect is allowed. Tablets of small size, round or diamond shape, packed at 1, 2 or 4 pieces in the package.

The dosage ranges from 25 to 100 mg, but there are preparations with an increased concentration to 150 mg. Take them only to appoint a doctor. During clinical studies, the safe daily dosage of sildenafil is established within 100 mg.

pharmachologic effect

The tool is used to improve the erectile function. It is assumed orally, refers to inhibitors of CGMF-specific phosphodiesterase in cavernous bodies. The mechanism of action is the activation of the enzyme due to the release of nitrogen oxide during sexual excitation. Sildenafil tablets have a powerful relaxing effect on isolated cavernous human bodies. The effect of the drug is peripheral effect.

Sildenafril's pharmacodynamics is essential, therefore, natural sexual excitement is necessary for exposure. The active substance is characterized by a strong effect, contributing to the relaxation of the muscles with a smooth musculature, strengthening blood supply and expansion of vessels in the genital organ. Metabolized in the liver, is removed mainly with wheel masses and urine.

History of creation

Initially studied the action and pharmacodynamics of Sildenafril to stimulate blood flow in myocardium. The drug was synthesized to create effective drugs against coronary heart disease, but its actions were not enough. In the process of research, "side effects" on increased blood supply to the body of the small pelvis, thanks to which the development was changed to the orientation, it was the possibility of applying the means to improve the potency and treatment of erectile dysfunction.

In the US, Sildenafil is produced under the Viagra brand of Pfizer. Thus, this is the same drug, the composition and pharmacodynamics of which are identical. Developments were carried out relatively recently - in 1992, but the brand began to be recognized very quickly and in demand all over the world.

Now Sildenafil has many analogues, many similar drugs use other mechanisms of impact and active substances, but, and the very name "Viagra" has become nominative.

Indications for use

The drug is used in physiological disorders of the erectile function. The activation of the inhibitor occurs during sexual excitation, and the drug itself does not affect this function, but only increases the relaxation of the smooth muscles of the penis, thereby improving the blood flow and a persistent erection is observed.

Most often, the drug is used to treat:

Erectile disorders of various etiologies;
Sexual dysfunction at different ages;
In integrated impotence therapy;
In the treatment of pulmonary hypertension.

The treatment diagram and reception of additional drugs must be coordinated with the attending physician. Usually, the means is used as needed, and not on a regular basis. Due to the constituency, the drug does not require adjustment in diagnosed renal or liver failure. At the same time, the combination of some medicines can reduce, or increase the effect of receiving siltenafine, so it is worth getting the recommendations of the doctor before taking.

Medicinal interaction

The drug cannot be taken with other means containing nitrates in any form. The simultaneous intake of enterosorbents reduces the suction, like oily food.

The blood concentration increases with simultaneous reception with:

Cimetidines;
Erythromycin;
Ketoconazole;
Calcium antagonists;
Beta adrenoblockers;
Hypoglycemic drugs.

Thanks to the vasodilatory effect, a decrease in blood pressure is possible, so additional consultation of the doctor is needed to patients with hypotension before taking.

At the age of 65, the effect of the drug may not be expressed as much, moreover, with the existing heart activities, it is also necessary to weigh all the "for" and "against" before appointing the medication Sildenafil.

Time of action

The drug is used orally, approximately an hour before sexual intercourse. The effect of the drug lasts about five hours, but only under the condition of sexual excitement. A single dosage is 50 mg. Maximum daily dose - 100 mg. If necessary, the tool is used in a dosage of 25 mg.

A large advantage of using the drug is the lack of an addiction effect.

Thus, the effect of the drug is not reduced over time and can be used in a long period.

Contraindications

Not always the benefits of the drug will be justified. Due to the content of nitrogen oxide, simultaneous reception with similar means is prohibited. For example, when using means containing nitrogen oxide or nitrates in any form.

In addition, the use of the tool is prohibited in the following cases:

Hypersensitivity to the components of the drug;
Deformation of the penis with blood violations.

When used, it is necessary to consult with the doctor to eliminate the risk of side effects and contraindications. This is especially important in old age when the high load can provoke the problems of the cardiovascular system.

Side effects

In the absence of medical contraindications, the drug is usually well tolerated. At the same time, side effects that are manifested in the form of headaches, redness of the face and the feeling of the heat of the heat are possible. Perhaps overall malaise, nasal sinuses. Sometimes - disorders of the digestive function, photosensitivity. Due to the stimulation of blood circulation and the production of hormone of CGMF-specific phosphodiesterase, violations of vision, a decrease in the sensitivity of the color of objects (blue and green shades), as well as an increased negative response to light.

If such symptoms appear, the drug should be discontinued, and also turn to the doctor to coordinate the replacement of funds to a similar one.

If negative reactions manifested themselves too much, enterosorbent and antihistamine drug can be adopted, and also appeal to the hospital for washing the stomach and receiving stabilizing agents

Reviews

Men's reviews for Sildenafil's reception are most positive. The drug helps strengthen the erection and extend the intercourse time, as well as normalize the sexual function.

The impact is preserved up to five hours, and regular use retains a positive impact, helping to conduct a full sex life without additional stimulation.

Negative feedback on Sildenafil is mostly raised on the uncomfortable sensations that may arise after consuming the means. The most frequent complaints - dizziness, noise in the ears and a tide of blood to face. Side effects are enhanced by simultaneously receiving alcoholic beverages, with which the pills are completely incompatible. As often, it is possible to take sildenafile dependent on the individual characteristics of the body, but if the side effects appear quite often, you should consult a doctor to select a more suitable analog.

Popular Analogues

The existing substance Sildenafil is part of many drugs of similar impact. Patented trademark - "Viagra", but there are also many similar drugs.

Analogues on the active substance:

"Dynamic";
"Maxigra";
"Erexezil";
"Sildenafil - C3";
"Potential";
"Pfiagra";
Sildigigra.

Compared to the analogue "Sylidichefryl" has a good value. This is due to the fact that the release of drugs is adjusted in India, and therefore it refers to the so-called generic. They are characterized by a large number of side effects, rather than the original products. That is why, the consequences of taking Sildenafil in some cases can be unpredictable. At the same time, if there are no medical contraindications, and the dosage is strictly observed, the risk of side effects is minimal. That is why many doctors of urologists prescribe a given tool for the treatment of impotence in men with less financial costs.

What is the difference between sildenafil from Viagra

In the market of pharmaceutical goods "Viagra" appeared relatively recently, but the popularity of this means for increasing potency has long become a numerous. Developers provided men a unique opportunity to strengthen and normalize sexual function almost at any age. For young men, she will help strengthen sexual desire and extend sex, and for the older age group - to return the possibility of a full sexual intercourse.

The original tool is expensive, so most consumers viagra is not available, especially for permanent use.

A feature of drug patenting is a short term protection of the original drug. Usually, patent is valid for 5-10 years, after which any pharmaceutical company can produce its own developing based on the substances and chemical compounds specified as part of the original. Of course, such drugs are produced under a different trade name and have no right to refer to the original brand to promote their products.

At the same time, this practice gives us more chances as customers to acquire an inexpensive analogue. In many countries, the method of prescribing drugs on the active substance and dosage is common, so it is possible to buy similar drugs at a more affordable price. We usually perform this "function" in a pharmacy, which, at the request of the patient, can offer an analogue of the prescribed drug in its absence, or an inflated value. Of course, this approach is incorrect, but the above-described drugs contain an absolutely identical active ingredient, and in the same dosage. Differences are additional substances, as well as a method of manufacturing and cleaning components.

Thus, the notorious "Viagra" has the same effect on the male organism, as well as "Sildenafil" and drugs containing it. According to the reviews of patients and doctors, which are prescribed this tool, the reaction can occur on different types of medicines, but a certain psychological effect is also observed. The use of sildenafil is not so effectively if the patient acquired it instead of the specified "Viagra", although the pharmatic market of both drugs is completely identical.

Comparison with popular analogues

In addition to the "Viagra" in the drug, there are still many varieties, which also includes the active component of Sildenafil. In addition, there are indirect analogues of the means whose effect also consists in stimulating the blood supply to the genital organs, but with the help of other active substances. The most famous in this group are Vardenafil and Tadalafil. All three active components are used to increase the eRtemic function in men, according to reviews, have approximately the same effect, but have some differences.

Comparative characteristics:

Vardenafil or Sildenafil, what is better? Compared to Vardenafil, the second drug is more studied and tested. At the same time, both drugs cause a strong and long-lasting erection and allow extending sexual intercourse with due psychological stimulation. The exposure period is approximately the same, and the reception of vardenafil is manifested with a smaller risk of side effects. The difference can be found in full compatibility of vardenafil with alcohol, as well as with more aggressive impact, because the erection occurs after 15-20 minutes after receiving the means.
Tadalafil or Sildenafil, what is better? Both drugs are sufficiently tested and have the same occurrence of the effect and contraindications. The difference is the duration of action. Sildenafil is about five hours, while Tadalafil has the highest possible effect among such drugs - up to 36 hours. In addition, in minor quantities, Tadalafil is compatible with alcoholic beverages, while Sildenafil and alcohol demonstrate complete incompatibility. The frequency of the occurrence of side effects in Sildenafil is slightly higher, so in this plan, preferences are not on its side.
Vizarsin or Sildenafil, what is better? According to the composition and pharmotics, both drugs are almost identical. Siltenafil is the main active substance, but in the "Vizarsin" means are presented more convenient for receiving dosage. The list of contraindications and side effects they are the same, and the cost is slightly different, depending on the manufacturer's company.

Modern preparations that stimulate sexual function in men differ in diversity, but only three active substances are taken as the basis of each of them. This is Sildenafil (Viagra trademark), Tadalafin (Sialis) and Vardenafil ("Levitra"). The last substance was synthesized relatively recently, in 2005, it is distinguished by a strong effect and a minimum number of side effects.

Among the advantages of Tadalafin is a continuous effect that is 36 hours. If you need this action, the best choice will preparations of this group. On the side of Sildenafin - sufficiently studied impact and positive health reviews all over the world. The ideal means, nevertheless, does not exist, so everyone should choose the drug according to individual preferences and quality of tolerance.

Storage conditions and shelf life of the drug

The drug is packaged in standard plastic blisters, the outer box is made of cardboard. There are different dosages and configurations. Usually it is 1, 2 or 4 tablets, but there is packing and more. Store away from direct sunlight in the cool (temperature not higher than +25 degrees) and protected from children. Storage time is 2 years after manufacture.

Tablets Sildenafil, instructions and reviews of which are provided in our information, are often used in the treatment of erectal dysfunction. They help to normalize the blood circulation of the penis, strengthen the erection and extend the sexual act. Apply as needed by the calculated dosage.

The tool has the minimum possible side effects and can be used in a long period without reducing efficiency.

The main active ingredient is used in the manufacture of all the well-known "Viagra", and, according to reviews, "works" is not worse. Features of reception, pharmacological action and similar funds are considered in our article.

Citation:Laurent O.B. Pharmacotherapy of erectile dysfunction // RMG. 2004. №8. P. 505.

"... It is sexual forces that form the behavior of the person. The culture mutes and suppresses instinctive sexual energy and sends it to the formation of this particular personality of the stereotypes of public behavior" Sigmund Freud

Polla life is an integral general health component and well-being. In the modern world there is a significant increase in violations of sexual function in men and women of any age and nationality. Erectile dysfunction (ED) in men is the most common genital disease. which is defined as the inability to achieve or maintain the erection of the penis sufficient for intercourse. According to epidemiological studies, about 150 million men of the whole world suffer from ED, and according to forecasts, this number will increase to 300 million by 2025. Erectile dysfunction inevitably associated with other global health problems of modern Russian, such as psychological factors (stress), cardiovascular diseases, diabetes, smoking and injury of pelvic organs as a result of radical prostatectomy and cystectomy, as well as with an ever-increasing number of drugs affecting erectile Function: hypotensive preparations, diuretics, antidepressants and synthetic hormone derivatives. Since the beginning of the 80s of the last century, fundamental studies of molecular mechanisms of erection have significantly expanded our knowledge in this area. Detailed mechanisms for the operation of smooth muscles and the neuronal transmission of signals in the cavernous bodies were opened. New information about intracellular regulation of the main process of erection, namely, the tone of the smooth muscles of cavernous bodies made it possible to carry out a therapeutic revolution in the treatment of erectile dysfunction: from surgical operations and intracable administration of vasoactive drugs to convenient oral medications acting by optimizing the biological mechanisms of the erectile function. To date, the effectiveness and safety of phosphodiesterase-5 inhibitors (Vardenafil, Sildenafil and Tadalafil) in the treatment of Ed, which has significantly changed the approach to the treatment tactics suffering from this disease has significantly changed the treatment of patients suffering from this disease.

Erection physiology

The erection is the result of filling the blood of cavernous bodies of the penis due to the decrease in the resistance of the arterial blood inflow during the relaxation of the smooth muscles of the trabecula, the arterioles and arteries, which, in turn, occurs as a result of the integrated interaction of neural, vascular and myogenic mechanisms transmitted by the help of cholinergic and nonadenergic -Nholinergic nerves (NNC) containing nitrogen oxide (NO), atrial Na-urethic factor, vasoactive intestinal polypeptide (VIP) and calcitoninogen-bound peptide (CGRP). During the sexual stimulation of NO from the NAS, the nerve endings of the cavernous fabric and the endothelium of the arteries initiates the expansion of the smooth muscles of trabecula and the arterioles of the cavernous bodies through the synthesis of cyclic guanosine monophosphate (CGMF) cyclase cyclase. The increase in the concentration of the CGMF causes a cascade of reactions with the activation of nucleotide-dependent protein kinase, phosphorylation of the actin-mosic system, the launch of Ca 2+ - channels, decrease in intracellular CA 2+ and, as a result, relaxing the smooth muscle. The discovery of NO and CGMF as the main substances responsible for the relaxation of the smooth muscles of the penis led to the appearance of a number of drugs capable of increasing the intracellular level of the CGMF: nitrogen oxide donors (nitroprusside Na, nitroglycerin, linxidomine) and type-type phosphodiesterase inhibitors (Fig. 1). The relaxation of the smooth muscles of the trabeculus of the penis can also occur through the CAMF-dependent mechanism. Preparations affecting the CAMF include prostaglandin E 1 (PGE 1), VIP, Forskolin.

Fig. 1. CGMF-dependent mechanism of erection

Etiology, pathogenesis and the concept of treatment of erectile dysfunction

Regardless of the large number of factors (arterial, cavernous, neurological, hormonal, medicinal, systemic diseases and psychological), which can cause a violation of an erectile function at different levels of this physiological act, the molecular mechanism for implementing the erection remains the same. Consequently, causing the relaxation of smooth muscles by increasing the level of CGMF or CAMF, in the overwhelming majority of cases, it is possible to restore the erection without affecting the cause of dysfunction. Thus, we do not cure the cause of erectile dysfunction - we optimize and strengthen the normal biological mechanisms for the emergence of the erection . Of course, in the presence of severe structural changes in the vascular and in the cavernous components of the erectile function, we cannot restore the erection conservatively, in such cases the operation requires an operation.

Regardless of the large number of factors (arterial, cavernous, neurological, hormonal, medicinal, systemic diseases and psychological), which can cause a violation of an erectile function at different levels of this physiological act, the molecular mechanism for implementing the erection remains the same. Consequently, causing the relaxation of smooth muscles by increasing the level of CGMF or CAMF, in the overwhelming majority of cases, it is possible to restore the erection without affecting the cause of dysfunction. Thus, we do not cure the cause of erectile dysfunction. Of course, in the presence of severe structural changes in the vascular and in the cavernous components of the erectile function, we cannot restore the erection conservatively, in such cases the operation requires an operation.

Taking into account the above, the diagnostic stage can be reduced, but still must allow you to answer 2 questions:

- What is the genesis of erectile dysfunction - psychological or organic?

Is conservative treatment possible?

A detailed history collected in an environment predisposing to an intimate conversation will allow in most cases to identify the psychological cause of erectile dysfunction. Undoubtedly, careful inspection of the patient and routine laboratory diagnostics (blood sugar, lipid profile (LDL / LPLP), testosterone and prolactin) to eliminate hormonal disorders, diabetes mellitus and other systemic diseases must be included in the patient survey algorithm with ED, however, the presence of these diseases Does not change, but only complements the treatment.

Treatment

Phosphodiesterase inhibitors (FDE) 5 types

By blocking the effect of the FDE-5, its inhibitors increase the concentration of CGMF, causing the relaxation of the smooth muscles of the Trabec and an erection.

Phosphodiesterase form the biochemically and structurally diverse group of proteins. They are classified depending on the affinity of the CAMF or to CGMF, from the kinetic parameters of the hydrolysis of nucleotides, on their relative sensitivity to inhibiting various substances, from altogetherteric regulation by other molecules and behavior of their anion exchange sites. Phosphodiesterase combines a similar catalytic domain of about 270 amino acids, but their N-terminal responsible for contact with regulatory cofactors, and the C-terminal varies widely. To date, 11 families of phosphodiesterases have revealed, having an application point in various organs and human tissues.

In the 90s of the last century, the presence of 2,3,4,5 types of phosphodiesterase in the erectile tissue of man was found. Parallel to molecular identification of the PDE isoenzymes, large forces were applied to assess their functional significance. Based on the results obtained during the study of Isaenzymes FDE in vitro.It was revealed that the smooth muscles of cavernous bodies are preferably regulated by the CGMF-dependent form of FDE-5.

Sildenafil

The selective inhibitor PDE5 Sildenafil citrate was first introduced in 1996 at the annual Congress of the American Urological Association. The appearance of the drug on the market in 1998 was a revolution in the pharmacological treatment of ED. This is the first drug that is not inferior in the effectiveness of intracremal therapy.

More than 20 double blind placebo-controlled studies of Sildenafil with the participation of more than 3,000 men with ED of various etiologies. The improvement in the erection noted an average of 78% of patients, the development of an erection sufficient for penetration was noted more than 75% of patients.

Studies that lasted 12 months revealed the preservation of the effect of the drug in 88% of patients.

The level of response in patients suffering from diabetes or exposed to surgical treatment or radiation therapy of the pelvic organs amounted to only 43-52%.

Side effects observed when taking siltenafil are due to the inhibition of phosphodiesterase-5 (headache (18%), tides (\u003e 10%), dyspeptic phenomena (6%)) and phosphodiesteraserase-6, enzyme participating in the reference mechanism on the retina ( "Blue vision" 2%). The safety of Sildenafil's use was comprehensively studied and discussed, especially in connection with the arising from vasodilation and severe hypotension as a result of the potency of Sildenafil (and other PDE5 inhibitors) nitrates. Taking PDE5 inhibitors with patients taking nitrates strictly contraindicated. To date, more than 500 deaths associated with the reception of sildenafil are known, which is approximately 50 deaths per 1 million recipes. Thus, patients having an EBS history and heart failure should be informed in detail to prevent serious adverse events.

Vardenafil

Vardenafil is a new efficient and high-selective phosphodiesterase-5 inhibitor. Vardenafil has a high biological equivalent of efficiency: a concentration that allows to suppress 50% of activity (IC 50) in the PDE-5 isolate is 0.7 nmol / l, that is, there was a 10-fold difference compared to 6.6 nmol / l for Sildenafil in The same conditions. In vivo. Vardenafil is selective to PDE-5 (isolated from human platelets), it has a weak cross-reactivity to the rest of the FDE isoforms (both for cowathy and to human). Vardenafil is more selective to PDE-5 than to PDE-1 and PDE-6 (ratio of the coefficients Ic 50 Ratios (\u003d IC 50 PDEX / IC 50 PDE-5) - amounted to 257 for PDE-1 (Sildenafil - 60) and 16 for FDE-6 (Sildenafil - 7.4)).

Vardenafil is taken once in a dose of 10 mg or 20 mg, the time to achieve maximum concentration in the blood plasma (T max) is 0.7-0.9 h, with 50% of patients reach an erection 30 minutes after taking the drug. Pharmacokinetically, he is similar to Sildenafil. The half-life of the drug (T 1/2) is 4-5 hours, while the response time to the drug (that is, the time from the beginning to the termination of the clinical activity of the drug) exceeds T 1/2. Due to the inhibitory effect of the drug on the FDE-5, the spectrum of vorenaphyl side effects is similar to that of Sildenafil: headache (\u003e 10%), tides (most frequent phenomenon) (\u003e 6%), dyspeptic phenomena (6%), violation of visual perception ( \u003e 0.1%).

Vardenafil was widely studied in large multicenter placebo-controlled studies in an extensive population of men with ED and traditionally complex for treating groups of patients with diabetes and patients after prostatectomy. Vardenafil was well tolerated in these groups of patients, the side effects were insignificant or moderate in gravity and possessed the transient character. The effectiveness of the drug in groups of patients with diabetes and patients after prostatectomy was, respectively, 72% and 65%. Depending on the degree of severity of ED, its effectiveness was 79% and 40% at a dose of 20 mg, respectively, with light and severe degrees (compared with 20% and 4% in the placebo group). Improving the erectile function did not depend on the age and etiology of ED. Regarding the cardiovascular safety of the drug, it was shown that it did not affect the ability of patients with IBS to maintain the level of physical activity equal to the necessary during the intercourse. Analysis of studies 3 phases revealed high efficiency and good tolerability of the drug in patients receiving hypotensive drugs, such as diuretics, B-blockers, calcium antagonists and ACF inhibitors. Summarizing the above, the effectiveness of vardenafil is proved in patients with different etiology of erectile dysfunction, including difficult to treat patients with diabetes and patients undergoing prostatectomy. Due to the rapid beginning of the action, the increased half-life period, the minimum interaction of the drug and food, the drug and alcohol, as well as the improved pharmacological profile, ensuring good safety, tolerability, and the favorable ratio of the effect to the side effect of Vardenafil is suitable for use for pharmacotherapy ED.

Tadalafil

Tadalafil ( Cialis® ) - This is another representative of a group of selective FDE inhibitors, recently submitted to international and Russian markets. Its chemical structure is significantly different from Formula Sildenafil. This drug has very weak activity against the majority of FDE Isaenzimov: the ratio of IC 50 for PDE-1,4,7,10 is more than 10,000 and 780 for PDE-6. However, Tadalafil (IC 50 \u003d 7.1) has less selectivity to PDE-11 compared with Sildenafil (IC 50 Ratio \u003d 203) and Vardenafil (IC 50 Ratio \u003d 346). To date, the physiological role of the FDE-11 is not defined. The preparation period is 17.5 hours, while clinical efficiency reaches 36 hours. In placebo-controlled (with a fixed dose) studies in 81% of patients with a wide population of Tadalafil significantly improved an erectile function, while 59% the erectile function recovered to a normal level, 75% of all sexual attempts were successful. In patients suffering from diabetes and received fixed doses of 10 mg or 20 mg, the improvement noted 61% and 75%, respectively, compared with 30% receiving placebo. Unlike Vardenafil and Sildenafil, the reception of oily food does not affect the pharmacokinetics of Tadalafil. The most frequent side effects were: headache (14%), Malgia (5%), dyspeptic phenomena (10%). While in contrast to Sildenafil and Vardenafil, when taking Sialis, blood tides are less likely to face, 6% of patients who took the drug felt pain in the back (placebo - 5%). This symptom decreased with repeated drug intake. It is assumed that this effect is not due to the action of Tadalafil on the FDE-11, because Also noted when receiving Vardenafil and Sildenafil at higher doses. Tadalafil at a dose of 20 mg does not significantly affect the hell and pulse. Also identified the relationship between tadalafil intake and an increase in the frequency of myocardial infarction. Like all PDE-5 inhibitors, Tadalafil should not be appointed in combination with nitrates. Thus, Tadalafil is another one alternative oral preparation for the treatment of erectile dysfunction from easy to severe degree . Due to the long period of half-life, increased (up to 36 hours) the time of response and convenience of receiving the drug with food and alcohol, tadalafil provides sexual partners great degree of spontaneity in sexual life .

Sildenafil, Vardenafil, Tadalafil: What kind of medicine for what patient?

All three drugs have a lot in common, but there are also differences in the characteristics. in vitro., on the basis of which you can predict some of the features of their clinical use. Among them are biological equivalent of efficiency ( potency.), selectivity and pharmacokinetics.

Biological equivalent of efficiency (or potential efficiency) is estimated by defining IC 50. The smaller IC 50, the more potentially efficiently the drug. When evaluating this parameter, it is necessary to remember that the characteristics are represented by different pharmaceutical companies, and slightly different results were obtained in different laboratories. The clinical efficacy of drugs depends on a number of other factors, such as, for example, dosage, bioavailability, metabolic rate, etc.

Table 1 shows biological equivalents of the effectiveness of drugs.

Selectivity The drug testifies to the selectivity of the effects of drugs on the necessary isoform of the enzyme compared to other isoenzymes and is estimated using the specified relationship:

Selectivity \u003d Biological equivalent of effectiveness against Isaenzyme FDE / Biological equivalent of effectiveness against FDE-5.

The lower the ratio, the higher the activity of the drug against this Isoenzyme PDE.

Data indicate that there is no significant activity of Vardenafil and Sildenafil against PDE-11 and Tadalafil against PDE-6 (Table 2).

The effect of sildenafil and vardenafil on PDE-6 leads to the transit violation of the color perception of vision without structural constant violations. FDE-11 was found in the testicles, pituitary gland and hearty myocytes. Until now, the role of this enzyme is not known. A special 6-month study confirmed the lack of influence of Tadalafil on spermatogenesis.

Pharmacokinetics : The activity of drugs begins long before T Mach and lasts longer t 1/2. In fact, all drugs operate in 30 minutes.

The duration of Tadalafil - up to 36 hours, while Vardenafil and Sildenafila - up to 4-5 hours (Table 3).

Clinical comparison of drugs: At the Department of Urology of the RMAPO on the basis of the GKB named after S.P. Botkin We conducted a comparative randomized cross-study study of the effectiveness of Sildenafil, Tadalafil, Vardenafil. Every 10 patients took each of the drugs for 4 weeks, with a 2-week break - only 30 patients. The effectiveness of the drug, side effects, as well as the assessment of patients with their preference in choosing a drug for treating ED is evaluated.

As a result of this study, we found that all three FDE5 inhibitors have high efficiency in men with ED. Of the characteristics, which emphasize patients when choosing a drug, it is obvious that Vardenafil and Sildenafil are like patients due to the good resistance of the erection and the rapid achievement of the erection, while 92% of patients who choose Cialis noted its duration of action. It should also be noted that only 50% of patients who choose Vardenafil and Tadalafil noted the low level of adverse phenomena of the drug, and 70% of patients who took Sildenafil. Our research data is largely similar to the study German Men's Health Study Group In which 447 men crossly accepted 50 mg of Sildenafil, 10 mg of Tadalafil and 10 mg of vardenafil (211 men), and a comparative study of the effectiveness of the maximum dose of Sildenafil, Tadalafil and Vardenafil (237 men). In this study, among patients receiving the drug in half of the maximum dose, almost half (46.8%) preferred Vardenafil, 34% - Sildenafil and 19.1% - Tadalafil. At the same time, 43 percent of patients who took PDE-5 inhibitors in the maximum dose, chosen vardenafil, 17% - sildenafil and almost 40% of Tadalafil. Patients prefer therapy with new FDE-5 inhibitors (more than 65% prefer drugs that are prescribed in half the most efficient dose and more than 80% of patients prefer the reception of the maximum dose of the drug). The essential result of this study is the lack of a statistical difference between drugs in the scale of erectile dysfunction, responsible for the vagina penetration and the completion of sexual intercourse.

Another independent study on patient preferences conducted prof. Porsta in 2003 In this study, 150 patients took part, each of which took at least 6 tablets of Sildenafil, Vardenafil and Tadalafil. At the end of the study, Sildenafil was preferred to continue 13% of patients to continue therapy, 30% - Vardenafil and 45% - Tadalafil, and the choice of Tadalafil in 96% of cases was due to its lengthy effect.

Thus, it is currently allowed to use and have a proven high and approximately equal effectiveness of three drugs, the FDE-5 inhibitor: Vardenafil, Sildenafil and Tadalafil. Apparently, no one, besides the patient himself, cannot choose the best preparation for it. The doctor should only inform the patient about the possible side effects and the peculiarities of each drug.

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