The drug "Vizarsin" (reviews from men note that the drug is effective, but can cause a side effect in the form of facial redness) is a medicine aimed at improving potency. It has a positive effect on sexual arousal, improves the quality of sexual intercourse, and makes it last longer.

Composition and release form

The drug "Vizarsin" (reviews claim that the effect after taking the tablet occurs within 20-40 minutes) is sold in almost all pharmacies. It is produced in the form of tablets with a dosage of 25, 50, 100 mg. The blister can contain from 1 to 4 tablets. Active substance drug - sildenafil citrate.

The medicine should be stored at temperature conditions not exceeding 30 °C. In a dark and cool place, out of reach of children. Its shelf life is five years. Made in Slovenia.

pharmachologic effect

The medicine "Vizarsin" (negative reviews from men claim that the drug does not give the desired effect and can cause severe headaches) is intended to restore the erectile system in men. Has a vasodilating effect.

The drug is the strongest selective inhibitor of phosphodiesterase type 5, but despite this, its use in therapy erectile dysfunction is safer than the use of similar medications.

The action of Vizarsin is aimed at stimulating blood flow to the genital area. As a result of this influence of the drug, mechanisms that relax muscle tissue penis. Similar influence contributes to the filling of the penis with blood, which, in turn, gives an erection. The medicine does not have a direct effect on the cavernous body of the penis, and muscle relaxation occurs due to indirect mechanical processes.

Vasodilation may also occur in other areas human body, which in some cases provokes the appearance of negative reactions after taking the medicine.

Sildenafil provokes a slight decrease blood pressure, which is temporary. On average, when taking a dose of 100 mg, blood pressure decreases by 8.4 mmHg. Art. This side effect occurs due to the vasodilating properties of the drug. Also, a single use of the drug at a dosage of 100 mg does not have a significant effect on ECG indicator in healthy people.

Sildenafil has no effect on cardiac output and does not affect the blood flow that passes through stenotic arteries.

Indications and contraindications

The drug "Vizarsin" (negative reviews from men in some cases note that the medicine works better if there is natural arousal, but if there is a fear of sexual intercourse, fear of sex, it will simply be useless) is intended for the treatment of erectile dysfunction, which results in the inability to achieve an erection and save it for quality sexual intercourse. Vizarsin gives results only in the presence of sexual stimulation.

Contraindications to its use should be taken into account before taking the tablets. So, you should not use the medicine if you have special sensitivity to the active or minor substances of the drug.

Men with medical conditions should not take the medication of cardio-vascular system, as well as for other pathologies in which sexual activity is strictly contraindicated. It is prohibited to use the medicine in patients with visual impairment caused by ischemic neuropathy. Contraindications to the use of tablets include severe liver dysfunction, arterial hypotension, recent myocardial infarction, and stroke.

It is worth refusing treatment with these tablets if there is congenital dystrophy retina. The drug is not recommended for use by persons under eighteen years of age. "Visarsin" is not intended for women.

Medicine "Vizarsin": instructions for use

This drug should be taken orally with water. The optimal dose is considered to be 50 mg/day. The tablet should be taken an hour before planned sexual intercourse. Based on individual sensations, the dosage can be either reduced to 25 mg/day or increased to 100 mg/day.

Maximum permissible daily norm equal to 100 mg/day. The medicine should be taken no more than once a day.

If the drug is taken at the same time as a meal, its effect occurs later than when taking tablets on an empty stomach.

For elderly patients and those with mild to moderate renal failure, no dose adjustment is required. In the presence of severe renal failure The dose rate of the drug should not exceed 25 mg/day.

Side effects

In some cases, Vizarsin tablets can cause negative phenomena, which are expressed in symptoms of hypersensitivity to the components of the drug.

Quite often men experience headache, drowsiness, dizziness, hypoesthesia. During the use of tablets, disturbances in the functioning of the visual apparatus were noticed, including malfunctions in color perception peace. Patients often noted redness of the skin of the face, increased heart rate and tachycardia.

Other negative reactions included nasal congestion and dyspepsia. Vomiting, dryness occurred infrequently oral cavity, nausea. There was also pain in chest, prolonged erection, myalgia, skin rash, priapism. A state of general weakness may occur.

Overdose

Vizarsin tablets, if used incorrectly, can cause an overdose, which is manifested by pain in the head, a rush of blood to the skin face, temporary nasal congestion, dizziness, impaired functioning of the visual apparatus, dyspepsia.

If such reactions occur, carry out symptomatic treatment. Hemodialysis will not give any result here.

General instructions

The drug "Vizarsin" for men should be prescribed after examining the patient and diagnosing erectile dysfunction, as well as after identifying the causes of its occurrence.

At cardiovascular diseases sexual activity poses a certain threat to health, so before prescribing medication to such patients, the doctor should carefully study their condition.

The active component, sildenafil, causes a systemic vasodilator effect, which can lead to a slight decrease in blood pressure. The doctor must assess the risk before prescribing pills undesirable consequences, which may occur due to the vasodilating properties of the drug.

Patients with left ventricular outflow tract obstruction exhibit excessive sensitivity to vasodilators. People with multiple system atrophy syndrome and blood pressure disorders should be careful when taking this drug.

"Visarsin" can increase the hypotensive effect of nitrates.

Medicines intended to eliminate sexual dysfunction, including those containing sildenafil, should be taken with caution by people with penile deformity and patients with priapism.

The combination of Vizarsin with other medications to eliminate sexual dysfunction is not recommended due to the lack of scientific research in this area.

When taking pills, disruption of the visual apparatus may occur, and sometimes progression of ischemic optical neuropathy.
If any side effects You should stop taking the drug and consult your doctor to review the prescription.

The combined use of sildenafil with alpha-blockers can provoke the occurrence of symptomatic hypotension in individual individuals. Arterial hypotension is observed here four hours after taking the drug. To minimize the risk of low blood pressure, you should first stabilize the body's condition by taking alpha-blockers. For such patients, Vizarsin is prescribed at a minimum dose of 25 mg/day, which can be increased if necessary.

Grapefruit juice, as well as a weak CYP3A4 inhibitor, increases the concentration of sildenafil in moderate doses.

There are no trials of the drug in patients with peptic ulcers and bleeding. Here, tablets are consumed after taking into account the risk-benefit ratio.

The drug "Vizarsin" contains lactose, which requires caution when taking the drug for persons with lactose intolerance and lactase deficiency, as well as patients diagnosed with glucose-galactose malabsorption.

The drug should not be used simultaneously with fatty foods, but it is allowed to take the drug “Vizarsin” with alcohol.

The medication does not affect the ability to drive or the speed of reactions. In some cases, due to visual impairment, working with certain mechanisms becomes impossible. This problem eliminated by replacing the medication or reducing the dosage.

Medicine "Vizarsin": analogues

If for some reason this drug is not suitable, then you can prefer it similar means containing sildenafil. There are many drugs that can replace the drug "Visarsin". It’s not difficult to find analogues in a pharmacy, here are the most popular ones:

“Viagra” (the cost of one 25 mg tablet is about 650 rubles);
“Viasan-LF” (the price of four 50 mg tablets is about 450 rubles);
“Erexesil” (one 50 mg tablet costs around 300 rubles);
“Taxier” (the price of four tablets with a dosage of 100 mg is 1000 rubles);
"Tornetis" (price of one tablet of 100 mg - 650 rubles);
“Olmax Strong” (the cost of two 50 mg tablets is 800 rubles);
"Dynamiko" (one 50 mg pill costs about 400 rubles);
“Maxigra” (price of one tablet 50 mg - 300 rubles);
“Sildenafil” (cost of four 50 mg pills - 300 rubles);
"Revacio" (90 tablets cost about 30 thousand rubles).

There are many drugs that can replace Vizarsin, and there are alternatives this medicine should be selected by the attending physician.

Cost of the drug

You can purchase the drug "Vizarsin" in almost every pharmacy. Its price may vary slightly depending on trade margin in the pharmacy chain. So, a 25 mg tablet costs about 150 rubles, one 50 mg tablet costs about 180 rubles. For four tablets (50 mg) of the drug "Vizarsin" the price fluctuates around 600-700 rubles. A tablet with a dosage of 100 mg can be bought for 230 rubles, and the price of four tablets in the same dosage is 500-700 rubles. Given its price category, this drug is affordable for most men.

1 tablet contains - sildenafil 100 mg

Excipients: hyprolose, mannitol, aspartame, neohesperidin dihydrochalcone, mint flavor, peppermint flavor, crospovidone type A, calcium silicate FM1000, magnesium stearate.
1 PC. - blisters (1) - cardboard packs.
1 PC. - blisters (2) - cardboard packs.
4 things. - blisters (1) - cardboard packs.
4 things. - blisters (2) - cardboard packs.
4 things. - blisters (3) - cardboard packs.

Clinical and pharmacological group:

A drug for the treatment of erectile dysfunction. PDE-5 inhibitor

Pharmacotherapeutic group:

Erectile dysfunction treatment, PDE-5 inhibitor

pharmachologic effect

Selective inhibitor of cycloguanosine monophosphate (cGMP)-specific PDE5. PDE5, responsible for the breakdown of cGMP, is found not only in the corpus cavernosum 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 corpus cavernosum, resulting in relaxation of smooth muscles and increased blood flow in the corpus cavernosum.
As 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 taking sildenafil leads to dilation of the blood vessels of the lungs and, to a lesser extent, other vessels.

Sildenafil is selective for PDE5 in vitro. Its activity against PDE5 is 10 times greater than that against other known PDE isoenzymes: PDE6, which is involved in transmitting the light signal in the retina of the eye; 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 heart contraction.

Sildenafil may cause mild and transient impairment of color discrimination (blue/green). The putative mechanism for 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 lower than its activity on PDE5.

Pharmacokinetics

After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages 40% (25-63%). After a single oral dose of 100 mg, Cmax 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 is reduced; Tmax increases by 60 minutes, and Cmax decreases by an average of 29%. Vd of sildenafil at steady state averages 105 liters. Sildenafil and its main circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. 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 sildenafil administration.

Sildenafil is metabolized mainly by the liver microsomal 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 concentration of the metabolite in plasma is approximately 40% of that of sildenafil. The N-desmethyl metabolite undergoes further metabolism; its terminal T1/2 is about 4 hours.

The total clearance of sildenafil from the body is 41 l/h, and T1/2 in the terminal phase is 3-5 hours. After oral administration, sildenafil is excreted in the form of metabolites mainly in feces (approximately 80% of the dose) and to a lesser extent in 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.

For renal mild insufficiency(CC 50-80 ml/min) and moderate (CC 30-49 ml/min) severity, the pharmacokinetic parameters of sildenafil after oral administration once (50 mg) do not change. In severe renal failure (creatinine clearance ≤30 ml/min), the clearance of sildenafil is reduced, which leads to an approximately twofold increase in AUC (100%) and C max (88%) compared with those with normal renal function in patients of the same age group.

In patients with liver cirrhosis (Child-Pugh class A and B), 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.

Indications

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

Dosage regimen

Treatment of erectile dysfunction: taken orally approximately 1 hour before planned sexual activity. A single dose is 50 mg. Taking into account effectiveness and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. Maximum single dose is 100 mg. The maximum frequency of use is 1 time/day. For elderly patients over 65 years of age and associated disorders for kidney or liver function, the dose is 25 mg.

Pulmonary hypertension

: orally 20 mg 3 times a day with an interval of about 6-8 hours, regardless of meals. Maximum daily dose is 60 mg. Patients with impaired renal function do not require dose adjustment, however, if tolerated poorly, the dose is reduced to 20 mg 2 times a day.

Side effect

From the side of the central nervous system: possible headache, hot flashes, dizziness, insomnia.

From the digestive system:

possible dyspepsia, asthenia, diarrhea, abdominal pain, nausea.

From the musculoskeletal system:

arthralgia, myalgia, increased muscle tone.

From the respiratory system:

nasal congestion, pharyngitis, rhinitis, sinusitis, infections respiratory tract, breathing problems.

From the side of the organ of vision:

changes in vision (mild and transient; mainly changes in the color of objects, as well as increased perception of light and blurred vision), conjunctivitis.

Others

: possible flu-like syndrome, development infectious diseases, symptoms of vasodilation, back pain, rash, infections urinary tract, dysfunction prostate gland; in isolated cases - priapism.

Contraindications for use

Simultaneous intake of nitric oxide or nitrate donors in any form, increased sensitivity to sildenafil.

Use for liver dysfunction

For liver dysfunction, the dose is 25 mg.

Use for renal impairment

For impaired renal function, the dose is 25 mg.

Use in children

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

Use in elderly patients

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

special instructions

Before starting to take sildenafil for the treatment of erectile dysfunction, a cardiovascular examination should be performed.
Use with caution in patients with anatomical deformation of the penis (such as 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 stomach and duodenum in the acute phase, with hereditary retinitis pigmentosa.

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

Impact on the ability to drive vehicles and operate machinery
Sildenafil does not affect the ability to drive vehicles or operate machinery.

Drug interactions

With simultaneous use of CYP3A4 inhibitors (erythromycin, cimetidine), the clearance of sildenafil decreases and the concentration of sildenafil in the blood plasma increases.

With the simultaneous use of indinavir, saquinavir, ritonavir, the plasma Cmax and AUC of sildenafil increases, which is due to inhibition of the CYP3A4 isoenzyme under the influence of indinavir, saquinavir, ritonavir.

Stronger CYP3A4 inhibitors, such as ketoconazole or itraconazole, can be expected to increase plasma concentrations of sildenafil

When used simultaneously with nitrates, the hypotensive effect of nitrates is enhanced.

A case of the development of symptoms of rhabdomyolysis after a single dose of sildenafil in a patient receiving simvastatin has been described.

Is medicine. A doctor's consultation is required.

Compound

Description of the dosage form

Oral dispersible tablets: round, slightly biconvex, white or almost white, with mint smell. Dark inclusions are allowed.

pharmachologic effect

pharmachologic effect- improves erectile function, vasodilating.

Pharmacodynamics

Sildenafil is a powerful selective inhibitor of cGMP-specific PDE-5. Restores impaired erectile function in conditions of sexual stimulation by increasing blood flow in the vessels of the penis.

Mechanism of action

The physiological process underlying penile erection involves the release of nitric oxide (NO) in the corpus cavernosum in response to sexual stimulation. Nitric oxide activates the enzyme guanylate cyclase, which leads to an increase in the concentration of cGMP and subsequent relaxation of the smooth muscle cells of the corpus cavernosum and promotes its filling with blood.

It does not have a direct relaxing effect on the isolated human corpus cavernosum, but enhances the effect of NO by inhibiting PDE5, which is responsible for the breakdown of cGMP. When the NO/cGMP system is activated due to sexual stimulation, inhibition of PDE-5 by sildenafil leads to an increase in cGMP levels in the corpus cavernosum.

To develop what you want pharmacological action sildenafil requires sexual stimulation.

Research in vitro showed that sildenafil is selective for PDE-5, which is involved in the development of erection. Its activity against PDE-5 is superior to that against other known PDEs. Sildenafil is 10 times less selective for PDE-6, which is involved in phototransmission in the retina. At maximum recommended doses, sildenafil is 80 times less selective for PDE-1 and 700 times or more less selective for PDE-2, 3, 4, 7, 8, 9, 10 and 11. The activity of sildenafil against PDE-5 is approximately 4000 times greater than its activity against PDE-3 (cAMP-specific PDE), which is involved in the regulation of myocardial contractility.

Sildenafil causes a slight and transient decrease in blood pressure, which in most cases does not have clinical manifestations. Maximum reduction SBP in a horizontal position after taking sildenafil at a dose of 100 mg averages 8.3 mmHg. Art. , and dBP - 5.3 mm Hg. Art.

This decrease in blood pressure is due to the vasodilating effect of sildenafil, possibly associated with an increase in the concentration of cGMP in vascular smooth muscle cells.

A single dose of sildenafil in a dose of up to 100 mg is not accompanied by clinically significant changes on the ECG in healthy volunteers.

Sildenafil has no effect on cardiac output and does not alter blood flow through stenotic arteries. In patients with erectile dysfunction and stable angina who regularly took antianginal drugs (except nitrates), the time before the onset of an angina attack during a test with physical activity

did not differ significantly after taking sildenafil compared with placebo. In some patients, 1 hour after taking 100 mg of sildenafil, the Farnsworth-Munsell 100 test revealed transient changes in the ability to distinguish shades of color (blue/green); 2 hours after taking sildenafil, these changes were absent. The putative mechanism for color vision impairment is considered to be inhibition of PDE-6. Sildenafil has no effect on visual acuity or contrast perception, electroretinogram, IOP or pupil diameter. It was noted that in patients with early age-related degeneration

macula, sildenafil at a dose of 100 mg did not cause clinically significant changes in vision assessed by special tests (visual acuity, Amsler grid, traffic light color difference, Humphrey perimetry and photostress).

A single dose of sildenafil 100 mg had no effect on sperm motility or morphology in healthy volunteers. More information about

clinical studies

In fixed-dose studies of sildenafil, the proportion of men reporting improved erections was 62% (25 mg), 74% (50 mg) and 82% (100 mg) compared with 25% in the placebo group. However, the frequency of sildenafil withdrawal was low and comparable to that in the placebo group. In all studies, the proportion of patients who noted an improvement in erection after using sildenafil was as follows: psychogenic erectile dysfunction (84%), mixed erectile dysfunction (77%), organic erectile dysfunction (68%), elderly patients (67%), diabetes (59%), IHD (69%), arterial hypertension (68%), transurethral resection of the prostate (61%), radical prostatectomy (43%), damage(83%), depression (75%). An analysis of the International Index of Erectile Dysfunction showed that in addition to improving erections, treatment with sildenafil also improved the quality of orgasm, sexual satisfaction and overall satisfaction. The safety and effectiveness of sildenafil was maintained during long-term use.

Pharmacokinetics

Suction. Sildenafil is rapidly absorbed. Tmax in blood plasma when taken on an empty stomach is 30-120 minutes (median - 60 minutes). Absolute bioavailability, on average, is about 41% (25-63%). The pharmacokinetics (AUC and Cmax) of sildenafil in the range of recommended doses (25-100 mg) are linear. Eating reduces the rate of absorption of sildenafil, and Tmax is extended by an average of 60 minutes. Cmax decreases, on average, by 29%.

Distribution. Vd of sildenafil at steady state is, on average, 105 liters. After a single oral dose of 100 mg of sildenafil, C max is approximately 440 ng/ml (coefficient of variation (CV) 40%). Since sildenafil and its main circulating N-demethylated metabolite are 96% bound to plasma proteins, the average plasma concentration of the free fraction of sildenafil is 18 ng/ml (38 nmol).

In healthy volunteers, 90 minutes after a single dose of 100 mg of sildenafil, less than 0.0002% of the dose (on average 188 ng) is detected in the semen.

Metabolism. Sildenafil is metabolized mainly in the liver under the influence of microsomal isoenzymes of cytochrome P450: CYP3A4 (main route) and CYP2C9(optional path). The main circulating active metabolite is formed as a result of N-demethylation of sildenafil. The selectivity of the metabolite to PDE is comparable to that of sildenafil, and its activity against PDE-5 in vitro is approximately 50% of the activity of unchanged sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers is about 40% of the concentration of sildenafil, the N-demethylated metabolite undergoes further metabolism, T1/2 is about 4 hours.

Excretion. The total clearance of sildenafil is 41 l/h, and the final half-life is 3-5 hours. Sildenafil is excreted in the form of metabolites, mainly by the intestines (approximately 80% of the dose) and, to a lesser extent, by the kidneys (approximately 13% of the dose) .

Special patient groups

Elderly patients. In healthy elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of sildenafil and its active N-demethylated metabolite in the blood plasma is approximately 90% higher than in young patients (18-45 years). Considering age characteristics binding to plasma proteins, the concentration of free sildenafil in the blood plasma increases by approximately 40%.

Renal dysfunction. In patients with mild or moderate impairment renal function (Cl creatinine 30-80 ml/min), the pharmacokinetics of sildenafil after a single dose of 50 mg did not change. The average AUC and C max of the N-demethylated metabolite increased by 126 and 73%, respectively, compared with healthy patients of the same age. Due to the high interindividual variability, these differences are not statistically significant. In severe renal failure (Cl creatinine less than 30 ml/min), the clearance of sildenafil is reduced, which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those in patients of the same age group without dysfunction kidney

Liver dysfunction. In patients with liver cirrhosis class A and B according to the Child-Pugh classification, the clearance of sildenafil is reduced, which leads to an increase in AUC (84%) and Cmax (47%) compared to patients with normal function liver of the same age group. Pharmacokinetics of sildenafil in patients with severe violation liver function has not been studied.

Indications of the drug Vizarsin ® Ku-tab ®

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

Effective only with sexual stimulation.

Contraindications

hypersensitivity to sildenafil or any other component of the drug;

simultaneous use with nitric oxide (NO) donors (for example amyl nitrite) or nitrates in any form, because sildenafil may enhance the antihypertensive effect of nitrates (mediated through NO/cGMP);

simultaneous use with other drugs for the treatment of erectile dysfunction (safety and effectiveness have not been studied, see “Special Instructions”);

simultaneous use with ritonavir;

loss of vision in one eye due to anterior ischemic optic neuropathy of non-arterial origin, regardless of whether it is associated or not with the use of PDE-5 inhibitors (see “Special Instructions”);

severe liver dysfunction;

arterial hypotension (blood pressure less than 90/50 mm Hg);

recent disorder cerebral circulation or myocardial infarction;

phenylketonuria;

hereditary retinal dystrophies (hereditary degenerative diseases of the retina), such as retinitis pigmentosa (some patients have genetic defects of retinal PDE), because the safety of using the drug Vizarsin ® Ku-tab ® in such patients has not been studied;

patients with congenital intolerance fructose (because it contains sorbitol);

children under 18 years of age and women.

Carefully: arterial hypertension (blood pressure above 170/100 mm Hg); life-threatening arrhythmias; left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM) or multiple system atrophy syndrome; anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease); conditions predisposing to priapism (sickle cell anemia, multiple myeloma or leukemia); simultaneous use of alpha-blockers; diseases accompanied by bleeding, or exacerbation of gastric or duodenal ulcer; episodes of anterior non-arteritic ischemic neuropathy; optic nerve in the anamnesis.

Use during pregnancy and breastfeeding

According to its registered indication, Vizarsin ® Ku-tab ® is not intended for use in women.

Side effects

When using sildenafil in clinical studies, the most common unwanted reactions were: headache, hot flashes, dyspepsia, blurred vision, nasal congestion, dizziness and impaired color vision (chromatopsia).

Frequency classification side effects WHO: very often - ≥1/10; often - from ≥1/100 to<1/10; нечасто — от ≥1/1000 до <1/100; редко — от ≥1/10000 до <1/1000; очень редко — от <1/10000; частота неизвестна — не может быть оценена на основе имеющихся данных.

Within each group, adverse effects are presented in order of decreasing severity.

From the immune system: rarely - hypersensitivity reactions.

From the nervous system: very often - headache; often - dizziness; infrequently - drowsiness, hypoesthesia; rarely - cerebrovascular accident, fainting; frequency unknown - transient ischemic attack, seizures, relapse of seizures.

From the side of the organ of vision: often - visual impairment, impaired color vision (chromatopsia); infrequently - damage to the conjunctiva, impaired lacrimation, other disorders of the organ of vision; frequency unknown - anterior ischemic optic neuropathy of non-arterial origin, retinal vascular occlusion, visual field defect.

Hearing and labyrinth disorders: often - vertigo, tinnitus; rarely - deafness*.

From the side of blood vessels: often - a feeling of hot flashes; rarely - increase/decrease in blood pressure.

From the side of the heart: infrequently - palpitations, tachycardia; rarely - myocardial infarction, atrial fibrillation; frequency unknown - ventricular arrhythmia, unstable angina, sudden cardiac death.

From the respiratory system, chest and mediastinal organs: often - nasal congestion; rarely - nosebleeds.

From the gastrointestinal tract: often - dyspepsia; infrequently - vomiting, nausea, dryness of the oral mucosa.

For the skin and subcutaneous tissues: uncommon - skin rash; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

From the musculoskeletal and connective tissue side: infrequently - myalgia.

From the kidneys and urinary tract: infrequently - hematuria.

From the genital organs and breast: uncommon - hematospermia, bleeding from the penis; frequency unknown - priapism, prolonged (long-lasting) erection.

General disorders and disorders at the injection site: infrequently - pain at work, increased fatigue.

Laboratory and instrumental data: infrequently - increase in heart rate.

* Hearing impairment: sudden deafness. Sudden decrease or loss of hearing has been observed in a small number of cases in post-marketing studies or clinical studies with all PDE5 inhibitors, including sildenafil.

Interaction

The influence of other drugs on the pharmacokinetics of sildenafil

In vitro studies

The metabolism of sildenafil mainly occurs under the influence of cytochrome P450 isoenzymes: CYP3A4 (main pathway) and CYP2C9(not the main path). Therefore, inhibitors of these isoenzymes may reduce the clearance of sildenafil.

In vivo studies

A population pharmacokinetic analysis of the results of a clinical study revealed a decrease in the clearance of sildenafil with simultaneous use of inhibitors of the CYP3A4 isoenzyme (such as ketoconazole, erythromycin, cimetidine). However, no increase in the frequency of adverse events was noted in these patients. For patients taking inhibitors of the CYP3A4 isoenzyme, treatment with sildenafil is recommended to begin with a dose of 25 mg.

The simultaneous use of sildenafil (100 mg once a day) with an HIV protease inhibitor - ritonavir (500 mg 2 times a day), a powerful inhibitor of cytochrome P450 - increases the Cmax and AUC of sildenafil in blood plasma by 300% (i.e. 4 times) and 1000% (i.e. 11 times), respectively. After 24 hours, the concentration of sildenafil in the blood plasma was approximately 200 ng/ml (when taking sildenafil alone - 5 ng/ml). Taking into account the results of a pharmacokinetic study, the simultaneous use of sildenafil with ritonavir is contraindicated.

Co-administration of the HIV protease inhibitor saquinavir (inhibitor of the CYP3A4 isoenzyme) at steady state (1200 mg 3 times daily) with sildenafil (100 mg once daily) increases the Cmax and AUC of sildenafil by 140 and 210%, respectively. Sildenafil has no effect on the pharmacokinetics of saquinavir. It is likely that more potent inhibitors of the CYP3A4 isoenzyme (ketoconazole and itraconazole) have a more pronounced effect on the pharmacokinetics of sildenafil.

With simultaneous use of sildenafil (100 mg once) with erythromycin (a specific inhibitor of the CYP3A4 isoenzyme) at steady state (500 mg 2 times a day for 5 days), the AUC of sildenafil increases by 182%. In healthy volunteers, azithromycin (500 mg/day for 3 days) does not cause a change in the pharmacokinetic parameters (AUC, Cmax, Tmax, elimination rate or T1/2) of sildenafil or its main circulating metabolite. Cimetidine (non-specific inhibitor of the CYP3A4 isoenzyme, 800 mg) in healthy volunteers increases the concentration of sildenafil (50 mg) in blood plasma by 56%.

Grapefruit juice, a weak inhibitor of the CYP3A4 isoenzyme in the intestinal wall, may slightly increase the concentration of sildenafil in the blood plasma.

A single use of an antacid (magnesium hydroxide and aluminum hydroxide) does not change the bioavailability of sildenafil.

Although interactions with the following drugs have not been specifically studied, population pharmacokinetic analysis did not reveal changes in the pharmacokinetics of sildenafil when used concomitantly with: isoenzyme inhibitors CYP2C9(such as tolbutamide, warfarin, phenytoin), isoenzyme inhibitors CYP2D6(such as SSRIs and tricyclic antidepressants), thiazides and thiazide-like diuretics, loop and potassium-sparing diuretics, ACE inhibitors, calcium antagonists, beta-blockers or isoenzyme inducers CYP450(such as rifampicin and barbiturates).

Nicorandil is a hybrid of a potassium channel activator and a nitrate. Due to the presence of nitrate in the drug, a serious interaction with sildenafil is possible.

The effect of sildenafil on the pharmacokinetics of other drugs

In vitro studies

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC 50 ≥150 µmol). The C max of sildenafil after taking recommended doses is approximately 1 µmol, so it is unlikely that sildenafil affects the clearance of substrates of these isoenzymes.

There is no data on the interaction of sildenafil with nonspecific PDE inhibitors such as theophylline or dipyridamole.

In vivo studies

Sildenafil acts on the NO/cGMP system, so it enhances the hypotensive effect of nitrates. Concomitant use with NO donors (such as amyl nitrite) or nitrates in any form is contraindicated.

In some patients, simultaneous use of sildenafil with alpha-blockers may lead to the development of symptomatic arterial hypotension. Arterial hypotension most often develops within 4 hours after taking sildenafil. Clinical studies examined the use of sildenafil (25, 50 or 100 mg) while taking the alpha-blocker doxazosin in doses of 4 or 8 mg in patients with benign prostatic hyperplasia and stable hemodynamics. An additional decrease in blood pressure was detected in the horizontal position of the patient by an average of 7/7, 9/5 and 8/4 mmHg. Art.

respectively, in a vertical position - on average by 6/6, 11/4 and 4/5 mm Hg. Art. CYP2C9 In patients with stable hemodynamics while taking doxazosin, when sildenafil was added to therapy, rare cases of the development of symptomatic orthostatic hypotension, clinically manifested by dizziness, but without the development of fainting, were noted.

Interaction of sildenafil (50 mg) with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the isoenzyme

, not found.

Undesirable effects of antihypertensive drugs, incl.

diuretics, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, vasodilators, centrally acting drugs, adrenergic neuron blockers, CCBs and alpha-blockers did not differ between patients treated with sildenafil or placebo.

In a drug interaction study of the simultaneous use of sildenafil (100 mg) with amlodipine in patients with arterial hypertension, an additional decrease in horizontal position of SBP by 8 mm Hg was noted. Art.

and DBP - by 7 mm Hg. Art.

The additional reduction in blood pressure is comparable to that observed with sildenafil alone in healthy volunteers.

Sildenafil (100 mg) at steady state did not affect the pharmacokinetic parameters of HIV protease inhibitors: saquinavir and ritonavir, which are substrates of the CYP3A4 isoenzyme.

Directions for use and doses

Inside.

Adults

Vizarsin ® Qu-tab ® , orally dispersible tablets, can be used as an alternative to Vizarsin ® , film-coated tablets, in patients who have difficulty swallowing tablets. Oral dispersible tablets are fragile. Therefore, tablets should not be squeezed through the foil of the package, because they may break. You should not take the tablet with wet hands, because the tablet may melt.

Remove the tablet as follows.

1. Take the blister and bend it along the tear line.

2. Open the blister by carefully pulling the edge of the foil.

3. Gently shake the tablet into your palm, then immediately place it on your tongue.

The tablet should be kept in the mouth for a few seconds until completely dissolved (to make it easier to swallow), then you can wash it down with liquid.

Special patient groups

Elderly patients. Do not mix the tablet in your mouth with food.

Renal dysfunction. In case of mild to moderate severity of renal failure (Cl creatinine 30-80 ml/min), no dose adjustment is required; in case of severe renal failure (Cl creatinine less than 30 ml/min) - the dose of Vizarsin ® Ku-tab ® should be reduced to 25 mg . Based on efficacy and tolerability, the dose may be increased to 50 or 100 mg.

Liver dysfunction. Since the elimination of sildenafil is impaired in patients with impaired liver function (for example, cirrhosis), the dose of the drug should be reduced to 25 mg. Based on efficacy and tolerability, the dose may be increased to 50 or 100 mg.

Concomitant use with other drugs

Concomitant use of ritonavir is contraindicated.

When used simultaneously with inhibitors of the CYP3A4 isoenzyme, with the exception of ritonavir (such as ketoconazole, erythromycin, cimetidine), the initial dose of Vizarsin ® Qu-tab ® should not exceed 25 mg.

To reduce the likelihood of developing orthostatic hypotension, it is necessary to achieve a stable hemodynamic state during alpha-blocker therapy before starting the use of sildenafil. The initial dose of Vizarsin ® Ku-tab ® should be reduced to 25 mg (see “Special instructions” and “Interaction”).

Overdose

Symptoms: with a single dose of sildenafil in doses up to 800 mg, adverse reactions were similar to those when taking the drug in lower doses, while the severity and frequency increased. Taking sildenafil at a dose of 200 mg did not lead to an increase in effectiveness, but the frequency of adverse reactions (headache, hot flashes, dizziness, dyspepsia, nasal congestion, visual impairment) increased.

Treatment: symptomatic. Hemodialysis is ineffective because sildenafil binds tightly to plasma proteins and is not excreted by the kidneys.

special instructions

Before using drug therapy, it is necessary to evaluate the medical history and conduct a clinical examination in order to diagnose erectile dysfunction and identify its possible causes.

Drugs for the treatment of sexual dysfunction, including sildenafil, should be used with caution in patients with anatomical deformities of the penis (such as angulation, cavernous fibrosis, or Peyronie's disease), as well as in patients with conditions predisposing to priapism (such as sickle cell anemia, multiple myeloma or leukemia).

Medicines to treat erectile dysfunction, including sildenafil, should not be used in men for whom sexual activity is not recommended.

Sexual activity poses a certain risk in the presence of cardiovascular diseases. Therefore, before starting any therapy for erectile dysfunction, it is necessary to assess the patient's condition.

The use of sildenafil is contraindicated in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, arterial hypotension (BP<90/50 мм рт. ст. ).

Sexual activity is undesirable for patients with life-threatening arrhythmias and arterial hypertension (BP ≥170/100 mm Hg).

There was no difference in the incidence of myocardial infarction (1.1 per 100 person-years) and cardiovascular mortality rate (0.3 per 100 person-years) with sildenafil compared with patients in the placebo group.

Cardiovascular complications

With post-marketing use of sildenafil, serious cardiovascular events (time-related to taking sildenafil) have been reported, incl.

Decreased blood pressure

Sildenafil should be used with caution in patients taking alpha-blockers, as concomitant use of sildenafil and alpha-blockers may lead to symptomatic hypotension in selected susceptible patients. Arterial hypotension most often develops within 4 hours after taking sildenafil. PDE5 inhibitors, including sildenafil, and alpha-blockers are vasodilators that have a hypotensive effect. With the simultaneous use of vasodilators, an excessive decrease in blood pressure may develop. Patients with unstable hemodynamics while using alpha-blockers are at increased risk of developing symptomatic arterial hypotension when used simultaneously with PDE-5 inhibitors. To minimize the risk of developing orthostatic hypotension in such patients, sildenafil therapy should be started only after hemodynamic parameters have stabilized while taking alpha-blockers. Consideration should be given to reducing the initial dose of sildenafil to 25 mg. If the patient is already receiving sildenafil, the use of alpha-blockers should be started with a low dose. When used simultaneously with PDE-5 inhibitors, a further decrease in blood pressure may be associated with a gradual increase in the dose of alpha-blockers. In addition, the doctor should explain to the patient what actions should be taken if orthostatic hypotension develops (for example, dizziness, lightheadedness, loss of consciousness). When these symptoms appear, the patient should sit down or take a horizontal position.

Visual impairment

When using all PDE-5 inhibitors, including sildenafil, in rare cases, the development of anterior ischemic optic neuropathy of non-arterial origin was observed, which was accompanied by deterioration or loss of vision. Most of these patients had risk factors such as excavation (deepening) of the optic nerve head, age over 50 years, diabetes mellitus, arterial hypertension, coronary artery disease, hyperlipidemia and smoking. The cause-and-effect relationship between the use of PDE-5 inhibitors and the development of anterior ischemic optic neuropathy of non-arterial origin has not been established. In case of sudden loss of vision, the patient should receive immediate medical attention and stop using the drug Vizarsin ® Ku-tab ® .

A small number of patients with hereditary retinitis pigmentosa have genetically determined retinal PDE defects. The safety of sildenafil in patients with retinitis pigmentosa has not been studied and therefore use in these patients is contraindicated.

Hearing impairment

Cases of sudden decrease or loss of hearing have been reported in patients using all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for hearing loss or impairment. There is no correlation between the use of PDE5 inhibitors and hearing impairment. In case of sudden decrease or loss of hearing, you must stop using the drug Vizarsin ® Ku-tab ® and immediately consult a doctor. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden decrease or loss of hearing has not been established.

Bleeding

Sildenafil potentiates the antiplatelet effect of sodium nitroprusside (NO donor) in vitro. There is no information on the safety of sildenafil in patients with bleeding or acute peptic ulcers. Therefore, sildenafil should be used with caution in such patients only after a careful assessment of the benefit/risk ratio.

Concomitant use with other drugs intended for the treatment of erectile dysfunction

The safety and effectiveness of sildenafil in combination with other drugs intended for the treatment of erectile dysfunction have not been studied. Therefore, the use of such combinations is contraindicated.

The drug Vizarsin ® Ku-tab ® is not intended for use in women.

Special information on excipients

Patients with congenital fructose intolerance should not take Vizarsin ® Ku-tab ® , because it contains sorbitol.

Vizarsin ® Qu-tab ® contains aspartame, which is a source of phenylalanine and may be harmful to people with phenylketonuria.

The drug was created to treat erectile dysfunction in men. Visarsin Ku-Tab promotes blood flow to the vessels of the penis without causing surges in blood pressure and other syndromes that occur when taking medications that increase potency. Read the instructions for use of this medication.

What is Vizarsin

The drug is intended to eliminate sexual dysfunction in men. The medicine is considered completely safe and can be used independently provided there are no obvious contraindications. The active substance of the drug ensures a full erection by stimulating blood flow to the male genital organ. Vizarsin Ku-Tab restores lost sexual activity and has a preventive effect against intimate problems.

Composition and release form

The drug is available in film-coated tablets in dosages of 25, 50 and 100 mg. Orally dispersible pills are white, biconvex and round in shape. The active ingredient of the drug is sildenafil. The drug Vizarsin includes auxiliary components: hyproloz, peppermint, aspartame and other components. Detailed description:

Component
Component	Dosage 25 mg	Dosage 50 mg	Dosage 100 mg
Sildenafil
Hyprolose
Aspartame
Mannitol
Crospovidone type A
Magnesium stearate
Mint flavor
Calcium silicate FM1000
Peppermint flavor
Neohesperidine dihydrochalcone

pharmachologic effect

The mechanism of action of the drug in the treatment of sexual dysfunction in men is achieved by acting on the cavernous and cavernous bodies of the penis. The active substance of the drug (sildenafil) causes their relaxation and enhances the effect of nitric oxide on tissues. Vizarsin does not have a direct effect on the development of erection. Its action is the result of activation of indirect mechanisms. In addition, the instructions indicate that taking sildenafil is ineffective without sexual stimulation.

After 60 minutes after resorption of the Vizarsin tablet, the active substance reaches its maximum concentration in the blood. Sidenafil is metabolized to a greater extent by liver cells. The total clearance of the active component is 41 l/h, and the final T1/2 is 3–5 hours. Excretion of the substance in the form of breakdown products is carried out mainly by the intestines - about 80% of the dose, and in a smaller amount by the kidneys - about 13% of the dose.

Indications for use

According to the instructions for use, the drug is recommended to be taken for the purpose of correcting sexual dysfunction, characterized by the inability of a man to maintain or achieve an erection of the penis necessary for normal sexual intercourse. It is noted that for the therapeutic effect of a medicinal substance to manifest itself, sexual arousal is required.

Instructions for use of Vizarsin

The drug is taken on an empty stomach: the effectiveness of sildenafil in this case increases. The coated tablet should be placed on the tongue and held in the mouth for a few seconds, then washed down with liquid. The daily dosage of the drug is 50 mg. If necessary, it can be doubled. It is recommended to take the medicine an hour before sexual intercourse. No dosage adjustment is required for elderly patients, while persons with pathologies of liver and kidney function are prescribed 25 mg of sildenafil per day.

special instructions

Before taking the drug, you should carefully study the instructions for its use. It is important to pay close attention to a number of special instructions. The instructions indicate that sildenafil should be taken with caution by patients with cardiovascular diseases, since the substance contributes to the exacerbation of ailments. In addition, it is better not to take tablets after fatty foods. In terms of speed of action, taking it on an empty stomach is more preferable.

Vizarsin is used with caution in case of anatomical defects of the penis, for example, cavernous fibrosis, angulation, as well as in the case of a high probability of developing pripiasm (painful erection not associated with sexual arousal). Along with this, consultation with a specialist requires the use of medicine by persons with acquired or congenital lactose deficiency.

Vizarsin for women

The drug was created for men and cannot be used to increase libido in women. The fact is that the pharmacological effect of the drug is based on the mechanism of sexual arousal, which is inherent only to representatives of the stronger sex. For this reason, the use of tablets by women is not justified.

Drug interactions

When taken simultaneously with CYP3A4 isoenzyme inhibitors (Erythromycin, Ketoconazole), the initial dose of the drug should not exceed 25 mg. Ignoring this recommendation is fraught with serious consequences for patients with insufficient kidney and liver function. The instructions prohibit combining the drug in question with Ritonavir. Intraconazole and Ketoconazole have a pronounced effect on the pharmacokinetics of sildenafil. When Vizarsin is taken together with nitrates, the likelihood of negative consequences of their interaction increases.

Vizarsin with alcohol

The instructions for use indicate that when ethanol is combined with sildenafil, there is no increase in the hypotensive properties of the former. At the same time, doctors do not recommend taking potency pills with alcohol, although there is no absolute ban on drinking alcohol during Vizarsin therapy. However, it is better to avoid drinking strong drinks while treating sexual dysfunction.

Side effects

Judging by the reviews of men, the drug is generally well tolerated. Taking the pills rarely causes serious side effects. The instructions indicate that the medicine for erection can cause negative effects from various organs and systems. Thus, a feeling of flushing in the face, tachycardia, and dry mouth may occur. On the part of the visual organs, chromatopsia often occurs, a violation of the blood circulation of the retina. Along with this, taking Vizarsin is fraught with the following side effects:

nausea;
vomiting;
dyspeptic disorders;
headache;
myalgia;
drowsiness;
nosebleeds;
an attack of angina pectoris;
allergic reactions.

Contraindications for Vizarsin

Before using the tablets, you should make sure that there are no restrictions on their use. Any liver pathology accompanied by severe functional insufficiency is an absolute contraindication for the use of Vizarsin. Due to the fact that sildenafil enhances the effect of antihypertensive drugs, it is prohibited to use it to eliminate erectile dysfunction in patients taking such medications. The use of Vizarsin is contraindicated in certain physiological and pathological conditions:

individual intolerance to the components of the drug;
retinal pathologies;
previous myocardial infarction and cerebral stroke;
coronary heart disease;
atherosclerosis;
hypertension;
under 18 years of age.

Viagra;

MaxiGroy;

Levitra;

Cialis;

Taxi driver;

Nitrest.

When offering an analogue drug, doctors take into account the patient’s concomitant pathologies and contraindications to prescribing a particular drug. Thus, Cialis is a suitable replacement for Visarsin for men suffering from cardiovascular diseases. In situations where a patient has impotence and erectile dysfunction, specialists usually prescribe Viagra or Maxigra.

Vizarsin price

The drug is freely available. You can buy the medicine at any pharmacy. Prices for medications that increase potency vary from 280 to 350 rubles. for one blister pack of tablets with a dosage of 50 mg. Judging by the reviews, the medicine can also be purchased on specialized websites. Depending on the form of release, prices for potency drugs in Moscow pharmacies are as follows:

Release form	Price, rubles
Vizarsin Ku-tab 25 mg N1 TB dispensed in the mouth/floor
Vizarsin Ku-tab 25 mg N4 TB dispensed in the mouth/floor
Vizarsin Ku-tab 50 mg N1 TB dispensed in the mouth/floor
Vizarsin Ku-tab 50 mg N4 TB dispensed in the mouth/floor
Vizarsin Ku-tab 100 mg N1 dispensed in the mouth/floor
Vizarsin Qu-tab 100 mg N4 dispensed in the mouth/floor

Catad_pgroup PDE5 inhibitors

Vizarsin Ku-tab - official instructions for use

Vizarsin® Q-Tab®

Registration number: LP-002481

Trade name: Vizarsin ® Ku-tab ®

International nonproprietary name: sildenafil

Dosage form: oral dispersible tablets

Compound

per tablet 25 mg
Active substance:
Sildenafil 25.00 mg
Excipients: hyprolose 1.50 mg, mannitol 40.50 mg, aspartame 0.375 mg, neohesperidin dihydrochalcone 0.125 mg, mint flavor 0.25 mg, *peppermint flavor 0.25 mg, crospovidone type A 10.00 mg, calcium silicate FM1000 20.00 mg, magnesium stearate 2.00 mg

per tablet 50 mg
Active substance:
Sildenafil 50.00 mg
Excipients: hyprolose 3.00 mg, mannitol 81.00 mg, aspartame 0.75 mg, neohesperidin dihydrochalcone 0.25 mg, mint flavor 0.50 mg, *peppermint flavor 0.50 mg, crospovidone type A 20.00 mg , calcium silicate FM1000 40.00 mg, magnesium stearate 4.00 mg

per tablet 100 mg
Active substance:
Sildenafil 100.00 mg
Excipients: hyprolose 6.00 mg, mannitol 162.00 mg, aspartame 1.50 mg, neohesperidin dihydrochalcone 0.50 mg, mint flavor 1.00 mg, *peppermint flavor 1.00 mg, crospovidone type A 40.00 mg , calcium silicate FM1000 80.00 mg, magnesium stearate 8.00 mg
*Peppermint flavor contains: maltodextrin 78%,
acacia gum 9%, sorbitol 3.5%, mint oil 3.5%,
levomenthol 0.9% and water q.s. up to 100%.

Description
Round, slightly biconvex tablets of white or almost white color with a mint odor. Dark inclusions are allowed.

Pharmacotherapeutic group: erectile dysfunction remedy
treatment – phosphodiesterase (PDE)-5 inhibitor

ATX code: G04BE03

Pharmacological properties

Pharmacodynamics
Sildenafil is a powerful selective inhibitor of cycloguanosine monophosphate (cGMP), a specific phosphodiesterase type 5 (PDE-5). Restores impaired erectile function in conditions of sexual stimulation by increasing blood flow in the vessels of the penis.

Mechanism of action
The physiological process underlying penile erection involves the release of nitric oxide (NO) in the corpus cavernosum in response to sexual stimulation. Nitric oxide activates the enzyme guanylate cyclase, which leads to an increase in the concentration of cGMP and subsequent relaxation of the smooth muscle cells of the corpus cavernosum and promotes its filling with blood. It does not have a direct relaxing effect on the isolated human corpus cavernosum, but enhances the effect of NO by inhibiting PDE-5, which is responsible for the breakdown of cGMP. When the NO/cGMP system is activated due to sexual stimulation, inhibition of PDE-5 by sildenafil leads to an increase in cGMP levels in the corpus cavernosum.

To develop the desired pharmacological action of sildenafil, sexual stimulation is required.

In vitro studies have shown that sildenafil is selective for PDE-5, which is involved in the development of erection. Its activity against PDE-5 is superior to that against other known phosphodiesterases. Sildenafil is 10 times less selective for PDE-6, which is involved in phototransmission in the retina. At maximum recommended doses, sildenafil is 80 times less selective for PDE-1 and 700 times or more for PDE-2, 3, 4, 7, 8, 9, 10 and 11. The activity of sildenafil against PDE-5 is approximately 4000 times greater than its activity against PDE-3 (cycloadenosine monophosphate (cAMP) - a specific phosphodiesterase), involved in the regulation of myocardial contractility.

Sildenafil causes a slight and transient decrease in blood pressure (BP), which in most cases has no clinical manifestations. The maximum decrease in systolic blood pressure in a horizontal position after taking sildenafil at a dose of 100 mg averages 8.3 mmHg. Art., and diastolic blood pressure - 5.3 mm Hg. Art. This decrease in blood pressure is due to the vasodilating effect of sildenafil, possibly associated with an increase in the concentration of cGMP in vascular smooth muscle cells.

A single dose of sildenafil in a dose of up to 100 mg is not accompanied by clinically significant changes in the electrocardiogram (ECG) in healthy volunteers. Sildenafil has no effect on cardiac output and does not alter blood flow through stenotic arteries.

In patients with erectile dysfunction and stable angina who regularly took antianginal drugs (except nitrates), the time to the onset of an angina attack during an exercise test did not differ significantly after taking sildenafil compared with placebo.

In some patients, 1 hour after taking 100 mg of sildenafil, the Farnsworth-Munsell 100 test revealed transient changes in the ability to distinguish shades of color (blue/green); 2 hours after taking sildenafil, these changes were absent. The proposed mechanism for color vision impairment is PDE-6 inhibition. Sildenafil has no effect on visual acuity or contrast perception, electroretinogram, intraocular pressure or pupil diameter. It was noted that in patients with early age-related macular degeneration, sildenafil at a dose of 100 mg did not cause clinically significant changes in vision, assessed by special tests (visual acuity, Amsler grid, traffic light color difference, Humphrey perimetry and photostress). A single dose of sildenafil 100 mg had no effect on sperm motility or morphology in healthy volunteers.

More information about clinical trials
In fixed-dose studies of sildenafil, the proportion of men reporting improved erections was 62% (25 mg), 74% (50 mg) and 82% (100 mg) compared with 25% in the placebo group. At the same time, the frequency of sildenafil withdrawal was low and comparable to that in the placebo group. In all studies, the proportion of patients who noted an improvement in erection after using sildenafil was as follows: psychogenic erectile dysfunction (84%), mixed erectile dysfunction (77%), organic erectile dysfunction (68%), elderly patients (67%), diabetes mellitus (59%), coronary heart disease (CHD) (69%), arterial hypertension (68%), transurethral resection of the prostate (61%), radical prostatectomy (43%), spinal cord injury (83%), depression (75 %). An analysis of the International Index of Erectile Dysfunction showed that in addition to improving erections, treatment with sildenafil also improved the quality of orgasm, sexual satisfaction and overall satisfaction.
The safety and effectiveness of sildenafil was maintained during long-term use.

Pharmacokinetics

Suction
Sildenafil is rapidly absorbed. The maximum concentration in blood plasma (Cmax) when taken on an empty stomach is achieved within 30-120 minutes (median 60 minutes). Absolute bioavailability, on average, is about 41% (25-63%). The pharmacokinetics (area under the concentration-time curve (AUC) and Cmax) of sildenafil in the range of recommended doses (25-100 mg) is linear. Eating reduces the rate of absorption of sildenafil, and the time to reach maximum concentration (TCmax) is extended by an average of 60 minutes, Cmax is reduced by an average of 29%.

Distribution
The volume of distribution (Vd) of sildenafil at steady state is, on average, 105 liters. After a single oral dose of 100 mg of sildenafil, Cmax is approximately 440 ng/ml (coefficient of variation (CV) 40%). Since sildenafil (and its main circulating N-demethylated metabolite) is 96% bound to plasma proteins, the average plasma concentration of the free fraction of sildenafil is 18 ng/ml (38 nM). In healthy volunteers, 90 minutes after a single dose of 100 mg of sildenafil, less than 0.0002% of the dose (on average 188 ng) is detected in the semen.

Metabolism
Sildenafil is metabolized mainly in the liver under the influence of microsomal cytochrome P450 isoenzymes: CYP3A4 (main pathway) and CYP2C9 (additional pathway). The main circulating active metabolite is formed as a result of N-demethylation of sildenafil. The selectivity of the metabolite to phosphodiesterases is comparable to that of sildenafil, and its activity against PDE-5 in vitro is approximately 50% of the activity of unchanged sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers is about 40% of the concentration of sildenafil. The N-demethylated metabolite undergoes further metabolism, its half-life (T½) is about 4 hours.

Removal
The total clearance of sildenafil is 41 l/hour, and the terminal half-life (T½) is 3-5 hours. Sildenafil is excreted as metabolites, mainly by the intestines (approximately 80% of the dose) and, to a lesser extent, by the kidneys (approximately 13% of the dose).

Pharmacokinetics of individual patient groups

Elderly patients
In healthy elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of sildenafil and its active N-demethylated metabolite in the blood plasma is approximately 90% higher than in young patients (18-45 years). Taking into account the age-related characteristics of binding to plasma proteins, the concentration of free sildenafil in the blood plasma increases by approximately 40%.

Renal dysfunction
In patients with mild or moderate renal impairment (creatinine clearance (CC) 30-80 ml/min), the pharmacokinetics of sildenafil did not change after a single dose of 50 mg. The mean AUC and Cmax of the N-demethylated metabolite increased by 126% and 73%, respectively, compared with age-matched healthy subjects. Due to the high interindividual variability, these differences are not statistically significant. In severe renal failure (creatinine clearance less than 30 ml/min), the clearance of sildenafil is reduced, leading to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those in patients of the same age group without impaired function. kidney

Liver dysfunction
In patients with Child-Pugh class A and B liver cirrhosis, the clearance of sildenafil is reduced, which leads to an increase in AUC (84%) and Cmax (47%) compared to patients with normal liver function in the same age group. The pharmacokinetics of sildenafil in patients with severe hepatic impairment has not been studied.

Indications for use
Treatment of erectile dysfunction, characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse. Effective only with sexual stimulation.

Contraindications
Hypersensitivity to sildenafil or any other component of the drug.

Concomitant use with nitric oxide (NO) donors (for example, amyl nitrite) or nitrates in any form, since sildenafil may enhance the antihypertensive effect of nitrates (mediated through NO/cGMP). Medicines for the treatment of erectile dysfunction, including sildenafil, should not be used in men for whom sexual activity is not recommended (for example, patients with severe cardiovascular disease such as unstable angina or severe heart failure).

The safety and effectiveness of sildenafil in combination with other drugs for the treatment of erectile dysfunction have not been studied. Therefore, simultaneous use is contraindicated (see section "Special instructions"). Concomitant use with ritonavir is contraindicated. Loss of vision in one eye due to anterior ischemic optic neuropathy of non-arterial origin, whether or not it is associated with the use of phosphodiesterase 5 (PDE-5) inhibitors (see section "Special Instructions").

Use is contraindicated in: severe liver dysfunction, arterial hypotension (BP less than 90/50 mm Hg), recent cerebrovascular accident or myocardial infarction, phenylketonuria, hereditary retinal dystrophies (hereditary degenerative diseases of the retina), such as retinitis pigmentosa ( some patients have genetic defects of retinal phosphodiesterases), since the safety of the use of the drug Vizarsin ® Ku-tab ® in such patients has not been studied.
According to its registered indication, Vizarsin ® Ku-tab ® is not intended for use in children under 18 years of age and women.

Carefully: arterial hypertension (BP above 170/100 mm Hg), life-threatening arrhythmias, obstruction of the outflow tract of the left ventricle of the heart (aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM)) or multiple system atrophy syndrome, anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease), conditions predisposing to priapism (sickle cell anemia, multiple myeloma or leukemia), concomitant use of alpha-blockers, diseases accompanied by bleeding, or exacerbation of gastric or duodenal ulcers, episodes of anterior non-arteritic ischemic optic neuropathy in the anamnesis.

Use during pregnancy and breastfeeding
According to its registered indication, Vizarsin ® Ku-tab ® is not intended for use in women.

Directions for use and doses

Sildenafil (100 mg) at steady state did not affect the pharmacokinetic parameters of HIV protease inhibitors: saquinavir and ritonavir, which are substrates of the CYP3A4 isoenzyme.
The drug Vizarsin ® Ku-tab ®, tablets dispersible in the oral cavity.

Can be used by patients who have difficulty swallowing tablets as an alternative to Vizarsin ®, the tablets of which are film-coated.
Orally dispersible tablets are fragile and should not be squeezed through the foil packaging as they may break.

Do not take the tablet with wet hands, as the tablet may begin to dissolve. The tablet must be removed as follows:

Bend the blister along the tear line.
Open the blister by carefully pulling the edge of the foil.
Carefully remove the tablet.
Then the tablet should be immediately placed on the tongue and kept in the mouth for several seconds until completely absorbed, then washed down with liquid.

2. Open the blister by carefully pulling the edge of the foil.
When using Vizarsin ® Ku-tab ® with fatty foods, the effect of the drug may develop later than when used on an empty stomach.

The recommended dose is 50 mg, taken as needed, approximately 1 hour before anticipated sexual activity. Depending on the effectiveness and tolerability, the dose of Vizarsin ® Ku-tab ® can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg.
The maximum recommended frequency of use of the drug is 1 time per day.

Special patient groups

Elderly patients
No dose adjustment of Vizarsin ® Ku-tab ® is required.

Renal dysfunction
In case of mild to moderate renal failure (creatinine clearance 30-80 ml/min), no dose adjustment is required; in case of severe renal failure (creatinine clearance less than 30 ml/min), the dose of Vizarsin ® Ku-tab ® should be reduced to 25 mg. Taking into account effectiveness and tolerability, the dose can be increased to 50 mg and 100 mg.

Liver dysfunction
Since the elimination of sildenafil is impaired in patients with impaired liver function (for example, cirrhosis), the dose of the drug should be reduced to 25 mg. Taking into account effectiveness and tolerability, the dose can be increased to 50 mg and 100 mg.

Concomitant use with other drugs
Concomitant use of ritonavir is contraindicated. When used simultaneously with inhibitors of the CYP3A4 isoenzyme (such as ketoconazole, erythromycin, cimetidine, with the exception of ritonavir), the initial dose of Vizarsin ® Kutab ® should not exceed 25 mg. To reduce the likelihood of developing orthostatic hypotension, it is necessary to achieve a stable hemodynamic state during alpha-blocker therapy before starting the use of sildenafil. The initial dose of Vizarsin ® Ku-tab ® should be reduced to 25 mg (see sections “Special instructions” and “Interaction with other drugs”).

Side effect
When using sildenafil in clinical studies, the most common adverse reactions were: headache, flushing, dyspepsia, visual disturbances, nasal congestion, dizziness and impaired color vision (chromatopsia).

World Health Organization (WHO) side effect frequency classification:
very often ≥1/10
often from ≥1/100 to<1/10
uncommon ≥1/1000 to<1/100
rarely from ≥1/10000 to<1/1000
very rarely from<1/10000
frequency unknown cannot be estimated from available data.
Within each group, adverse effects are presented in order of decreasing severity.

Immune system disorders:
rarely: hypersensitivity reactions.

Nervous system disorders:
very often: headache;
often: dizziness;
uncommon: drowsiness, hypoesthesia;
rarely: cerebrovascular accident, fainting;
frequency unknown: transient ischemic attack, seizures, relapse of seizures.

Visual disorders:
often: visual impairment, impaired color vision (chromatopsia);
uncommon: damage to the conjunctiva, impaired lacrimation, other visual disturbances;
frequency unknown: anterior ischemic optic neuropathy of non-arterial origin, retinal vascular occlusion, visual field defect.

Hearing and labyrinth disorders:
often: vertigo, tinnitus;
rare: deafness*.

Vascular disorders:
often: feeling of “hot flashes”;
rarely: increase/decrease in blood pressure.

Cardiac disorders:
uncommon: palpitations, tachycardia;
rarely: myocardial infarction, atrial fibrillation;
frequency unknown: ventricular arrhythmia, unstable angina, sudden cardiac death.

Disorders of the respiratory system, chest and mediastinal organs:
often: nasal congestion;
rarely: nosebleeds.

Gastrointestinal disorders:
often: dyspepsia;
uncommon: vomiting, nausea, dry oral mucosa.

Disorders of the skin and subcutaneous tissues:
uncommon: skin rash;
frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Musculoskeletal and connective tissue disorders:
uncommon: myalgia.

Renal and urinary tract disorders:
uncommon: hematuria.

Disorders of the genital organs and breast:
uncommon: hematospermia, bleeding from the penis;
frequency unknown: priapism, prolonged (long-lasting) erection.

General disorders and disorders at the injection site:
uncommon: chest pain, fatigue.

Laboratory and instrumental data:
uncommon: increased heart rate.

*Hearing impairment: sudden deafness. Sudden decrease or loss of hearing has been observed in a small number of cases in post-marketing studies or clinical studies with all PDE5 inhibitors, including sildenafil.

Overdose
Symptoms: with a single dose of sildenafil in doses up to 800 mg, adverse reactions are similar to those when taking the drug in lower doses, while the severity and frequency increased. Taking sildenafil at a dose of 200 mg did not lead to an increase in effectiveness, but the frequency of adverse reactions (headache, hot flashes, dizziness, dyspepsia, nasal congestion, visual impairment) increased.
Treatment: symptomatic. Hemodialysis is ineffective because sildenafil is tightly bound to plasma proteins and is not excreted by the kidneys.

Interaction with other drugs

The influence of other drugs on the pharmacokinetics of sildenafil
In vitro studies:
The metabolism of sildenafil mainly occurs under the influence of cytochrome P450 isoenzymes: CYP3A4 (main route) and CYP2C9 (non-main route). Therefore, inhibitors of these isoenzymes may reduce the clearance of sildenafil.

In vivo studies:
A population pharmacokinetic analysis of the results of a clinical study revealed a decrease in the clearance of sildenafil with simultaneous use of inhibitors of the CYP3A4 isoenzyme (such as ketoconazole, erythromycin, cimetidine). However, no increase in the frequency of adverse events was noted in these patients. For patients taking inhibitors of the CYP3A4 isoenzyme, treatment with sildenafil is recommended to begin with a dose of 25 mg. Concomitant use of sildenafil (100 mg once daily) with the HIV protease inhibitor ritonavir (500 mg twice daily) (a potent inhibitor of cytochrome P450) increases the Cmax and AUC of sildenafil in blood plasma by 300% (i.e. 4 times ) and 1000% (i.e. 11 times), respectively. After 24 hours, the concentration of sildenafil in the blood plasma was approximately 200 ng/ml (when taking sildenafil alone - 5 ng/ml). Taking into account the results of a pharmacokinetic study, the simultaneous use of sildenafil with ritonavir is contraindicated.

Co-administration of the HIV protease inhibitor saquinavir (an inhibitor of the CYP3A4 isoenzyme) at steady state (1200 mg three times daily) with sildenafil (100 mg once daily) increases the Cmax and AUC of sildenafil by 140% and 210%, respectively. Sildenafil has no effect on the pharmacokinetics of saquinavir. It is likely that more potent inhibitors of the CYP3A4 isoenzyme (ketoconazole and itraconazole) have a more pronounced effect on the pharmacokinetics of sildenafil.

With simultaneous use of sildenafil (100 mg once) with erythromycin (a specific inhibitor of the CYP3A4 isoenzyme) at steady state (500 mg twice daily for 5 days), the AUC of sildenafil increases by 182%. In healthy volunteers, azithromycin (500 mg per day for 3 days) does not cause changes in the pharmacokinetic parameters (AUC, Cmax, TCmax, elimination rate or T1/2) of sildenafil or its main circulating metabolite. Cimetidine (a nonspecific inhibitor of the CYP3A4 isoenzyme) (800 mg) in healthy volunteers increases the concentration of sildenafil (50 mg) in blood plasma by 56%. Grapefruit juice, a weak inhibitor of the CYP3A4 isoenzyme in the intestinal wall, may slightly increase the concentration of sildenafil in the blood plasma.

A single use of an antacid (magnesium hydroxide and aluminum hydroxide) does not change the bioavailability of sildenafil. Although interactions with the following drugs have not been specifically studied, population pharmacokinetic analysis did not reveal changes in the pharmacokinetics of sildenafil when used concomitantly with: CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors and tricyclic antidepressants), thiazides and thiazide-like diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, beta-blockers or inducers of the CYP450 isoenzyme (such as rifampicin and barbiturates). Nicorandil is a hybrid of a potassium channel activator and a nitrate. Due to the presence of nitrate in the drug, a serious interaction with sildenafil is possible.

The effect of sildenafil on the pharmacokinetics of other drugs

In vitro studies
Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 µmol). The Cmax of sildenafil after taking recommended doses is approximately 1 µmol, so it is unlikely that sildenafil affects the clearance of substrates of these isoenzymes. There is no data on the interaction of sildenafil with nonspecific phosphodiesterase inhibitors, such as theophylline or dipyridamole.

In vivo studies
Sildenafil acts on the NO/cGMP system, so it enhances the hypotensive effect of nitrates. Simultaneous use with NO donors (such as amyl nitrite) or nitrates in any form is contraindicated. In some patients, simultaneous use of sildenafil with alpha-blockers may lead to the development of symptomatic arterial hypotension. Arterial hypotension most often develops within 4 hours after taking sildenafil. Clinical studies examined the use of sildenafil (25 mg, 50 mg or 100 mg) while taking the alpha-blocker doxazosin in doses of 4 mg or 8 mg in patients with benign prostatic hyperplasia and stable hemodynamics. An additional decrease in blood pressure was detected in the horizontal position of the patient, on average by 7/7, 9/5 and 8/4 mm Hg. Art., respectively, and in a vertical position - on average, by 6/6, 11/4 and 4/5 mm Hg. Art. In patients with stable hemodynamics while taking doxazosin, when sildenafil was added to therapy, rare cases of the development of symptomatic orthostatic hypotension, clinically manifested by dizziness, but without the development of fainting, were noted.

There was no interaction between sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the CYP2C9 isoenzyme. Sildenafil (50 mg) does not cause an additional prolongation of bleeding time when used simultaneously with acetylsalicylic acid (150 mg).

Sildenafil (50 mg) does not potentiate the hypotensive effect of ethanol in healthy volunteers (Cmax of ethanol in the blood serum averaged 80 mg/dL).
Adverse effects of antihypertensive drugs, including diuretics, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, vasodilators, centrally acting drugs, adrenergic neuron blockers, slow calcium channel blockers and alpha blockers, did not differ in patients using sildenafil or placebo. In a drug interaction study of the simultaneous use of sildenafil (100 mg) with amlodipine in patients with arterial hypertension, an additional decrease in horizontal systolic blood pressure of 8 mm Hg was noted. Art. and diastolic blood pressure - by 7 mm Hg. Art. The additional reduction in blood pressure is comparable to that observed with sildenafil alone in healthy volunteers. Sildenafil (100 mg) at steady state did not affect the pharmacokinetic parameters of HIV protease inhibitors: saquinavir and ritonavir, which are substrates of the CYP3A4 isoenzyme.

special instructions
Before using drug therapy, it is necessary to evaluate the medical history and conduct a clinical examination in order to diagnose erectile dysfunction and identify its possible causes. Drugs for the treatment of sexual dysfunction, including sildenafil, should be used with caution in patients with anatomical deformities of the penis (such as angulation, cavernous fibrosis, or Peyronie's disease), as well as in patients with conditions predisposing to priapism (such as sickle cell anemia, multiple myeloma or leukemia).
Medicines to treat erectile dysfunction, including sildenafil, should not be used in men for whom sexual activity is not recommended. Sexual activity poses a certain risk in the presence of diseases of the cardiovascular system. Therefore, before starting any therapy for erectile dysfunction, it is necessary to assess the patient's condition. The use of sildenafil is contraindicated in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, arterial hypotension (BP< 90/50 мм рт. ст.). Сексуальная активность нежелательна для пациентов c угрожающими жизни аритмиями, артериальной гипертензией (АД >170/100 mm Hg. Art.). There was no difference in the incidence of myocardial infarction (1.1 per 100 person-years) and cardiovascular mortality rate (0.3 per 100 person-years) with sildenafil compared with patients in the placebo group.

Cardiovascular complications
Serious cardiovascular events (time-related to the use of sildenafil) have been reported with post-marketing use of sildenafil, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, arterial hypertension and arterial hypotension. Most of the patients had cardiovascular risk factors. Many of the complications developed during or immediately after sexual intercourse and some shortly after using sildenafil without sexual activity. It is impossible to determine a cause-and-effect relationship with any factors.

myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, arterial hypertension and arterial hypotension. Most patients had cardiovascular risk factors. Many of the complications developed during or immediately after sexual intercourse, and some occurred shortly after using sildenafil without sexual activity. It is impossible to determine a cause-and-effect relationship with any factors.
Sildenafil has a systemic vasodilatory effect, leading to a slight and transient decrease in blood pressure. Before using sildenafil, the physician should carefully assess the risk of possible unwanted 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 (eg, aortic stenosis, HOCM) or the rare multiple system atrophy syndrome, which manifests as severe impairment of autonomic blood pressure regulation.

Sildenafil has a systemic vasodilatory effect, leading to a slight and transient decrease in blood pressure. Before using sildenafil, the physician should carefully assess the risk of possible unwanted vasodilatory effects in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (for example, aortic stenosis, HOCM) or the rare multiple system atrophy syndrome, manifested by severe impairment of autonomic blood pressure regulation.
Sildenafil should be used with caution in patients taking alpha-blockers, as concomitant use of sildenafil and alpha-blockers may lead to symptomatic hypotension in selected susceptible patients. Arterial hypotension most often develops within 4 hours after taking sildenafil. PDE5 inhibitors, including sildenafil, and alpha-blockers are vasodilators with hypotensive effects.

With the simultaneous use of vasodilators, an excessive decrease in blood pressure may develop. Patients with unstable hemodynamics while using alpha-blockers are at increased risk of developing symptomatic arterial hypotension when used simultaneously with PDE-5 inhibitors.

To minimize the risk of developing orthostatic hypotension in such patients, sildenafil therapy should be started only after hemodynamic parameters have stabilized while taking alpha-blockers. Consideration should be given to reducing the initial dose of sildenafil to 25 mg. If the patient is already receiving sildenafil, the use of alpha-blockers should be started with a low dose. When used simultaneously with PDE-5 inhibitors, a further decrease in blood pressure may be associated with a gradual increase in the dose of alpha-blockers. In addition, the doctor should explain to the patient what actions should be taken if orthostatic hypotension develops (for example, dizziness, lightheadedness, loss of consciousness). When these symptoms appear, the patient should sit down or take a horizontal position.

Visual impairment
When using all PDE-5 inhibitors, including sildenafil, in rare cases the development of anterior ischemic optic neuropathy of non-arterial origin was observed, which was accompanied by deterioration or loss of vision. Most of these patients had risk factors such as excavation (deepening) of the optic nerve head, age over 50 years, diabetes mellitus, arterial hypertension, coronary artery disease, hyperlipidemia and smoking. A cause-and-effect relationship between the use of PDE-5 inhibitors and the development of anterior ischemic optic neuropathy of non-arterial origin has not been established. In case of sudden loss of vision, the patient should receive immediate medical attention and stop using the drug Vizarsin ® Ku-tab ® . A small number of patients with hereditary retinitis pigmentosa have genetically determined defects in retinal phosphodiesterases. The safety of sildenafil in patients with retinitis pigmentosa has not been studied and therefore use in these patients is contraindicated.

Hearing impairment
Cases of sudden decrease or loss of hearing have been reported in patients using all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for hearing loss or impairment. There was no correlation between the use of PDE5 inhibitors and hearing impairment. In case of sudden decrease or loss of hearing, you must stop using the drug Vizarsin ® Ku-tab ® and immediately consult a doctor. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden decrease or loss of hearing has not been established.

Bleeding
Sildenafil potentiates the antiplatelet effect of sodium nitroprusside (NO donor) in vitro. There is no information on the safety of sildenafil in patients with bleeding or acute peptic ulcers. Therefore, sildenafil should be used with caution in such patients only after a careful assessment of the benefit/risk ratio.
Concomitant use with other drugs intended for the treatment of erectile dysfunction
The safety and effectiveness of sildenafil in combination with other drugs intended to treat erectile dysfunction have not been studied. Therefore, the use of such combinations is contraindicated.
The drug Vizarsin ® Ku-tab ® is not intended for use in women.

Special information on excipients
Patients with congenital fructose intolerance should not take Vizarsin ® Ku-tab ® , since it contains sorbitol.
Vizarsin ® Qu-tab ® contains aspartame, which is a source of phenylalanine and may be harmful to people with phenylketonuria.

Impact on the ability to perform potentially hazardous activities that require special attention and quick reactions (for example, driving vehicles, working with moving mechanisms)
There is no data on the negative effect of the drug Vizarsin ® Ku-Tab ® in recommended doses on the ability to drive a car or operate machinery. Patients should assess their individual susceptibility to taking the drug Vizarsin ® Ku-Tab ® , since a decrease in blood pressure, development of visual impairment (chromatopsia, blurred visual perception) and dizziness are possible, especially at the beginning of treatment and when changing the dosage regimen.

Release form
Orally dispersible tablets 25 mg, 50 mg and 100 mg.
1 or 4 tablets per blister made of combined material OPA/Al/PVC, PET/Al foil (OPA/Al/PVC, PET/Al peel off foil).
1, 2 blisters (blister of 1 tablet) or 1, 2, 3 blisters (blister of 4 tablets) are placed in a cardboard pack along with instructions for use.

Storage conditions
At a temperature not exceeding 25 °C, in the original packaging.
Keep out of the reach of children.

Best before date
2 years. Do not use the drug after the expiration date.

Vacation conditions
Dispensed by prescription.

Manufacturer:
JSC "KRKA, d.d., Novo mesto", Shmareshka cesta 6, 8501 Novo mesto,
Slovenia

Representative office of JSC "KRKA, d.d., Novo mesto" in the Russian Federation /
Organization receiving consumer complaints:
123022, Russian Federation, Moscow, st. 2nd Zvenigorodskaya,
13, p. 41