Vizarsin Ku-tab - instructions for use, dose, side effects, contraindications

Excipients: giprolose 1.50 mg, mannitol 40.50 mg, aspartame 0.375 mg, neohesperidinedihydrochalcon 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

For one tablet of 50 mg:

Active substance: sildenafil 50.00 mg

Excipients: giprolose 3.00 mg, mannitol 81.00 mg, aspartame 0.75 mg, neohesperidindihydrohalcon 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

For one tablet, 100 mg:

Active substance: sildenafil 100.00 mg

Excipients: giprolose 6.00 mg, mannitol 162.00 mg, aspartame 1.50 mg, neohesperidinedihydrochalcon 0.50 mg, mint flavor 1.00 mg, * mint flavor pepper 1.00 mg, crospovidone type A 40.00 mg, calcium silicate FM1000 80.00 mg, magnesium stearate 8.00 mg

* Flavor of peppermint contains: maltodextrin 78%, acacia gum 9%, sorbitol 3.5%, mint field oil 3.5%, levomentola 0.9% and water q.s. up to 100%

Description:

Round, slightly biconcave tablets white or almost white, with a minty smell. Presence of dark inclusions is allowed.

Pharmacotherapeutic group:Erectile dysfunction remedy - PDE5-inhibitor

ATX: & nbsp

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

G.04.B.E.03 Sildenafil

Pharmacodynamics:

Sildenafil is a potent selective inhibitor of cyclo-guanosine monophosphate (cGMP), a specific type 5 phosphodiesterase (PDE-5). Restores impaired erectile function in conditions of sexual stimulation of increased blood flow in the vessels of the penis.

Mechanism of action

The physiological process underlying the erection of the penis includes the release of nitric oxide (NO) in a cavernous body against a background of 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 cavernous body and contributes to its filling with blood.

Does not have a direct relaxing effect on the isolated cavernous body of a person, but enhances the effect NO by inhibition of PDE-5, which is responsible for the degradation of cGMP. When the system is activated NO/ cGMP on the background of sexual stimulation inhibition of PDE-5 under the influence of sildenafil leads to an increase in the level of cGMP in the cavernous body.

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

Research in vitro showed that sildenafil selective for PDE-5, involved in the development of erection. Its activity against PDE-5 is superior to that of other known phosphodiesterases. Sildenafil is 10 times less selective in relation to PDE-6, which takes part in the photoreference in the retina. At the 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 with respect to PDE-5 is approximately 4000 times greater than its activity against PDE-3 (cycloadenosine monophosphate (cAMP) - 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 reduction of systolic blood pressure in a horizontal position after sildenafil at a dose of 100 mg, on average, 8.3 mm Hg. and diastolic blood pressure is 5.3 mm Hg. Art. This blood pressure reduction due vasodilatory effect of sildenafil possibly associated with an increase in cGMP concentration in vascular smooth muscle cells. A single dose of sildenafil at a dose of 100 mg is not accompanied by a clinically significant changes in the electrocardiogram (ECG) in healthy volunteers. Sildenafil does not affect cardiac output and does not change blood flow through stenosed arteries.

In patients with erectile dysfunction and stable angina, regularly taking antianginal medications (other than nitrate), the time to occurrence of angina during exercise test did not differ significantly after sildenafil versus placebo.

Some patients after 1 hour after ingestion of 100 mg of sildenafil via Munselya Farnsworth-100 test revealed transient changesthe ability to distinguish between shades of color (blue / green), 2 hours after taking sildenafil, these changes were absent. The suggested mechanism for the violation of color perception is the inhibition of PDE-6. Sildenafil does not have an effect on visual acuity or perception of contrast, electroretinogram, intraocular pressure or the diameter of the pupil. It was noted that in patients with early age macular degeneration sildenafil in a dose of 100 mg once did not cause clinically significant changes in vision, evaluated by special tests (visual acuity, Amsler's grating, color difference, Humphrey perimeter and photostress).

A single dose of sildenafil in a dose of 100 mg did not affect the motility or morphology of spermatozoa in healthy volunteers.

More information about clinical trials

In studies on fixed doses of sildenafil, the percentage of men who reported an improvement in erection 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,(84%), mixed erectile dysfunction (77%), organic erectile dysfunction (68%), elderly patients (67%), diabetes mellitus (59%), ischemic heart disease (CHD) (69%), hypertension (68%), transurethral resection of the prostate (61%), radical prostatectomy (43%), spinal cord injury (83%), depression (75%). Analysis of the international index of erectile dysfunction showed that in addition to improving erection, sildenafil treatment also increased the quality of orgasm, allowing satisfaction from sexual intercourse and general satisfaction. The safety and effectiveness of sildenafil persisted with prolonged use.

Pharmacokinetics:

Suction

Sildenafil is rapidly absorbed. The maximum concentration in the blood plasma (C_mOh) when taken on an empty stomach is achieved within 30-120 minutes (median 60 min). Absolute bioavailability, on average, is about 41% (25-63%). Pharmacokinetics (area under the concentration-time curve (AUC) and C_mOh) sildenafil in the recommended dosage range (25-100 mg) is linear.The intake of food reduces the rate of sildenafil absorption, and the time to reach the maximum concentration (TC_mOh) is elongated, on average, by 60 min, C_mOh is reduced, on average, by 29%.

Distribution

Volume of distribution (V_d) sildenafil in the equilibrium state is, on average, 105 liters. After a single oral intake of 100 mg of sildenafil C_mOh is about 440 ng / ml (coefficient of variation (CV) 40%). Because the sildenafil (and its main circulating N-detylated metabolite) are 96% bound to blood plasma proteins, the average plasma concentration of the free sildenafil fraction is 18 ng / ml (38 nM).

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

Metabolism

Sildenafil is metabolized mainly in the liver under the action of microsomal isoenzymes of cytochrome P450: CYP3A4 (main path) and CYP2C9 (additional path). The main circulating active metabolite is formed as a result of N-detylation of sildenafil. The selectivity of the metabolite to phosphodiesterases is comparable to that of sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of unchanged sildenafil.The concentration of metabolite in the blood plasma of healthy volunteers is about 40% of the concentration of sildenafil. N-detylated metabolite undergoes further metabolism, its half-life (T_1/2) is about 4 hours.

Excretion

The total clearance of sildenafil is 41 liters / hour, and the final half-life (T_1/2) - 3-5 hours. Sildenafil is excreted in the form of metabolites, mainly by the intestine (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-detylated metabolite in blood plasma is approximately 90% higher than in young patients (18-45 years). Given the age-related features of binding to blood plasma proteins, the concentration of free sildenafil in blood plasma increases by about 40%.

Impaired renal function

In patients with mild to moderate renal impairment (creatinine clearance 30 to 80 mL / min), the pharmacokinetics of sildenafil after single administration of 50 mg remained unchanged. Average AUC and C_mOh N-detylated metabolite increased by 126% and 73%, respectively, compared with healthy patients of the same age. Due to the high interindividual variability, these differences are statistically insignificant. In severe renal failure (CC less than 30 ml / min), the clearance of sildenafil decreases, which leads to approximately two-fold increase in the value AUC (100%) and C_mOh (88%) compared with those in patients of the same age group without renal dysfunction.

Impaired liver function

In patients with cirrhosis of Class A and B liver according to Child-Pugh classification, clearance of sildenafil decreases, which leads to an increase AUC (84%) and C_mOh (47%) compared with patients with normal liver function of the same age group. The pharmacokinetics of sildenafil in patients with severe impairment of liver function have not been studied.

Indications:

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

Effective only with sexual stimulation.

Contraindications:

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

Simultaneous application with donators of nitric oxide (NO) (eg, amyl nitrite) or nitrates in any form, t. sildenafil can enhance the antihypertensive effect of nitrates (mediated through NO/ cGMP).

Drugs for the treatment of erectile dysfunction, including sildenafil, should not be used in men who are not recommended sexual activity (for example, patients with severe cardiovascular diseases, 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 has not been studied. Therefore, simultaneous use is contraindicated (see section "Special instructions").

Contraindicated simultaneous use with ritonavir.

Loss of vision in one eye due to anterior ischemic optic neuropathy of non-arterial genesis, whether or not it is associated with phosphodiesterase-5 (PDE-5) inhibitors (see section "Specific guidance").

The use is contraindicated for: severe liver function abnormalities, arterial hypotension (blood pressure less than 90/50 mm Hg), recently suffered impaired cerebral circulation or myocardial infarction, phenylketonuria, hereditary retinal dystrophies (hereditary degenerative diseases of the retina), such as retinitis pigmentosa in some patients there are genetic defects of the phosphodiesterase of the retina). the safety of the use of the drug Vizarsin® Ku-tab® in such patients has not been studied.

According to the registered indication, the drug Vizarsin® Ku-tab® is not intended for use in children under 18 years of age and women.

Patients with congenital intolerance to fructose should not take the drug Vizarsin® Ku-tab®, tk. it includes sorbitol.

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) or multiple systemic 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 administration of alpha-adrenoblockers, diseases accompanied by bleeding, or exacerbation of peptic ulcer of the stomach or duodenum, episodes of anterior non-artery ischemic neuropathy of the optic nerve in the anamnesis.

Pregnancy and lactation:

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

Dosing and Administration:

Adults

Preparation Vizarsin® Ku-tab®, tablets dispersible in the oral cavity. Can be used by patients who have difficulty swallowing the tablet, as an alternative to the drug Vizarsin®, whose tablets are film-coated.

Tablets dispersible in the oral cavity are fragile, so they should not be squeezed out through the foil packaging, because they can break. Do not take the tablet with wet hands, because the tablet can begin to dissolve.

Remove the tablet as follows:

Blister containing 1 tablet: Fig. 1

Blister containing 4 tablets:

1. Bend the blister along the line of the rupture.

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

3. Carefully remove the tablet.

4. Then the tablet follows immediately put on the tongue and hold in the mouth for a few seconds until complete resorption, then you can drink it with liquid (Figure 2).

Do not mix the tablet in your mouth with food. When using the drug Vizarsin® Ku-Tab^® with fatty food, the action of the drug can develop later than when it is applied on an empty stomach.

The recommended dose is 50 mg, which is taken if necessary, about 1 hour before the alleged sexual activity. Depending on the effectiveness and tolerability of the dose of the drug Vizarsin^® Ku-Tab^® can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. Maximum Recommended frequency of application of the drug is 1 time per day.

Special patient groups

Elderly patients

Correction of the dose of the drug Vizarsin® Ku-tab^® not required.

Impaired renal function

For mild to moderate severity renal failure (KK 30-80 ml / min) dose adjustment is not is required in severe renal disease Insufficiency (CC less than 30 ml / min) - dose of the drug Vizarsin® Ku-tab^® should be reduce to 25 mg.

Taking into account the effectiveness and tolerability, the dose can be increased to 50 mg and 100 mg.

Impaired liver function

Since the excretion of sildenafil is disrupted in patients with impaired liver function (for example, with cirrhosis of the liver), the dose should be reduced to 25 mg.

Taking into account the effectiveness and tolerability, the dose can be increased to 50 mg and 100 mg.

Simultaneous use with other medicinal products

Simultaneous application ritonavir it is contraindicated.

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

To reduce the likelihood of orthostatic hypotension, it is necessary to achieve a stable state of hemodynamics against the background of therapy alpha-blockers before starting the use of sildenafil. It is necessary to reduce the initial dose of the drug Vizarsin® Ku-tab^® up to 25 mg (see sections "Special instructions" and "Interaction with other medicinal products").

Side effects:

In the use of sildenafil in clinical studies, the most common adverse reactions were: headache, sensation of hot flashes, dyspepsia, visual impairment, nasal congestion, dizziness and color dysfunction (chromatopsy).

Classification of the frequency of development of side effects of the World Health Organization (WHO):

Often	≥1/10
often	from ≥1 / 100 to <1/10
infrequently	from ≥1 / 1000 to <1/100
rarely	from ≥1 / 10000 to <1/1000
rarely	from <1/10000
frequency unknown	can not be estimated from the available data.

In each group, undesirable effects are presented in order of decreasing severity.

Immune system disorders:

rarely: hypersensitivity reactions.

Disturbances from the nervous system:

very often: headache;

often: dizziness;

infrequently: drowsiness, hypoesthesia;

rarely: impaired cerebral circulation, fainting;

frequency unknown: transient ischemic attack, convulsions, relapse of convulsions.

Disturbances on the part of the organ of sight:

often: impaired vision, violation of color perception (chromatopsy);

infrequently: defeat of the conjunctiva, violation of lacrimation, other violations of the organ of vision;

frequency unknown: anterior ischemic optic neuropathy of non-arterial genesis, occlusion of retinal vessels, visual field defect.

Hearing disorders and labyrinthine disorders:

often: vertigo, tinnitus;

rarely: deafness *.

Vascular disorders:

often: a sense of "tides";

rarely: increase / decrease in blood pressure.

Heart Disease:

infrequently: palpitation, tachycardia;

rarely: myocardial infarction, atrial fibrillation;

frequency unknown: ventricular arrhythmia, unstable angina, sudden cardiac death.

Disturbances from the respiratory system, chest and mediastinal organs:

often: nasal congestion;

rarely: epistaxis.

Disorders from the gastrointestinal tract:

often: indigestion;

infrequent: vomiting, nausea, dryness of the oral mucosa.

Disturbances from the skin and subcutaneous tissues:

infrequently: skin rash;

frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Disturbances from musculoskeletal and connective tissue:

infrequently: myalgia.

Disorders from the kidneys and urinary tract:

infrequently: hematuria.

Violations of the genitals and mammary gland:

infrequently: hematospermia, bleeding from the penis;

frequency unknown: priapism, prolonged (prolonged) erection.

General disorders and disorders at the site of administration:

infrequently: chest pain, increased fatigue.

Laboratory and instrumental data:

infrequently: increased heart rate.

* Hearing impairment: sudden deafness. Sudden loss or loss of hearing was observed in a small number of cases in the study of post-marketing application or clinical studies using all PDE-5 inhibitors, including sildenafil.

Overdose:

Symptoms: with a single dose of sildenafil in doses up to 800 mg, adverse reactions are similar to those with lower doses, with the severity and frequency increasing. Taking sildenafil 200 mg did not increase the effectiveness, but the frequency of adverse reactions (headache, sensation of "hot flashes", dizziness, dyspepsia, nasal congestion, visual impairment) increased.

Treatment: symptomatic. Hemodialysis is ineffective, because. sildenafil is firmly bound by plasma proteins and is not excreted by the kidneys.

Interaction:

The effect of other drugs on the pharmacokinetics of sildenafil

Research in vitro:

The metabolism of sildenafil, mainly occurs under the action of cytochrome P450 isoenzymes: CYP3A4 (main path) and CYP2C9 (not the main way). Consequently, inhibitors of these isoenzymes can reduce the clearance of sildenafil.

Research in vivo:

In a population pharmacokinetic analysis of the results of a clinical study, a decrease in the clearance of sildenafil was detected with simultaneous application of inhibitors of the isoenzyme CYP3A4 (such as ketoconazole, erythromycin, cimetidine). There was no increase in the incidence of adverse events in these patients. Patients taking inhibitors isoenzyme CYP3A4, treatment with sildenafil is recommended to begin with a dose of 25 mg.

Simultaneous use of sildenafil (100 mg once daily) with an HIV protease inhibitor - ritonavir (500 mg twice daily) (a potent inhibitor of cytochrome P450) increases C_mOh 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 (with the intake of only sildenafil - 5 ng / ml). Given the results of the pharmacokinetic study, the simultaneous use of sildenafil with ritonavir is contraindicated.

Simultaneous use of an HIV protease inhibitor - saquinavir (inhibitor of isoenzyme CYP3A4) in an equilibrium state (1200 mg three times a day) with sildenafil (100 mg once a day) increases C_mOhand AUC sildenafil by 140% and 210%, respectively. Sildenafil does not affect the pharmacokinetics of saquinavir. Probably more potent inhibitors of isoenzyme CYP3A4 (ketoconazole and itraconazole) have a more pronounced effect on the pharmacokinetics of sildenafil.

With the simultaneous use of sildenafil (100 mg once) with erythromycin (specific inhibitor of the isoenzyme CYP3A4) in the equilibrium state (500 mg twice a day for 5 days), the sildenafil AUC increases by 182%.

In healthy volunteers azithromycin (500 mg per day for 3 days) does not cause changes in pharmacokinetic parameters (AUC, C_max, TS_max, the elimination rate or T_1/2sildenafil or its main circulating metabolite.

Cimetidine (nonspecific inhibitor of the isoenzyme CYP3A4) (800 mg) in healthy volunteers increases the concentration of sildenafil (50 mg) in blood plasma by 56%.

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

Single application antacid (magnesium hydroxide and aluminum hydroxide) does not change the bioavailability of sildenafil.

Although the interaction with the drugs listed below was not specifically studied, the population pharmacokinetic analysis revealed no changes in the pharmacokinetics of sildenafil when applied simultaneously with: inhibitors of the CYP2C9 isoenzyme (such as: tolbutamide, warfarin, phenytoin), inhibitors of isoenzyme CYP2D6 (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 isoenzyme inducers CYP450 (such as: rifampicin and barbiturates).

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

Effect of sildenafil on the pharmacokinetics of other drugs

Research in vitro

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

Research in vivo

Sildenafil has an effect on the system NO/ cGMP, so it increases the hypotensive effect of nitrates. Simultaneous application with donators NO (such as: amyl nitrite) or nitrates in any form is contraindicated.

In some patients, simultaneous use of sildenafil with alpha-blockers can lead to the development of symptomatic arterial hypotension. Arterial hypotension most often develops within 4 hours after taking sildenafil.In clinical studies, the use of sildenafil (25 mg, 50 mg or 100 mg) was studied with the use of an alpha-blocker - doxazosin in doses of 4 mg or 8 mg in patients with benign prostatic hyperplasia and stable hemodynamics. There was an additional decrease in blood pressure in the horizontal position of the patient, on average, by 7/7, 9/5 and 8/4 mm Hg. respectively, and in the vertical position - on average, by 6/6, 11/4 and 4/5 mm Hg. Art. In patients with stable hemodynamics against the background of doxazosin, when added to sildenafil therapy, rare cases of symptomatic orthostatic hypotension, clinically manifested by dizziness, but without the development of syncope, were noted.

The interaction of sildenafil (50 mg) with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by isoenzyme CYP2C9, it is not revealed.

Sildenafil (50 mg) does not cause an additional prolongation of bleeding time when used with acetylsalicylic acid (150 mg).

Sildenafil (50 mg) does not potentiate hypotensive effect ethanol in healthy volunteers (C_mOh ethanol in the blood serum was, on average, 80 mg / dL).

Undesirable effects antihypertensive drugs, including diuretics, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, vasodilators, central action drugs, adrenergic neuron blockers, slow calcium channel blockers and alpha-adrenoblockers, did not differ in patients who used sildenafil or placebo. In a study on the drug interaction of simultaneous application of sildenafil (100 mg) with amlodipine in patients with arterial hypertension, an additional decrease in the horizontal position of the systolic blood pressure by 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 of sildenafil alone in healthy volunteers.

Sildenafil (100 mg) in equilibrium did not affect the pharmacokinetic indices of HIV protease inhibitors: saquinavir and ritonavir, which are the substrates of the isoenzyme CYP3A4.

Special instructions:

Before applying the drug therapy, you need to assess the history and conduct a clinical examination 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).

Drugs for the treatment of erectile dysfunction, including sildenafil, should not be used in men who are not recommended sexual activity.

Sexual activity represents 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, suffered in the last 6 months by myocardial infarction or stroke, arterial hypotension (BP <90/50 mm Hg). Sexual activity is undesirable for patients with life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg).There is no difference in the incidence of myocardial infarction (1.1 per 100 person-years) and mortality from cardiovascular disease (0.3 per 100 person-years) with sildenafil compared with patients in the placebo group.

Cardiovascular complications

In the postmarketing use of sildenafil, serious cardiovascular events (time-related with sildenafil administration) including severe cardiovascular events have been reported. myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhages, 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 - soon after the use of sildenafil without sexual activity. It is impossible to determine the cause-and-effect relationship with any factors.

Decreased blood pressure

Sildenafil has a systemic vasodilator effect, resulting in a slight and transient decrease in blood pressure. Before using sildenafil, the doctor should carefully evaluate the risk of possible unwantedvasodilator effects in patients with the corresponding 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, GOKMP) or a rare syndrome of multiple systemic atrophy, manifested by severe disruption of autonomic BP regulation.

Simultaneous use with alpha-blockers

Sildenafil should be used with caution in patients taking alpha-blockers, since the simultaneous use of sildenafil and alpha-blockers can lead to symptomatic arterial hypotension in selected susceptible patients. Arterial hypotension most often develops within 4 hours after taking sildenafil. PDE-5 inhibitors, including sildenafil, and alpha-adrenoblockers are vasodilators that have an antihypertensive effect. With the simultaneous use of vasodilators, it is possible to develop excessive blood pressure lowering. Patients with unstable hemodynamics against the background of the use of alpha-adrenoblockers are at increased risk of developing symptomatic arterialhypotension with simultaneous use with PDE-5 inhibitors. In order to minimize the risk of orthostatic hypotension in such patients, sildenafil therapy should be started only after stabilization of hemodynamic parameters is achieved against the background of the adrenoblocker administration. Consider the possibility of reducing the initial dose of sildenafil to 25 mg. If the patient is already receiving sildenafil, the use of alpha-blockers should start with a low dose. When used simultaneously with PDE-5 inhibitors, a further reduction in blood pressure is possibly 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 in case of development of orthostatic hypotension (for example, dizziness, pre-stupor, loss of consciousness). When these symptoms appear, the patient should sit down or take a horizontal position.

Visual disturbances

When all PDE-5 inhibitors are used, including sildenafil, in rare cases, development of anterior ischemic optic neuropathy of non-arterial genesis was observed, which was accompanied by deterioration or loss of vision.Most of these patients had risk factors, such as excavating the optic nerve head, age over 50, diabetes, hypertension, ischemic heart disease, hyperlipidemia and smoking. The causal relationship between the use of PDE5 inhibitors and the development of anterior ischemic optic neuropathy of non-arterial genesis has not been established. In case of sudden loss of vision, the patient should be given immediate medical attention and stop using Vizarsin® Ku-tab®.

A small number of patients with hereditary pigment retinitis have genetically caused defects of the phosphodiesterase of the retina. The safety of sildenafil in patients with retinitis pigmentosa has not been studied, therefore, the use in these patients is contraindicated.

Hearing impairment

In patients with the use of all PDE-5 inhibitors, including sildenafil, there were cases of sudden decrease or loss of hearing. Most of these patients had risk factors for reducing or hearing loss. Correlations between the use of PDE-5 inhibitors and hearing impairment have not been revealed. In the event of sudden loss or loss of hearing, stop using Vizarsin® Ku-tab® and contact a doctor immediately.The causal relationship between the use of PDE-5 inhibitors and sudden decrease or loss of hearing is not established.

Bleeding

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

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

The safety and efficacy 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 preparation Vizarsin® Ku-tab® is not intended for use in women.

Special information on excipients

Patients with congenital intolerance to fructose should not take the drug Vizarsin® Ku-tab®, tk. it includes sorbitol.

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

Effect on the ability to drive transp. cf. and fur:

Data on the adverse effects of the drug Vizarsin® Ku-Tab® at the recommended doses on the ability to drive or work with the mechanisms there. Patients should evaluate the individual susceptibility to taking Vizarsin® Ku-Tab®, possibly a decrease in blood pressure, the development of visual impairment (chromatopsy, blurred vision) and dizziness, especially at the beginning of treatment and when changing the dosage regimen.

Form release / dosage:

Tablets dispersible in the oral cavity, 25 mg, 50 mg and 100 mg.

Packaging:

By 1 or 4 tablets in a blister of the combined material OPA / Al / PVC, PET / Al foil (OPA/Al/PVC, PET / Al peel off foil).

For 1, 2 blisters (a blister for 1 tablet) or 1, 2, 3 blisters (blister for 4 tablets) are placed in a pack of cardboard along with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002481

Date of registration:27.05.2014

Expiration Date:27.05.2019

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp