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

Excipients: cellulose microcrystalline (avicel PH 101) 36.88 mg, calcium hydrophosphate 51.00 mg, croscarmellose sodium 6.00 mg, hypromellose 4.50 mg, microcrystalline cellulose (avicel PH 102) 15.00 mg, magnesium stearate 1.50 mg ;

film sheath: * Opadrai II 31K58875 white 5.00 mg.

For one tablet of 50 mg:

active substance: sildenafil citrate 70.24 mg (equivalent to sildenafil 50.00 mg);

Excipients: cellulose microcrystalline (avicel PH 101) 73.76 mg, calcium hydrophosphate 102.00 mg, croscarmellose sodium 12.00 mg, hypromellose 9.00 mg, microcrystalline cellulose (avicel PH 102) 30.00 mg, magnesium stearate 3.00 mg ;

film sheath: * Opadrai II 31K58875 white 10.00 mg.

For one tablet, 100 mg:

active substance: sildenafil citrate 140.48 mg (equivalent to sildenafil 100.00 mg);

Excipients: cellulose microcrystalline (avicel PH 101) 147.52 mg, calcium hydrophosphate 204.00 mg, croscarmellose sodium 24.00 mg, hypromellose 18.00 mg, microcrystalline cellulose (Avicel PH 102) 60.00 mg, magnesium stearate 6,00 mg;

film sheath: * Opadrai II 31K58875 white 20.00 mg.

* Opadrai II 31K58875 white - a mixture of hypromellose 28%, lactose monohydrate 40%, titanium dioxide 24%, triacetin 8%.

Description:

Tablets 25 mg: oval, biconvex tablets, covered with a film shell of white or almost white color, engraved on one side with the number 25.

50 mg tablets: oval, biconvex tablets, covered with a white or almost white film shell, engraved on one side with the number 50.

Tablets 100 mg: oval, biconvex tablets, covered with a film shell of white or almost white color, with a digit engraved on one side 100.

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 cyclic guanosine monophosphate (cGMP) -specific phosphodiesterase type 5 (PDE5).

Mechanism of action

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

Sildenafil does not have a direct relaxing effect on an isolated cavernous human body, but enhances the effect NO by inhibiting PDE5, which is responsible for the degradation of cGMP.

Sildenafil is selective for PDE5 under conditions in vitro, its activity against PDE5 is higher than that of other known isoenzymes of phosphodiesterase: PDE6 - 10 times, PDE1 - more than 80 times, PDE2, PDE4, PDE7-FDE11 - more than 700 times.

Sildenafil is 4000 times more selective for PDE5 than with PDE3, which is of paramount importance, since PDE3 is one of the key enzymes in the regulation of myocardial contractility.

A mandatory condition for the effectiveness of sildenafil is sexual stimulation.

Clinical data

Cardiac examinations

The use of sildenafil in doses up to 100 mg did not lead to clinically significant changes in the electrocardiogram (ECG) in healthy volunteers.The maximum decrease in systolic blood pressure (SBP) in the "lying" position after taking sildenafil in a dose of 100 mg was 8.3 mm Hg. st, and diastolic blood pressure (DBP) - 5.3 mm Hg. Art. A more pronounced but also transient effect on blood pressure (BP) was noted in patients taking nitrates (see the sections "Contraindications" and "Interaction with other drugs").

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

In a double-blind, placebo-controlled study, 144 patients with erectile dysfunction and stable angina,taking antianginal drugs (except nitrates), performed physical exercises until the moment when the severity of symptoms of angina decreased. The duration of the exercise was significantly longer (19.9 seconds, 0.9-38.9 seconds) in patients taking sildenafil in a single dose 100 mg compared with patients receiving placebo.

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

Research of visual disorders

In some patients, an easy and transient impairment in the ability to distinguish between shades of color (blue / green) was detected 1 hour after taking 100 mg of sildenafil with the Farnsworth-Munssel test 100. After 2 hours after taking sildenafil, these changes were absent.It is believed that impaired color vision is caused by inhibition of PDE6, which is involved in the process of transmitting light in the retina of the eye. Sildenafil did not affect visual acuity, contrast perception, electroretinogram, intraocular pressure or pupil diameter.

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

Efficiency

The efficacy and safety of sildenafil was evaluated in 21 randomized, double-blind, placebo-controlled studies of up to 6 months in 3000 patients aged 19 to 87 years with erectile dysfunction of different etiology (organic, psychogenic or mixed).

Efficacy was assessed globally with the use of the diary of erections, the international index of erectile function (validated questionnaire on the status of sexual function), and a partner survey.The effectiveness of sildenafil, defined as the ability to achieve and maintain an erection sufficient for a satisfactory sexual intercourse, has been demonstrated in all studies conducted and has been confirmed in long-term studies lasting 1 year.

In studies using a fixed dose, the ratio of patients who reported that the therapy improved their erection was 62% (a dose of sildenafil 25 mg), 74% (a dose of sildenafil 50 mg) and 82% (a dose of sildenafil 100 mg) compared to 25% in the placebo group. Analysis of the international index of erectile function showed that, in addition to improving erection, sildenafil treatment also increased the quality of orgasm, allowing satisfaction from sexual intercourse and general satisfaction.

According to generalized data, 59% of patients with diabetes, 43% of patients undergoing radical prostatectomy and 83% of patients with spinal cord injuries (compared with 16%, 15% and 12% in the placebo group, respectively) were among the patients reporting improvement in erectile dysfunction with sildenafil. ).

Pharmacokinetics:

The pharmacokinetics of sildenafil in the recommended dose range is linear.

Suction

After oral administration sildenafil quickly absorbed. Absolute bioavailability averages about 40% (from 25% to 63%). In conditions in vitro Sildenafil at a concentration of about 1.7 ng / ml (3.5 nM) suppresses human PDE5 activity by 50%. After a single dose of sildenafil in a dose of 100 mg, the average maximum concentration (C_mOh) of free sildenafil in male blood plasma is about 18 ng / ml (38 nM). FROM_mOh when taking sildenafil inside fasting is achieved on average for 60 minutes (from 30 minutes to 120 minutes). At reception simultaneously with fat food the speed of absorption decreases: With_mOh decreases by an average of 29%, and the time to reach the maximum concentration (TC_mOh) is increased by 60 min, but the degree of absorption does not change significantly (area under the pharmacokinetic curve "concentration-time" (AUC) is reduced by 11%).

Distribution

The volume of distribution of sildenafil in the equilibrium state averages 105 liters. The connection between sildenafil and its main circulating N-detyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of sildenafil. Less than 0.0002% of the dose of sildenafil (an average of 188 ng) was found in the sperm 90 minutes after taking the drug.

Metabolism

Sildenafil is metabolized mainly in the liver under the action of isoenzyme CYP3A4 (main path) and isoenzyme CYP2C9 (additional path). The main circulating active metabolite formed as a result of N-detylation of sildenafil, undergoes further metabolism. The selectivity of this metabolite in relation to PDE is comparable to that of sildenafil, and its activity against PDE5 under conditions in vitro is about 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. N-detyl metabolite is subjected to further metabolism, its half-life (T₁_/₂) is about 4 hours.

Excretion

The total clearance of sildenafil is 41 l / h, and the final T_1/2- 3-5 hours. After oral administration, as well as after intravenous administration sildenafil is excreted as metabolites, mainly by the intestine (about 80% of the dose taken internally) and to a lesser extent by the kidneys (about 13% of the dose taken internally).

Pharmacokinetics in specific patient groups

Elderly patients

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

Impaired renal function

In mild (creatinine clearance 50 to 80 ml / min) and moderate (KK 30-49 ml / min) renal failure, the pharmacokinetics of sildenafil after single ingestion at a dose of 50 mg does not change.

In severe renal failure (CC <30 ml / min), the clearance of sildenafil decreases, which leads to an approximately two-fold increase in the value AUC (100%) and C_mOh (88%) in comparison with those in patients of the same age group with normal renal function.

Impaired liver function

In patients with cirrhosis of the liver (class A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase in the value AUC (84%) and C_mOh (47%) compared with those in patients of the same age group with normal liver function. The pharmacokinetics of sildenafil in patients with severe hepatic impairment (Child-Pugh class C) has 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.

Sildenafil is effective only with sexual stimulation.

Contraindications:

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

Use in patients who receive permanently or intermittently donators of nitric oxide, organic nitrates or nitrites in any form, since sildenafil strengthens the hypotensive effect of nitrates (see section "Interaction with other drugs").

The safety and efficacy of the drug Vizarsin® with simultaneous use with other treatments for erectile dysfunction have not been studied, so the use of such combinations is not recommended (see section "Special instructions").

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

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

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

Carefully:

Anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease) (see section "Special instructions"), diseases predisposing to the development of priapism (sickle-cell anemia, multiple myeloma, leukemia, thrombocythemia) (see.Special instructions "), diseases accompanied by bleeding, exacerbation of peptic ulcer, hereditary retinitis pigmentosa (see section" Special instructions "), chronic heart failure, unstable angina transferred to the last 6 months myocardial infarction, stroke or life threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg) or arterial hypotension (BP <90/50 mm Hg) (see section "Special instructions").

Pregnancy and lactation:

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

Dosing and Administration:

Inside.

The recommended dose for most adult patients is 50 mg about 1 hour before sexual activity. With regard to efficacy and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of application is 1 time per day.

Impaired renal function

With a mild and moderate degree of renal failure (CK 30-80 ml / min) dose adjustment is not required, with severe renal failure (CK <30 ml / min) - dose of sildenafil should be reduced to 25 mg.

Impaired liver function

Since the excretion of sildenafil is disrupted in patients with liver damage (in particular, with cirrhosis), the dose of Vizarsin® should be reduced to 25 mg.

Simultaneous use with other drugs

When used simultaneously with ritonavir, the maximum single dose of the drug Vizarsin® should not exceed 25 mg, and the frequency of application is 1 every 48 hours (see section "Interaction with other drugs").

With simultaneous application with inhibitors of isoenzyme CYP3A4 (erythromycin, saquinavir, ketoconazole, itraconazole) the initial dose of the drug Vizarsin® should be 25 mg (see section "Interaction with other drugs"). To minimize the risk of orthostatic hypotension in patients taking α-blockers, the use of Vizarsin® should be started only after stable hemodynamics have been achieved in these patients. It should also consider the desirability of reducing the initial dose of sildenafil (see sections "Special instructions" and "Interaction with other drugs").

Elderly patients

Correction of the dose of Vizarsin® is not required.

Side effects:

The most common side effects were headache and "hot flashes".

Usually the side effects of sildenafil are weak or moderate and are transient.

In studies using a fixed dose, it has been shown that the incidence of certain adverse events increases with increasing doses.

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

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

Immune system disorders:

infrequently: reactions of increased sensitivity (including skin rash), allergic reactions.

Disturbances on the part of the organ of sight:

often: blurred vision, impaired vision, cyanopsy;

infrequent: pain in the eyes, photophobia, photopsy, chromatopsy, reddening of eyes / injections of sclera, change in brightness of light perception, mydriasis, conjunctivitis, eye hemorrhage, cataracts, tearing device malfunction;

rarely: edema of the eyelids and adjacent tissues, a feeling of dryness in the eyes, the presence of rainbow circles in the field of view around the light source,increased eye fatigue, vision of objects in yellow color (xanthopsia), vision of objects in red (erythropsy), conjunctival hyperemia, irritation of the mucous membrane of the eyes, unpleasant sensations in the eyes;

frequency unknown: non-arterial anterior ischemic optic nerve neuropathy (NPINZN), retinal vein occlusion, visual field defect, diplopia *, temporary loss of vision or visual acuity, increased intraocular pressure, retinal edema, retinal vascular disease, vitreous detachment / vitreous tract.

Hearing disorders and labyrinthine disturbances:

infrequently: sudden decrease or loss of hearing, tinnitus, pain in the ears.

Violations from the heart and blood vessels:

often: "hot flashes";

infrequent: tachycardia, palpitation, decreased blood pressure, increased heart rate, unstable angina, atrioventricular blockade, myocardial ischemia, cerebral vascular thrombosis, cardiac arrest, heart failure, abnormalities in ECG readings, cardiomyopathy;

rarely: atrial fibrillation.

Violations of the blood and lymphatic system:

infrequently: anemia, leukopenia.

Disorders from the metabolism and nutrition:

infrequent: thirst, swelling, gout, uncompensated diabetes mellitus, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

Disturbances from the respiratory system, chest and mediastinal organs:

often: nasal congestion;

infrequently: epistaxis, rhinitis, asthma, dyspnoea, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum discharge, increased cough;

rarely: a feeling of tightness in the throat, dryness of the mucous membrane of the nasal cavity, swelling of the nasal mucosa.

Disorders from the gastrointestinal tract:

often: nausea, dyspepsia;

infrequently: gastroesophageal reflux disease, vomiting, abdominal pain, dryness of oral mucosa, glossitis, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, deviation of "liver" functional tests from normal, rectal bleeding;

rarely: hypoesthesia of the oral mucosa.

Disturbances from musculoskeletal and connective tissue:

often: back pain;

infrequently: myalgia, pain in the extremities, arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis,synovitis.

Disorders from the kidneys and urinary tract:

infrequently: cystitis, nocturia, urinary incontinence, hematuria.

Violations of the genitals and mammary gland:

infrequently: enlargement of the mammary glands, violation of ejaculation, swelling of the genitals, anorgasmia, hematospermia, damage to the tissues of the penis;

rarely: a prolonged erection and / or priapism.

Disorders from the nervous system and the psyche:

very often: headache;

often: dizziness;

infrequently: drowsiness, migraine, ataxia, muscle hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression symptoms, insomnia, unusual dreams, increased reflexes, hypoesthesia;

rarely: convulsions *, repeated convulsions *, fainting.

Disturbances from the skin and subcutaneous tissues:

infrequently: skin rash, urticaria, herpes simplex, pruritus, increased sweating, skin ulceration, contact dermatitis, exfoliative dermatitis;

frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis.

General disorders and disorders at the site of administration:

infrequent: fever, facial swelling, photosensitivity reaction, shock, asthenia, increased fatigue, pain of various localizations, chills,casual falls, pain in the chest, accidental trauma;

rarely: irritability.

* Adverse effects identified during post-marketing research.

Cardiovascular complications

During the postmarketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension), which had a temporary connection with the use of sildenafil. Most of these patients, but not all of them, had risk factors for cardiovascular complications.

Many of these adverse events were observed soon after sexual activity, and some of them were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct link between the observed undesirable phenomena and these or other factors.

Visual disorders

In rare cases, during the post-marketing application of all PDE5 inhibitors, including sildenafil, they reported on NPINZN, a rare disease and the reason for the reduction or loss of vision. Most of these patients had risk factors, in particular, a reduction in the ratio of the diameter of the excavation and the optic disc ("stagnant disk"), age over 50 years, diabetes, hypertension, coronary heart disease, hyperlipidemia and smoking.

In the observational study, it was assessed whether the recent use of preparations of the class of PDE5 inhibitors with the acute onset of NPINZH was related. The results indicate an approximately twofold increase in the risk of NPINZ within 5 T_1/2 after using the inhibitor PDE5. According to the published literature, the annual incidence of NPIH is 2.5-11.8 cases per 100 000 men aged ≥ 50 years in the general population.

It should be recommended to patients in the event of a sudden loss of vision to stop sildenafil therapy and immediately consult a doctor.

Persons who already had a case of NPINZ have an increased risk of recurrence of NPINZN. Therefore, the physician should discuss this risk with such patients,and discuss with them the potential risk of adverse effects of PDE5 inhibitors. PDE5 inhibitors, including sildenafil, these patients should be used with caution and only in situations where the expected benefit exceeds the risk.

When using the drug Vizarsin® in doses exceeding the recommended, undesirable phenomena were similar to those noted above, but were usually more common.

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 strongly binds to blood plasma proteins and is not excreted by the kidneys.

Interaction:

The effect of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of isoenzymes CYP3A4 (main path) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inductors, respectively, increase the clearance of sildenafil. There was a decrease in clearance of sildenafil with simultaneous application of inhibitors of isoenzyme CYP3A4 (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the isoenzyme CYP3A4, with simultaneous admission with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma by 56%. A single dose of 100 mg of sildenafil concurrently with erythromycin (500 mg / day, 2 times a day for 5 days), a mild isoenzyme inhibitor CYP3A4, on the background of achieving a constant concentration of erythromycin in the blood, leads to an increase AUC sildenafil by 182%. With the simultaneous administration of sildenafil (once 100 mg) and saquinavir (1200 mg / day 3 times a day), an HIV protease inhibitor and an isoenzyme CYP3A4, against the background of achieving a constant concentration of saquinavir in the blood C_mOh sildenafil increased by 140%, a AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir. More potent inhibitors of isoenzyme CYP3A4, such as ketoconazole and itraconazole, can cause and stronger changes in the pharmacokinetics of sildenafil.

Simultaneous use of sildenafil (once 100 mg) and ritonavir (500 mg twice a day), an HIV protease inhibitor and a strong inhibitor of cytochrome P450, against the background of achieving a constant concentration of ritonavir in the blood leads to an increase in C_mOhsildenafil by 300% (4 times), a AUC on 1000% (in 11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng / ml (after a single application of one sildenafil - 5 ng / ml).

If sildenafil take in recommended doses of patients receiving simultaneously strong inhibitors of the isoenzyme CYP3A4, then C_mOh free sildenafil does not exceed 200 nM, and the drug is well tolerated.

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

In studies involving healthy volunteers with the simultaneous use of bosentan, an endothelin receptor antagonist (a moderate isoenzyme inducer CYP3A4, CYP2C9 and, possibly, CYP2C19) at an equilibrium concentration (125 mg twice daily) and sildenafil at an equilibrium concentration (80 mg 3 times a day) there was a decrease AUC and C_mOh sildenafil at 62.6% and 52.4%, respectively.The use of sildenafil increased AUC and C_mOh bosentan by 49.8% and 42%, respectively. It is assumed that the simultaneous use of sildenafil with powerful isoenzyme inducers CYP3A4, such as rifampicin, can lead to a greater decrease in the concentration of sildenafil in the blood plasma.

Inhibitor inhibitors CYP2C9 (tolbutamide, warfarin), isoenzyme CYP2D6 (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists do not affect the pharmacokinetics of sildenafil.

Azithromycin (500 mg / day for 3 days) has no effect on AUC, FROM_mOh, TS_mOh, the rate constant of excretion and T_1/2sildenafil or its main circulating metabolite.

Effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 (IC₅₀ > 150 μmol). When taking sildenafil in the recommended doses of its C_max is about 1 μmol, so it is unlikely that sildenafil can affect the clearance of the substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter and with their use for acute indications. In this regard, the use of sildenafil concomitantly with nitrates or donators NO it is contraindicated.

With simultaneous administration of α-adrenoblocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the mean additional decrease in SBP / DBP in the prone position was 7 / 7 mm Hg. st., 9/5 mm Hg. Art. and 8/4 mm Hg. st., respectively, and in the standing position - 6/6 mm Hg. st., 11/4 mm Hg. Art. and 4/5 mm Hg. art., respectively. It is reported that rare cases of development in such patients of symptomatic orthostatic hypotension, manifested in the form of dizziness (without fainting). In certain sensitive patients receiving α-blockers, simultaneous use of sildenafil can lead to symptomatic arterial hypotension.

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

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

Simultaneous use of sildenafil in an equilibrium state (80 mg 3 times a day) leads to an increase AUC and C_mOh bosentane (125 mg 2 times per day) by 49.8% and 42%, respectively.

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

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

In patients with arterial hypertension, signs of interaction between sildenafil (100 mg) with amlodipine was not detected.

The average additional decrease in blood pressure in the "lying" position is 8 mm Hg. Art. (SBP) and 7 mm Hg. Art. (DBP).

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

Special instructions:

To diagnose erectile dysfunction, determine their possible causes and choose an adequate treatment, you must collect a complete medical history and conduct a thorough physical examination.

Means for treating erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis,Peyronie's disease) or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia) (see "With caution").

During postmarketing studies, cases of development of prolonged erection and priapism were reported. If the erection persists for more than 4 hours, you should immediately seek medical help. If priapism therapy has not been performed immediately, it can lead to damage to the penile tissue and an irreversible loss of potency.

Drugs intended for the treatment of erectile dysfunction should not be used in men for whom sexual activity is undesirable. Sexual activity represents a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient to a cardiovascular system examination. Sexual activity is undesirable in patients with heart failure, unstable angina, transferred to the last 6 months myocardial infarction or stroke, life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg.or arterial hypotension (BP <90/50 mm Hg) (see the section "With caution"). In clinical studies, there was no difference in the incidence of myocardial infarction (1,1 on 100 people per year) or the death rate from cardiovascular diseases (0.3 per 100 people per year) in patients who received sildenafil, compared with patients receiving placebo.

Cardiovascular complications

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

Arterial hypotension

Viagra has systemic vasodilatory effect resulting in a transient decrease in blood pressure that is not clinically significant phenomenon and does not lead to any consequences in most patients. Nevertheless, prior to the appointment of the drug Vizarsin®, the physician should carefully evaluate the risk of possible undesirable manifestations of vasodilating action in patients with the corresponding diseases, especially against the background of sexual activity.

Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with a rare syndrome of multiple systemic atrophy, manifested severe violation of the regulation of blood pressure from the autonomic nervous system.

Since the simultaneous use of sildenafil and α-adrenoblockers can lead to symptomatic arterial hypotension in selected sensitive patients,preparation Vizarsin ® should be used with caution in patients taking α-blockers (see section "Interaction with other drugs"). To minimize the risk of orthostatic hypotension in patients taking α-adrenoblockers, the use of Vizarsin® should be started only after stabilization of hemodynamics in these patients has been achieved. It should also consider the desirability of reducing the initial dose of the drug Vizarsin® (see section "Method of administration and dose"). The doctor should inform patients about what actions should be taken in case of symptoms of orthostatic hypotension.

Visual disorders

In rare cases, during the post-marketing use of all PDE5 inhibitors, including sildenafil, non-arteritis anterior ischemic neuropathy of the optic nerve was reported - a rare disease and the cause of a decrease or loss of vision. Most of these patients had risk factors, in particular, a reduction in the ratio of the diameter of the excavation and the optic disc ("stagnant disk"), age over 50 years, diabetes, hypertension, coronary heart disease, hyperlipidemia and smoking.

In the observational study, it was assessed whether the recent use of preparations of the class of PDE5 inhibitors with the acute onset of NPINZH was related. The results indicate an approximately twofold increase in the risk of NPINZ within 5 T_1/2after using the inhibitor PDE5. According to the published literature, the annual incidence of NPIH is 2.5-11.8 cases per 100 000 men aged ≥ 50 years in the general population.

It should be recommended to patients in the event of a sudden loss of vision to stop sildenafil therapy and immediately consult a doctor. Persons who already had a case of NPINZ have an increased risk of recurrence of NPINZN. Therefore, the physician should discuss this risk with such patients, and discuss with them the potential chance of adverse effects of PDE5 inhibitors. PDE5 inhibitors, including sildenafil, these patients should be used with caution and only in situations where the expected benefit exceeds the risk.

A small number of patients with hereditary pigment retinitis have genetically determined impairments of the functions of the retina phosphodiesterase.Information on the safety of sildenafil in patients with retinitis pigmentosa absent, therefore, the drug Vizarsin® should be used with caution (see section "With caution").

Hearing Impairment

Some postmarketing studies report cases of sudden deterioration or hearing loss associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden deterioration or loss of hearing. The causal relationship between the use of PDE5 inhibitors and sudden deterioration of hearing or loss of hearing is not established. In the event of sudden hearing impairment or hearing loss when taking Vizarsin®, immediately consult a physician.

Bleeding

Sildenafil increases the antiaggregant effect of sodium nitroprusside, donator NO, on human platelets in conditions in vitro.

Data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of peptic ulcer of the stomach and duodenum are absent, therefore, the drug Vizarsin in these patients should be used with caution (see the section "With caution").

The frequency of nasal bleeding in patients with pulmonary hypertension associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%). In patients who received sildenafil in combination with a vitamin K antagonist, the frequency of nasal bleeding was higher (8,8%) than in patients who did not take a vitamin K antagonist (1.7%).

Simultaneous use with other drugs for the treatment of erectile dysfunction

The safety and efficacy of Vizarsin® concomitantly with other PDE5 inhibitors or other drugs for the treatment of pulmonary hypertension containing sildenafil or other means of treating erectile dysfunction have not been studied, so the use of such combinations is not recommended (see the section "Contraindications").

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

Since the development of dizziness, the reduction of blood pressure, the development of chromatopsy, blurred vision, etc., side effects, when taking sildenafil, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.Also, you should carefully consider the individual effect of the drug Vizarsin ® in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Form release / dosage:

Film coated tablets, 25 mg, 50 mg and 100 mg.

Packaging:

1, 2, 4 tablets in a blister of PVC-aluminum foil.

1 blister (1, 2, 4 tablets), 2 or 3 blisters (4 blisters each) 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:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000475

Date of registration:01.03.2011 / 02.03.2016

Expiration Date:Unlimited

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

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Vizarsin® (Vizarsin®)