Vizarsin, pills 100mg, 4pcs

Composition

per 25 mg/50 mg/100 mg tablet:

Active ingredient:

Sildenafil Citrate 35.12 mg (equivalent to sildenafil 25.00 mg)/Sildenafil Citrate 70.24 mg (equivalent to sildenafil 50.00 mg)/Sildenafil Citrate 140.48 mg (equivalent to sildenafil 100.00 mg)

Excipients: microcrystalline cellulose (avicel PH 101), calcium hydrophosphate, croscarmellose sodium, hypromellose, microcrystalline cellulose (avicel PH 102), magnesium stearate

Film shell

* Opadray II 31K58875 white

* Opadray II 31K58875 white-a mixture of hypromellose, lactose monohydrate, titanium dioxide, triacetin.

Pharmacological action

of erectile dysfunction treatment agent-PDE5-inhibitor

Clinical Pharmacology

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 cGMP levels, subsequent relaxation of the smooth muscle tissue of the cavernous body, and increased blood flow.

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

Sildenafil is selective for PDE5 in vitro, its activity against PDE5 exceeds that of other known phosphodiesterase isoenzymes: PDE6-by 10 times, PDE1-by more than 80 times, PDE2, PDE4, PDE7-PDE11-by more than 700 times. Sildenafil is 4000 times more selective for PDE5 compared to PDE3, which is of crucial importance, since PDE3 is one of the key enzymes in the regulation of myocardial contractility.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

Clinical data

Cardiological studies

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 supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg, and diastolic blood pressure (DBP) – 5.3 mm Hg. A more pronounced, but also transient effect on blood pressure (BP) was observed 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 coronary 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 disrupt blood flow in stenosed coronary arteries, and also led to an increase (by approximately 13%) in adenosine-induced coronary flow in both stenosed and intact coronary arteries.

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

A randomized, double-blind, placebo-controlled study examined the effect of varying the dose of sildenafil (up to 100 mg) in men (n = 568) with erectile dysfunction and hypertension taking more than two antihypertensive drugs. Sildenafil improved erections in 71% of men compared to 18% in the placebo group. The incidence of adverse events was comparable to that in other patient groups, as well as in those taking more than three antihypertensive drugs.

Visual impairment studies

In some patients,1 hour after taking sildenafil at a dose of 100 mg, the Farnsworth-Munsel 100 test revealed a slight and transient violation of the ability to distinguish shades of color (blue/green).2 hours after taking sildenafil, these changes were absent. Color vision disorders are thought to be caused by inhibition of PDE6, which is involved in retinal light transmission. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure, or pupil diameter.

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

Efficiency

The efficacy and safety of sildenafil were evaluated in 21 randomized, double-blind, placebo-controlled trials lasting up to 6 months in 3,000 patients aged 19 to 87 years with erectile dysfunction of various etiologies (organic, psychogenic, or mixed). Efficacy was evaluated globally using the erectile Diary, the International Index of erectile Function (validated sexual function questionnaire), and the partner survey. The efficacy of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all studies conducted and has been confirmed in long-term studies lasting 1 year. In fixed-dose studies, the ratio of patients who reported that therapy improved their erections was 62% (25 mg sildenafil),74% (50 mg sildenafil), and 82% (100 mg sildenafil), compared to 25% in the placebo group. Analysis of the international index of erectile function showed that in addition to improving erections, treatment with sildenafil also increased the quality of orgasm, allowed achieving satisfaction from sexual intercourse and overall satisfaction.

Overall,59% of patients with diabetes mellitus,43% of patients who underwent radical prostatectomy, and 83% of patients with spinal cord injuries reported improved erections during treatment with sildenafil (compared to 16%,15%, and 12% in the placebo group, respectively).

Pharmacokinetics

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

Suction

After oral use, sildenafil is rapidly absorbed. Absolute bioavailability averages about 40% (from 25% to 63%). Under in vitro conditions, sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) suppresses the activity of human PDE5 by 50%. After a single 100 mg dose of sildenafil, the average maximum concentration (cmax) of free sildenafil in the blood plasma of men is about 18 ng / ml (38 nM). _Cmax when taking sildenafil orally on an empty stomach is reached on average within 60 minutes (from 30 minutes to 120 minutes). When taken simultaneously with fatty foods, the absorption rate decreases: Cmax decreases by an average of 29%, and the time to reach the maximum concentration (TC_max) increases by 60 minutes, but the degree of absorption does not change significantly (the area under the pharmacokinetic curve “concentration-time” (AUC) decreases by 11%).

Distribution

The volume of distribution of sildenafil at steady state averages 105 liters.

The association of sildenafil and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of sildenafil. Less than 0.0002% of the sildenafil dose (average 188 ng) was detected in semen 90 minutes after taking the drug.

Metabolism

Sildenafil is mainly metabolized in the liver by the CYP3A4 isoenzyme (main pathway) and the CYP2C9 isoenzyme (secondary pathway). The main circulating active metabolite formed as a result of N-demethylation of sildenafil undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of sildenafil, and its activity against PDE5 in vitro is about 50% of that of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism, its half-life (T_1/2) is about 4 hours.

Deduction

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

Pharmacokinetics in special patient groups

Elderly patients

In healthy elderly patients (older than 65 years), 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 50-80 ml/min) and moderate (creatinine clearance 30-49 ml/min) renal insufficiency, the pharmacokinetics of sildenafil after a single oral dose of 50 mg do not change. In severe renal insufficiency (creatinine clearance < 30 ml/min), sildenafil clearance decreases, resulting in approximately a twofold increase in AUC (100%) and_cmax (88%) compared to those in patients of the same age group with normal renal function.

Impaired liver function

In patients with cirrhosis of the liver (Child-Pugh class A and B), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and_Cmax (47%) compared to 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) have not been studied.

Indications

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

Sildenafil is only effective with sexual stimulation.

Use during pregnancy and lactation

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

Contraindications

Hypersensitivity to sildenafil or any other component of the drug.

Use in patients receiving continuous or intermittent nitric oxide donors, organic nitrates or nitrites in any form, as sildenafil increases the hypotensive effect of nitrates (see the section “Interaction with other drugs”).

Concomitant use of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulants, such as riociguat, is contraindicated, as this may lead to symptomatic hypotension (see section “Interaction with other drugs”).

The safety and efficacy of Visarsin® when used concomitantly with other drugs for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended (see the section “Special instructions”).

Severe hepatic insufficiency (Child-Pugh class C).

Simultaneous use of ritonavir.

Severe cardiovascular diseases (severe heart failure, unstable angina, stroke or myocardial infarction in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP >

Patients with episodes of non-arteriitic anterior ischemic optic neuropathy with loss of vision in one eye.

Hereditary retinitis pigmentosa (see the section “Special instructions”).

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

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

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

Side effects

The most common side effects were headache and hot flashes.

Usually, the side effects of sildenafil are mild to moderate and transient.

Fixed-dose studies have shown that the frequency of some adverse events increases with increasing dose.

Classification of the incidence of side effects recommended by the World Health Organization (WHO):

very common ≥ 1/10

common ≥ 1/100 to < 1/10

uncommon ≥ 1/1000 to < 1/100

rare ≥ 1/10000 to < 1/1000

very rare < 1/10000

frequency unknown cannot be estimated based on available data.

Immune system disorders:

infrequently: hypersensitivity reactions (including skin rash), allergic reactions.

Visual disturbances:

frequent: blurred vision, blurred vision, cyanopsia;

infrequent: eye pain, photophobia, photopsia, chromatopsia, eye redness/injection of the sclera, changing the brightness of cvetovete, mydriasis, conjunctivitis, hemorrhage in the tissue of the eye, cataract, a disorder of the lacrimal apparatus;

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

the frequency is unknown: porteriana anterior ischemic neuropathy of the optic nerve (NESN), occlusion of retinal veins, defect of the visual fields, diplopia*, temporary vision loss or decreased visual acuity, increased intraocular pressure, retinal edema, vascular diseases of the retina, vitreous detachment/vitreal traction.

Hearing disorders and labyrinth disorders:

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

Disorders of the heart and blood vessels:

often: hot flashes;

infrequently: tachycardia, palpitation, decreased blood pressure, increased blood pressure, increased heart rate, unstable angina, atrioventricular block, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, ECG abnormalities, cardiomyopathy;

rarely: atrial fibrillation, sudden cardiac death?, ventricular arrhythmia?.

Disorders of the blood and lymphatic system:

infrequently: anemia, leukopenia.

Metabolic and nutritional disorders:

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

Respiratory, thoracic and mediastinal disorders:

common: nasal congestion;

infrequent: nosebleeds, rhinitis, asthma, dyspnoea, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum volume, increased cough;

rarely: feeling of tightness in the throat, dryness of the nasal mucosa, swelling of the nasal mucosa.

Disorders of the gastrointestinal tract:

often: nausea, dyspepsia;

infrequently: gastroesophageal reflux disease, vomiting, abdominal pain, dry oral mucosa, glossitis, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, deviation of “liver” functional tests from the norm, rectal bleeding;

rarely: hypesthesia of the oral mucosa.

Musculoskeletal and connective tissue disorders:

common: back pain;

uncommon: myalgia, limb pain, arthritis, osteoarthritis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.

Kidney and urinary tract disorders:

infrequently: cystitis, nocturia, urinary incontinence, hematuria.

Genital and breast disorders:

infrequently: breast enlargement, ejaculation disorder, genital edema, anorgasmia, hematospermia, penile tissue damage;

rarely: prolonged erection and / or priapism, penile bleeding.

Disorders of the nervous system and psyche:

very common: headache;

common: dizziness;

infrequent: somnolence, migraine, ataxia, muscle hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depressive symptoms, insomnia, unusual dreams, increased reflexes, hypesthesia;

rarely: cerebral circulation disorders, transient ischemic attack, convulsions*, recurrent convulsions*, syncope.

Skin and subcutaneous tissue disorders:

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 injection site:

infrequently: heat sensation, facial swelling, photosensitivity reaction, shock, asthenia, increased fatigue, pain of various localization, chills, accidental falls, chest pain, accidental injuries;

rarely: irritability.

* Side effects identified during post-marketing studies.

Cardiovascular complications

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

Visual impairments

In rare cases, NSAIDs – a rare condition and cause of vision loss or loss-were reported during post-marketing use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors, such as a reduced ratio of excavation diameters to the optic disc (“congestive disc”), age over 50 years, diabetes mellitus, hypertension, CHD, hyperlipidemia, and smoking. An observational study evaluated whether recent use of PDE5 inhibitors was associated with acute onset of NSAID. The results indicate an approximately twofold increase in the risk of NSAIDs within 5 T_1/2 after the use of a PDE5 inhibitor. According to published literature data, the annual incidence of NPINZD is 2.5-11.8 cases per 100,000 men aged ≥ 50 years in the general population. Patients with sudden vision loss should be advised to discontinue sildenafil therapy and consult their doctor immediately. Individuals who have already had a case of NSAIDs have an increased risk of recurrence of NSAIDs. Therefore, the physician should discuss this risk with such patients, as well as discuss with them the potential risk of adverse effects of PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in these patients and only in situations where the expected benefit outweighs the risk.

When using Visarsin® in doses higher than recommended, adverse events were similar to those noted above, but usually occurred more frequently.

Interaction

Effect of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of the isoenzymes CYP3A4 (main pathway) and CYP2C9, so inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, respectively, increase the clearance of sildenafil. A decrease in the clearance of sildenafil was observed with the simultaneous use of inhibitors of the CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the CYP3A4 isoenzyme, when taken concomitantly with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma by 56%. A single dose of 100 mg of sildenafil simultaneously with erythromycin (500 mg / day 2 times a day for 5 days), a moderate inhibitor of the CYP3A4 isoenzyme, while achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%. When taking sildenafil (100 mg once) and saquinavir (1200 mg/day 3 times a day), an HIV protease inhibitor and CYP3A4 isoenzyme, while achieving a constant concentration of saquinavir in the blood, the_cmax of sildenafil increased by 140%, and the AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir. Stronger inhibitors of the CYP3A4 isoenzyme, such as ketoconazole and itraconazole, can also cause stronger changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P –₄₅₀, on the background to achieve a constant concentration of ritonavir in the blood leads to an increase in C_{max of} sildenafil by 300% (4 times), a AUC by 1000% (11-fold). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng / ml (after a single application of sildenafil alone-5 ng/ml). This is consistent with the effect of ritonavir on a wide range of cytochrome P_{450 substrates}. Sildenafil does not affect the pharmacokinetics of ritonavir. Given these data, concomitant use of ritonavir and sildenafil is not recommended. In any case, the maximum dose of sildenafil should never exceed 25 mg within 48 hours.

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

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

In studies involving healthy volunteers with simultaneous use of endothelioma antagonist of receptors, bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) at steady concentration (125 mg 2 times a day) and sildenafil concentration in equilibrium (80 mg 3 times a day) showed a decrease in AUC and C_{max of} sildenafil 62.6% and 52.4%, respectively. Sildenafil increased bosentan AUC and_cmax by 49.8% and 42%, respectively. It is suggested that the concomitant use of sildenafil with potent inducers of the CYP3A4 isoenzyme, such as rifampicin, may lead to a greater decrease in the concentration of sildenafil in blood plasma.

Inhibitors of the CYP2C9 isoenzyme (tolbutamide, warfarin), the CYP2D6 isoenzyme (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 the AUC, _{cmax, TC max}, elimination rate constant and T_1/2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other medications

Sildenafil is a weak inhibitor of the isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1AND CYP3A4 (IR₅₀ > 150 mmol). When taking sildenafil at the recommended doses, its_cmax is about 1 mmol, so it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter, and when they are used for acute indications. In this regard, the use of sildenafil simultaneously with nitrates or NO donors is contraindicated.

Riociguat

In preclinical studies, an additive effect was observed in the form of a decrease in systemic blood pressure when using PDE5 inhibitors in combination with riociguat. In clinical studies, riociguat has been shown to enhance the antihypertensive effects of PDE5 inhibitors. There was no evidence of a favorable clinical effect of the combination in the studied populations. Concomitant use of riociguate and PDE5 inhibitors, including sildenafil, is contraindicated (see section “Contraindications”).

When the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg,50 mg and 100 mg) were co – administered in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional reduction in SBP/DBP in the supine position was 7/7 mm Hg,9/5 mm Hg and 8/4 mm Hg, respectively, and in the standing position-6/6 mm Hg,11/4 mm Hg and 4/5 mm Hg., respectively. Rare cases of symptomatic orthostatic hypotension have been reported in such patients, which manifested itself in the form of dizziness (without fainting). In some sensitive patients receiving alpha-blockers, concomitant use of sildenafil may lead to symptomatic hypotension.

There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the CYP2C9 isoenzyme.

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

Simultaneous use of sildenafil at steady state (80 mg 3 times a day) leads to an increase in the AUC and_cmax of bosentan (125 mg 2 times a 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 enhance the hypotensive effect of alcohol in healthy volunteers with a maximum blood alcohol concentration of 0.08% (80 mg/dl) on average.

In patients with arterial hypertension, there were no signs of interaction between sildenafil (100 mg) and amlodipine.

The average additional reduction in blood pressure in the supine position is 8 mm Hg (SBP) and 7 mm Hg (DBP).

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

How to take it, course of use and dosage

Inside.

The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Depending on the 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

In mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), no dose adjustment is required, in severe renal insufficiency (creatinine clearance < 30 ml/min), the dose of sildenafil should be reduced to 25 mg.

Impaired liver function

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

Concomitant use with other medicinal products

Concomitant use with ritonavir is not recommended. In any case, the maximum dose of Visarsin® should not exceed 25 mg, and the frequency of use-1 time in 48 hours (see the section “Interaction with other drugs”).

When used concomitantly with inhibitors of the CYP3A4 isoenzyme (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Visarsin® should be 25 mg (see the section “Interaction with other drugs”).

To minimize the risk of orthostatic hypotension in patients taking alpha-blockers, Visarsin® should be started only after stable hemodynamics have been achieved in these patients. Consideration should also be given to reducing the initial dose of sildenafil (see sections “Special instructions” and “Interactions with other medicinal products”).

Elderly patients

No dose adjustment of Visarsin® is required.

Overdose

Symptoms: with a single dose of sildenafil in doses up to 800 mg, adverse reactions are similar to those with lower doses of the drug, 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 disturbances) increased.

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

Description

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

50 mg tablets: oval biconvex tablets, film-coated in white or almost white color, with the number 50 engraved on one side.

100 mg tablets: oval biconvex tablets, film-coated in white or almost white color, with the number 100 engraved on one side.

Special instructions

Anatomical deformity of the penis (angulation, cavernous fibrosis or Peyronie’s disease) (see the section “Special instructions”), diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocytemia) (see the section “Special instructions”), diseases accompanied by bleeding, stomach and duodenal ulcer in the acute stage, liver function disorders, severe renal failure (CC less than 30 ml/min), patients with a history of anterior non-arteritic ischemic optic neuropathy (see section “Special instructions”), concomitant use of alpha-blockers.

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

Impaired renal function

In mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), no dose adjustment is required, in severe renal insufficiency (creatinine clearance < 30 ml/min), the dose of sildenafil should be reduced to 25 mg.

Impaired liver function

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

Elderly patients

No dose adjustment of Visarsin® is required.

To diagnose erectile dysfunction, determine their possible causes, and choose appropriate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination. Treatment of erectile dysfunction should be used with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, Peyronie’s disease) or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia) (see the section “With caution”).

Cases of prolonged erections and priapism have been reported in post-marketing studies. If an erection persists for more than 4 hours, you should immediately seek medical help. If priapism therapy is not carried out immediately, it can lead to penile tissue damage and permanent loss of potency. Drugs intended for the treatment of erectile dysfunction should not be used by men for whom sexual activity is undesirable.

Sexual activity poses a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient for a cardiovascular examination. Sexual activity is undesirable in patients with heart failure, unstable angina, a history of myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg) or arterial hypotension (BP > Taking sildenafil in such patients is contraindicated (see the section “Contraindications”). Clinical studies have shown no differences in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular mortality (0.3 per 100 people per year) in patients treated with sildenafil compared to patients treated with placebo.

Cardiovascular complications

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

Arterial hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. However, before prescribing Visarsin®, the doctor should carefully assess the risk of possible undesirable manifestations of vasodilating effects 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 exit tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with a rare syndrome of multiple systemic atrophy, manifested by a severe violation of blood pressure regulation by the autonomic nervous system.

Since the simultaneous use of sildenafil and alpha-blockers may lead to symptomatic hypotension in some sensitive patients, Visarsin® should be used with caution in patients taking alpha-blockers (see the section “Interaction with other drugs”). To minimize the risk of orthostatic hypotension in patients taking alpha-blockers, Visarsin® should be started only after the hemodynamic parameters have stabilized in these patients. Consideration should also be given to reducing the initial dose of Visarsin® (see section “Dosage and use”). The doctor should inform patients about what actions should be taken in case of symptoms of orthostatic hypotension.

Visual impairments

In rare cases, post-marketing use of all PDE5 inhibitors, including sildenafil, reported non-arteriitic anterior ischemic optic neuropathy – a rare disease and cause of reduced or lost vision. Most of these patients had risk factors, such as a reduced ratio of excavation diameters to the optic disc (“congestive disc”), age over 50 years, diabetes mellitus, hypertension, CHD, hyperlipidemia, and smoking. An observational study evaluated whether the recent use of drugs of the PDE5 inhibitor class is associated with acute onset of NSAID. The results indicate an approximately twofold increase in the risk of NSAIDs within 5 T_1/2 after the use of a PDE5 inhibitor. According to published literature data, the annual incidence of NPINZD is 2.5-11.8 cases per 100,000 men aged ≥ 50 years in the general population. Patients with sudden vision loss should be advised to discontinue sildenafil therapy and consult their doctor immediately.Individuals who have already had a case of NSAIDs have an increased risk of recurrence of NSAIDs. Therefore, the doctor should discuss this risk with these patients, as well as discuss with them the potential for adverse effects of PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in these patients and only in situations where the expected benefit outweighs the risk. In patients with episodes of NSAID development with loss of vision in one eye, sildenafil is contraindicated (see section “Contraindications”).

A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of retinal phosphodiesterase functions. There is no information on the safety of sildenafil in patients with retinitis pigmentosa, so sildenafil should not be used in such patients (see the section “Contraindications”).

Hearing disorders

Some post-marketing studies have reported cases of sudden hearing impairment or 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. No causal relationship has been established between the use of PDE5 inhibitors and sudden hearing impairment or hearing loss. In case of sudden hearing loss or loss of hearing while taking Visarsin®, you should immediately consult your doctor.

Bleeding issues

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a NO donor, on human platelets in vitro. There are no data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so Visarsin® should be used with caution in such patients (see the section “With caution”). The incidence of nosebleeds 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 treated with sildenafil in combination with a vitamin K antagonist, the incidence of nosebleeds 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 Visarsin® concomitantly with other PDE5 inhibitors or other drugs for the treatment of pulmonary hypertension containing sildenafil or other agents for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended (see the section “Contraindications”).

Since taking sildenafil may cause dizziness, a decrease in blood pressure, the development of chromatopsia, blurred vision, etc. side effects, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions. You should also pay close attention to the individual effect of Visarsin® in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Form of production

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

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

1 blister (blister of 1,2,4 tablets),2 or 3 blisters (blister of 4 tablets) in a cardboard pack together with the instructions for use.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf

life is 5 years.

Do not use the drug after the expiration date.

Active ingredient

Sildenafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For men, For adults as prescribed by a doctor

Indications

Erectile Dysfunction