Sildenafil-SZ, 100 mg, film-coated tablets, 4 pcs.

Description and main characteristics

Sildenafil is a drug used by men to increase potency. Contains the active ingredient of the same name and is available in the form of granules with different dosages of the main component - from 35 to 140.5 mg per 1 piece. The most well-known brand of the drug, which also contains sildenafil, is Viagra.

The product is dispensed from pharmacies only with a prescription. The shelf life is 3 years from the date of production. It must be stored under standard conditions - a dark place, temperature up to 25 degrees.

Description of the drug SILDENAFILUM

After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages 40% (25-63%). After a single oral dose of 100 mg, Cmax is 18 ng/ml and is achieved when taken on an empty stomach for 30-120 minutes. When taking sildenafil in combination with fatty foods, the rate of absorption is reduced; Tmax increases by 60 minutes, and Cmax decreases by an average of 29%. The Vd of sildenafil at steady state is on average 105 liters. Sildenafil and its main circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is independent of the total concentration of sildenafil. Less than 0.0002% of the dose (mean 188 ng) was detected in semen 90 minutes after sildenafil administration.

Sildenafil is metabolized mainly by the liver microsomal isoenzymes CYP3A4 (the main route) and CYP2C9.

The main circulating metabolite, which is formed as a result of N-desmethylation of sildenafil, undergoes further metabolism. In terms of selectivity of action on PDE, the metabolite is comparable to sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil itself. The concentration of the metabolite in plasma is approximately 40% of that of sildenafil. The N-desmethyl metabolite undergoes further metabolism; its terminal T1/2 is about 4 hours.

The total clearance of sildenafil from the body is 41 l/h, and T1/2 in the terminal phase is 3-5 hours. After oral administration, sildenafil is excreted in the form of metabolites mainly in feces (approximately 80% of the dose) and to a lesser extent in urine ( approximately 13% of the dose).

In elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of the free active substance in plasma is approximately 40% higher than its concentration in young (18-45 years) patients.

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

In patients with liver cirrhosis (Child-Pugh class A and B), the clearance of sildenafil is reduced, resulting in an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group .

Contraindications

The use of Silenafil has a fairly wide range of contraindications:

• hypersensitivity to the active substance or auxiliary components of the drug;
• severe disturbances in liver function;
• low blood pressure (less than 90/50);
• recently suffered pathologies associated with cerebral circulatory disorders;
• recent myocardial infarction;
• phenylkenothuria;
• loss of vision in one eye;
• hereditary retinal dystrophy;
• simultaneous use with Amylnitrite, nitrates and other nitric oxide NO donors;
• simultaneous use with the drug "Ritonavir";
• children under 18 years of age.

There are other contraindications. For example, the drug is not recommended for use by men who should not be sexually active due to severe heart failure.

Hypertensive patients with blood pressure above 170/100 should take this medication with caution, as well as in the presence of:

• severe arrhythmia that threatens life;
• left ventricular obstruction;
• conditions that predispose to prialism;
• ischemic optic neuropathy;
• anatomical deviations of the penis (deformation, Peyronie's disease and others).

Sildenafil-SZ, 100 mg, film-coated tablets, 4 pcs.

To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination. Erectile dysfunction treatments should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie's disease) or risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia) (see "Contraindications", Caution) .

).

Medicines intended to treat erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.

Sexual activity poses a certain risk in the presence of heart disease, therefore, before starting any therapy for erectile dysfunction, the doctor should refer the patient to an examination of the cardiovascular system.

Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP <90/50 mm Hg. Art.) (see “Contraindications”, With caution

). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of death from cardiovascular diseases (0.3 per 100 people per year) in patients treated with Sildenafil-SZ, compared with patients receiving placebo.

Cardiovascular complications

During post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported. ), which had a temporary association with the use of sildenafil. The majority of these patients had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors.

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 Sildenafil-SZ, the physician should carefully assess the risk of possible undesirable manifestations of the vasodilating effect in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.

Since the combined use of sildenafil and α-blockers may lead to symptomatic hypotension in some sensitive patients, Sildenafil-SZ should be administered with caution to patients taking α-blockers (see “Interactions”). To minimize the risk of developing postural hypotension in patients taking α-blockers, Sildenafil-SZ should be started only after hemodynamic stability has been achieved in these patients. You should also consider the advisability of reducing the initial dose of Sildenafil-SZ (see “Dosage and Administration”). The physician should inform patients about what actions to take if symptoms of postural hypotension occur.

Visual impairment

Rare cases of anterior non-arteritic ischemic optic neuropathy as a cause of deterioration or loss of vision have been reported with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as optic disc excavation, age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. A cause-and-effect relationship between the use of PDE5 inhibitors and the development of anterior non-arteritic ischemic optic neuropathy has not been identified. The physician should inform the patient about the increased risk of developing anterior non-arteritic ischemic optic neuropathy if this condition has already been noted. In case of sudden loss of vision, patients should receive the necessary medical attention immediately. A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of the retinal PDE. There is no information on the safety of using the drug Sildenafil-SZ in patients with retinitis pigmentosa, so sildenafil should be used with caution (see “Contraindications”, With caution

).

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. If there is a sudden deterioration or loss of hearing while taking sildenafil, you should immediately consult your doctor.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro.

There are no data on the safety of using sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so Sildenafil-SZ should be used with caution in these patients (see “Contraindications”,
With caution
). The incidence of epistaxis 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%, placebo - 2.4 %). Patients receiving sildenafil in combination with a vitamin K antagonist had a higher incidence of epistaxis (8.8%) than patients not taking a vitamin K antagonist (1.7%).

Use in conjunction with other means of treating erectile dysfunction.

The safety and effectiveness of Sildenafil-SZ in combination with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see “Contraindications”).

Impact on the ability to drive vehicles and operate machinery.

While taking Sildenafil-SZ, no negative effects on the ability to drive a car or use other technical equipment were observed. However, since taking sildenafil may reduce blood pressure, develop chromatopsia, blurred vision, etc. side effects, you should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Side effects

In some cases (often due to an overdose), minor side effects are possible:

• dyspepsia;
• dizziness;
• headache;
• feeling of nasal congestion;
• flushes of blood;
• temporary vision problems;
• noise in ears;
• hypersensitivity reactions.

In rare cases, the following were observed:

• temporary deafness;
• cardiopalmus;
• nosebleeds;
• skin rash;
• nausea;
• myalgia;
• chest pain;
• fast fatiguability;
• an erection that lasts too long.

"Sildenafil": instructions for use

The drug is taken orally and washed down with a small volume of water. The standard single dosage is 50 mg one hour before sexual intercourse. If the effect is insufficient, increase the dosage by 2 times (subject to normal tolerance and absence of contraindications). The maximum amount per day is 100 mg, frequency of use is 1 time per day.

For older people, the same dosages are established. In this case, the daily intake rate can be adjusted in the presence of certain diseases:

1. Renal dysfunction – 25 mg.
2. Liver dysfunction – 25 mg.
3. Simultaneous use with other drugs such as Ketoconazole, Cimetidine (except Ritonavir), Erithoromycin - up to 25 mg.

These restrictions are not “hard” ones. If the effect is insufficient, the daily dosage can be gradually increased to 50 mg, then to 100 mg.

Sildenafil SZ tablets 50 mg 20 pcs (Northern Star)

Registration Certificate Holder

NORTH STAR (Russia)

Dosage form

Medicine - Sildenafil-SZ (Sildenafil-SZ)

Description

Film-coated tablets

blue, round, biconvex; at the break - white or almost white.

1 tab.

sildenafil citrate 70.2 mg, which corresponds to the content of sildenafil 50 mg

Excipients

: microcrystalline cellulose 102 - 54 mg, lactose monohydrate (milk sugar) - 53.8 mg, croscarmellose sodium (primellose) - 10 mg, povidone K30 (medium molecular weight polyvinylpyrrolidone) - 10 mg, magnesium stearate - 2 mg.

Shell composition:

Opadry II (polyvinyl alcohol, partially hydrolyzed - 2.4 mg, titanium dioxide (E171) - 1.374 mg, macrogol (polyethylene glycol 3350) - 1.212 mg, talc - 0.888 mg, aluminum varnish based on brilliant blue - 0.1152 mg, iron oxide dye (II ) yellow (E172) - 0.0102 mg, iron dye oxide (II) black (E172) - 0.0006 mg).

1 PC. — cellular contour packages (1) — cardboard packs. 2 pcs. — cellular contour packages (1) — cardboard packs. 4 things. — cellular contour packages (1) — cardboard packs. 6 pcs. — cellular contour packages (1) — cardboard packs. 6 pcs. — cellular contour packages (2) — cardboard packs. 7 pcs. — cellular contour packages (1) — cardboard packs. 7 pcs. — cellular contour packages (2) — cardboard packs. 8 pcs. — cellular contour packages (1) — cardboard packs. 10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — cellular contour packages (2) — cardboard packs. 20 pcs. — polymer jars (1) — cardboard packs. 20 pcs. — polymer bottles (1) — cardboard packs.

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 during sexual stimulation.

Contraindications for use

• use in patients receiving continuous or intermittent nitric oxide donors, organic nitrates or nitrites in any form, since sildenafil enhances the hypotensive effect of nitrates;
• According to its registered indication, the drug Sildenafil-SZ is not intended for use in children and adolescents under the age of 18 years;
• According to its registered indication, the drug Sildenafil-SZ is not intended for use in women;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Concomitant use of sildenafil with ritonavir is not recommended;
• hypersensitivity to sildenafil or any other component of the drug.

The safety and effectiveness of Sildenafil-SZ when used in combination with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended.
Carefully:

• anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease);
• diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia);
• diseases accompanied by bleeding;
• exacerbation of peptic ulcer of the stomach and duodenum;
• hereditary retinitis pigmentosa;
• heart failure, unstable angina, myocardial infarction in the last 6 months, stroke or life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP <90/50 mm Hg);
• in patients with episodes of anterior non-arteritic ischemic optic neuropathy (history).

pharmachologic effect

Sildenafil is a powerful selective inhibitor of cycloguanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

Mechanism of action

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

Sildenafil does not have a direct relaxant effect on the isolated human corpus cavernosum, but enhances the effect of nitric oxide (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 - 10 times; PDE1 - more than 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. Sildenafil is 4000 times more selective for PDE5 compared to PDE3, which is of utmost 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

Cardiac research

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

In a study of the hemodynamic effect of sildenafil at a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis of at least one coronary artery), resting systolic and diastolic blood pressure decreased by 7% and 6%, accordingly, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output or impair blood flow in stenotic coronary arteries, and also resulted in an increase (by approximately 13%) in 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) exercised until their angina symptoms improved. The duration of the 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 medications. Sildenafil improved erections in 71% of men compared to 18% in the placebo group. The incidence of adverse effects was comparable to that in other patient groups, as well as in individuals 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-Munsell 100 test revealed a mild and transient impairment in the ability to distinguish shades of color (blue/green). 2 hours after taking the drug, these changes were absent. Color vision impairment is thought to be caused by inhibition of PDE6, which is involved in light transmission in the retina. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure, or pupil diameter.

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

Efficiency

The effectiveness and safety of sildenafil was assessed in 21 randomized, double-blind, placebo-controlled studies lasting up to 6 months in 3,000 patients aged 19 to 87 years with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The effectiveness of the drug was assessed globally using an erection diary, the International Index of Erectile Function (a validated questionnaire about the state of sexual function) and a partner interview.

The effectiveness 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 was confirmed in long-term studies lasting 1 year. In fixed-dose studies, the proportion of patients reporting that therapy improved their erections was: 62% (25 mg sildenafil dose), 74% (50 mg sildenafil dose), and 82% (100 mg sildenafil dose) compared with 25% in the placebo group. Analysis of the International Index of Erectile Function showed that in addition to improving erection, treatment with sildenafil also increased the quality of orgasm, achieved satisfaction from sexual intercourse and overall satisfaction.

According to the pooled data, among patients who reported improved erections with sildenafil treatment, 59% of patients with diabetes, 43% of patients who had undergone radical prostatectomy, and 83% of patients with spinal cord injury (versus 16%, 15% and 12% in the placebo group, respectively).

Drug interactions

The influence of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the influence of the cytochrome isoenzymes CYP3A4 (the main pathway) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, accordingly, increase the clearance of sildenafil. A decrease in the clearance of sildenafil was noted with simultaneous use of inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a nonspecific inhibitor of the cytochrome CYP3A4 isoenzyme, when taken together with sildenafil (50 mg), causes an increase in plasma sildenafil concentrations by 56%. A single dose of sildenafil in a dose of 100 mg together with erythromycin (500 mg 2 times a day for 5 days), a specific inhibitor of the cytochrome 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 (single 100 mg) and saquinavir (1200 mg/day 3 times/day), an inhibitor of HIV protease and isoenzyme CYP3A4, while achieving a constant concentration of saquinavir in the blood, Cmax of sildenafil increased by 140%, and AUC increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir.

Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, may cause more severe changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), an HIV protease inhibitor and a strong cytochrome P450 inhibitor, while achieving a constant concentration of ritonavir in the blood leads to an increase in Cmax of sildenafil by 300% (4 times ), and AUC by 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng/ml (after a single dose of sildenafil alone - 5 ng/ml), which is consistent with information about the pronounced effect of ritonavir on the pharmacokinetics of various cytochrome P450 substrates. Sildenafil has no effect on the pharmacokinetics of ritonavir. The combined use of sildenafil with ritonavir is not recommended.

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

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

Inhibitors of the cytochrome CYP2C9 isoenzyme (tolbutamide, warfarin), the cytochrome CYP2D6 isoenzyme (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, 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, Tmax, elimination rate constant and T1/2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes -1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50>150 µmol). When sildenafil is taken at recommended doses, its Cmax is approximately 1 µmol, so it is unlikely that sildenafil could affect the clearance of substrates of these isoenzymes.

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

When co-administering the alpha-blocker 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 average additional reduction in systolic/diastolic blood pressure in the supine position was 7 /7 mmHg art., 9/5 mm Hg. and 8/4 mm Hg, respectively, and in the standing position - 6/6 mm Hg, 11/4 mm Hg. and 4/5 mmHg, respectively. Rare cases of symptomatic postural hypotension, manifested in the form of dizziness (without fainting), have been reported in such patients. In selected 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 cytochrome CYP2C9 isoenzyme.

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

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 ethanol in healthy volunteers with a maximum ethanol concentration in the blood of an average of 0.08% (80 mg/dL).

In patients with arterial hypertension, no signs of interaction between sildenafil (100 mg) and amlodipine were detected. The average additional reduction in blood pressure in the supine position is 8 mm Hg. (systolic) and 7 mm Hg. (diastolic).

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

Dosage regimen

The drug is taken orally.

The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Taking into account effectiveness 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 use is 1 time/day.

For mild to moderate renal failure (creatinine clearance 30-80 ml/min)

no dose adjustment is required; in case of
severe renal failure (creatinine clearance <30 ml/min),
the dose of sildenafil should be reduced to 25 mg.

Since the elimination of sildenafil is impaired in patients with liver damage (particularly cirrhosis)

, the dose of Sildenafil-SZ should be reduced to 25 mg.

Dose adjustment of Sildenafil-SZ in elderly patients

not required.

Concomitant use with other drugs

When used together with ritonavir, the maximum single dose of Sildenafil-SZ should not exceed 25 mg, and the frequency of use should not exceed 1 time every 48 hours.

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

To minimize the risk of developing postural hypotension in patients taking alpha-blockers, Sildenafil-SZ should be started only after hemodynamic stabilization has been achieved in these patients. The advisability of reducing the initial dose of sildenafil should also be considered.

Overdose

Symptoms:

with a single dose of Sildenafil-SZ in a dose of up to 800 mg, adverse events were comparable to those when taking the drug in lower doses, but were more common.

Treatment:

carrying out symptomatic therapy. Hemodialysis does not accelerate the clearance of sildenafil, because the latter actively binds to plasma proteins and is not excreted by the kidneys.

Side effect

The most common side effects were headache and flushing.

Typically, the side effects of Sildenafil-SZ are mild or moderate and transient.

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

The frequency of adverse reactions is presented according to the following classification: very often (≥1/10%), often (from ≥1% to <10%), infrequently (from ≥0.1% to <1%), rarely (from ≥0.01% to < 0.1%), very rare (<0.01%), frequency unknown (cannot be determined based on available data).

From the immune system:

uncommon - hypersensitivity reactions (including skin rash), allergic reactions.

From the hematopoietic system:

infrequently - anemia, leukopenia.

Metabolism and nutrition:

uncommon - feeling of thirst, edema, gout, uncompensated diabetes mellitus, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

From the side of the organ of vision:

often - blurred vision, blurred vision, cyanopsia; uncommon - eye pain, photophobia, photopsia, chromatopsia, redness of the eyes/scleral injections, changes in the brightness of light perception, mydriasis, conjunctivitis, hemorrhage in the eye tissue, cataracts, disruption of the lacrimal apparatus; rarely - swelling of the eyelids and adjacent tissues, a feeling of dryness in the eyes, the presence of rainbow circles in the field of vision around the light source, increased eye fatigue, seeing objects in yellow (xanthopsia), seeing objects in red (erythropsia), conjunctival hyperemia, irritation of the mucous membrane membranes of the eyes, discomfort in the eyes; frequency unknown - non-arteritic anterior ischemic optic neuropathy, retinal vein occlusion, visual field defect, diplopia*, temporary loss of vision or decreased visual acuity, increased intraocular pressure, retinal edema, retinal vascular disease, vitreous detachment/vitreal traction.

On the part of the hearing organ:

Uncommon: sudden decrease or loss of hearing, tinnitus, ringing in the ears, ear pain.

From the nervous system:

very often - headache; often - dizziness; uncommon - drowsiness, migraine, ataxia, hypertonicity, neuralgia, neuropathy, paresthesia, tremor, vertigo, symptoms of depression, insomnia, unusual dreams, increased reflexes, hypoesthesia; rarely - convulsions*, repeated convulsions*, fainting, cerebrovascular accident, transient ischemic attack.

From the cardiovascular system:

often - “hot flashes”; uncommon - tachycardia, palpitations, decreased or increased blood pressure, increased heart rate, unstable angina, AV block, myocardial infarction, cerebral thrombosis, cardiac arrest, heart failure, abnormal ECG readings, cardiomyopathy; rarely - atrial fibrillation, sudden cardiac death*, ventricular arrhythmia*.

From the respiratory system:

often - nasal congestion; uncommon - nosebleeds, rhinitis, asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased volume of sputum, increased cough; rarely - a feeling of tightness in the throat, dryness of the nasal mucosa, swelling of the nasal mucosa.

From the digestive system:

often - nausea, dyspepsia; uncommon - gastroesophageal reflux disease, vomiting, abdominal pain, dry oral mucosa, glossitis, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, abnormal liver function tests, rectal bleeding; rarely - hypoesthesia of the oral mucosa.

From the musculoskeletal system:

often - back pain; uncommon - myalgia, pain in the limbs, arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.

From the urinary system:

uncommon - cystitis, nocturia, urinary incontinence, hematuria.

From the genital organs and breast:

uncommon - enlarged mammary glands, impaired ejaculation, swelling of the genitals, anorgasmia, hematospermia, damage to penile tissue; rarely - prolonged erection and/or priapism, bleeding from the penis.

For the skin and subcutaneous tissues:

uncommon - skin rash, urticaria, herpes simplex, itching, increased sweating, skin ulceration, contact dermatitis, exfoliative dermatitis; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis.

Other:

infrequently - feeling of heat, swelling of the face, photosensitivity reaction, shock, asthenia, increased fatigue, pain of various localizations, chills, occasional burning, pain in the chest, accidental injuries; rarely irritability.

* Side effects identified during post-marketing studies.

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, hypertension and hypotension) were reported, which had temporary association 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 occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors.

Visual impairment

In rare cases, during post-registration use of all PDE5 inhibitors, incl. sildenafil, non-arteritic anterior ischemic optic neuropathy (NAIOPN), a rare disease and cause of decreased or loss of vision, has been reported. Most of these patients had risk factors, including decreased papilledema/disc ratio (“congestive disc”), age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. An observational study assessed whether recent use of the PDE5 inhibitor class of drugs was associated with acute onset of NPINSID. Results indicate an approximately two-fold increase in the risk of NPINSID within 5 half-lives of PDE5 inhibitor use. According to the published literature, the annual incidence of NPINSID is 2.5-11.8 cases per 100,000 men aged ≥50 years in the general population. In case of sudden loss of vision, patients should be advised to stop sildenafil therapy and consult a doctor immediately. Individuals who have already had a case of NPIND have an increased risk of recurrent NPIND. Therefore, the physician should discuss this risk with such patients, as well as discuss with them the potential for adverse effects from PDE5 inhibitors. PDE5 inhibitors, incl. sildenafil should be used with caution in such patients and only in situations where the expected benefit outweighs the risk.

When using the drug Sildenafil-SZ in doses exceeding the recommended ones, adverse events were similar to those noted above, but usually occurred more often.

special instructions

To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination. Treatments for 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 the development of priapism (sickle cell anemia, multiple myeloma, leukemia).

Medicines intended to treat erectile dysfunction should not be prescribed to 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 an examination of the condition of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP <90/50 mm Hg. Art.). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of death from cardiovascular diseases (0.3 per 100 people per year) in patients receiving Sildenafil-SZ compared with patients receiving placebo.

Cardiovascular complications

During post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported. ), which had a temporary association 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 occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection 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 Sildenafil-SZ, the physician should carefully assess the risk of possible undesirable manifestations of the vasodilating effect in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.

Since the combined use of sildenafil and alpha-blockers may lead to symptomatic hypotension in some sensitive patients, Sildenafil-SZ should be administered with caution to patients taking alpha-blockers. To minimize the risk of developing postural hypotension in patients taking alpha-blockers, Sildenafil-SZ should be started only after hemodynamic stability has been achieved in these patients. The advisability of reducing the initial dose of Sildenafil-SZ should also be considered. The physician should inform patients about what actions to take if symptoms of postural hypotension occur.

Visual impairment

Rare cases of anterior non-arteritic ischemic optic neuropathy have been reported as a cause of deterioration or loss of vision with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as optic disc excavation, age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. A cause-and-effect relationship between the use of PDE5 inhibitors and the development of anterior non-arteritic ischemic optic neuropathy has not been identified. The physician should inform the patient about the increased risk of developing anterior non-arteritic ischemic optic neuropathy if this condition has already been noted. In case of sudden loss of vision, patients should receive the necessary medical attention immediately. A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of retinal phosphodiesterases. There is no information on the safety of using Sildenafil-SZ in patients with retinitis pigmentosa, so sildenafil should be used with caution.

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. If there is a sudden deterioration in hearing or hearing loss while taking sildenafil, you should consult your doctor immediately.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide 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 Sildenafil-SZ should be used with caution in these patients. The incidence of epistaxis in patients with PH associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3%, placebo 2.4%). In patients receiving sildenafil in combination with a vitamin K antagonist, the incidence of epistaxis was higher (8.8%) than in patients not taking a vitamin K antagonist (1.7%).

Use in conjunction with other means of treating erectile dysfunction

The safety and effectiveness of using Sildenafil-SZ in combination with other drugs for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended.

Impact on the ability to drive vehicles and machinery

While taking sildenafil, no negative effects on the ability to drive a car or use other technical equipment were observed.

However, since when taking sildenafil, a decrease in blood pressure, the development of chromatopsia, blurred vision and other side effects is possible, you should be careful about the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Storage conditions

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25°C.

Best before date

Shelf life: 3 years.

Use during pregnancy and breastfeeding

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

Use for renal impairment

Restrictions for impaired renal function - With caution. For mild to moderate renal failure (creatinine clearance 30-80 ml/min), no dose adjustment is required; for severe renal failure (creatinine clearance <30 ml/min), the dose of sildenafil should be reduced.

Use for liver dysfunction

Restrictions for liver dysfunction - With caution. Since the elimination of sildenafil is impaired in patients with liver damage (in particular, with cirrhosis), the dose of Sildenafil-SZ should be reduced.

Use in elderly patients

Restrictions for elderly patients - No restrictions.

No dose adjustment of Sildenafil-SZ is required in elderly patients.

Use in children

Restrictions for children - Contraindicated.

According to its registered indication, the drug Sildenafil-SZ is not intended for use in children and adolescents under the age of 18 years.

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

NORTH STAR NAO (Russia)

111524 Moscow st. Elektrodnaya, 2, building 34, room. 47 Tel./fax

special instructions

One-time use is allowed without consulting a doctor, except in cases associated with severe pathologies of the cardiovascular system, kidneys or liver. For long-term use, preliminary consultation with a specialist is recommended.

In extremely rare cases, cardiac instability may occur. In case of overdose, myocardial infarction, including death, cannot be ruled out. Complications can develop during, after, or even without sexual intercourse.

Sildenafil leads to dilation of blood vessels, which leads to a slight, reversible decrease in blood pressure. Therefore, on the eve of the appointment, the doctor should assess the possible risks associated with a decrease in blood pressure.

Sildenafil-SZ

Registration number

LP-002313

Dosage form

Film-coated tablets

Compound

1 film-coated tablet contains:

Dosage 25 mg:

active substance: sildenafil citrate in terms of sildenafil – 25 mg; excipients (core): microcrystalline cellulose – 50.0 mg; lactose monohydrate (milk sugar) – 61.5 mg; croscarmellose sodium (primellose) – 7.5 mg; povidone (medium molecular weight polyvinylpyrrolidone) – 4.5 mg; magnesium stearate – 1.5 mg; excipients (shell): Opadry II (polyvinyl alcohol, partially hydrolyzed - 2.0 mg; titanium dioxide E 171 - 1.145 mg; macrogol (polyethylene glycol 3350) - 1.01 mg; talc - 0.74 mg; aluminum varnish based brilliant blue – 0.096 mg; iron oxide (II) yellow E 172 – 0.0085 mg; iron oxide (II) black E 172 – 0.0005 mg).

Dosage 50 mg:

active substance: sildenafil citrate in terms of sildenafil – 50 mg; excipients (core): microcrystalline cellulose – 54.0 mg; lactose monohydrate (milk sugar) – 74.0 mg; croscarmellose sodium (primellose) – 10.0 mg; povidone (medium molecular weight polyvinylpyrrolidone) – 10.0 mg; magnesium stearate – 2.0 mg; excipients (shell): Opadry II (polyvinyl alcohol, partially hydrolyzed - 2.4 mg; titanium dioxide E 171 - 1.374 mg; macrogol (polyethylene glycol 3350) - 1.212 mg; talc - 0.888 mg; aluminum varnish based on brilliant blue - 0 ,1152 mg; iron oxide (II) yellow E 172 – 0.0102 mg; iron oxide (II) black E 172 – 0.0006 mg).

Dosage 100 mg:

active substance: sildenafil citrate in terms of sildenafil – 100 mg excipients (core): microcrystalline cellulose – 83.5 mg; lactose monohydrate (milk sugar) – 83.5 mg; croscarmellose sodium (primellose) – 15.0 mg; povidone (medium molecular weight polyvinylpyrrolidone) – 15.0 mg; magnesium stearate – 3.0 mg; excipients (shell): Opadry II (polyvinyl alcohol, partially hydrolyzed - 3.6 mg; titanium dioxide E 171 - 2.061 mg; macrogol (polyethylene glycol 3350) - 1.818 mg; talc - 1.332 mg; aluminum varnish based on brilliant blue – 0.1728 mg; iron oxide (II) yellow E 172 – 0.0153 mg; iron oxide (II) black E 172 – 0.0009 mg).

Description

Blue film-coated tablets, round, biconvex. The tablets are white or almost white when broken.

ATX code

[G04BE03]

Pharmacological properties

Pharmacodynamics

Sildenafil is a powerful selective inhibitor of cycloguanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).
Mechanism of action
The physiological mechanism of erection is associated with the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation.
This, in turn, leads to an increase in cGMP levels, subsequent relaxation of the smooth muscle tissue of the corpus cavernosum and increased blood flow. Sildenafil does not have a direct relaxant effect on the isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting PDE5, which is responsible for the breakdown of cGMP. Sildenafil is selective against PDE5 in vitro
, its activity against PDE5 exceeds that against other known phosphodiesterase isoenzymes: PDE6 – 10 times; PDE1 – more than 80 times; PDE2, PDE4, PDE7-PDE11 – more than 700 times. Sildenafil is 4000 times more selective for PDE5 compared to PDE3, which is of utmost 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 Cardiac studies
The use of sildenafil in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers.
The maximum decrease in systolic pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mmHg. Art., and diastolic pressure – 5.3 mm Hg. Art. A more pronounced, but also transient effect on blood pressure (BP) was observed in patients taking nitrates (see sections “Contraindications” and “Interaction with other drugs”). In a study of the hemodynamic effect of sildenafil at a single dose of 100 mg in 14 patients with severe coronary artery disease (CAD) (more than 70% of patients had stenosis of at least one coronary artery), resting systolic and diastolic blood pressure decreased by 7 % and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output or impair blood flow in stenotic coronary arteries, and also resulted in an increase (by approximately 13%) in 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) exercised until their angina symptoms improved. The duration of the 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 medications. Sildenafil improved erections in 71% of men compared to 18% in the placebo group. The incidence of adverse effects was comparable to that in other patient groups, as well as in individuals taking more than three antihypertensive drugs. Studies of visual impairment
In some patients, 1 hour after taking sildenafil at a dose of 100 mg, the Farnsworth-Munsell 100 test revealed a mild and transient impairment in the ability to distinguish shades of color (blue/green).
2 hours after taking the drug, these changes were absent. Color vision impairment is thought to be caused by inhibition of PDE6, which is involved in light transmission in the retina. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure, or pupil diameter. In a placebo-controlled crossover study of patients with proven early-onset macular degeneration (n = 9), sildenafil in a single dose of 100 mg was well tolerated. There were no clinically significant changes in vision assessed by specific visual tests (visual acuity, Amsler grating, color perception, color transmission simulation, Humphrey perimeter, and photostress). Efficacy
The effectiveness and safety of sildenafil were assessed in 21 randomized, double-blind, placebo-controlled studies lasting up to 6 months in 3,000 patients aged 19 to 87, with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The effectiveness of the drug was assessed globally using an erection diary, the International Index of Erectile Function (a validated questionnaire about the state of sexual function) and a partner interview. The effectiveness 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 was confirmed in long-term studies lasting 1 year. In fixed-dose studies, the proportion of patients who reported that therapy improved their erections was: 62% (sildenafil 25 mg dose), 74% (sildenafil 50 mg dose), and 82% (sildenafil 100 mg dose) compared with 25%. in the placebo group. Analysis of the International Index of Erectile Function showed that in addition to improving erection, treatment with sildenafil also increased the quality of orgasm, achieved satisfaction from sexual intercourse and overall satisfaction. According to the pooled data, among patients who reported improved erections with sildenafil treatment, 59% of patients with diabetes, 43% of patients who had undergone radical prostatectomy and 83% of patients with spinal cord injury (versus 16%, 15% and 12% in the placebo group, respectively) ).

Pharmacokinetics

The pharmacokinetics of sildenafil in the recommended dose range is linear.
Absorption
After oral administration, sildenafil is rapidly absorbed.
Absolute bioavailability averages about 40% (from 25% to 63%). In vitro,
sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) inhibits human PDE5 activity by 50%.
After a single dose of sildenafil 100 mg, the average maximum concentration of free sildenafil in blood plasma (Cmax) in men is about 18 ng/ml (38 nM). Cmax when taking sildenafil orally on an empty stomach is achieved on average within 60 minutes (from 30 minutes to 120 minutes). When taken in combination with fatty foods, the rate of absorption decreases: Cmax decreases by an average of 29%, and the time to reach maximum concentration (Tmax) increases by 60 minutes, but the degree of absorption does not significantly change (the area under the concentration-time pharmacokinetic curve (AUC) decreases by 11%). Distribution
The volume of distribution of sildenafil at steady state averages 105 liters.
The binding of sildenafil and its main circulating N-demethyl metabolite to plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the sildenafil dose (average 188 ng) was found in semen 90 minutes after dosing. Metabolism
Sildenafil is metabolized mainly in the liver under the influence of the cytochrome CYP3A4 isoenzyme (major pathway) and the cytochrome CYP2C9 isoenzyme (minor pathway).
The main circulating active metabolite, formed as a result of N-demethylation of sildenafil, undergoes further metabolism. The selectivity of this metabolite for PDE is comparable to that of sildenafil, and its activity against PDE5 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. The N-demethyl metabolite undergoes further metabolism; its half-life (T1/2) is about 4 hours. Elimination
The total clearance of sildenafil is 41 l/hour, and the final T1/2 is 3-5 hours.
After oral administration, as after intravenous administration, sildenafil is excreted in the form of metabolites, mainly by 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 groups of patients Elderly patients
In healthy elderly patients (over 65 years of age), the clearance of sildenafil is reduced, and the concentration of free sildenafil in the blood plasma is approximately 40% higher than in young patients (18-45 years of age).
Age does not have a clinically significant effect on the incidence of side effects. Impaired renal function
With mild (creatinine clearance (CL) 50-80 ml/min) and moderate (CL 30-49 ml/min) degrees of renal failure, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change.
In severe renal failure (creatinine clearance ≤ 30 ml/min), the clearance of sildenafil is reduced, which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared to those with normal renal function in patients of the same age group. Liver dysfunction
In patients with liver cirrhosis (stages A and B according to the Child-Pugh classification), the clearance of sildenafil is reduced, which leads to an increase in AUC (84%) and Cmax (47%) compared to those with normal liver function in patients the same age group. The pharmacokinetics of sildenafil in patients with severe liver dysfunction (Child-Pugh stage C) has not been studied.

Indications for use

Treatment of erectile dysfunction, characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse. Sildenafil is only effective during sexual stimulation.

Contraindications

Hypersensitivity to sildenafil or to any other component of the drug Use in patients receiving continuous or intermittent nitric oxide donors, organic nitrates or nitrites in any form, since sildenafil enhances the hypotensive effect of nitrates (see section “Interaction with other drugs”) Safety and the effectiveness of the drug Sildenafil when used together with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see section “Special instructions”) According to the registered indication, the drug Sildenafil is not intended for use in children under 18 years of age. According to the registered indication, the drug Sildenafil not intended for use in women Lactase deficiency, lactose intolerance, glucose-galactose malabsorption. Concomitant use of sildenafil with ritonavir is not recommended.\ With caution

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 section “Special instructions”). Diseases accompanied by bleeding. Exacerbation of peptic ulcer of the stomach and duodenum. Hereditary retinitis pigmentosa (see section “Special instructions”). Heart failure, unstable angina, myocardial infarction, stroke or life-threatening arrhythmias in the last 6 months, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP < 90/50 mm Hg) (see. section "Special instructions"). In patients with episodes of anterior non-arteritic ischemic optic neuropathy (history). Use during pregnancy and breastfeeding
According to the registered indication, the drug is not intended for use in women.

Directions for use and doses

Inside. The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Taking into account effectiveness 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 use is once a day. Renal dysfunction

For mild to moderate renal failure (creatinine clearance 30-80 ml/min), no dose adjustment is required; for severe renal failure (creatinine clearance <30 ml/min), the dose of sildenafil should be reduced to 25 mg.
Liver dysfunction
Since the elimination of sildenafil is impaired in patients with liver damage (particularly cirrhosis), the dose of Sildenafil should be reduced to 25 mg.
Combined use with other drugs
When used together with ritonavir, the maximum single dose of Sildenafil should not exceed 25 mg, and the frequency of use should be 1 time per 48 hours (see section “Interaction with other drugs”).
When used together with inhibitors of the cytochrome CYP3A4 isoenzyme (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Sildenafil should be 25 mg (see section “Interaction with other drugs”). To minimize the risk of postural hypotension in patients taking α-blockers, Sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. You should also consider the advisability of reducing the initial dose of sildenafil (see sections “Special instructions” and “Interaction with other drugs”). Elderly patients
No dose adjustment of Sildenafil is required.

Side effect

Typically, the side effects of Sildenafil are mild or moderate and transient. Fixed-dose studies have shown that the incidence of some adverse events increases with increasing dose.

When using the drug Sildenafil in doses exceeding the recommended ones, adverse events were similar to those noted above, but usually occurred more often. General condition disorders:

facial swelling, photosensitivity reactions, shock, asthenia, pain, chills, abdominal pain, chest pain.
Allergic reactions:
hypersensitivity reactions (including skin rash), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).
Disorders of the central and peripheral nervous system:
drowsiness, insomnia, hypoesthesia, paresthesia, ataxia, neuralgia, neuropathy, tremor, depression, unusual dreams, decreased reflexes, stroke, transient ischemic attack, convulsions, incl.
recurrent. Cardiovascular system disorders:
tachycardia, increased or decreased blood pressure, myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina, AV block, cerebral thrombosis, heart failure, ECG abnormalities, cardiomyopathy, sudden death, syncope.
Respiratory disorders:
nosebleeds, asthma, shortness of breath, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum production, increased cough.
Gastrointestinal disorders: vomiting, nausea, dry oral mucosa, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, rectal bleeding, gingivitis. Visual disorders:
eye pain, eye redness/scleral injections, conjunctival damage, lacrimation disorders, anterior ischemic optic neuropathy, retinal vascular occlusion, visual field defects, mydriasis, cataracts, eye pain.
Hearing disorders:
vertigo, tinnitus, ear pain, deafness.
Blood and lymphatic system disorders:
anemia, leukopenia.
Metabolic and nutritional disorders:
thirst, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.
Musculoskeletal disorders:
arthritis, arthrosis, myalgia, tendon rupture, tendovaginitis, bone pain, myasthenia gravis, synovitis.
Skin and subcutaneous tissue disorders:
urticaria, herpes simplex, itching, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.
Disorders of the genitourinary system:
cystitis, nocturia, frequent urination, gynecomastia, urinary incontinence, ejaculation disorders, genital swelling, anorgasmia.
Reproductive system disorders:
prolonged erection and/or priapism.

Overdose

With a single dose of Sildenafil in doses up to 800 mg, adverse events were comparable to those when taking the drug in lower doses, but were more common. Treatment is symptomatic. Hemodialysis does not accelerate the clearance of sildenafil, since the latter actively binds to plasma proteins and is not excreted by the kidneys.

Interaction with other drugs

The influence of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the influence of the cytochrome CYP3A4 (main pathway) and CYP2C9 isoenzymes, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, accordingly, increase the clearance of sildenafil.
A decrease in the clearance of sildenafil was noted with simultaneous use of inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a nonspecific inhibitor of the cytochrome CYP3A4 isoenzyme, when taken together with sildenafil (50 mg), causes an increase in plasma sildenafil concentrations by 56%. A single dose of 100 mg of sildenafil together with erythromycin (500 mg/day 2 times a day for 5 days), a specific inhibitor of the cytochrome CYP3A4 isoenzyme, against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%. When taking sildenafil (single 100 mg) and saquinavir (1200 mg/day 3 times a day), an inhibitor of HIV protease and cytochrome 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 has no effect on the pharmacokinetics of saquinavir. Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, may cause more severe changes in the pharmacokinetics of sildenafil. The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), an HIV protease inhibitor and a strong inhibitor of cytochrome P450, while achieving a constant concentration of ritonavir in the blood leads to an increase in Cmax of sildenafil by 300% (4 times ), and AUC by 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng/ml (after a single dose of sildenafil alone - 5 ng/ml), which is consistent with information about the pronounced effect of ritonavir on the pharmacokinetics of various cytochrome P450 substrates. Sildenafil has no effect on the pharmacokinetics of ritonavir. The combined use of sildenafil with ritonavir is not recommended. If sildenafil is taken in recommended doses by patients simultaneously receiving strong inhibitors of the cytochrome CYP3A4 isoenzyme, then the Cmax of free sildenafil does not exceed 200 nM, and the drug is well tolerated. A single dose of an antacid (magnesium hydroxide/aluminum hydroxide) does not affect the bioavailability of sildenafil. Inhibitors of the cytochrome CYP2C9 isoenzyme (tolbutamide, warfarin), the cytochrome CYP2D6 isoenzyme (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, 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, Tmax, elimination rate constant and T1/2 of sildenafil or its main circulating metabolite. Effect of sildenafil on other drugs
Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50>150 µmol).
When sildenafil is taken at recommended doses, its Cmax is approximately 1 µmol, so it is unlikely that sildenafil could affect the clearance of substrates of these isoenzymes. Sildenafil enhances the hypotensive effect of nitrates both with long-term use of the latter and when they are prescribed for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated. When taking the α-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) simultaneously in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional reduction in systolic/diastolic blood pressure in the supine position was 7/ 7 mmHg art., 9/5 mm Hg. and 8/4 mm Hg, respectively, and in a standing position – 6/6 mm Hg, 11/4 mm Hg. and 4/5 mmHg, respectively. Rare cases of symptomatic postural hypotension, manifested in the form of dizziness (without fainting), have been reported in such patients. In selected sensitive patients receiving α-blockers, concomitant use of sildenafil may lead to symptomatic hypotension. signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the cytochrome CYP2C9 isoenzyme.
Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome CYP3A4 isoenzyme, at their constant blood levels. 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, no signs of interaction between sildenafil (100 mg) and amlodipine were detected. The average additional reduction in blood pressure in the supine position is 8 mm Hg. (systolic) and 7 mm Hg. (diastolic). The use of sildenafil in combination with antihypertensive drugs does not lead to additional side effects.

special instructions

To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination. Erectile dysfunction treatments 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 section C caution"). Medicines intended to treat erectile dysfunction should not be prescribed to 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 an examination of the condition of the cardiovascular system. Sexual activity is not advisable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP < 90/50 mm Hg. Art.) (see section “With caution”). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular death (0.3 per 100 people per year) in patients treated with Sildenafil compared with patients who received placebo. Cardiovascular complications

During post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) have been reported. ), which had a temporary association 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 occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors. 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 Sildenafil, the physician should carefully assess the risk of possible undesirable manifestations of the vasodilating effect in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system. Since the combined use of sildenafil and α-blockers can lead to symptomatic hypotension in some sensitive patients, Sildenafil should be administered with caution to patients taking α-blockers (see section "Interaction with other drugs"). To minimize the risk of developing postural hypotension in patients taking α-blockers, Sildenafil should be started only after hemodynamic stability has been achieved in these patients. You should also consider the advisability of reducing the initial dose of Sildenafil (see section “Dosage and Administration”). The physician should inform patients about what actions to take if symptoms of postural hypotension occur. Visual disturbances
Rare cases of anterior non-arteritic ischemic optic neuropathy as a cause of deterioration or loss of vision have been reported with the use of all PDE5 inhibitors, including sildenafil.
Most of these patients had risk factors such as optic disc excavation, age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. A cause-and-effect relationship between the use of PDE5 inhibitors and the development of anterior non-arteritic ischemic optic neuropathy has not been identified. The physician should inform the patient about the increased risk of developing anterior non-arteritic ischemic optic neuropathy if this condition has already been noted. In case of sudden loss of vision, patients should receive the necessary medical attention immediately. A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of retinal phosphodiesterases. There is no information on the safety of using Sildenafil in patients with retinitis pigmentosa, so sildenafil should be used with caution (see section "With caution"). Hearing Impairment
Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including sildenafil.
Most of these patients had risk factors for sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. If there is a sudden deterioration in hearing or hearing loss while taking sildenafil, you should consult your doctor immediately. Bleeding
Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide 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, therefore Sildenafil should be used with caution in these patients (see section "With caution"). The incidence of epistaxis in patients with PH 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%). Patients receiving sildenafil in combination with a vitamin K antagonist had a higher incidence of epistaxis (8.8%) than patients not receiving a vitamin K antagonist (1.7%). Use in conjunction with other means of treating erectile dysfunction.
The safety and effectiveness of Sildenafil in combination with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see section “Contraindications”).

Impact on the ability to drive vehicles and operate machinery

While taking sildenafil, no negative effects on the ability to drive a car or use other technical equipment were observed. However, since taking sildenafil may reduce blood pressure, develop chromatopsia, blurred vision, etc. side effects, you should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Release form

Film-coated tablets, 25 mg, 50 mg and 100 mg 1, 2, 4 or 10 tablets per blister pack. 20 tablets in polymer jars or polymer bottles. Each jar, bottle, 1 blister pack of 1, 2, 4 or 10 tablets along with instructions for use are placed in a cardboard box.

Best before date

3 years. Do not use after the expiration date stated on the packaging.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Vacation conditions

On prescription.

Prescription drug

Prescription drug