Sildenafil-SZ, pills 100mg, 14pcs

Composition

1 tab. sildenafil (in the form of citrate)100 mg

Auxiliary substances:

microcrystalline cellulose – 83.5 mg,

lactose monohydrate (milk sugar) – 83.5 mg,

croscarmellose sodium (primellose) – 15 mg,

povidone (polyvinylpyrrolidone medium molecular weight) – 15 mg,

magnesium stearate-3 mg.

Shell composition:  

Opadray II (polyvinyl alcohol, partially hydrolyzed-3.6 mg, titanium dioxide (E171) – 2.061 mg, macrogol (polyethylene glycol 3350) – 1.818 mg, talc-1.332 mg, aluminum varnish based on diamond blue-0.1728 mg, iron oxide (II) yellow (E172) – 0.0153 mg, iron oxide (II) black (E172) – 0.0009 mg).

Pharmacological action

Pharmacodynamics

Sildenafil is a potent selective inhibitor of cGMP-specific 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 nitric oxide (NO) by inhibiting PDE-5, which is responsible for the breakdown of cGMP.

Sildenafil is selective for PDE-5 in vitro, its activity against PDE-5 exceeds that of other known PDE isoenzymes: PDE-6 — by 10 times; PDE-1-by more than 80 times; PDE-2, PDE-4, PDE-7 — PDE-11 — by more than 700 times. Sildenafil is 4000 times more selective for PDE-5 compared to PDE-3, which is of crucial importance, since PDE-3 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 ECG changes in healthy volunteers. The maximum decrease in sBP in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg, and dBP-5.3 mm Hg. 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 in a single dose of 100 mg in 14 patients with severe 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 sBP 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 with 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 events was comparable to that in other patient groups, as well as in individuals taking more than three antihypertensive medications.

Studies of visual impairments. In some patients,1 hour after taking sildenafil at a dose of 100 mg, the Farnsworth-Mansel 100 test revealed a slight and transient violation of the ability to distinguish shades of color (blue/green).2 hours after taking the drug, these changes were absent. It is believed that color vision disorders are caused by inhibition of PDE-6, which is involved in the process of light transmission in the retina of the eye. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, IOP, 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, Hamuri perimeter, and photostress).

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). The effectiveness of the drug was evaluated globally using the erectile diary, the international index of erectile function (validated questionnaire on the state of sexual function) 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 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 versus 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,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 is on average about 40% (from 25 to 63%). In vitro, sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) suppresses the activity of human PDE-5 by 50%. After a single 100 mg dose of sildenafil, the average Cmax of free sildenafil in the blood plasma of men is about 18 ng / ml (38 nM) and is achieved when sildenafil is taken orally on an empty stomach for an average of 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not change significantly (AUC decreases by 11%).

The distribution

of sildenafil Vss 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 the drug. Less than 0.0002% of the sildenafil dose (average 188 ng) was detected in semen 90 minutes after taking the drug.

Metabolism

Sildenafil is primarily metabolized in the liver by the cytochrome SURZA 4 isoenzyme (major pathway) and the cytochrome SURZA 2C9 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 against PDE is comparable to that of sildenafil, and its activity against PDE-5 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; T1 / 2 is about 4 hours.

Deduction

The total clearance of sildenafil is 41 l / h, and the final T1/2 is 3-5 hours. After oral use, as well as after intravenous use, sildenafil is excreted as 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 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 (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 do not change after a single oral dose of 50 mg. 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 with normal renal function in patients of the same age group.

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

Contraindications

— apTreatment 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).

Drugs intended for the treatment of 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 a cardiovascular examination. 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 > 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-SZ compared to patients treated with placebo.

Cardiovascular complications

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) 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.

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 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 combined use of sildenafil and alpha-blockers can lead to symptomatic hypotension in some sensitive patients, Sildenafil-SZ should be prescribed with caution to patients taking alpha-blockers. To minimize the risk of postural hypotension in patients taking alpha-blockers, Sildenafil-SZ should be started only after the hemodynamic parameters have stabilized in these patients. Consideration should also be given to reducing the initial dose of Sildenafil-SZ. The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Visual impairments

Rare cases of anterior non-arteritic ischemic optic neuropathy have been reported as causes of visual impairment or loss with all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as an excavated optic disc, age over 50 years, diabetes mellitus, hypertension, CHD, hyperlipidemia, and smoking. No causal relationship was found between the use of PDE5 inhibitors and the development of anterior non-arteritic ischemic optic neuropathy. The doctor should inform the patient about the increased risk of developing anterior non-arteritic ischemic neuropathy of the optic nerve, if this condition has already been noted. In case of sudden loss of vision, patients should immediately receive the necessary medical care. 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-SZ in patients with retinitis pigmentosa, so sildenafil should be used with caution.

Hearing disorders

Some post-marketing and clinical 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 sildenafil, you should immediately consult your doctor.

Bleeding issues

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. The incidence of nosebleeds 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 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%).

Use in conjunction with other means of treating erectile dysfunction.

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

Influence on the ability to drive motor vehicles and manage mechanisms

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

However, since taking sildenafil may reduce blood pressure, develop chromatopsia, blurred vision and other 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.

Form of production

Film-coated tablets of blue color, round, biconvex; on the break – white or almost white color.

Storage conditions

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

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Sildenafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets