Sildenafil instruction and price in pharmacies

active ingredient: sildenafil;

1 tablet contains sildenafil citrate in the transfer to sildenafil 25 mg or 50 mg or 100 mg;

auxiliary substances: microcrystalline cellulose; calcium hydrophosphate; aluminum hydroxide; sodium croscarmellose; poidon; magnesium stearate; silicon dioxide colloidal anhydrous; dry mixture “Opadry II white” containing titanium dioxide (E 171), talc, polyethylene glycol (macrogol), polyvinyl alcohol; indigocarin (E 132);candorin “Silver Shine”.

Medicinal form

Tablets coated

Basic physical and chemical properties: pills covered with a shell, from blue to blue with a mother-of-pearl shade of round shape, with a double-edged surface. Marble is allowed.

Pharmacotherapeutic group

Means used in erectile dysfunction. Sildenafil ATX code G04B E03.

Pharmacological properties

Pharmacodynamics.

The mechanism of action. Sildenafil is an oral drug for the treatment of erectile dysfunction. In sexual excitement, the drug recovers a reduced erectile function by increasing the flow of blood to the penis.

The physiological mechanism that causes erection involves the release of nitric oxide (NO) in cavernous bodies during sexual excitement. Released nitric oxide activates the enzyme guanylate cyclase, which stimulates the increase of the level of cyclic guanosine monophosphate (cGMP), which, in turn, causes relaxation of smooth muscle of the cavernous bodies, contributing to the flow of blood.

Sildenafil is a potent selective inhibitor of cGMP-specific phosphodiesterase 5 (PDE5) in cavernous bodies, where FDE5 is responsible for the disintegration of cGMP. The effect of sildenafil on the erection is peripheral.Sildenafil does not exert a direct relaxing effect on isolated cavernous human body, but potentially enhances the relaxing effect of NO on this tissue. When activating the metabolic pathway NO / cGMP, which occurs during sexual stimulation, inhibition by sildenafil PDE5 leads to an increase in the level of cGMP in cavernous bodies.Thus, in order for sildenafil to produce the desired pharmacological effect, sexual anxiety is required.

Effect on pharmacodynamics. Sildenafil is selective for PDE5, which is actively involved in the erection process.The effect of sildenafil on PDE5 is more powerful than other known phosphodiesterases, in particular, 10 times more potent than the effect on FDE6, which is involved in the processes of photoconversion in the retina. When applying the maximum recommended doses, the selectivity of sildenafil to PDE5 in 80 times exceeds its selectivity to PDE1, 700 times higher than to FDE2, FDEE, FDE4, FDE7, FDE8, FDE9, FDE10 and FDE11. In particular, the selectivity of sildenafil to PDE5 is 4000 times greater than its selectivity to FDEZ – cAMP-specific isoform phosphodiesterase, which is involved in the regulation of cardiac contractility.

Pharmacokinetics.

Absorption. Sildenafil is rapidly absorbed. The maximum plasma concentration of the drug is achieved within 30 to 120 minutes (with a median of 60 minutes) after oral administration on an empty stomach. The mean absolute bioavailability after oral administration is 41% (range from 25 to 63%). In the recommended range of doses (25 to 100 mg), the AUC and C max of sildenafil after oral administration are increased proportionally to the dose.

When taking sildenafil during meals, the degree of absorption decreases with an average extension of T max of 60 minutes and an average decrease of C max by 29%.

Distribution. The average equilibrium volume of distribution (V d ) is 105 liters, which indicates the distribution of the drug in the tissues of the body. After single oral administration of sildenafil in a dose of 100 mg, the mean maximum total plasma concentration of sildenafil is approximately 440 ng / ml (the variation factor is 40%). Since the binding of sildenafil and its major N-desmethyl metabolite to plasma proteins reaches 96%, the mean maximum plasma concentration of free sildenafil reaches 18 ng / ml (38 nmol). The degree of binding to plasma proteins does not depend on the total concentration of sildenafil.

In individuals who used sildenafil once in a dose of 100 mg, 90 minutes in the ejaculate was defined to be less than 0.0002% (an average of 188 ng) of the applied dose.

Biotransformation. The metabolism of sildenafil is mainly due to microsomal isoenzymes of the liver CYP3A4 (main pathway) and CYP2C9 (secondary pathway). The main circulating metabolite is formed by N-demethylation of sildenafil. The selectivity of the metabolite relative to PDE5 is comparable to the selectivity of sildenafil, and the activity of the metabolite relative to PDE5 is approximately 50% of the activity of the starting material. Plasma concentration of this metabolite is about 40% of the concentration of sildenafil in plasma. The N-demethylated metabolite undergoes further metabolism, and T 1/2 is approximately 4 hours.

Elimination. The total clearance of sildenafil is 41 l / h, giving  about 3 – 5 hours. Both oral and intravenous excretion of sildenafil in the form of metabolites is mainly done with feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the oral dose administered).

Pharmacokinetics in special patient groups.

Elderly patients. In elderly patients (aged 65 years) there was a decrease in clearance of sildenafil, which resulted in an increase in plasma concentrations of sildenafil and its active N-demethylated metabolite by approximately 90% compared with the corresponding concentrations in younger subjects (18-45 years). Due to age differences in binding to blood plasma proteins, the corresponding increase in plasma concentration of free sildenafil was approximately 40%.

Renal insufficiency. In subjects with mild to moderate renal impairment (creatinine clearance 30-80 ml / min), the pharmacokinetics of sildenafil remained unchanged after single oral administration at 50 mg. The mean AUC and C max of the N-demethylated metabolite were elevated by 126% and 73% respectively, compared with those in subjects of the same age without impaired renal function. However, due to high individual variability, these differences were not statistically significant. In patients with severe renal impairment (creatinine clearance less than 30 ml / min), the clearance of sildenafil decreased, resulting in a mean increase in AUC and C max of 100% and 88%, respectively, compared with subjects of the same age without impaired renal function. Additionally, the AUC and C max values ​​of the N-demethylated metabolite were significantly increased by 200% and 79% respectively.

Hepatic insufficiency. The clearance of sildenafil decreased in subjects with mild to moderate degree of cirrhosis of the liver (Classes A and B in the Childe-Pugh Classification), which resulted in an increase in AUC (84%) and C max (47%) compared with those of the same age without violations liver function. The pharmacokinetics of sildenafil in patients with severe liver function disorders have not been studied.

Indication

The drug is recommended for men with erectile dysfunction, which is defined as the inability to achieve or maintain the erection of the penis, necessary for a successful sexual intercourse.

For effective drug action, sexual anxiety is required.

Contraindication

  • Hypersensitivity to the active substance or any of the excipients of the drug.
  • Simultaneous administration of nitric oxide (such as amyl nitrite) or nitrates in any form is contraindicated because it is known that sildenafil has an effect on the metabolism of nitric oxide / cyclic guanosine monophosphate (cGMP) and potentiates the hypotensive effect of nitrates.
  • Concomitant use of PDE5 inhibitors (including sildenafil) with guanylate cyclase stimulants, such as riociuugat, is contraindicated, as it can lead to symptomatic hypotension (see section “Interaction with other drugs and other types of interactions”).
  • Conditions in which sexual activity is not recommended (eg severe cardiovascular disorders such as unstable angina or severe heart failure).
  • Eye loss due to non-arterial forward ischemic optic neuropathy, regardless of whether this pathology is associated with prior use of PDE5 inhibitors or not.
  • The presence of such diseases as severe hepatic dysfunction, arterial hypotension (arterial pressure below 90/50 mm Hg), recent stroke or myocardial infarction and known hereditary degenerative retinal diseases such as retinitis pigmentum (a small number of these patients have genetic disorders of the phosphodiesterase of the retina), since the safety of sildenafil was not investigated in such subgroups of patients.

Interaction with other drugs and other types of interactions.

Effects of other drugs on sildenafil. The metabolism of sildenafil occurs predominantly with the isoform Z4 (main path) and isoform 2C9 (secondary pathway) of cytochrome P450 (CYP). Therefore, inhibitors of these isoenzymes can reduce the clearance of sildenafil, and the inducers of these isoenzymes can increase the clearance of sildenafil.

There is evidence of a decrease in the clearance of sildenafil when it is co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although concomitant use of sildenafil and CYP3A4 inhibitors did not increase the incidence of adverse events, the use of an initial dose of sildenafil 25 mg should be considered.

Concomitant use of the HIV-protease inhibitor ritonavir, a very potent CYP inhibitor, in equilibrium (500 mg once daily) and sildenafil (a single dose of 100 mg) resulted in a 300% increase in C max of sildenafil (4-fold) and plasma elevation AUC of sildenafil by 1000% (11 times). After 24 hours, the plasma level of sildenafil was still about 200 ng / ml, compared to about 5 ng / ml, typical of sildenafil alone, which corresponds to a significant effect of ritonavir on a wide range of CYP substrates. Sildenafil does not affect the pharmacokinetics of ritonavir.Given these pharmacokinetic data, the concomitant use of sildenafil and ritonavir is not recommended (see section “Peculiarities of use”); in any case, the maximum dose of sildenafil should under no circumstances exceed 25 mg for 48 hours.

Concomitant use of the HIV-protective protease inhibitor of saquinavir, a CYP3A4 inhibitor, at a dose equivalent to 1200 mg three times a day, and sildenafil (100 mg once) resulted in an increase in C max of sildenafil by 140% and an increase in systemic exposure (AUC) of sildenafil by 210%. The effects of sildenafil on the pharmacokinetics of saquinavir have not been identified (see section “Method of administration and dose”). More potent CYP3A4 inhibitors, such as ketoconazole and itraconazole, are expected to have a more pronounced effect.

Sildenafil systemic exposure to 182% (AUC) was observed when sildenafil (100 mg once) and erythromycin, a moderate inhibitor of CYP3A4, in equilibrium (500 mg twice daily for 5 days) were used. No effects of azithromycin (500 mg daily for 3 days) were observed on AUC, C max , T max , elimination rate constant, and further T ½ sildenafil or its main circulating metabolite. Cimetidine (an inhibitor of cytochrome P450 and a non-specific CYP3A4 inhibitor) at a dose of 800 mg when administered concomitantly with sildenafil 50 mg resulted in a 56% increase in plasma concentrations of sildenafil.

Grapefruit juice is a weak inhibitor of CYP3A4 in the intestinal wall and can cause moderate increases in levels of sildenafil in plasma.

Single use of antacids (magnesium hydroxide / aluminum hydroxide) did not affect the bioavailability of sildenafil.

The pharmacokinetics of sildenafil did not change with its concomitant use with medicinal products belonging to the CYP2C9 inhibitor group (tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-type diuretics, loop and potassium-sparing diuretics, angiotensin converting enzyme inhibitors, calcium antagonists, β-adrenergic antagonists, or CYP metabolism inducers (such as rifampicin, arbituraty).

Concomitant use of an antagonist of endothelin bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly CYP2C19) in equilibrium (125 mg twice daily) and equilibrium sildenafil (80 mg three times daily) resulted in a 62-fold reduction in AUC and C max of sildenafil, 6% and 55.4% respectively. Therefore, the concomitant use of such potent inducers of CYP3A4 as rifampicin may lead to a more pronounced decrease in the concentration of sildenafil in plasma.

Nicorandil is a hybrid of calcium channel activator and nitrate. The nitrate component makes it possible for its serious interaction with sildenafil.

Effects of sildenafil on other medicines. Sildenafil is a weak inhibitor of isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and Z4 cytochrome P450 (IR 50 > 150μmol). Since peak plasma concentration of sildenafil is approximately 1 μmol, the effect of the drug on the clearance of substrates of these isoenzymes is unlikely.

There is no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline and dipyridamole.

As it is known that sildenafil has an effect on the metabolism of nitric oxide / cyclic guanosine monophosphate (cGMP), it has been found that sildenafil potentiates the hypotensive effect of nitrates, therefore its simultaneous use with nitric oxide donors or with any form of nitrates is contraindicated (see section ” Contraindication”).

Riotsiguat Preclinical studies have shown an additive systemic effect of lowering blood pressure, while simultaneous use of PDE5 inhibitors with riocigoate. Clinical studies have shown that riociuugat exacerbates the antihypertensive effect of PDE5 inhibitors. Patients who participated in the study did not show a positive clinical benefit from the simultaneous use of PDE5 inhibitors with riocigoate. Concomitant use of riosciuate with inhibitors of FDE5 (including sildenafil) is contraindicated (see section “Contraindications”).

Simultaneous administration of sildenafil and α-adrenergic blockers may lead to the development of symptomatic hypotension in some patients who are prone to this. This reaction most often occurred within 4 hours after the use of sildenafil (see section “Usage and dose” and “Usage characteristics”). Concurrent use of the α-adrenergic blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) simultaneously in patients with benign prostatic hyperplasia, stabilized in the use of doxazosin, had an average additional reduction in blood pressure in a position lying at 7/7 mm Hg. Art., 9/5 mm Hg. Art. and 8/4 mm Hg. Art. and the average decrease in blood pressure in the position standing at 6/6 mm Hg. Art., 11/4 mm Hg. Art., 4/5 mm Hg. Art. in accordance. At the simultaneous use of sildenafil and doxazosin in patients whose stabilization was achieved with the use of doxazosin, the development of symptomatic orthostatic hypotension, namely, dizziness and arousal, but without syncope, was sometimes reported.

No significant interactions were observed with concomitant use of sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg) metabolised by CYP2C9.

Sildenafil (50 mg) did not lead to prolonged bleeding time caused by acetylsalicylic acid (150 mg).

Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol with an average maximum level of ethanol in the blood of 80 mg / dl.

Patients treated with sildenafil did not observe any differences in the profile of side effects while co-administering such classes of antihypertensive drugs as diuretics, β-adrenergic blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilator and central action), adrenergic blockers neurons, calcium channel blockers and α-adrenergic blockers. When sildenafil (100 mg) and amlodipine were administered concomitantly, patients with arterial hypertension had an additional decrease in systolic blood pressure at a position of 8 mm Hg. Art. The corresponding reduction in diastolic blood pressure was 7 mm Hg. Art. By their size, these additional reductions in blood pressure were comparable to those observed with sildenafil alone.

Sildenafil 100 mg did not affect the pharmacokinetic parameters of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of CYP3A4.

The use of sildenafil in equilibrium (80 mg three times a day) resulted in an increase in AUC and C max ofbosentan (125 mg twice daily) by 49.8% and 42% respectively.

Application features

Prior to the treatment, it is necessary to collect the medical history of the patient and to conduct a physical examination for the diagnosis of erectile dysfunction and to determine its possible causes.

Risk factors for cardiovascular disease.Since sexual activity is accompanied by a certain risk from the heart, before the onset of any treatment for erectile dysfunction, the physician should evaluate the state of the cardiovascular system of the patient. Sildenafil has vasodilating effect, which is manifested by a mild and short-term decrease in blood pressure. Prior to the administration of sildenafil, the physician should carefully consider whether this effect may adversely affect patients with certain underlying diseases, especially in combination with sexual activity. Patients with increased sensitivity to vasodilators include patients with left ventricular outflow tract obstruction (eg, aortic stenosis, hypertrophic obstructive cardiomyopathy) or patients with rare multiple-systemic atrophy syndrome, one of which is a severe disorder of regulation of blood pressure from the autonomic nervous system.

The drug potentiates the hypotensive effect of nitrates (see section “Contraindications”).

Severe adverse reactions were reported from the cardiovascular system, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhages, transient ischemic attack, arterial hypertension and arterial hypotension, which over time coincided with the use of sildenafil. In most patients, but not all, there were risk factors for cardiovascular disease. Many of these adverse reactions were observed during or immediately after sexual intercourse, and only a few occurred shortly after the use of sildenafil without sexual activity. Therefore, it is impossible to determine whether the development of such adverse reactions is directly related to the risk factors, or their development is due to other factors.

Priapism. Means for treating erectile dysfunction, including sildenafil, should be prescribed with caution to patients with anatomical deformities of the penis (such as angulation, cavernous fibrosis, or Peyron’s disease) or patients with conditions that contribute to the development of priapism (such as sickle cell anemia, multiple myeloma or leukemia).

Reported cases of prolonged erection and priapism. If the erection lasts more than 4 hours, patients should seek immediate medical attention. In the absence of immediate treatment, priapism can lead to damage to the penis tissues and to permanent loss of potency.

Concomitant use with other FDE5 inhibitors or other drugs for the treatment of erectile dysfunction. The safety and efficacy of concomitant use of sildenafil with other PDE5 inhibitors or other drugs for the treatment of pulmonary hypertension containing sildenafil or with other drugs for the treatment of erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.

Influence on vision. Spontaneous reports of visual defects have been associated with the use of sildenafil and other PDE5 inhibitors (see section “Adverse Reactions”). Spontaneous reports were reported on cases of non-arterial forward ischemic neuropathy of the optic nerve, and reported as associated with the use of sildenafil and other PDE5 inhibitors (see section “Adverse Reactions”). Patients should be warned that in the event of a sudden visual impairment, the use of the drug should be stopped and immediately contact the doctor (see section “Contraindications”).

Simultaneous application with ritonavir. Simultaneous use of sildenafil and ritonavir is not recommended (see section “Interaction with other drugs and other types of interactions”).

Simultaneous administration with α-adrenergic blockers. Sildenafil should be used with caution in patients using α-adrenergic blockers, since such combination may lead to symptomatic hypotension in some patients who are prone to these events. Symptomatic hypotension usually occurs within 4 hours after the use of sildenafil. In order to minimize the possible development of postural hypotension in patients using α-adrenergic blockers, their condition should be stabilized with α-adrenergic blockers before the use of sildenafil. The starting dose of 25 mg should also be considered (see section “Method of administration and dose”). In addition, patients should be informed about how to deal with symptoms of orthostatic hypotension.

Effect on bleeding. Sildenafil in vitro potentiates the antiagregative effects of sodium nitroprusside. There is no safety information on the use of sildenafil in patients with impaired blood coagulation or acute peptic ulcer. Thus, the use of sildenafil in patients with this group is possible only after careful assessment of the benefit / risk ratio.

After application of a dose of 100 mg, no effect on morphology or sperm motility is observed.

Loss of hearing. Doctors should advise patients to discontinue the use of PDE5 inhibitors, including sildenafil, and seek immediate medical attention in the event of a sudden decrease or loss of hearing. These phenomena, which may also be accompanied by a ringing in the ears and dizziness, have been reported to the association in time with the use of PDE5 inhibitors, including sildenafil. It is impossible to determine whether these phenomena are directly related to the use of FDE5 inhibitors or other factors.

Simultaneous use with antihypertensive drugs. Sildenafil carries a systemic vasodilator effect and can further reduce blood pressure in patients who use antihypertensive drugs. When concomitant administration of amlodipine (5 mg or 10 mg) and sildenafil (100 mg), an average supplemental decrease in systolic pressure of 8 mm Hg was observed orally. Art. and diastolic – at 7 mm Hg. Art.

Sexually Transmitted Diseases. Application of the drug does not protect against sexually transmitted diseases. It is necessary to instruct patients about the necessary preventive measures to protect against sexually transmitted diseases, including the human immunodeficiency virus.

Use during pregnancy or breastfeeding

The drug is not intended for use by women.

Ability to influence the reaction rate when driving with motor vehicles or other mechanisms

Studies on the effect of the drug on the ability to drive vehicles and work with other mechanisms was not carried out. Since sildenafil has been reported as having dizziness and vision impairment, patients need to find out what their individual reaction to the drug is before driving a vehicle or operating machinery.

Method of administration and dose

The drug is used orally.

Adults The recommended dose of the drug is 50 mg and is used, if necessary, approximately an hour before sexual activity. Depending on the efficacy and tolerability of the drug, the dose may be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The frequency of application of the maximum recommended dose of the drug is 1 time per day. When using the drug during meals, the effect of the drug may come at a later time than when it is used on an empty stomach.

Elderly patients. There is no need to adjust the dose to elderly patients (≥ 65 years).

Patients with renal insufficiency. For patients with mild and moderate renal insufficiency (creatinine clearance of 30-80 ml / min), the recommended dose of the drug is the same as described above in the section “Adults”.

Since in patients with severe renal insufficiency (clearance of creatinine <30 ml / min) the clearance of sildenafil is reduced, a dose of 25 mg should be considered. Depending on the efficacy and tolerability of the drug, if necessary, the dose can be increased gradually to 50 mg and up to 100 mg.

Patients with hepatic insufficiency. Because in patients with hepatic insufficiency (eg cirrhosis), clearance of sildenafil is reduced, a dose of 25 mg should be considered. Depending on the efficacy and tolerability of the drug, if necessary, the dose can be increased gradually to 50 mg and up to 100 mg.

Patients who use other medicines. If patients simultaneously use CYP3A4 inhibitors (see section “Interaction with other drugs and other types of interactions”), the use of an initial dose of 25 mg (with the exception of ritonavir, which is not recommended concomitantly with sildenafil, should be considered, see section “Peculiarities of the use »)

In order to minimize the possible development of postural hypotension in patients using α-adrenergic blockers, their condition should be stabilized with α-adrenergic blockers before the use of sildenafil. You should also consider the use of an initial dose of 25 mg (see section “Features of Use” and “Interaction with Other Drugs and Other Interactions”).

Children

The drug is not indicated for use by persons under the age of 18 years.

Overdose

At a single dose of sildenafil up to 800 mg, adverse reactions were similar to those observed with lower doses of sildenafil, but were more frequent and more severe. The use of 200 mg sildenafil did not result in increased efficacy but increased the incidence of adverse reactions (headache, tidal, dizziness, dyspepsia, nasal congestion, visual impairment).

In case of overdose, regular supportive measures should be taken if necessary. Acceleration of clearance of sildenafil in hemodialysis is unlikely due to the high degree of binding of the drug to plasma proteins and the absence of elimination of sildenafil with urine.

Adverse reactions

Infectious and invasive diseases: rhinitis.

From the immune system: Hypersensitivity.

On the nervous system: headache, dizziness, drowsiness, hypothesis, stroke, transient ischemic attack, seizures, recurrent seizures, syncope, ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes, anxiety , transient global amnesia.

Visual disturbances : disturbances of color perception (chloropenia, chromatopsia, cyanopsia, erythropoiesis, xanthopsis), visual impairment, eye disturbances, sore throat disorders (dryness in the eyes, disturbances of sore throat and increased lacrimation), pain in the eyes, photophobia, photophobia, eye hyperemia , visual acuity, conjunctivitis, occlusion of the retina, retinal hemorrhage, arteriosclerotic retinopathy, retinal damage, glaucoma, visual field defects, diplopia, visual acuity reduction, myopia, asthenia, floating turbidity of vitreous tonsil latia, irritation from the iris, mydriasis, the appearance of shining circles around the source of light (halo) in the field of vision, swelling of the eyes, swelling of the eyes, violation of the eyes, conjunctiva hyperemia, eye irritation, abnormal sensations in the eyes, swelling of the eyelids, blurred sclera, eye bleeding, cataract, dry eyes, temporary loss of vision, redness of the eyes, burning in the eyes, increased intraocular pressure, edema of the retina, vascular diseases of the retina or bleeding, detachment of the vitreous body.

Reported cases of non-arterial forward ischemic neuropathy of the optic nerve, which causes the loss of vision, including permanent vision loss that has been associated with the use of PDE5 inhibitors, including sildenafil.Many of the patients, but not all, had available anatomical or vascular risk factors for the development of non-arterial forward ischemic optic neuropathy, including (but not necessarily limited to) the following: the low ratio of the diameter of the digestion and the optic nerve (steady-state optic disc), age more more than 50 years old, hypertension, coronary artery disease, hyperlipidemia and smoking. It is impossible to determine whether these events are associated with the use of PDE5 inhibitors or with available anatomical or vascular risk factors, or with a combination of all these factors or with other factors.

On the organs of the hearing and vestibular apparatus: ringing in the ears, deafness, earache.

There have been reported cases of sudden decrease or loss of hearing associated with timing with the use of sildenafil. In some cases, there were reports of medical conditions and other factors that could play a role in the development of hearing impaired reactions. In many cases there is no information on further medical surveillance. It is impossible to determine whether these effects are directly related to the use of sildenafil, with available risk factors for hearing loss, with a combination of these factors or with other factors.

From the side of the heart: tachycardia, heart palpitations, sudden cardiac death, myocardial infarction, ventricular arrhythmia, atrial fibrillation, unstable angina, angina pectoris, AV block, myocardial ischemia, sudden cardiac arrest, ECG disturbances, cardiomyopathy.

From the vessels: blood flushes, blood flow to the face, hot flushes, hypertension, hypotension, migraine, postural hypotension, thrombosis of the vessels of the brain.

Severe cardiovascular, cerebrovascular and vascular events, including cerebrovascular haemorrhage, subarachnoid and intracerebral bleeding and pulmonary haemorrhages, were associated with time with sildenafil.Most patients, but not all, had existing cardiovascular risk factors. It has been reported that many of these events occurred during or immediately after sexual activity, and several events arose immediately when using sildenafil without sexual activity. Other effects have arisen over the next few hours or days after the use of sildenafil and sexual activity. It is impossible to establish whether these effects are directly related to the use of sildenafil, with sexual activity, with existing risk factors, or with a combination of these factors, or with other factors.

From the respiratory system, the chest and mediastinum: nasal congestion, nasal bleeding, nasal congestion, sore throat sensation, nasal congestion, dryness in the nose, asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation , tightening cough.

From the digestive tract: nausea, dyspepsia, gastroesophageal reflux disease, vomiting, pain in the upper abdomen, dry mouth, hypoesthesia of the oral cavity, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, disturbances of liver tests, rectal bleeding , gingivitis.

From the skin and subcutaneous tissue: rash, Stevens-Johnson syndrome, Lyell’s syndrome, urticaria, herpes, itching, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

From the musculoskeletal system and connective tissue: myalgia, limb pain, arthritis, arthrosis, tendon rupture, tenosinovitis, bone pain, myasthenia, synovitis.

From the urinary system: hematuria, cystitis, nocturia, increased frequency of urination, urinary incontinence.

From the reproductive system and mammary glands: bleeding from the penis, priapism, hematospermia, prolonged erection, breast enlargement, ejaculation, edema of the genital organs, anorgasmia.

From the system of blood and lymphatic system: anemia, leukopenia.

The development of vaso-occlusive crises requiring hospitalization was reported when sildenafil was administered to patients with pulmonary arterial hypertension, secondary to serotonucleic anemia. The clinical relevance of this information for patients who use the drug for the treatment of erectile dysfunction is unknown.

Metabolism and nutrition disorders: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

General disorders and administration site reactions: chest pain, fatigue, feeling of heat, irritation, facial edema, photosensitivity reaction, shock, asthenia, pain, sudden loss, abdominal pain, sudden damage, back pain.

Survey: Increased heart rate.

Reporting suspected adverse reactions . The reporting of suspected adverse reactions after registration of a medicinal product is important. This allows continuous monitoring of the relationship between benefit and risks associated with the use of this drug. Doctors should report any suspected adverse reactions in accordance with legal requirements.

Expiration date.

3 years (dosage 25 mg) from the date of manufacture of the drug in the package «in bulk».

5 years (dosage of 50 mg or 100 mg) from the date of manufacture of the drug in the package “in bulk”.

Storage conditions. Store in original packaging at a temperature not exceeding 25  C.

Keep out of the reach of children.

Packaging.

Tablets № 1, №4 (1×4) in the blister boxes in the box.

Category of departure. By prescription.

Producer

Limited Liability Company “Pharmaceutical Firm” Verteks “.