Inside, if necessary, with a little water. The recommended dose is 50 mg, which is taken as needed, about 1 hour before the expected sexual activity. Depending on the efficacy and tolerability, the dose of Sildenafil-SZ can be increased to 100 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of use of the drug is 1 time / day. Special patient groups In elderly patients, dose adjustment of Sildenafil-SZ is not required. In case of mild and moderate renal failure (CC 30-80 ml / min), dose adjustment is not required; in severe renal failure (CC less than 30 ml / min), the dose of Sildenafil-SZ should be reduced to 25 mg. Taking into account the effectiveness and tolerability, the dose can be increased to 50 mg and 100 mg. Since the elimination of sildenafil is impaired in patients with impaired liver function (for example, with liver cirrhosis), the dose of the drug should be reduced to 25 mg. Taking into account the effectiveness and tolerability, the dose can be increased to 50 mg and 100 mg. Concomitant use with other drugs Concomitant use of ritonavir is contraindicated. When used simultaneously with inhibitors of the CYP3A4 isoenzyme (such as ketoconazole, erythromycin, cimetidine, with the exception of ritonavir), the initial dose of Sildenafil-SZ should not exceed 25 mg. To reduce the likelihood of developing orthostatic hypotension, it is necessary to achieve a stable state of hemodynamics during therapy with alpha-blockers before starting the use of sildenafil. The initial dose of Sildenafil-SZ should be reduced to 25 mg.

Hypersensitivity to sildenafil or to any other component of the drug; simultaneous use with donors of nitric oxide (NO) (for example, amyl nitrite) or nitrates in any form, since sildenafil can enhance the antihypertensive effect of nitrates (mediated through NO / cGMP); drugs for the treatment of erectile dysfunction, including sildenafil, should not be used in men who are not recommended for sexual activity (for example, patients with severe cardiovascular diseases such as unstable angina pectoris or severe heart failure); the safety and efficacy of sildenafil in combination with other drugs for the treatment of erectile dysfunction has not been studied; therefore, simultaneous use is contraindicated; concomitant use with ritonavir is contraindicated; loss of vision in one eye due to anterior ischemic optic neuropathy of non-arterial genesis, regardless of whether or not it is associated with the use of PDE-5 inhibitors; use is contraindicated in: severe liver dysfunction, arterial hypotension (blood pressure less than 90/50 mm Hg), recent cerebral circulation disorder or myocardial infarction, phenylketonuria, hereditary retinal dystrophies (hereditary degenerative retinal diseases), such as retinitis pigmentosa ( some patients have genetic defects of retinal phosphodiesterases), since the safety of using the drug Sildenafil-SZ in such patients has not been studied. According to a registered indication,

Sildenafil-SZ is not intended for use in children under 18 years of age and women.

Carefully

• arterial hypertension (blood pressure more than 170/100 mm Hg);
• life-threatening arrhythmias;
• obstruction of the outflow tract of the left ventricle of the heart (aortic stenosis, hypertrophic obstructive cardiomyopathy (GOKMP));
• multiple system atrophy syndrome; anatomical deformity of the penis (angulation, cavernous fibrosis, or Peyronie's disease); conditions that predispose to priapism (sickle cell anemia, multiple myeloma, or leukemia);
• simultaneous intake of alpha-blockers;
• bleeding diseases; exacerbation of stomach ulcer or duodenal ulcer;
• history of episodes of development of anterior non-arteritic ischemic neuropathy of the optic nerve.

Application during pregnancy and lactation:

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

Application for violations of liver function:

Since the elimination of sildenafil is impaired in patients with impaired liver function (for example, with liver cirrhosis), the dose of the drug should be reduced to 25 mg.

Application for impaired renal function:

In case of mild and moderate renal failure (CC 30-80 ml / min), dose adjustment is not required; in severe renal failure (CC less than 30 ml / min), the dose of Sildenafil-SZ should be reduced to 25 mg.

Application in children:

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

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

When sildenafil was used in clinical trials, the most common adverse reactions were: headache, hot flashes, dyspepsia, visual impairment, nasal congestion, dizziness, and color deficiency (chromatopsia). Classification of the incidence of side effects, according to WHO: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥ 1/10000 to <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from available data). In each group, adverse effects are presented in order of decreasing severity. From the immune system: rarely - hypersensitivity reactions. From the nervous system: very often - headache; often - dizziness; infrequently - drowsiness, hypesthesia; rarely - cerebral circulation disorder, fainting; frequency unknown - transient ischemic attack, convulsions, recurrent seizures. From the side of the organ of vision: often - visual impairment, impaired color perception (chromatopsia); infrequently - damage to the conjunctiva, impaired lacrimation, other disorders of the organ of vision; frequency unknown - anterior ischemic optic neuropathy of non-arterial genesis, occlusion of retinal vessels, visual field defect. On the part of the organ of hearing and labyrinth disorders: often - vertigo, tinnitus; rarely - deafness *. From the side of the vessels: often - a feeling of "hot flashes"; rarely - increase / decrease in blood pressure. From the heart: infrequently - palpitations, tachycardia; rarely - myocardial infarction, atrial fibrillation; frequency unknown - ventricular arrhythmia, unstable angina pectoris, sudden cardiac death. From the respiratory system: often - nasal congestion; rarely: nosebleeds. From the gastrointestinal tract: often - dyspepsia; infrequently - vomiting, nausea, dryness of the oral mucosa. On the part of the skin and subcutaneous tissues: infrequently - skin rash; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome). From the musculoskeletal system: infrequently - myalgia. From the urinary system: infrequently - hematuria. From the genitals and mammary gland: infrequently - hematospermia, bleeding from the penis; frequency unknown - priapism, prolonged (prolonged) erection. General reactions: infrequently - chest pain, increased fatigue. Laboratory and instrumental data: infrequently - an increase in heart rate.

* Hearing impairment: sudden deafness. Sudden hearing loss or loss has been observed in a small number of cases in post-marketing studies or clinical trials with all PDE5 inhibitors, including sildenafil.

The effect of other drugs on the pharmacokinetics of sildenafil:

In vitro studies: Sildenafil metabolism mainly occurs under the action of cytochrome P450 isoenzymes: CYP3A4 (major route) and CYP2C9 (minor route). Therefore, inhibitors of these isoenzymes can reduce the clearance of sildenafil.

In vivo studies:

In a population pharmacokinetic analysis of the results of a clinical study, a decrease in the clearance of sildenafil was revealed with the simultaneous use of inhibitors of the isoenzyme CYP3A4 (such as ketoconazole, erythromycin, cimetidine). At the same time, there was no increase in the frequency of adverse events in these patients. For patients taking inhibitors of the isoenzyme CYP3A4, it is recommended to start treatment with sildenafil with a dose of 25 mg. The simultaneous use of sildenafil (100 mg 1 time / day) with an HIV protease inhibitor - ritonavir (500 mg 2 times / day) (a potent inhibitor of cytochrome P450) increases the Cmax and AUC of sildenafil in blood plasma by 300% (i.e., 4 times) and 1000% (i.e., 11 times), respectively. After 24 hours, the concentration of sildenafil in the blood plasma was approximately 200 ng / ml (when taking sildenafil alone - 5 ng / ml). Given the results of a pharmacokinetic study, concomitant use of sildenafil with ritonavir is contraindicated. The simultaneous use of an HIV protease inhibitor - saquinavir (an inhibitor of the isoenzyme CYP3A4) in an equilibrium state (1200 mg 3 times / day) with sildenafil (100 mg 1 time / day) increases the Cmax and AUC of sildenafil by 140% and 210%, respectively. Sildenafil has no effect on the pharmacokinetics of saquinavir. It is likely that more potent inhibitors of the isoenzyme CYP3A4 (ketoconazole and itraconazole) have a more pronounced effect on the pharmacokinetics of sildenafil.

With the simultaneous use of sildenafil (100 mg once) with erythromycin (a specific inhibitor of the isoenzyme CYP3A4) in an equilibrium state (500 mg 2 times / day for 5 days), the AUC of sildenafil increases by 182%. In healthy volunteers, azithromycin (500 mg per day for 3 days) does not cause changes in pharmacokinetic parameters (AUC, Cmax, TCmax, elimination rate or T1 / 2 of sildenafil or its main circulating metabolite.

Cimetidine (a non-specific inhibitor of the isoenzyme CYP3A4) (800 mg) in healthy volunteers increases the concentration of sildenafil (50 mg) in blood plasma by 56%.

Grapefruit juice, a weak inhibitor of the CYP3A4 isoenzyme in the intestinal wall, may slightly increase the plasma concentration of sildenafil.

A single use of an antacid (magnesium hydroxide and aluminum hydroxide) does not alter the bioavailability of sildenafil.

Although the interaction with the drugs listed below has not been specifically studied, population pharmacokinetic analysis did not reveal changes in the pharmacokinetics of sildenafil when used simultaneously with: inhibitors of the isoenzyme CYP2C9 (such as tolbutamide, warfarin, phenytoin), inhibitors of the isoenzyme CYP2D6 (such as selective serotonin inhibitors ), thiazides and thiazide-like diuretics, loop and potassium-sparing diuretics, ACE inhibitors, calcium channel blockers, beta-blockers or inducers of the CYP450 isoenzyme (such as rifampicin and barbiturates).

Nicorandil is a hybrid of a potassium channel activator and nitrate. Due to the presence of nitrate in the drug, a serious interaction with sildenafil is possible.

Effect of sildenafil on the pharmacokinetics of other drugs

In vitro studies:

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50> 150 μmol). The Cmax of sildenafil after taking the recommended doses is approximately 1 μmol, therefore it is unlikely that sildenafil affects the clearance of substrates of these isoenzymes. There is no data on the interaction of sildenafil with non-specific PDE inhibitors, such as theophylline or dipyridamole.

In vivo studies:

Sildenafil has an effect on the NO / cGMP system, therefore it enhances the hypotensive effect of nitrates. Simultaneous use with NO donors (such as amyl nitrite) or nitrates in any form is contraindicated.

In some patients, the simultaneous use of sildenafil with alpha-blockers can lead to the development of symptomatic arterial hypotension. Arterial hypotension most often develops within 4 hours after taking sildenafil. In clinical trials, the use of sildenafil (25 mg, 50 mg or 100 mg) was studied while taking the alpha-blocker - doxazosin at doses of 4 mg or 8 mg in patients with benign prostatic hyperplasia and stable hemodynamics. An additional decrease in blood pressure was revealed in the horizontal position of the patient, on average, by 7/7, 9/5, and 8/4 mm Hg. Art. respectively, and in an upright position - on average, by 6/6, 11/4 and 4/5 mm Hg. Art. In patients with stable hemodynamics while taking doxazosin when added to therapy with sildenafil, there have been rare cases of symptomatic orthostatic hypotension, clinically manifested by dizziness, but without the development of fainting.

Interactions of sildenafil (50 mg) with golbutamide (250 mg) or warfarin (40 mg), which are metabolized by the CYP2C9 isoenzyme, have not been identified. Sildenafil (50 mg) does not cause additional prolongation of bleeding time when used simultaneously with acetylsalicylic acid (150 mg).

Sildenafil (50 mg) does not potentiate the hypotensive effect of ethanol in healthy volunteers (Cmax of ethanol in serum was, on average, 80 mg / dl). Undesirable effects of antihypertensive drugs, incl. diuretics, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, vasodilators, centrally acting drugs, adrenergic neuron blockers, slow calcium channel blockers and alpha-blockers did not differ in patients who used sildenafil or placebo. In a study to study the drug interaction of the simultaneous use of sildenafil (100 mg) with amlodipine in patients with arterial hypertension, an additional decrease in the horizontal position of systolic blood pressure by 8 mm Hg was noted. Art. and diastolic blood pressure - by 7 mm Hg. Art. The additional reduction in blood pressure is comparable to that with sildenafil alone in healthy volunteers.

Sildenafil (100 mg) in the equilibrium state did not affect the pharmacokinetic parameters of HIV protease inhibitors: saquinavir and ritonavir, which are substrates of the CYP3A4 isoenzyme.

Symptoms: with a single dose of sildenafil in doses up to 800 mg, adverse reactions are similar to those when the drug is taken at lower doses, while the severity and frequency increased. Taking sildenafil at a dose of 200 mg did not lead to an increase in efficacy, but the frequency of adverse reactions (headache, hot flashes, dizziness, dyspepsia, nasal congestion, visual impairment) increased.

Treatment: symptomatic. Hemodialysis is ineffective, since sildenafil is strongly bound by blood plasma proteins and is not excreted by the kidneys.

Before using drug therapy, it is necessary to assess the history and conduct a clinical examination in order to diagnose erectile dysfunction and identify its possible causes. Drugs for the treatment of sexual dysfunction, including sildenafil, should be used with caution in patients with anatomical deformities of the penis (such as angulation, cavernous fibrosis, or Peyronie's disease) and in patients with conditions predisposing to priapism (such as sickle cell anemia, multiple myeloma or leukemia). Medicines for the treatment of erectile dysfunction, including sildenafil, should not be used in men who are not recommended for sexual activity. Sexual activity poses a certain risk in the presence of diseases of the cardiovascular system. Therefore, before starting any therapy for erectile dysfunction, it is necessary to assess the patient's condition. The use of sildenafil is contraindicated in patients with heart failure, unstable angina pectoris, myocardial infarction or stroke, arterial hypotension (blood pressure <90/50 mm Hg) in the last 6 months. Sexual activity is undesirable for patients with life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg). There is no difference in the incidence of myocardial infarction (1.1 per 100 person-years) and the rate of mortality from cardiovascular diseases (0.3 per 100 person-years) when using sildenafil compared with patients in the placebo group.

Cardiovascular complications:

With the post-marketing use of sildenafil, serious cardiovascular events (associated in time with the use of sildenafil) have been reported, including myocardial infarction, unstable angina pectoris, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, and arterial hypertension. Most of the patients had cardiovascular risk factors. Many of the complications developed during or immediately after intercourse, and some soon after sildenafil was used without sexual activity. It is impossible to determine the causal relationship with any factors.

Decrease in blood pressure:

Sildenafil has a systemic vasodilator effect, leading to a slight and transient decrease in blood pressure. Before using sildenafil, the physician should carefully assess the risk of possible unwanted vasodilating effects in patients with relevant diseases, especially against the background of sexual activity. An increased susceptibility to vasodilators is observed in patients with left ventricular outflow tract obstruction (eg, aortic stenosis, GOKMP) or the rare multiple systemic atrophy syndrome, manifested by severe impairment of autonomic BP regulation.

Concomitant use with alpha-blockers:

Sildenafil should be used with caution in patients taking alpha-blockers, since the simultaneous use of sildenafil and alpha-blockers can lead to symptomatic arterial hypotension in some susceptible patients. Arterial hypotension most often develops within 4 hours after taking sildenafil. PDE5 inhibitors, including sildenafil, and alpha-blockers are vasodilators with an antihypertensive effect. With the simultaneous use of vasodilators, an excessive decrease in blood pressure may develop. Patients with unstable hemodynamics on the background of the use of alpha-blockers are at an increased risk of developing symptomatic arterial hypotension when used simultaneously with PDE-5 inhibitors. To minimize the risk of orthostatic hypotension in such patients, sildenafil therapy should be started only after hemodynamic parameters have stabilized while taking alpha-blockers. Consideration should be given to reducing the starting dose of sildenafil to 25 mg. If the patient is already receiving sildenafil, alpha-blockers should be started at a low dose. With simultaneous use with PDE-5 inhibitors, a further decrease in blood pressure may be associated with a gradual increase in the dose of alpha-blockers. In addition, the doctor should explain to the patient what actions to take if orthostatic hypotension develops (for example, dizziness, lightheadedness, loss of consciousness). When these symptoms appear, the patient should sit down or take a horizontal position.

Visual impairment:

With the use of all PDE-5 inhibitors, including sildenafil, in rare cases, the development of anterior ischemic optic neuropathy of non-arterial genesis was observed, which was accompanied by deterioration or loss of vision. Most of these patients had risk factors such as excavation (deepening) of the optic nerve head, age over 50, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia, and smoking. A causal relationship between the use of PDE-5 inhibitors and the development of anterior ischemic optic neuropathy of non-arterial genesis has not been established. In case of sudden loss of vision, the patient should receive immediate medical attention and discontinue use of Sildenafil-SZ. A small number of patients with hereditary retinitis pigmentosa have genetically determined defects in retinal phosphodiesterases. The safety of sildenafil in patients with retinitis pigmentosa has not been studied, therefore the use in these patients is contraindicated.

Hearing impairment:

Cases of sudden hearing loss or loss have been reported in patients with all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for hearing loss or hearing loss. No correlation was found between the use of PDE-5 inhibitors and hearing impairment. In case of sudden hearing loss or loss, it is necessary to stop using Sildenafil-SZ and consult a doctor immediately. A causal relationship between the use of PDE-5 inhibitors and sudden hearing loss or loss has not been established.

Bleeding: 

Sildenafil potentiates the antiplatelet effect of sodium nitroprusside (NO donor) in vitro. There is no information on the safety of sildenafil in patients with bleeding or peptic ulcers in the acute stage. Therefore, sildenafil should be used with caution in these patients only after a careful assessment of the benefit / risk ratio.

Simultaneous use with other drugs:

drugs intended for the treatment of 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 contraindicated. Sildenafil-SZ is not intended for use in women.

Influence on the ability to drive vehicles and mechanisms:

There are no data on the negative effect of the drug Sildenafil-SZ in the recommended doses on the ability to drive a car or work with mechanisms. Patients should assess their individual susceptibility to taking Sildenafil-SZ, since a decrease in blood pressure, the development of visual impairment (chromatopsia, blurred vision) and dizziness are possible, especially at the beginning of treatment and when changing the dosage regimen.

 

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