active ingredient: sildenafil;
1 coated tablet contains sildenafil citrate equivalent to sildenafil 50mg or 100mg
auxiliary substances: microcrystalline cellulose, calcium hydrophosphate anhydrous, sodium croscarmellose, magnesium stearate, Opadry II cyan 31K80956 (lactose, hypromellose, titanium dioxide (E 171), triacetin, Indigo (E 132)), Opadry transparent 02K19253 (hypromellose, triacetin) , purified water.
Basic physico-chemical properties:
tablets of 50 mg: blue, round, biconvex film-coated tablets, embossed "125" on one side and embossed "J" and the fault line-on the other;
100 mg tablets: blue, round, biconvex film-coated tablets, embossed " 126 "on one side and embossed" J " and fault line on the other.
Remedies used for erectile dysfunction. Sildenafil. ATC code G04B E03.
Pharmacological. Sildenafil is an oral drug intended for the treatment of erectile dysfunction. In sexual arousal drug restores reduced erectile function by increasing blood flow to the penis.
The physiological mechanism that leads to erection, including the release of nitric oxide (NO) in cavernous bodies during sexual arousal. The released nitric oxide activates the enzyme guanylate cyclase, which stimulates an increase in the level of cyclic guanosine monophosphate (cGMP), which, in turn, causes relaxation of the smooth muscles of cavernous bodies, contributing to blood flow.
Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase 5 (PDE-5) in cavernous bodies, where PDE-5 is responsible for the breakdown of cGMP. The effects of sildenafil on erection are peripheral character. Sildenafil does not have a direct relaxing effect on isolated human cavernous bodies, but powerfully enhances the relaxing effect of NO on this tissue. When you activate a metabolic pathway NO/cGMP, what happens when sexual stimulation, inhibition of PDE5 sildenafilom leads to increased levels of cGMP in the cavernous bodies. Thus, in order for sildenafil to cause the necessary pharmacological effect, sexual arousal is necessary.
In vitro studies have shown the selectivity of sildenafil exposure to PDE-5, which is actively involved in the erection process. The effect of sildenafil on PDE5 is more powerful than on other known phosphodiesterases. This effect is 10 times more powerful than the effect on PDE6, which is involved in the processes of photo-rotation in the retina. When using the maximum recommended doses of selectivity of sildenafil in PDE-5 to 80 times greater than its selectivity for ФДЕ1, 700 times higher than in ФДЕ2, PDAS, ФДЕ4, ФДЕ7, ФДЕ8, ФДЕ9, ФДЕ10 and ФДЕ11. In particular, the selectivity of sildenafil in PDE5 4000 times greater than its selectivity for FDEZ - cGMP-specific PDE isoforms involved in the regulation of cardiac contractility.
There is evidence that specific clinical studies have been conducted to assess the time during which the use of sildenafil leads to erections in response to sexual stimulation. In clinical studies involving patients treated with sildenafil fasting, during peoplesmart the median time to beginning of erection of patients who achieved erections with rigidity of 60% (sufficient to complete sexual intercourse) was 25 minutes (range 12-37 minutes) . In another study using rigiscan sildenafil was still able to cause an erection 4-5 hours after application.
Sildenafil causes a slight and short-term decrease in blood pressure, in most cases, has no clinical manifestations. The average maximum decrease in systolic blood pressure in the lying position after oral administration of sildenafil at a dose of 100 mg was 8.4 mm Hg. the corresponding change in diastolic blood pressure in the lying position was 5.5 mm Hg. these decreases in blood pressure are in good agreement with the vasodilating effect of sildenafil, possibly due to increased levels of cGMP in the smooth muscle of the blood vessels. Single oral administration of sildenafil at a dose of up to 100 mg in healthy volunteers did not cause any clinically significant changes in ECG.
There are data on the study of the hemodynamic effects due to a single oral sildenafil in a dose of 100 mg in patients with severe coronary artery disease (stenosis at least one coronary artery more than 70%): the average systolic and diastolic blood pressure at rest decreased by 7% and 6% respectively relative to the original level. The average pulmonary systolic blood pressure decreased by 9%. Sildenafil would not lead to a change in the parameters of cardiac output and did not reduce blood flow through stenosed coronary arteries.
No clinically significant differences were demonstrated for time to the occurrence of limiting angina with the use of sildenafil compared to placebo in studies using the exercise test in patients with erectile dysfunction and chronic stable angina pectoris who are constantly used antianginal medications (except nitrates).
Easy and temporary violation of the ability to distinguish colors (blue/green) was detected in some patients after 1:00 after the application of sildenafil at a dose of 100 mg. These effects completely disappeared in 2:00 after the drug administration. A possible mechanism for this change in color recognition is associated with inhibition of PDE6 involved in the photoperetic cascade of reactions in the retina. Sildenafil does not affect visual acuity or contrast sensitivity. In studies involving patients with documented macular dystrophy, the use of sildenafil (once at a dose of 100 mg) did not cause significant changes in the results of the studies (visual acuity, Amsler grid, simulation of traffic light color recognition, Humphrey perimeter and photostress).
Single oral administration of sildenafil at a dose of 100 mg by healthy volunteers had no effect on sperm motility or morphology.
There are clinical studies of the use of sildenafil in patients aged 19 to 87 years. The following groups of patients were presented: elderly patients, patients with hypertension, patients with diabetes, coronary artery disease, hyperlipidemia, spinal cord injuries, depression, transurethral resection of the prostate gland, radical prostatectomy. Patient groups were not represented or were not included in clinical studies: patients after surgery on the organs of the pelvis, patients post-radiotherapy, patients with severe renal or hepatic impairment and patients with certain cardiovascular diseases.
In fixed dose studies, the number of patients reported to have improved erectile function was higher than in the placebo group. In controlled clinical studies, the number of sildenafil cancellations was low and similar to those in the placebo group.
In all these studies, patients reported improvement in the application of sildenafil with psychogenic erectile dysfunction mixed erectile dysfunction, organic erectile dysfunction, elderly patients, diabetes, coronary heart disease, hypertension, transurethral resection of the prostate, radical prostatectomy, spinal cord injury, depression. The safety and efficacy of sildenafil has been confirmed by these long-term studies.
Absorption. Sildenafil is rapidly absorbed. The maximum plasma concentration of the drug is achieved within 30-120 minutes (with a median of 60 minutes) after its oral administration on an empty stomach. The average bioavailability after oral administration is 41% (with a range of values from 25 to 63%). In the recommended dose range (25 to 100 mg), AUC and max sildenafil after oral administration are increased in proportion to the dose.
In the application of sildenafil during meals extent of absorption is reduced, with an average lengthening of the T max of 60 minutes and an average reduction in C max of 29%.
Distribution. The average equilibrium volume of distribution (V d ) is 105 liters, which indicates the distribution of the drug in the body tissues. After a single oral administration of sildenafil at a dose of 100 mg, the average maximum total plasma concentration of sildenafil is approximately 440 ng/ml (coefficient of variation is 40%). Since the binding of sildenafil and its main N-desmetil metabolite to plasma proteins reaches 96%, the average 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 concentrations of sildenafil.
There is evidence that in healthy volunteers who received sildenafil once at a dose of 100 mg, after 90 minutes, less than 0.0002% (an average of 188 ng) of the dose was determined in the ejaculate.
Metabolism. Sildenafil metabolism is carried out mainly with the participation of microsomal liver isoenzymes CYP3A4 (the main path) and CYP2C9 (minor route). The main circulating metabolite is formed by n-demethylation of sildenafil. The selectivity of the metabolite relative to PDE - 5 is comparable to the selectivity of sildenafil, and the activity of the metabolite relative to PDE-5 is approximately 50% of the activity of the starting substance. The plasma concentration of this metabolite is approximately 40% of the concentration of sildenafil in plasma. N-demethylated metabolite undergoes further metabolism, during its half-life is approximately 4:00.
Breeding. The total clearance of sildenafil is 41 l/h, which leads to its half-life 3-5 hours. Both after administration and after administration, sildenafil excretion in the form of metabolites is carried out mainly with feces (about 80% of the oral dose) and to a lesser extent - with urine (about 13% of the oral dose).
Patients of advanced age. There is evidence that healthy elderly volunteers (over 65 years) had decreased clearance of sildenafil, which led to an increase in plasma concentrations of sildenafil and its active N-demetilirovannogo metabolite by about 90% compared with the corresponding concentrations in healthy young volunteers (18-45 years). Due to age differences in plasma protein binding, the corresponding increase in the plasma concentration of free sildenafil was approximately 40%.
Renal failure. In patients with impaired renal function or moderate (creatinine clearance 30 to 80 ml/min) the pharmacokinetics of sildenafil was unchanged after a single oral dose of 50 mg. Average AUC and C max of the N-demethylated metabolite increased 126% and 73%, respectively, compared to such indicators in volunteers of similar age without renal dysfunction. However, due to the high individual variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance below 30 ml/min), sildenafil clearance was reduced, which resulted in average increases in AUC and C max of 100% and 88%, respectively, compared to volunteers of similar age without renal dysfunction. In addition, the AUC and C max of the N-demethylated metabolite significantly increased 79% and 200%, respectively.
Liver failure. In volunteers with cirrhosis of the liver, mild and moderate (classes a and B according to the classification of child Pugh) clearance of sildenafil decreased, which led to an increase in AUC (84%) and C max (47%) compared with volunteers of the same age without impaired liver function. Pharmacokinetics of sildenafil in patients with impaired hepatic function was not studied heavily.
Treatment of erection disorders, which are defined as inability to achieve and maintain the erection of the penis necessary for successful sexual intercourse.
For the effective action of the drug requires sexual arousal.
Hypersensitivity to the active substance or any of the auxiliary substances of the drug.
Concurrent use of nitric oxide donors (such as amyl nitrite) or nitrates in any form is contraindicated because it is known that sildenafil affects the metabolic pathways of nitric oxide/cyclic guanosine monophosphate (cGMP) and potentiates hypotensive effect of nitrates.
The simultaneous use of inhibitors PDE-5 (including sildenafil) called guanylate cyclase stimulants such as riociguat, is contraindicated because it may lead to symptomatic hypotension (see Section "Interaction with other medicinal products and other forms of interaction").
Conditions in which sexual activity is not recommended (e.g., severe cardiovascular disorders such as unstable angina and severe heart failure).
Loss of vision by one eye due to nonarterial anterior ischemic neuropathy of the optic nerve, regardless of whether this pathology is associated with previous use of PDE-5 inhibitors or not.
The abnormal liver function, severe, hypotension (blood pressure below 90/50 mm Hg. St.), Recently moved stroke or myocardial infarction and known hereditary degenerative retinal disorders such as retinitis pigmentosa (a small number of these patients have genetic disorders of retinal PDE) , as the safety of sildenafil has not been investigated in these subgroups of patients.
Interaction with other medicinal products and other forms of interaction
The effect of other drugs on sildenafil.
Metabolism of sildenafil occurs mainly with the participation of the ZA4 isoforms (major route) and 2C9 isoforms (minor route) cytochrome P450 (CYP). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance.
The decrease in clearance of sildenafil was demonstrated while the use of CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although the simultaneous use of sildenafil and CYP3A4 inhibitors and increase in the frequency of side effects was not observed, the recommended initial dose of sildenafil is 25 mg.
The simultaneous use of HIV protease inhibitor, a very powerful P450 inhibitor, in a state of equilibrium concentration (500 mg once a day) and sildenafil (a single dose of 100 mg) led to an increase in C max sildenafil by 300% (4 times) and an increase in plasma AUC sildenafil by 1000% (11 times). After 24 hours, plasma levels of sildenafil were still approximately 200 ng/ml compared to about 5 ng/ml, typical of sildenafil alone, corresponding to the significant effect of ritonavir on a wide range of P450 substrates. Sildenafil does not affect the pharmacokinetics of ritonavir. Given these pharmacokinetic data, the simultaneous use of sildenafil and ritonavir is not recommended; in any case, the maximum dose of sildenafil under what circumstances should not exceed 25 mg for 48 hours.
Coadministration of protease inhibitors HIV of saquinavir, a CYP3A4 inhibitor, at a dose that provides the equilibrium concentration (1200 mg three times daily) and sildenafil (100 mg dose) led to an increase in sildenafil C max 140% and an increase in systemic exposure (AUC) to sildenafil by 210%. No influence of sildenafil on the pharmacokinetics of saquinavir was revealed. It is assumed that more potent CYP3A4 inhibitors such as ketoconazole and Itraconazole will have a more pronounced effect.
In the application of sildenafil (100 mg dose) and erythromycin, a specific CYP3A4 inhibitor, at steady state (500 mg twice a day for 5 days) was observed increase in systemic exposure to sildenafil 182% (AIS). Healthy male volunteers had no effect of azithromycin (500 mg for 3 days) on AUC, with max , t max , elimination rate constant and subsequent half-life of sildenafil or its main circulating metabolite. Cimetidine (cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor) at a dose of 800 mg, while the use of sildenafil at a dose of 50 mg in healthy volunteers led to an increase in plasma concentrations of sildenafil by 56%.
Grapefruit juice is a weak CYP3A4 inhibitor in the intestinal wall and can cause moderate increases in plasma levels of sildenafil.
One-time use of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.
Although specific interaction studies with all drugs has not been conducted, according to the population pharmacokinetic analysis pharmacokinetics of sildenafil has not changed while the use of drugs belonging to the group of inhibitors of CYP2C9 (tolbutamide, warfarin, phenytoin) and inhibitors of CYP2D6 (such as selective inhibitors of serotonin reuptake, tricyclic antidepressants), thiazide group and tiazidopodobnye diuretics, loop and potassium-sparing diuretics, inhibitors of the enzyme angiotensin peretvorjuvach, calcium antagonists, antagonists of beta-adrenergic receptors, or inducers of CYP450 metabolism (such as rifampicin, barbiturates).
Nicorandil is a hybrid of calcium channel activator and nitrate. Nitrate component determines the possibility of its serious interaction with sildenafil.
The effect of sildenafil on other drugs.
Sildenafil is a weak inhibitor of isoform 1A2, 2C9, 2C19, 2D6, 2E1 and ZA4 (IR 50 > 150 µmol) of cytochrome P450. Since the peak plasma concentrations of sildenafil are approximately 1 µmol, the effect of the drug on the clearance of substrates of these isoferments is unlikely.
There is no evidence of the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline and dipyridamole.
Since it is known that sildenafil affects the metabolism of nitric oxide/cyclic guanosine monophosphate (cGMP), it was found that this drug potentiates the hypotensive effect of nitrates, so its simultaneous use with nitric oxide donors or nitrates in any form is contraindicated.
The simultaneous use of sildenafil and alpha-adrenoreceptor blockers can lead to the development of symptomatic hypotension in some predisposed patients. This reaction often occurs within 4: 00 after the use of sildenafil. In the course of the research the specific interaction between drugs blocker alpha-adrenergic doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) was used simultaneously to patients with benign hyperplasia of the prostate, stabilization of a condition which was achieved with the use of doxazosin. In these populations there was an average additional decrease of arterial pressure in the lying position by 7/7 mm Hg. art., 9/5 mm Hg. article and 8/4 mm Hg. C. the average reduction of blood pressure in the standing position on 6/6 mm Hg. art., 11/4 mm Hg. art., 4/5 mm Hg. the article under. While the use of sildenafil and doxazosin in patients, the stabilization of which was achieved by the use of doxazosin, sometimes reported the development of symptomatic orthostatic hypotension. In these, it has been reported cases of dizziness and faint as before, but without syncope.
No significant interactions were observed with simultaneous use of sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), which were metabolized by CYP2C9.
Sildenafil (50 mg) did not lead to an increase in bleeding time caused by acetylsalicylic acid (150 mg).
Sildenafil (50 mg) without potentiating the antihypertensive the effect of alcohol in healthy volunteers at medium maximum levels of ethanol in the blood 80 mg/DL.
Patients receiving sildenafil, there was no difference in side effect profile compared to placebo while the use of such classes of antihypertensive drugs, like diuretics, beta-adrenergic receptors, ACE inhibitors, angiotensin II antagonists, antihypertensive medicinal products (vasodilator and centrally acting) , adrenergic neuron blockers, calcium channel blockers and blockers of alpha-adrenergic receptors. In a special study of interaction with the simultaneous use of sildenafil (100 mg) and amlodipine in patients with hypertension, there was an additional decrease in systolic blood pressure in the lying position of 8 mm Hg. reduction of diastolic blood pressure was 7 mm Hg. article the magnitude of these additional reductions in blood pressure were comparable with those observed with the use of sildenafil in healthy volunteers.
Sildenafil at a dose of 100 mg did not affect the pharmacokinetic parameters of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of CYP3A4.
Riociguat. These studies showed additive systemic effect of lowering blood pressure, while the use of inhibitors PDE-5 riociguat. Patients who participated in the studies did not observed clinical effect of the simultaneous application of inhibitors of PDE-5 riociguat. Contraindicated simultaneous application riociguat with inhibitors PDE-5 (including sildenafilom) (see Section "Contraindications").
Prior to therapy, it is necessary to collect the medical history of the patient and conduct a physical examination to diagnose erectile dysfunction and determine its possible causes.
Since sexual activity is accompanied by a certain risk from the heart, before any treatment of erectile dysfunction, the doctor should assess the state of the cardiovascular system of the patient. Sildenafil has a vasodilating effect, which is manifested by a slight and short-term decrease in blood pressure. Prior to sildenafil's appointment, the physician should carefully consider whether such an effect can have an adverse effect on patients with certain underlying diseases, especially when combined with sexual activity. To patients with hypersensitivity to vasodilators include patients with obstruction of the excretory tract of the left ventricle (eg aortic stenosis, hypertrophic obstructive cardiomyopathy), or patients with a rare syndrome, Multisystem atrophy, one manifestation of which is severe dysregulation of blood pressure the autonomic nervous system.
The drug potentiates the hypotensive effect of nitrates.
Severe adverse reactions 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 coincided with the use of the drug, were reported. In most patients, but not all, there was the risk factors of cardiovascular diseases. Many of these adverse reactions were observed during or immediately after sexual intercourse, and only a few occurred shortly after use of the drug without sexual activity. Therefore, it is impossible to determine whether the development of such adverse reactions is directly related to risk factors or their development is due to other factors.
Funds for the treatment of erectile dysfunction, including sildenafil, should be administered with caution in patients with anatomical deformities of the penis (such as angulation, cavernous fibrosis or Peyronie's disease) or patients with conditions that contribute to the development of priapism (such as sickle cell anemia, multiple myeloma or leukemia).
Safety and efficacy of simultaneous use of sildenafil with other methods of treatment of erectile dysfunction were studied. Therefore, the use of such combinations is not recommended.
Visual disorders and non-arterial anterior ischemic optic neuropathy associated with sildenafil and other PDE-5 inhibitors were reported. Patients should be warned that in case of sudden visual impairment of the drug should be stopped and immediately consult a doctor.
Simultaneous use of sildenafil and ritonavir is not recommended.
Patients taking alpha-adrenoreceptor blockers should use sildenafil with caution, since this combination can lead to symptomatic hypotension in some predisposed patients. Symptomatic hypotension usually occurs within 4: 00 after the use of sildenafil. To minimize the risk of orthostatic hypotension, sildenafil therapy should be started only in hemodynamically stable patients taking alpha-adrenoreceptor blockers. The recommended starting dose for such patients is 25 mg of sildenafil. In addition, patients should be informed how to act in case of symptoms of orthostatic hypotension.
Studies of human platelets have shown that in vitro sildenafil potentiates the antiplatelet effects of sodium nitroprusside. There is no information regarding the safety of the use of sildenafil in patients with coagulation disorders or acute peptic ulcer disease. Thus, the use of sildenafil in patients of this group is possible only after a thorough assessment of the ratio of benefit and risk.
Film shell tablets contains lactose. The drug should not be used for men with such rare hereditary disorders as galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Hearing loss. Physicians should advise patients to stop use of inhibitors of PDE5, including sildenafil, and seek immediate medical help in case of sudden decrease or loss of hearing. These phenomena, which may also be accompanied by tinnitus and dizziness, have been reported to the Association over time with the use of PDE-5 inhibitors, including sildenafil preparations. It is impossible to determine whether these phenomena are associated with the use of PDE-5 inhibitors or other factors.
The simultaneous use of antihypertensive drugs. Sildenafil has systemic vasodilatory effect and may further reduce blood pressure in patients using antihypertensive drugs. In a separate study of drug interaction with simultaneous use of amlodipine (5 mg or 10 mg) and sildenafil (100 mg), an average additional reduction in systolic pressure by 8 mm of Hg was orally observed. art. and diastolic-7 mm Hg. art.
Sexually transmitted diseases. The use of sildenafil does not protect against sexually transmitted diseases. Consideration should be given to instructing patients on the necessary precautions to protect against sexually transmitted diseases, including human immunodeficiency virus.
Fertility. After taking 100 mg healthy volunteers had no effect on the morphology or mobility of sperm.
Application during pregnancy and lactation.
The drug is not intended for use by women.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms.
Studies of the effect of the drug on the ability to drive vehicles and work with other mechanisms were not carried out.
Since the use of sildenafil reported cases of dizziness and visual impairment, before you get behind the wheel of a vehicle or work with mechanisms, patients need to find out what their individual reaction to the use of the drug.
Method of application and doses
The drug is used orally.
For the effective action of the drug requires sexual arousal.
The recommended dose is 50 mg and is used, if necessary, about an hour before sexual intercourse. Depending on the effectiveness and tolerance of the drug dose can be increased to 100 mg or reduced to 25 mg. the Maximum recommended dose is 100 mg.
The maximum recommended frequency of the drug is 1 time per day. In applying the drug during eating effect of the drug may occur later than when applying it on an empty stomach.
Patients of advanced age.
There is no need for dose correction in elderly patients.
Patients with renal insufficiency.
For patients with mild to moderate renal insufficiency (creatinine clearance of 30 to 80 ml/min), the recommended dose is similar to the dose indicated above in the Adults section.
Since in patients with severe renal insufficiency (creatinine clearance below 30 ml/min) sildenafil clearance is reduced, the recommended dose is 25 mg. depending on the efficacy and tolerance of the drug, the dose can be increased to 50 mg and 100 mg.
Patients with liver failure.
Because patients with hepatic insufficiency (e.g. cirrhosis), sildenafil clearance is reduced, recommended dose is 25 mg depending on efficacy and tolerability the dose may be increased to 50 mg and 100 mg.
Patients using other drugs (e.g. ketoconazole, erythromycin, cimetidine, ritonavir) Detailed information is given in the section "Interaction with other medicinal products and other forms of interaction".
The recommended initial dose of the drug to patients who use CYP3A4 inhibitors, with the exception of ritonavir, the use of which is not recommended with sildenafilom, is 25 mg.
In order to minimize the risk of orthostatic hypotension the condition of patients taking alpha-adrenoreceptor blockers, we need to stabilize before sildenafil can be used. The recommended initial dose of sildenafil is 25 mg.
The drug is indicated for use by persons under the age of 18 years.
When applying a single dose of sildenafil to 800 mg adverse reactions were similar to those observed in the application of sildenafil at lower doses, but were more common and were heavier. The use of sildenafil at a dose of 200 mg did not lead to increased efficiency, but caused an increase in the number of cases of adverse reactions (headache, blood spills, dizziness, dyspepsia, nasal congestion, visual impairment).
In case of overdose, if necessary, resort to the usual supportive measures. Acceleration of clearance of sildenafil in hemodialysis is unlikely due to the high degree of binding of the drug with plasma proteins and the lack of elimination of sildenafil with urine.
The most common adverse reactions were headache, blood spills, dyspepsia, visual impairment, nasal congestion, dizziness and impaired color perception.
All clinically significant adverse reactions, which were observed in studies more often than in placebo, are listed below in accordance with the classification "System-organ-class" and frequency: very often (? 1/10), often (? 100 and <1/10 ), infrequently (? 1000 and <1/100) and rarely (? 10000 and <1/1000). In addition, the frequency of clinically significant adverse reactions which were reported in post-marketing experience, defined as unknown.
From the immune system: rarely-hypersensitivity reactions.
From the nervous system: very often - headache; often - dizziness, rarely - drowsiness, hypesthesia; rare a stroke, fainting; frequency is unknown transient ischemic attack, seizures, recurrent court.
From the organ of vision: often-visual impairment, impaired color perception infrequently - disorders of the conjunctiva, tear, other disorders of the organs of vision; the frequency is unknown-nearterial anterior ischemic neuropathy of the optic nerve, vascular occlusion of the retina, visual field defects.
On the part of hearing and vestibular apparatus: uncommon - vertigo, tinnitus rare deafness (the number of reported cases of sudden hearing loss or sudden hearing loss in the case of PDE5, including sildenafil).
From the vessels: often-tides of blood to the face; rarely-hypertension, hypotension.
From the heart: infrequently-tachycardia, tachycardia rarely-myocardial infarction, atrial fibrillation frequency unknown-ventricular arrhythmia, unstable angina, sudden cardiac death.
From the respiratory system of the chest and credos