Erosil of the tab. of 100 mg No. 1

Translation of the instruction Mose

EROSIL of a tablet of 50 mg, tablets of 100 mg

Instruction

on medical use of medicine

Erosil

(erosil)

Ingredients:

Active ingredient: sildenafil;

1 tablet supports a sildenafil of citrate in terms of 100% sildenafit 50 mg;

excipients: lactose, monohydrate; magnesium gluconate; icing sugar; calcium stearate; Lemon fragrance; dye tartrazine (E 102).

Main physical and chemical properties: biconvex tablets of yellow color with impregnations with a distributive hyphen on the one hand and a logo of firm with another.

Dosage form.

Tablet.

50 mg No. 1, 50 of mg No. 2, 50 of mg No. 4;

100 mg No. 1, 100 of mg No. 2, 100 of mg No. 4.

Pharmacotherapeutic group.

Means, applied in erectile dysfunction. sildenafit.

Code of automatic telephone exchange G04B E03.

Pharmacological properties.

Pharmacodynamics.

action Mechanism. Erosil — oral medicine which is applied to treatment of disturbances of an erection at men. Drug represents citrate salt of a sildenafil, selection inhibitor cyclic guanozinmonofosfat (tsGMF) — specific phosphodiesterase of type 5 (FDE5).

Physiological mechanism of an erection of a penis consists in release of nitrogen oxide (NO) in a cavernous body at sexual stimulation. NO activates enzyme guanylate cyclase that causes increase in level of the cyclic guanozinmonofosfat (tsGMF), relaxation of corpulent muscles of a cavernous body and strengthening of inflow of blood to them.

Sildenafil has no direct weakening action on the isolated cavernous human body, but enhances efficiency of nitrogen oxide (NO), oppressing phosphodiesterase of type 5 (FDE5) that is responsible for degradation of tsGMF in a cavernous body.

When at sexual stimulation the local release NO happens, oppression of FDE5 sildenafily causes increase in the tsGMF level in a cavernous body owing to what there occurs relaxation of corpulent muscles and inflow of blood to a cavernous body amplifies.

Use of a sildenafil in the recommended doses is inefficient

in the absence of sexual excitement.

Influence on a pharmacodynamics. The researches in vitro showed that sildenafit FDE5 is selection relatively. Its influence on FDE5 stronger, than other known phosphodiesterases (by 10 times stronger, than FDE6, by 80 times — than FDE1, by 700 times — than FDE2, FDE3, FDE4, FDE7 — FDE11). In particular sildenafit has by 400 times the best selectivity concerning FDE5, than FDE3, tsGMF of a specific isoform of phosphodiesterase which takes part in processes of regulation of warm reductions.

Disorder of vision. At use of a sildenafil in a dose of 100 mg at some patients in 1 hour the easy non-constant disturbance of distinction of color is revealed (by Farnsworth-Munsell 100 test) (blue/green); in 2 hours after administration of medicament these changes disappeared.

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Probable mechanism of disturbance of color sight consider oppression of FDE6 which takes part in the course of transfer of light in a retina. Results of the researches in vitro show that the effect of a sildenafil on FDE6 by 10 times concedes it to activity concerning FDE5. Sildenafil does not affect visual acuity, contrast of perception, the electroretinogram, intraocular pressure or a pupilometriya.

Efficiency. The efficiency of a sildenafil which was estimated concerning ability of medicament to provide approach and preservation of an erection is sufficient for carrying out sexual intercourse, was shown and remained at prolonged use of medicament (1 year).

improvement of an erection was observed by

In a research at reception of a sildenafil in doses of 25 mg 50 mg 100 mg in 62%, 74%, 82% respectively. Except improvement of erectile function, the analysis IIEF (international index of erectile function) showed that treatment sildenafily raises also an orgasm and satisfaction from sexual intercourse.

sildenafily improvement was noted by

At treatment at 59% of patients with diabetes; at patients who transferred radical prostatectomy — 43% sick with an injury of a spinal cord — 83%.

Pharmacokinetics.

Sildenafil is quickly absorbed by

. The maximum plasma concentration of medicament are reached within 30–120 minutes (with a median of 60 minutes) after its oral administration on an empty stomach. The average absolute bioavailability after oral administration is 41% (with a range of values from 25 to 63%). In the recommended range of doses (from 25 to 100 mg) the indicators of AUC and S _max a sildenafila after its oral administration raise in proportion to a dose.

At use of a sildenafil during meal the extent of absorption decreases with average lengthening of T _max to 60 minutes and average decrease in the C _max for 29%.

Average equilibrium volume of distribution (V _d ) is made by 105 l that demonstrates distribution of medicament in body tissues. After single oral administration of a sildenafil in a dose of 100 mg the average maximum general plasma concentration of a sildenafil makes about 440 ng/ml (coefficient of variation is 40%). As linking of a sildenafil and its main N-desmetil-metabolite with proteins of blood plasma reaches 96%, average maximum plasma concentration of a free sildenafil reaches 18 ng/ml (38th nmol). Extent of linking with proteins of blood plasma does not depend on the general concentration of a sildenafil.

At healthy volunteers who applied sildenafit once in a dose 100 mg, in 90 minutes in a ¾yakulyata less than 0.0002% (on average 188 ng) from the applied dose were defined.

Biotransformation. Metabolism of a sildenafil is carried out mainly with the participation of microsomal isoenzymes of a liver of CYP3A4 (main way) and CYP2C9 (minor way). The main circulating metabolite is formed by N-demethylation of a sildenafil. The selectivity of a metabolite in relation to FDE5 is comparable to selectivity of a sildenafil, and the activity of a metabolite in relation to FDE5 is about 50% of activity of initial substance. Plasma concentration of this metabolite make about 40% of concentration of a sildenafil in blood plasma. N-demetilirovanny a metabolite is exposed to further metabolism, and the period of its semi-removal is about 4 hours.

General clearance of a sildenafil is 41 l/h, predetermining the period of its semi-removal lasting 3-5 hours. Both after peroral, and after intravenous use the excretion of a sildenafil in the form of metabolites is carried out mainly with a stake (about 80% of the entered oral dose) and, to a lesser extent, with urine (about 13% of the entered oral dose).

Patients of advanced age. At healthy volunteers of advanced age (the age of 65 years is also more senior) the decrease in clearance of a sildenafil was noted that predetermined increase in plasma concentration of a sildenafil and its active N-demetilirovannogo of a metabolite approximately for 90% in comparison with the corresponding concentration at healthy volunteers of younger age (18–45 years). Due to the age differences in linking with proteins of blood plasma the corresponding increase in plasma concentration of a free sildenafil was about 40%.

Renal failure. At volunteers with renal failures of light and moderate severity (clearance of creatinine from 30 to 80 ml/min.), the pharmacokinetics of a sildenafil remained invariable after its single oral administration in a dose of 50 mg. Averages of AUC and C _max N-demetilirovannogo of a metabolite increased by 126% and 73% respectively in comparison with such indicators at volunteers of similar age without renal failures. However because of high these differences were not interindividual variability significant. At volunteers with heavy renal failures (the clearance of creatinine is lower than 30 ml/min.) the clearance of a sildenafil decreased that led to average increases in AUC and C _max for 100% and 88% respectively in comparison with volunteers of similar age without renal failures. Besides, max AUC and C _values metabolite N-demetilirovannogo considerably increased by 79% and 200% respectively.

Liver failure. At volunteers with cirrhosis of light and moderate severity (classes A and B on classification of Chaylda-Pyyu) the clearance of a sildenafil decreased that led to increase in AUC (84%) and the C _max (47%) in comparison with volunteers of similar age without disturbances of functions of a liver. The pharmacokinetics of a sildenafil at patients with disturbances of functions of a liver of heavy degree was not studied.

Clinical characteristics.

Indication.

Treatment of disturbances of an erection which are defined as inability to reach and support the penis erection necessary for successful sexual intercourse. it is required by

For effective action of Erosil to p sexual excitement.

Contraindication.

— hypersensitivity to active agent or any of medicament excipients.

— Simultaneous use with donors of nitrogen oxide (such as amyle nitrite) or nitrates in any form is contraindicated as it is known that sildenafit influence on ways of metabolism of oxide of nitrogen / cyclic has a guanozinmonofosfata (tsGMF) and exponentiates hypotensive effect of nitrates.

— States at which the sexual activity is not recommended (for example, heavy cardiovascular disorders, such as unstable stenocardia or heart failure of heavy degree).

— Loss of sight on one eye as a result of not arterial front ischemic neuropathy of an optic nerve irrespective of, is connected this pathology with the previous use of FDE5 inhibitors or not.

— Presence of such diseases as an abnormal liver function of heavy degree, arterial hypotension (arterial blood pressure is lower than 90/50 mm Hg.), recently had stroke or a myocardial infarction and the known hereditary degenerative diseases of a retina, such as pigmentary retinitis (a small amount of such patients has genetic disorders of phosphodiesterases of a retina) as safety of a sildenafil was not investigated in such subgroups of patients.

Interaction with other medicines and other types of interactions.

Effects of other medicines on sildenafit

.

Research in vitro.

Metabolism of a sildenafil happens mainly with participation izoform_ 3A4 (the main way) and izoform_ 2C9 (a minor way) P450 cytochrome (CYP) therefore inhibitors of these isoenzymes are capable to reduce clearance of a sildenafil, and inductors of these isoenzymes can increase clearance to a sildenaf_l.

Research in Vivo.

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notes decrease in clearance of a sildenafil at its simultaneous use with CYP3A4 inhibitors (such as ketokonazol, erythromycin, Cimetidinum). Though at simultaneous use of a sildenafil and CYP3A4 inhibitors growth of frequency of by-effects was not observed, the recommended initial dose of a sildenafil makes 25 mg.

Simultaneous use of inhibitor of HIV protease of a ritonavir, very powerful P450 inhibitor, in a condition of equilibrium concentration (500 mg of 1 times a day) and a sildenafila (single dose of 100 mg) led to increase in the maximum concentration (the C _max ) sildenafit for 300% (by 4 times) and to increase in the plasma area under a curve "concentration time" (AUC) sildenafit for 1000% (by 11 times). In 24 hours the plasma levels of a sildenafil still were about 200 ng/ml in comparison with the level about 5 ng/ml characteristic of use sildenafit separately that corresponds to considerable influence of a ritonavir on a wide range of P450 substrates. Sildenafil does not influence pharmacokinetics of a ritonavir. Considering these pharmacokinetic data simultaneous use of a sildenafil and ritonavir is not recommended; anyway the maximum dose of a sildenafil under any circumstances should not exceed 25 mg within 48 hours.

Simultaneous use of inhibitor of HIV protease of a sakvinavar, CYP3A4 inhibitor, in a dose which provides equilibrium concentration (1200 mg three times a day) and a sildenafila (100 mg odnkratno) led to increase in the C _max sildenafit for 140% and to increase in system exposure (AUC) in a sildenafil by 210%. Influence of a sildenafil on pharmacokinetics of a sakvinavir is not revealed. It is supposed that more powerful CYP3A4 inhibitors, such as ketokonazol and itrakonazol, will have more significant influence.

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At use of a sildenafil (100 mg one-time) and erythromycin, moderate CYP3A4 inhibitor, in an equilibrium state (500 mg twice a day within 5 days) observed increase in system exposure of a sildenafil for 182% (AUC). At male healthy volunteers the azithromycin influence (500 mg a day within 3 days) on AUC, S _max , by T _max , a constant of speed of elimination and further elimination half-life of a sildenafil or its main circulating metabolite was not observed. Cimetidinum (inhibitor of P450 cytochrome and nonspecific CYP3A4 inhibitor) in a dose of 800 mg at simultaneous use with sildenafily in a dose of 50 mg at healthy volunteers led to increase in plasma concentration of a sildenafil for 56%.

Grapefruit juice is weak CYP3A4 inhibitor in a wall of intestines and can cause moderate increase in plasma levels of a sildenafil.

Single use of antiacid means (hydroxide aluminum hydroxide magnesium) does not affect bioavailability of a sildenafil.

Though researches of specific interaction with all medicines were not conducted by

, according to the population pharmacokinetic analysis the pharmacokinetics of a sildenafil did not change at its simultaneous use with medicines which belong to group of CYP2C9 inhibitors (tolbutamide, warfarin, Phenytoinum), groups of CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), group of thiazide and tiazidopodobny diuretics, loopback and kaliysberegayushchy diuretics, inhibitors of angiotensin-converting enzyme, antagonists of calcium, antagonists of β-adrenoceptors or inductors of metabolism CYP450 (such as rifampicin, barbiturates).

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It was reported that simultaneous use of the antagonist of endothelin of a bosentan (the moderate inductor CYP3A4, CYP2C9 and, perhaps, CYP2C19) in an equilibrium state (twice for day) and a sildenafila in an equilibrium state (80 mg three times for day) led 125 mg to decrease in AUC and Cmax of a sildenafil by 62.6% and 55.4% respectively. Therefore simultaneous use of such powerful inductors CYP3A4 as rifamp_n, can lead to more significant decrease in concentration a sildenaf_la in blood plasma.

Nikorandil represents a hybrid of the activator of calcium channels and nitrate. The nitrate component predetermines a possibility of its serious interaction with sildenafily.

Effects of a sildenafil on other medicines.

Research in vitro.

Sildenafil — weak inhibitor of isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (_k ₅₀ 150 µmol) P450 cytochrome. As peak plasma concentration of a sildenafil make about 1 µmol, influence of a sildenafil on clearance of substrates of these isoenzymes improbable.

do not have the interactions of a sildenafil and such nonspecific inhibitors of phosphodiesterase given relatively as theophylline and Dipiridamolum.

Research in Vivo.

As knows that sildenafit has influence on nitrogen oxide metabolism / the cyclic guanozinmonofosfat (tsGMF), it was established that this medicament exponentiates hypotensive effect of nitrates therefore its simultaneous use with donors of nitrogen oxide or with nitrates in any form is contraindicated.

simultaneous use of a sildenafil and blockers of α-adrenoceptors can lead

U of some patients predisposed to it to development of symptomatic hypotension that most often arose for 4 hours after use of a sildenafil. During the researches of specific interaction of medicines the blocker of α-adrenoceptors docsazozin (4 mg and 8 mg), also sildenafit (25 mg, 50 mg and 100 mg) applied at the same time to patients with a benign hyperplasia of a prostate whose stabilization of a state was reached at use of a docsazozin. In these studied populations the average additional lowering of arterial pressure in a prone position on 7/7 mm Hg, 9/5 mm Hg and 8/4 mm Hg, and an average lowering of arterial pressure in a standing position on 6/6 mm Hg, 11/4 mm Hg, 4/5 mm Hg respectively was observed. At simultaneous use of a sildenafil and docsazozin to patients whose stabilization of a state was reached at use of a docsazozin, it was sometimes reported about development of symptomatic orthostatic hypotension. In these messages it was talked of cases of dizziness and a preunconscious state, but without syncope.

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did not observe any significant interactions at simultaneous use of a sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg) which are metabolized by CYP2C9.

Sildenafil (50 mg) did not lead

to lengthening of the bleeding time caused by use of acetylsalicylic acid (150 mg).

Sildenafil (50 mg) did not exponentiate hypotensive effect of alcohol of healthy volunteers at the average maximum levels of ethanol of blood of 80 mg/dl.

sildenafit

At patients who applied, no differences of a profile of side effects in comparison with placebo at simultaneous use of such classes of hypotensive medicines were observed as diuretics, blockers of β-adrenoceptors, APF inhibitors, antagonists of angiotensin ІІ, antihypertensive medicines (vasodilating and the central action), blockers of adrenergichny neurons, blockers of calcium channels and blockers of α-adrenoceptors. In a special research of interaction at simultaneous use of a sildenafil (100 mg) and an amlodipina to patients with arterial hypertension the additional decrease in systolic arterial blood pressure in a prone position on 8 mm Hg was observed.

Corresponding decrease in diastolic arterial blood pressure was 7 mm Hg. In size these additional lowerings of arterial pressure were comparable to those which were observed at use only of a sildenafil at healthy volunteers.

Sildenafil in a dose of 100 mg did not influence pharmacokinetic indicators of inhibitors of HIV protease, a sakvinavir and a ritonavir which are CYP3A4 substrates.

Knows that use of a sildenafil in an equilibrium state (80 mg three times for day) led to increase in AUC and Cmax a bosentana (125 mg twice per day) for 49.8% and 42% respectively.

Feature of use.

should collect by

By the beginning of therapy the medical anamnesis of the patient and to perform physical examination for diagnosis of erectile dysfunction and definition of its possible reasons.

Risk factors of cardiovascular diseases. As the sexual activity is followed by a certain risk from heart, by the beginning of any treatment of erectile dysfunction the doctor has to estimate a condition of a cardiovascular system of the patient. Sildenafil has vasodilating effect which is shown by a slight and short-term lowering of arterial pressure. Before purpose of a sildenafil the doctor has to weigh carefully, or can have such effect adverse impact on patients with certain basic diseases, especially in a combination with sexual activity. With hypersensitivity to vazodilatator patients with obstruction of an output path of a left ventricle (for example an aorta stenosis, a hypertrophic subaortic stenosis) or patients with a rare syndrome of a multisystem atrophy, one of manifestations of which heavy heavy disturbance of regulation of arterial blood pressure belong to patients from the autonomic nervous system.

Sildenafil exponentiates hypotensive effect of nitrates.

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It was reported about heavy side reactions from a cardiovascular system, including a myocardial infarction, unstable stenocardia, a sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhages, the tranzitorny ischemic attack, arterial hypertension and arterial hypotension which on time ran together using a sildenafil. Most of patients, but not at all, had risk factors of cardiovascular diseases. Many such side reactions were observed in time or right after sexual intercourse, and happened soon after use of a sildenafil without sexual activity only a few. Therefore it is impossible to define, or development of such side reactions directly is connected with risk factors, or their development is predetermined by other factors.

Priapism. Means for treatment of erectile dysfunction including sildenafit, patients should appoint with care with anatomic deformations of a penis (such as angulation, cavernous fibrosis or Peyroni's disease) or to patients with states which promote development of a priapism (such as crescent and cellular anemia, multiple myeloma or leukemia).

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It was reported about cases of the prolonged erection and a priapism. If the erection lasts more than 4 hours, patients should ask for medical care immediately. In the absence of immediate treatment the priapism can lead to damage of tissues of penis and to permanent loss of potency.

Simultaneous use with other FDE5 inhibitors or other medicaments for treatment of erectile dysfunction. Safety and efficiency of simultaneous use sildenafit with other FDE5 inhibitors or other medicaments for treatment of hypertensia of a pulmonary artery which contain sildenafit (for example Revatsio), or with other medicaments for treatment of erectile dysfunction were not studied. Therefore use of such combinations is not recommended.

Influence on sight. Spontaneous messages about appearance of defects of sight arrived is associated with use of a sildenafil and other FDE5 inhibitors (see the section "Side reactions"). About cases of not arterial front ischemic neuropathy of an optic nerve which is a rare state spontaneous messages came and it was reported in an observation research it is associated with use of a sildenafil and other FDE5 inhibitors (see the section "Side reactions"). Patsiyentov it is necessary to warn what he in case of a sudden disorder of vision of use of the medicament Erosil should be stopped and to see immediately a doctor (see the section "Contraindications").

Simultaneous application with ritonaviry. Simultaneous use of a sildenafil and ritonavir is not recommended (see. section "Interaction with Other Medicines and Other Types of Interactions").

Simultaneous application with blockers of α-adrenoceptors. To patients who apply blockers of α-adrenoceptors to apply sildenafit follows with care as such combination can lead to symptomatic hypotension in some patients, inclined to it. Symptomatic hypotension usually arises within 4 hours after use of a sildenafil. For the purpose of minimization of risk of developing orthostatic hypotension the therapy sildenafily can be begun only at hemodynamically stable patients who apply blockers of α-adrenoceptors. The recommended initial dose represents to such patients 25 mg of a sildenafil. Besides, it is necessary to inform patients how to work in case of symptoms of orthostatic hypotension.

Influence on bleedings. Researches of thrombocytes of the person showed that in vitro sildenafit exponentiates anti-aggregation effects of Natrium nitroprussicum. There is no information concerning safety of use of a sildenafil to patients with disturbances of fibrillation or an acute round ulcer. Thus, use of a sildenafil to patients of this group perhaps only after careful assessment of a ratio of advantage and risk.

Drug Erosil contains lactose therefore it should not be applied to men with such rare inherited disorders as intolerance of a galactose, insufficiency of Lappa lactase or malabsorption of glucose galactose.

Hearing loss. Doctors should advise patients to stop use of FDE5 inhibitors, including the medicament Erosil and to ask immediately for medical care in cases of sudden decrease or a hearing loss. About these phenomena which can be also followed by a ring in ears and dizziness, it was reported with association in time using FDE5 inhibitors, including the medicament Erosil. To define, or these phenomena are directly connected with use of FDE5 inhibitors or with other factors it is impossible.

Simultaneous use with hypotensive drugs. Erosil has systemic vasodilating action and can reduce further arterial blood pressure at patients who apply hypotensive medicines. In a separate research of medical interaction the simultaneous use of an amlodipin (5 mg or 10 mg) and to the medicament Erosil (100 mg) was orally observed average additional decrease in systolic pressure by 8 mm Hg. and diastolic — on 7 mm Hg.

Disease which are transferred sexually. Use of the medicament Erosil does not protect from diseases which are transmitted sexually. It is necessary to consider the possibility to instruct patients of rather necessary preservatives for protection against diseases which are transmitted sexually, including a human immunodeficiency virus.

Use during pregnancy or feeding by a breast.

Drug is not intended to

for use by women.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

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Research of influence of medicament on ability to drive the car or to work with other mechanisms was not conducted.

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As during clinical trials of a sildenafil observed dizziness and a disorder of vision, patients need to know the individual reaction to Erosil's reception before driving the car or to work with other mechanisms.

Route of administration and doses.

Drug is used orally.

Adult. The recommended dose of medicament makes 50 mg and is applied in case of need approximately for an hour to sexual activity. Depending on efficiency and tolerance of medicament it is possible to increase a dose to 100 mg or to lower to 25 mg. The maximum recommended dose makes 100 mg. Frequency of use of the maximum recommended dose of medicament is 1 time a day. At use of medicament during reception of food the effect of medicament can come later, than at its use on an empty stomach.

Patients of advanced age. Need for dose adjustment to patients of advanced age (≥ 65 years) is absent.

Patients with a renal failure. To patients with a renal failure of light and moderate severity (clearance of creatinine of 30-80 ml / hv) the recommended dose of medicament is same as it is given above in the section "Adults".

As at patients with a renal failure of heavy degree (clearance of creatinine

Patients with a liver failure. As at patients with a liver failure (for example cirrhosis) the clearance of a sildenafil is reduced, it is necessary to consider the possibility of use of a dose of 25 mg. Depending on efficiency and tolerance of medicament if necessary it is possible to increase a dose gradually to 50 mg and up to 100 mg.

Patients who apply other medicines. If patients at the same time apply CYP3A4 inhibitors (see the section "Interaction with Other Medicines and Other Types of Interactions"), it is necessary to consider the possibility of use of an initial dose of 25 mg (except for a ritonavir whose use along with sildenafily is not recommended, see the section "Features of Use").

for the purpose of minimization of possible development of postural hypotension in patients who apply blockers of α-adrenoceptors their state needs to be stabilized by means of blockers of α-adrenoceptors prior to use of a sildenafil. Also it is necessary to consider the possibility of use of an initial dose of 25 mg (see the section "Features of Use" and "Interaction with Other Medicines and Other Types of Interactions").

Children.

Drug is not shown to

to use by persons aged up to 18 years.

Overdose.

At use of a single dose of a sildenafil up to 800 mg the side reactions were similar to those which were observed at use of a sildenafil in the lowest doses, but met more often and were heavier. did not lead use of a sildenafil in a dose of 200 mg to increase in efficiency, but caused growth of quantity of cases of development of side reactions (a headache, rushes of blood, dizziness, dyspepsia, congestion of a nose, disturbances from organs of sight).

in case of overdose if necessary are applied by the ordinary supporting actions.

Acceleration of clearance of a sildenafil at a hemodialysis is improbable

as a result of high extent of linking of medicament with proteins of blood plasma and lack of elimination sildenafit with urine.

Side reactions.

such side reactions as a headache, rushes of blood, dyspepsia, congestion of a nose, a dorsodynia, dizziness, nausea, inflows of heat, a disorder of vision, blue vision and an eclipse of sight are Most often possible

.

Infectious and invasive diseases: rhinitis.

from the immune system: hypersensitivity.

from nervous system: headache, dizziness, drowsiness, hypesthesia, stroke, tranzitorny ischemic attack, spasms, recurrence of spasms, syncope.

from organs of sight: disturbance of perception of color, a visual disturbance, an eclipse of sight, slezovideleniye disorder, eye pain, photophobia, a photopsia, hyperaemia of eyes, sight brightness, conjunctivitis, not arterial front ischemic neuropathy of an optic nerve, occlusion of vessels of a retina, retinalniya hemorrhage, an arteriosclerotic retinopathy, disturbance from a retina, glaucoma, defects of a field of vision, a diplopia, decrease in visual acuity, shortsightedness, an asthenopia, floating opacities of a vitreous, disturbance from an iris of the eye, the mydriasis, emergence of the shining circles around a light source (Galo) under review, swelled an eye, a swelling of eyes, disturbances from eyes, hyperaemia of a conjunctiva, irritation of eyes, abnormal feelings, in eyes swelled never, obestsvecheny scleras.

from organs of hearing: a ring in ears, deafness.

from a cardiovascular system: tachycardia, the strengthened heartbeat, a sudden cardiac death, a myocardial infarction, ventricular arrhythmia, fibrillation peredserd, unstable stenocardia, rushes of blood suit, inflows of heat, hypertensia, hypotension.

from a respiratory system, a thorax and mediastinum: congestion of a nose, nasal bleeding, congestion of adnexal bosoms of a nose, feeling of compression in a throat, a rhinedema, dryness in a nose.

from digestive tract: nausea, dyspepsia, a gastroesophageal reflux disease, vomiting, pain in an upper part of a stomach, dryness in a mouth, a hypesthesia of an oral cavity.

from skin and hypodermic fabric: rash, Stephens-Johnson's syndrome, toxic epidermal necrolysis.

from the musculoskeletal system and connective tissue: myalgia, extremity pain.

from an urinary system: hamaturia.

from a reproductive system and mammary glands: bleeding from a penis, a priapism, a gematospermiya, the prolonged erection.

General disorders: stethalgia, increased fatigue, feeling of heat, irritation.

Disorder, revealed as a result of inspection: the increased heart rate.

Expiration date.