Vizarsin tab. Q-tab disp. 100 mg No. 4

Pharmacological properties

Pharmacodynamics. sildenafit - it is the oral therapeutic means applied to treatment of disturbances of an erection at men. in particular, at sexual stimulation it restores the broken erection by strengthening of inflow of blood to a penis.

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 the tsGMF level, relaxation of unstriated muscles of a cavernous body and strengthening of inflow of blood in them.

Sildenafil is a powerful selection inhibitor of specific FDE-5 of tsGMF in a cavernous body where FDE-5 — responsible for disintegration of tsGMF. Sildenafil possesses the peripheral center of action on an erection. Sildenafil does not render the direct weakening effect on the isolated cavernous human body, but considerably enhances the weakening effect NO on this fabric. At activation of a way NO/tsGMF which takes place at sexual stimulation the oppression of FDE-5 by means of a sildenafil leads to increase in the tsGMF levels in a cavernous body. Therefore sexual stimulation that sildenafit is necessary made target positive pharmacological impact.

Research in vitro was shown that sildenafit is FDE-5 selection relatively which is involved in process of an erection. Its influence is more expressed on FDE-5, than on other known FDE. There is a 10-fold selectivity concerning FDE-6 which is involved in process of phototransformation in a retina. At most recommended doses there is a 80-fold selectivity concerning FDE-1 and more 700-fold — FDE-2,-3,-4,-7,-8,-9,-10 and-11 is relative. In particular, sildenafit has more than 4000-fold selectivity concerning FDE-5, than FDE-3, the FDE tsGMF-specific isoform which takes part in control of reduction of heart.

Pharmacokinetics. Absorption. Sildenafil is quickly absorbed. The C _max which were observed, reached within 30–120 min. (on average 60 min.) after oral administration are able on an empty stomach. The average absolute oral bioavailability is 41% (range of 25-63%). After oral administration of a sildenafil of AUC and C _max increase in proportion to increase in a dose within the recommended dosing range (25–100 mg).

At reception of a sildenafil together with food the speed of absorption decreases with an average delay in t _max 60 min. and with average decrease in the C _max for 29%.

Distribution. The average volume of distribution in a stable state (V _d ) for a sildenafil is 105 l that demonstrates its penetration into fabrics. After intake of a single dose of 100 mg the average maximum general concentration of a sildenafil in blood plasma makes about 440 ng/ml (CV 40%). As sildenafit (and its main metabolite of N-dezmetil in the general circle of blood circulation) for 96% contacts proteins of blood plasma, it leads to average C _max a free sildenafil in blood plasma of 18 ng/ml (38 Hm). Linking with proteins does not depend on the general concentration of drug.

At the healthy volunteers accepting (100 mg once), less than 0.0002% (on average 188 ng) the entered dose were defined in an ejaculate in 90 min. after a dosage.

Metabolism. Sildenafil is mainly metabolized by means of microsomal isoenzymes of a liver of CYP 3A4 (the main way) and CYP 2C9 (a minor way). The main metabolite in the general blood-groove is formed by N-demethylation of a sildenafil. This metabolite has selectivity to FDE similar to a sildenafil, and activity of in vitro for FDE-5 about 50% of initial drug. Concentration of this metabolite in blood plasma makes about 40% of those concentration which were observed for a sildenafil. N-dezmetil metabolite is metabolized further with final T _½ about 4 h

Removal. The general clearance of a sildenafil is 41 l/h with the final phase T _½ 3–5 h. After inclusion or in in uses sildenafit it is removed in the form of metabolites, mainly with a stake (about 80% of the dose accepted inside) and to a lesser extent with urine (about 13% of the dose entered inside).

Pharmacokinetics in special groups of patients

Patients of advanced age. At healthy volunteers of advanced age (65 years or are more senior) noted reduced clearance of a sildenafil which brought to higher (approximately for 90%) to concentration of a metabolite of a sildenafil of N-dezmetila in blood plasma in comparison with those which were observed at healthy young volunteers (at the age of 18–45 years). Through an age difference in linking with proteins of blood plasma the corresponding increase in concentration of a free sildenafil in blood plasma was about 40%.

Renal failure. At volunteers with slight and moderate renal failures (clearance of creatinine of 30-80 ml/min.) the pharmacokinetics of a sildenafil did not change after single oral administration of 50 mg. Averages of AUC and C _max a metabolite of N-dezmetila increased respectively by 126 and 73% in comparison with the corresponding age groups of volunteers without renal failure. However because of high interpersonal variability these differences were not significant. At volunteers with a heavy renal failure (clearance of creatinine of 30 ml/min.) the clearance of a sildenafil was reduced, leading to average increase in AUC and C _max respectively for 100 and 88% in comparison with the corresponding age groups of volunteers without renal failure. Besides, max AUC and C _values a metabolite of N-dezmetila were considerably increased, respectively by 79 and 200%.

Liver failure. At volunteers with easy and moderate degree of cirrhosis (degree And yes In on a scale Chayld — I Drink) the clearance of a sildenafil was reduced that led to increase in AUC (84%) and the C _max (47%) in comparison with the corresponding age groups of volunteers without abnormal liver function. The pharmacokinetics of a sildenafil at patients with abnormal liver functions of heavy degree was not studied.

Indication

Drug vizarsin q-tab is recommended to be used at men with erectile dysfunction which is defined as inability to reach or support the penis erection necessary for successful sexual intercourse. vizarsin q-tab is necessary for effective effect of medicament sexual excitement.

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for oral administration at adult men.

Tablet should be put in a mouth on language where it is quickly dissolved in saliva then it can be swallowed easily. The pill can be taken both with liquid, and without it. It is difficult to remove from a mouth whole a tablet which is dispersed. As a tablet brittle, it should be accepted right after opening of the blister.

Tablet which are dispersed can be an alternative to medicament of Vizarsin, a tablet, film coated, for patients who experience difficulties when swallowing tablets, coated. In need of use of a dose of 100 mg the second pill should be taken only after full disintegration of the first tablet.

Adult. The recommended dose makes 50 mg which is taken if necessary approximately for 1 h before sexual intercourse. Considering efficiency and shipping, the dose can be raised to 100 mg or to lower to 25 mg. The maximum recommended dose makes 100 mg. The maximum recommended reception frequency — 1 time a day. The efficiency of medicament Vizarsin Q-Tab can be shown later at reception with food in comparison with use on an empty stomach.

Patients of advanced age. For patients of advanced age of dose adjustment it is not required.

Patients with a renal failure. To patients with a renal failure easy and moderate severity (clearance of creatinine of 30-80 ml/min.) the mode of dosing is not changed. As at patients with a heavy renal failure (clearance of creatinine of 30 ml/min.) the clearance of a sildenafil is reduced, use of medicament it is necessary to begin 25 mg with a dose. Depending on efficiency and tolerance of medicament if necessary the dose can be raised gradually to 50 and 100 mg.

Patients with an abnormal liver function. As at patients with a liver failure the clearance of a sildenafil is reduced, for example in cirrhosis, use of medicament it is necessary to begin 25 mg with a dose. Depending on efficiency and tolerance of medicament if necessary the dose can be raised gradually to 50 and 100 mg.

Patients who apply other medicines. If patients apply at the same time CYP inhibitors 3A4 (see 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. Special INSTRUCTIONS).

for the purpose of minimization of possible development of postural hypotension in the patients accepting blockers of α-adrenoceptors, their state it is necessary to stabilize 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. Special INSTRUCTIONS and INTERACTIONS).

Contraindication

Hypersensitivity to active ingredient or any other component of drug.

Influencing exchange NO/tsGMF, sildenafit strengthens hypotensive effect of nitrates therefore its co-administration with donors NO (such as amyle nitrite) or nitrates in any form is contraindicated.

Drugs for treatment of disturbances of an erection, including sildenafit, should not be applied at patients to whom the sexual activity is undesirable (for example patients with severe forms of cardiovascular diseases, such as unstable stenocardia or heart failure of heavy degree).

Loss of sight on one eye owing to not arterial front ischemic neuropathy of an optic nerve irrespective of, is connected this pathology with the previous use of FDE-5 inhibitors or not.

Presence of such diseases as abnormal liver function of heavy degree, arterial hypotension (ABP of 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 FDE of a retina) as safety of a sildenafil was not investigated in such subgroups of patients.

Most frequent side reactions about which reported in clinical trials among the patients accepting sildenafit

, there were a headache, rushes of blood, dyspepsia, congestion of a nose, a dorsodynia, dizziness, nausea, inflows of heat, a disorder of vision, blue vision and turbidity of sight. information on side reactions within post-marketing observation of use of a sildenafil was collected within more than 10 years. all clinically important side reactions revealed in clinical trials with a frequency of emergence are provided below is higher, than at intake of placebo, on the systems of an organism and frequency: very often (≥1/10), it is frequent (≥1/100, 1/10), infrequently (≥1/1000, 1/100), is rare (≥1/10,000, 1/1000).

frequency of emergence of clinically important side reactions about which it was reported from post-marketing experience as it is unknown is Also included by

.

side effects are provided to

In each group on frequency as decrease in their gravity.

Infectious and invasive diseases: infrequently — rhinitis.

from the immune system: infrequently — hypersensitivity.

from nervous system: very often — a headache; often — dizziness; infrequently — drowsiness, a hypesthesia; seldom — a stroke, the tranzitorny ischemic attack, spasms *, a recurrence of spasms *, a syncope.

from an organ of sight: often — disturbance of perception of color **, disorders of vision, turbidity of sight; infrequently — disturbances of a slezootdeleniye ***, eye pain, photophobia, a photopsia, hyperaemia of eyes, sight brightness, conjunctivitis; seldom — a nearterialna front ischemic neuropathy of an optic nerve *, occlusion of vessels of a retina *, retinal hemorrhage, an arteriosclerotic retinopathy, disturbances 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, conjunctiva hyperaemia, irritation of eyes, abnormal feelings in eyes, the century, decolouration of a sclera swelled.

from an organ of hearing and a vestibular mechanism: infrequently — dizziness, a ring in ears; seldom — deafness.

from heart: infrequently — tachycardia, the strengthened heartbeat; seldom — a sudden cardiac death *, a myocardial infarction, ventricular arrhythmia *, fibrillation of auricles, unstable stenocardia.

from vessels: often — rushes of blood to the person, inflows of heat; infrequently — AG, arterial hypotension.

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

from a GIT: often — nausea, dyspepsia; infrequently — a gastroesophageal reflux disease, vomiting, pain in an upper part of a stomach, dryness in a mouth; seldom — a hypesthesia of an oral cavity.

from skin and hypodermic fabric: infrequently — rash; seldom — Stephens's syndrome — Johnson *, toxic epidermal nekroliz*.

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

from an urinary system: infrequently — a hamaturia.

from a reproductive system and mammary glands: seldom — bleeding from a penis, a priapism *, a gematospermiya, a long erection.

General disturbances and reactions in the injection site: infrequently — a stethalgia, increased fatigue, feeling of heat; seldom — irritation.

Inspection: infrequently — increase in ChSS.

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* It was reported only at a research after medicament entry into the market.

** Disturbance of perception of color: chloropsiya, chromatopsia, blue vision, red vision, xanthopsia.

*** Disturbance of dacryagogue: dryness in eyes, disturbance of a slezootdeleniye and increase in dacryagogue.

Below-mentioned phenomena noted

at 2% of patients during controlled clinical trials; the causal interrelation is not defined. Messages included the phenomena which had probable communication with medicament use. The phenomena which were not specified were lungs, and messages were very inexact to matter.

General. Face edema, photosensitization, shock, asthenia, pain, sudden falling, abdominal pain, sudden damage.

from a cardiovascular system: stenocardia, AV blockade, migraine, postural hypotension, ischemia of a myocardium, fibrinferments of vessels of a brain, sudden cardiac arrest, change of results on the ECG, a cardiomyopathy.

from digestive system: glossitis, colitis, dysphagy, gastritis, gastroenteritis, esophagitis, stomatitis, disturbance of results of hepatic tests, rectal bleeding, ulitis.

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

Disturbance of metabolism and food: thirst, hypostasis, gout, unstable diabetes, hyperglycemia, peripheral hypostases, hyperuricemia, hypoglycemia, hypernatremia.

from a musculoskeletal system: arthritis, arthrosis, a rupture of a sinew, tenosinovit, an ostealgia, a myasthenia, a synovitis.

from nervous system: ataxy, neuralgia, neuropathy, paresthesias, tremor, vertigo, depression, insomnia, abnormal dreams, decrease in reflexes.

from a respiratory system: OH, short wind, laryngitis, pharyngitis, sinusitis, bronchitis, the strengthened salivation, strengthening of cough.

from skin: urticaria, herpes, an itching, the increased sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

Specific feelings: sudden decrease or a hearing loss, ear pain, a hematopsia, a cataract, dryness in eyes.

from an urogenital system: cystitis, a nocturia, the increased frequency of urinations, increase in mammary glands, urine incontinence, disturbance of an ejaculation, hypostasis of genitals, an anorgazmiya.

Experience of use after entry into the market. As report about such side reactions voluntarily and messages arrive from population of unknown volume, it is not always possible to estimate authentically their frequency and to establish a causal relationship with medicine exposure. These phenomena were noted as because of their gravity, frequency of messages, lack of accurate alternative communication, and because of a combination of these factors.

Cardiovascular and cerebrovascular phenomena. It was reported about the serious cardiovascular, cerebrovascular and vascular phenomena, including cerebrovascular bleeding, subarachnoidal and intra cerebral bleeding and pulmonary bleeding which were connected in time using a sildenafil. Most of patients, but not everything, had factors of cardiovascular risk. It was reported that many of these phenomena arose in time or right after sexual activity, and several phenomena arose at once at use of a sildenafil without sexual activity. Other phenomena developed within the next hours or days after use of a sildenafil and sexual activity. It is impossible to establish whether have these phenomena direct link with medicament use, sexual activity, the available risk factors or a combination of these factors or other factors.

Blood and lymphatic systems: vazookklyuzivny crisis. In the small beforehand suspended medicament use study sildenafit at patients from the pulmonary AG secondary on the sickemia relation, about development of vazookklyuzivny crises in which hospitalization was required, it was reported more often than at placebo use. Sildenafit clinical value of this information for the patients accepting for the purpose of treatment of erectile dysfunction, is an unknown.

Nervous system: alarm, tranzitorny global amnesia.

Specific feelings. Hearing. After medicament entry into the market it was reported about the cases of sudden decrease or a hearing loss connected on time using a sildenafil. It was in certain cases reported about existence of medical states and other factors which could play a role in development of side reactions from hearing. In many cases information on further medical observation is absent. To define whether these phenomena directly using a sildenafil are connected, with the available risk factors of a hearing loss, a combination of these factors or other factors, it is impossible.

Sight. Temporary loss of sight, reddening of eyes, burning in eyes, increase in intraocular pressure, retina hypostasis, vascular diseases of a retina or bleeding, amotio of a vitreous.

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After medicament entry into the market it was seldom reported about cases of not arterial front ischemic neuropathy of an optic nerve that is the reason of decrease in sight, including continuous loss of sight which were associated in time using FDE-5 inhibitors, including sildenafit. Many of patients, but not everything, had anatomic or vascular risk factors of developing not arterial front ischemic neuropathy of an optic nerve, including (but not necessarily being limited) the following: the low ratio of diameter of excavation and an optic disk (stagnant optic disk), age is more senior than 50 years, hypertensia, coronary artery diseases, a lipidemia and smoking. It is impossible to define whether these phenomena directly using FDE-5 inhibitors or are connected with the available anatomic or vascular risk factors, a combination of all these factors or with other factors.

Report on the suspected side reactions. The report on the suspected side reactions after registration of medicine is important. It allows to carry out continuous monitoring of a ratio between the advantage and risks connected with use of this drug. Doctors should report on any suspected side reactions according to requirements of the legislation.

Special instructions

For diagnostics of disturbances of an erection, definition of possible causes of illness and purpose of adequate treatment needs to study attentively a case history of the patient and to perform careful medical examination.

Risk factors of cardiovascular diseases. Before any treatment of disturbances of an erection it is necessary to consider a condition of a cardiovascular system of patients as there is a certain risk from a cardiovascular system connected with sexual activity. Sildenafil has vasodilating properties that leads to easy and passing decrease in the ABP. Before purpose of a sildenafil the doctor has to weigh carefully risk of undesirable manifestations of vasodilating action at patients with certain associated diseases against the background of sexual activity. The hypersensitivity to vasodilators is observed at patients with left ventricular obstruction (for example an aorta stenosis, a subaortic hypertrophic stenosis) or patients with a rare syndrome of a multisystem atrophy, one of manifestations of which is heavy disturbance of regulation of the ABP from the autonomic nervous system.

Vizarsin Q-Tab strengthens hypotensive effect of nitrates (see CONTRAINDICATIONS).

During the period after implementation of medicament in broad medical practice it was reported about serious cardiovascular complications, including a myocardial infarction, unstable stenocardia, a sudden cardiac death, ventricular arrhythmia, a cerebrovascular hemorrhage, the tranzitorny ischemic attack, AG and arterial hypotension. The majority, but not everything, from these patients had cardiovascular risk factors in the anamnesis. The vast majority of such cases is registered during or right after sexual loading, an insignificant part — through the short period after reception of a sildenafil without sexual activity. It is impossible to establish direct dependence of such cases using a sildenafil, sexual loading, the accompanying cardiovascular diseases, a combination of these factors or other factors.

Priapism. Including sildenafit the medicaments intended for treatment of disturbances of an erection, it is necessary to apply with care at patients with anatomic deformation of a penis (an angulation, cavernous fibrosis or a disease of Peyroni or patients with states which contribute to the development of a priapism (sickemia, a multiple myeloma or leukemia).

Simultaneous use with other FDE-5 inhibitors or other medicaments for treatment of erectile dysfunction. Safety and efficiency of simultaneous use sildenafit with other FDE-5 inhibitors or other medicaments for treatment of hypertensia of a pulmonary artery, containing sildenafit, or with other types of treatment concerning erectile dysfunction were studied therefore it is not recommended to apply such combinations.

Influence on sight. Visual impairments and cases of not arterial front ischemic neuropathy of an optic nerve are noted in connection with reception of a sildenafil and other FDE-5 inhibitors (see. Side EFFECTS). To patients Vizarsin Q-Tab is recommended to stop in case of a sudden disorder of vision administration of medicament in and to see immediately a doctor (see CONTRAINDICATIONS).

Ritonavir. Simultaneous use of a sildenafil and ritonavir is not recommended (see INTERACTIONS).

Blockers of α-adrenoceptors. Sildenafil is recommended to apply with care at patients who accept at the same time blockers of α-adrenoceptors as in certain cases it can lead to symptomatic hypotension at some predisposed patients. Symptomatic hypotension usually arises during 4 h after use of a sildenafil. To minimize risk of developing postural hypotension, it is necessary to reach stabilization of indicators of the ABP by means of blockers of α-adrenoceptors before use of a sildenafil. Also it is necessary to consider the possibility of use of an initial dose of 25 mg (see USE). Besides, it is necessary to inform patients how to work in case of symptoms of orthostatic hypotension.

Influence on bleeding. Researches of thrombocytes of the person of in vitro demonstrate that sildenafit enhances anti-aggregation effect of Natrium nitroprussicum. There is no information on safety concerning purpose of a sildenafil to patients with tendency to bleeding or with acute stomach ulcer therefore to this group of patients sildenafit it is necessary to appoint only after careful assessment of advantage and risk.

After reception of 100 mg by healthy volunteers noted influence on morphology or mobility of spermatozoa (see the Pharmacodynamics).

Hearing loss. The patient should stop use of FDE-5 inhibitors, including medicament Vizarsin Q-Tab and to ask immediately for medical care in case 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 on time using FDE-5 inhibitors, including medicament Vizarsin Q-Tab. To define whether these phenomena directly using FDE-5 inhibitors or are connected with other factors, it is impossible.

Simultaneous use with hypotensive drugs. Vizarsin Q-Tab has systemic vasodilating action and can lower further the arterial blood pressure at the patients applying hypotensive medicines. In a separate research of medicinal interaction the simultaneous use of an amlodipin (5 mg or 10 mg) and medicament Vizarsin Q-Tab (100 mg) is orally noted average additional decrease in systolic arterial blood pressure by 8 mm Hg. and diastolic arterial blood pressure — on 7 mm Hg.

Disease, sexually transmitted. Vizarsin Q-Tab does not protect medicament use from diseases, sexually transmitted. It is necessary to consider the possibility to instruct patients of rather necessary precautionary measures for protection against diseases, sexually transmitted, including HIV.

Drug Vizarsin Q-Tab contains aspartame (E951) which is a phenylalanine source. Drug can be harmful to men with phenylketonuria.

Drug Vizarsin Q-Tab contains sorbite (E420). Men with rare hereditary diseases of intolerance of fructose should not use drug.

Use during pregnancy and feeding by a breast. Drug Vizarsin Q-Tab is not intended for use for women.

Children. Drug is shown to use for persons aged up to 18 years.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Researches of influence of medicament on ability to drive the car and to work with mechanisms were not conducted. As during clinical trials of use of a sildenafil it was reported about cases of dizziness and disturbance from an organ of sight, before control of vehicles or work with other mechanisms patients need to find out what their individual reaction to medicament use Vizarsin Q-Tab.

Influence of other medicines on sildenafit

Interaction

Research in vitro. Metabolism of a sildenafil is mediated mainly by an isoform of P450 (CYP) 3A4 cytochrome (main way) and 2C9 (a minor way). Thus, inhibitors of these isoenzymes can reduce removal of a sildenafil.

Research in Vivo. Data of researches showed decrease in clearance of a sildenafil at a concomitant use of CYP inhibitors 3A4 (ketokonazol, erythromycin, Cimetidinum).

, it is necessary to consider the possibility of use of an initial dose of a sildenafil of 25 mg.

Simultaneous use of inhibitor of HIV protease which is highly specific P450 inhibitor in equilibrium (500 mg 2 times a day) with sildenafily (100 mg once) leads concentration to 300% (by 4 times) to increase in the C _max a sildenafila and 1000% to increase (by 11 times) AUC of a sildenafil in blood plasma. In 24 h the concentration of a sildenafil in blood plasma makes about 200 ng/ml while at use of a sildenafil its concentration reached 5 ng/ml. It is connected with the effects caused ritonaviry on P450 isoenzymes. Sildenafil did not influence pharmacokinetics of a ritonavir. On the basis of these pharmacokinetic results the concomitant use of a sildenafil with ritonaviry is not recommended, however the maximum dose of a sildenafil under no circumstances should not exceed 25 mg during 48 h

Simultaneous use of inhibitor of HIV protease of a sakvinavir, CYP inhibitor 3A4, in equilibrium (1200 mg) with sildenafily (100 mg once) concentration leads 3 times a day to increase for 140% of the C _max sildenafit also to increase by 210% of AUC of a sildenafil. Influence of a sildenafil on pharmacokinetics of a sakvinavir is not revealed (see USE). It is supposed that more powerful CYP inhibitors 3A4, such as ketokonazol and itrakonazol, will have more significant influence.

At introduction of a single dose of 100 mg of a sildenafil with erythromycin, specific CYP inhibitor 3A4, in a stable state (500 mg 2 times a day every day within 5 days) increase by 182% of system exposure of a sildenafil (AUC) happened. At male healthy volunteers the azithromycin influence (500 mg/days during 3 days) on AUC, C _max , Tmax, a constant of speed of elimination and the subsequent T _½ a sildenafil or its main metabolite in blood circulation is noted. Cimetidinum (inhibitor of P450 cytochrome and nonspecific CYP inhibitor 3A4) 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 CYP inhibitor 3A4 in a wall of intestines and can cause moderate increase in level of a sildenafil in blood plasma.

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

, according to the population pharmacokinetic analysis, the pharmacokinetics of a sildenafil did not change at simultaneous use with the medicines belonging to group of CYP inhibitors 2C9 (tolbutamide, warfarin, Phenytoinum), group of CYP inhibitors 2D6 (selective serotonin reuptake inhibitors, tricyclic antidepressants), group of thiazide and tiazidopodobny diuretics, loopback and kaliysberegayushchy diuretics, APF inhibitors, antagonists of calcium, antagonists of β-adrenoceptors or inductors of metabolism of CYP 450 (rifampicin, barbiturates).

during the research with participation of healthy male volunteers the simultaneous use of the antagonist of endothelin of a bosentan (moderate inductor CYP 3A4, CYP 2C9 and, perhaps, CYP 2C19) in an equilibrium state (2 times a day) and a sildenafila in an equilibrium state (80 mg 3 times a day) led 125 mg to decrease in AUC and C _max sildenafit for 62.6 and 55.4% respectively. Therefore simultaneous use of such powerful inductors CYP 3A4 as rifampicin, can lead to more significant decrease in concentration of a sildenafil in blood plasma.

Nikorandil is a hybrid of the activator of calcium channels and nitrate. Because of a nitrate component it has potential to serious interaction with sildenafily.

Influence of a sildenafil on other medicines

Research in vitro. Sildenafil is a weak inhibitor of isoforms of P450 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 cytochrome (IC ₅₀ 150 microns). Considering that the C _max sildenafila in blood plasma makes about 1 micron, it is improbable,