Vizarsin Q-Tab 50 mg 4 tablet — Made in Slovenia — Free Delivery

Pharmacological properties

Pharmacodynamics. Sildenafil is an oral therapeutic agent used to treat erectile dysfunction in men. in particular, with sexual stimulation, it restores a disturbed erection by increasing blood flow to the penis.

The physiological mechanism of penile erection is the release of nitric oxide (NO) in the corpus cavernosum upon sexual stimulation. NO activates the enzyme guanylate cyclase, which causes an increase in cGMP levels, relaxation of the smooth muscles of the corpus cavernosum and increased blood flow in them.

Sildenafil is a potent selective inhibitor of the specific PDE-5 cGMP in the corpus cavernosum, where PDE-5 is responsible for the breakdown of cGMP. Sildenafil has a peripheral center of action on erection. Sildenafil does not have a direct relaxing effect on the isolated human corpus cavernosum, but significantly enhances the relaxing effect of NO on this tissue. When the NO / cGMP pathway is activated, which occurs during sexual stimulation, inhibition of PDE-5 by sildenafil leads to an increase in cGMP levels in the corpus cavernosum. Therefore, sexual stimulation is necessary in order for sildenafil to have a targeted positive pharmacological effect.

In vitro studies have shown that sildenafil is selective for PDE-5, which is involved in the erection process. Its effect is more pronounced on PDE-5 than on other known PDEs. There is a 10-fold selectivity for PDE-6, which is involved in the phototransformation process in the retina. At the maximum recommended doses, there is an 80-fold selectivity for PDE-1 and more than 700-fold for PDE-2, -3, -4, -7, -8, -9, -10 and -11. In particular, sildenafil has more than 4000-fold selectivity for PDE-5 than PDE-3, a cGMP-specific isoform of PDE, which is involved in the control of cardiac contraction.

Pharmacokinetics. Absorption. Sildenafil is rapidly absorbed. The observed Cmax was reached within 30–120 minutes (on average 60 minutes) after oral administration on an empty stomach. The mean absolute oral bioavailability is 41% (range 25–63%). After oral administration of sildenafil, AUC and Cmax increase in proportion to the dose increase within the recommended dosage range (25–100 mg).

When sildenafil is taken with food, the absorption rate decreases with an average delay in tmax of 60 minutes and with an average decrease in Cmax by 29%.

Distribution. The average volume of distribution at steady state (Vd) for sildenafil is 105 liters, which indicates its penetration into the tissues. After oral administration of a single dose of 100 mg, the average maximum total plasma concentration of sildenafil is approximately 440 ng / ml (CV 40%). Since sildenafil (and its main metabolite N-desmethyl in the general circulation) binds to plasma proteins by 96%, this leads to an average Cmax of free sildenafil in blood plasma of 18 ng / ml (38 Nm). Protein binding does not depend on the total concentration of the preparation.

In healthy volunteers taking sildenafil (100 mg once), less than 0.0002% (mean 188 ng) of the administered dose was detected in the ejaculate 90 minutes after dosing.

Metabolism. Sildenafil is mainly metabolized by hepatic microsomal isoenzymes CYP 3A4 (major route) and CYP 2C9 (minor route). The main metabolite in the general circulation is formed by N-demethylation of sildenafil. This metabolite has a selectivity for PDE similar to sildenafil and an in vitro activity for PDE-5 of about 50% of the parent preparation. The plasma concentration of this metabolite is approximately 40% of those observed for sildenafil. The metabolite N-desmethyl is further metabolized with a final T1 / 2 of about 4 hours.

Excretion. The total clearance of sildenafil is 41 l / h with a terminal phase T½ 3-5 hours 13% of the oral dose).

Pharmacokinetics in special patient groups

Elderly patients. In healthy elderly volunteers (65 years or older), a reduced clearance of sildenafil was noted, which led to higher (approximately 90%) plasma concentrations of the sildenafil metabolite N-desmethyl compared with those observed in healthy young volunteers (aged 18–45 years old). Due to the age-related difference in binding to blood plasma proteins, the corresponding increase in plasma concentrations of free sildenafil was approximately 40%.

Renal failure In volunteers with mild to moderate renal impairment (creatinine clearance 30–80 ml / min), the pharmacokinetics of sildenafil did not change after a single oral dose of 50 mg. The average AUC and Cmax of the N-desmethyl metabolite increased by 126 and 73%, respectively, compared with the corresponding age groups of volunteers without renal impairment. However, due to the high interpersonal variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance 30 ml / min), sildenafil clearance was reduced, leading to an average increase in AUC and Cmax by 100 and 88%, respectively, compared with the corresponding age groups of volunteers without renal impairment. In addition, the AUC and Cmax values ​​of the N-desmethyl metabolite were significantly increased, by 79% and 200%, respectively.

Liver failure. In volunteers with mild to moderate liver cirrhosis (grade A and B on the Child-Pugh scale), the clearance of sildenafil was reduced, which led to an increase in AUC (84%) and Cmax (47%) compared with the corresponding age groups of volunteers without impairment of function liver. The pharmacokinetics of sildenafil in patients with severe hepatic impairment have not been studied.

Indications

Vizarsine q-tab is recommended for men with erectile dysfunction, which is defined as the inability to achieve or maintain an erection of the penis necessary for successful intercourse. for the effective action of the preparation vizarsin q-tab, sexual arousal is needed.

Application

The preparation is intended for oral administration in adult men.

The tablet must be placed in the mouth on the tongue, where it dissolves quickly in saliva, after which it can be easily swallowed. The tablet can be taken with or without liquid. It is difficult to remove a dispersed tablet from the mouth. Since the tablet is fragile, it should be taken immediately after opening the blister.

Dispersible tablets can be an alternative to Vizarsin, film-coated tablets, for patients who have difficulty swallowing film-coated tablets. If it is necessary to use a dose of 100 mg, the second tablet should be taken only after the complete disintegration of the first tablet.

Adults. The recommended dose is 50 mg, which is taken if necessary about 1 hour before intercourse. Given the efficacy and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of admission is 1 time per day. The effectiveness of the preparation Vizarsin Q-Tab may appear later when taken with food than when taken on an empty stomach.

Elderly patients. For elderly patients, dose adjustment is not required.

Patients with impaired renal function. Patients with renal insufficiency of mild and moderate severity (creatinine clearance 30–80 ml / min) do not change the dosage regimen. Since the clearance of sildenafil is reduced in patients with severe renal impairment (creatinine clearance 30 ml / min), the use of the preparation should be started with a dose of 25 mg. Depending on the effectiveness and tolerability of the preparation, if necessary, the dose can be gradually increased to 50 and 100 mg.

Patients with impaired liver function. Since the clearance of sildenafil is reduced in patients with hepatic impairment, for example, in cirrhosis, the use of the preparation should be started with a dose of 25 mg. Depending on the effectiveness and tolerability of the preparation, if necessary, the dose can be gradually increased to 50 and 100 mg.

Patients who are using other medicines. If patients are concomitantly using CYP 3A4 inhibitors (see INTERACTIONS), an initial dose of 25 mg should be considered (with the exception of ritonavir, which is not recommended concomitantly with sildenafil, see SPECIAL INSTRUCTIONS).

In order to minimize the possible development of postural hypotension in patients taking α-adrenergic receptor blockers, their condition must be stabilized with α-adrenergic receptor blockers before using sildenafil. You should also consider using an initial dose of 25 mg (see SPECIAL INSTRUCTIONS and INTERACTIONS).

Contraindications

Hypersensitivity to the active substance or any other component of the preparation.

By affecting the exchange of NO / cGMP, sildenafil enhances the hypotensive effect of nitrates, therefore, its simultaneous administration with NO donors (such as amyl nitrite) or nitrates in any form is contraindicated.

Preparations for the treatment of erectile dysfunction, including sildenafil, should not be used in patients for whom sexual activity is undesirable (for example, patients with severe cardiovascular disease, such as unstable angina pectoris or severe heart failure).

Loss of vision in one eye due to non-arterial anterior ischemic neuropathy of the optic nerve, regardless of whether this pathology is associated with previous use of PDE-5 inhibitors or not.

The presence of diseases such as severe liver dysfunction, arterial hypotension (BP 90/50 mm Hg), recent stroke or myocardial infarction, and known hereditary degenerative retinal diseases such as retinitis pigmentosa (a small number of such patients have genetic disorders Retinal PDE), since the safety of sildenafil has not been studied in these patient subgroups.

Side effects

The most common adverse reactions reported in clinical studies among patients taking sildenafil were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, hot flashes, blurred vision, cyanopsia, and blurred vision. information on adverse reactions in the framework of post-marketing surveillance of the use of sildenafil has been collected for more than 10 years. below are all clinically important adverse reactions identified in clinical studies with a frequency of occurrence higher than with placebo, by body systems and frequency: very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10,000, 1/1000).

Also included is the incidence of clinically important adverse reactions reported from post-marketing experience as unknown.

In each frequency group, side effects are presented in order of decreasing severity.

Infectious and invasive diseases: infrequently - rhinitis.

From the immune system: infrequently - hypersensitivity.

From the nervous system: very often - headache; often - dizziness; infrequently - drowsiness, hypesthesia; rarely - stroke, transient ischemic attack, seizures *, recurrent seizures *, syncope.

From the side of the organ of vision: often - impaired color perception **, visual impairment, blurred vision; infrequently - lacrimation disorders ***, eye pain, photophobia, photopsia, redness of the eyes, brightness of vision, conjunctivitis; rarely - non-arterial anterior ischemic neuropathy of the optic nerve *, retinal vascular occlusion *, retinal hemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, floating opacities from the vitreous body, disorders iris, mydriasis, the appearance of luminous circles around the light source (halo) in the field of view, eye edema, eye swelling, eye disorders, conjunctival hyperemia, eye irritation, abnormal sensations in the eyes, eyelid edema, scleral discoloration.

On the part of the organ of hearing and vestibular apparatus: infrequently - dizziness, ringing in the ears; rarely - deafness.

From the side of the heart: infrequently - tachycardia, increased heart rate; rarely - sudden cardiac death *, myocardial infarction, ventricular arrhythmia *, atrial fibrillation, unstable angina pectoris.

From the side of the vessels: often - flushes of blood to the face, hot flashes; infrequently - hypertension, arterial hypotension.

From the respiratory system, chest and mediastinum: often - nasal congestion; infrequently - nosebleeds, congestion of the paranasal sinuses; rarely - a feeling of constriction in the throat, swelling of the nasal mucosa, dryness in the nose.

From the gastrointestinal tract: often - nausea, dyspepsia; infrequently - gastroesophageal reflux disease, vomiting, pain in the upper abdomen, dry mouth; rarely - oral hypesthesia.

On the part of the skin and subcutaneous tissue: infrequently - rash; rarely - Stevens-Johnson syndrome *, toxic epidermal necrolysis *.

From the musculoskeletal system and connective tissue: infrequently - myalgia, pain in the limbs.

From the urinary system: infrequently - hematuria.

From the reproductive system and mammary glands: rarely - bleeding from the penis, priapism *, hematospermia, prolonged erection.

General disorders and reactions at the injection site: infrequently - chest pain, fatigue, a feeling of heat; rarely - irritation.

Surveys: infrequently - increased heart rate.

* Reported only in post-market research.

** Impaired color perception: chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia.

*** Violation of lacrimation: dry eyes, impaired lacrimation and increased lacrimation.

The following phenomena were observed in 2% of patients during controlled clinical trials; the causal relationship has not been determined. The reports included events that were likely to be related to the use of the preparation. The phenomena that were not listed were light and the messages were very imprecise to make a difference.

General. Facial edema, photosensitivity, shock, asthenia, pain, sudden fall, abdominal pain, sudden injury.

From the side of the cardiovascular system: angina pectoris, AV blockade, migraine, postural hypotension, myocardial ischemia, cerebral vascular thrombosis, sudden cardiac arrest, changes in ECG results, cardiomyopathy.

From the digestive system: glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, impaired liver function tests, rectal bleeding, gingivitis.

On the part of the blood and lymphatic system: anemia, leukopenia.

Metabolic and nutritional disorders: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

From the musculoskeletal system: arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.

From the nervous system: ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.

From the respiratory system: BA, shortness of breath, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.

Skin disorders: urticaria, herpes, itching, increased sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

Specific sensations: sudden hearing loss or loss, ear pain, bleeding in the eye, cataracts, dry eyes.

On the part of the urogenital system: cystitis, nocturia, increased frequency of urination, enlargement of the mammary glands, urinary incontinence, impaired ejaculation, edema of the genitals, anorgasmia.

Post-market experience. Since such adverse reactions are voluntarily reported and reported from a population of unknown size, it is not always possible to reliably estimate their frequency and establish a causal relationship with preparation exposure. These phenomena have been noted both because of their severity, frequency of reporting, lack of clear alternative link, and a combination of these factors.

Cardiovascular and cerebrovascular phenomena. Serious cardiovascular, cerebrovascular and vascular events have been reported, including cerebrovascular bleeding, subarachnoid and intracerebral bleeding, and pulmonary hemorrhage, which have been associated with the use of sildenafil over time. Most, but not all, patients had cardiovascular risk factors. It has been reported that many of these phenomena occurred during or immediately after sexual activity, and several phenomena occurred immediately when sildenafil was used without sexual activity. Other phenomena developed over the next hours or days after the use of sildenafil and sexual activity. It is impossible to establish whether these phenomena are directly related to the use of the preparation, sexual activity, existing risk factors or a combination of these factors or other factors.

Circulatory and lymphatic systems: vaso-occlusive crisis. In a small, pre-suspended study of the use of sildenafil in patients with pulmonary hypertension secondary to sickle cell anemia, the development of vaso-occlusive crises requiring hospitalization was reported more often than with placebo. The clinical relevance of this information to patients taking sildenafil for the treatment of erectile dysfunction is unknown.

Nervous system: anxiety, transient global amnesia.

Specific sensations. Hearing. After the preparation was launched on the market, cases of sudden hearing loss or loss associated with time with the use of sildenafil have been reported. In some cases, the presence of medical conditions and other factors have been reported that may play a role in the development of adverse reactions from hearing. In many cases, there is no information on further medical follow-up. It is impossible to determine whether these phenomena are directly related to the use of sildenafil, with the existing risk factors for hearing loss, a combination of these factors or other factors.

Vision. Temporary loss of vision, redness of the eyes, burning in the eyes, increased intraocular pressure, retinal edema, retinal vascular disease or bleeding, detachment of the vitreous humor.

After the preparation was launched on the market, cases of non-arterial anterior ischemic neuropathy of the optic nerve were rarely reported, which is the cause of visual impairment, including permanent loss of vision, which were associated with the use of PDE-5 inhibitors, including sildenafil, over time. Many, but not all, of the patients had anatomical or vascular risk factors for developing non-arterial anterior ischemic optic neuropathy, including, but not necessarily limited to: low excavation diameter to optic nerve head (congestive optic disc), age over 50 , hypertension, coronary artery disease, hyperlipidemia, and smoking. It is impossible to determine whether these events are directly related to the use of PDE-5 inhibitors or with existing anatomical or vascular risk factors, a combination of all these factors, or with other factors.

Suspected Adverse Reactions Report. Reporting suspected adverse reactions following registration of a medicinal product is essential. This allows continuous monitoring of the balance between benefits and risks associated with the use of this preparation. Physicians should report any suspected adverse reactions as required by law.

Special instructions

To diagnose erectile dysfunction, determine the possible causes of the disease and prescribe adequate treatment, it is necessary to carefully study the patient's medical history and conduct a thorough medical examination.

Risk factors for cardiovascular disease. Before starting any treatment for erectile dysfunction, it is necessary to take into account the state of the cardiovascular system of the patients, since there is a certain risk from the cardiovascular system associated with sexual activity. Sildenafil has vasodilating properties, which leads to a mild and transient decrease in blood pressure. Before prescribing sildenafil, the physician should carefully weigh the risk of undesirable manifestations of vasodilatory action in patients with certain concomitant diseases associated with sexual activity. Hypersensitivity to vasodilators is observed in patients with left ventricular obstruction (for example, aortic stenosis, obstructive hypertrophic cardiomyopathy) or in patients with a rare syndrome of multisystem atrophy, one of the manifestations of which is severe impairment of blood pressure regulation by the autonomic nervous system.

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

In the period after the introduction of the preparation into widespread medical practice, serious cardiovascular complications were reported, including myocardial infarction, unstable angina pectoris, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension and arterial hypotension. Most, but not all, of these patients had a history of cardiovascular risk factors. The overwhelming majority of such cases were registered during or immediately after sexual activity, a small part - after a short period after taking sildenafil without sexual activity. It is impossible to establish a direct relationship of such cases with the use of sildenafil, sexual stress, concomitant cardiovascular diseases, a combination of these factors or other factors.

Priapism. Preparations intended for the treatment of erectile dysfunction, including sildenafil, should be used with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, or Peyronie's disease, or in patients with conditions that contribute to the development of priapism (sickle cell anemia, multiple myeloma, or leukemia). ).

Concomitant use with other PDE-5 inhibitors or other preparations for the treatment of erectile dysfunction. The safety and efficacy of the simultaneous use of sildenafil with other PDE-5 inhibitors or other preparations for the treatment of pulmonary artery hypertension containing sildenafil, or with other treatments for erectile dysfunction, have been studied, therefore, the use of such combinations is not recommended.

Effects on vision. Visual defects and cases of non-arterial anterior ischemic neuropathy of the optic nerve were noted in connection with the use of sildenafil and other PDE-5 inhibitors (see SIDE EFFECTS). Patients are advised to stop taking Vizarsin Q-Tab in case of sudden visual impairment and immediately consult a doctor (see CONTRAINDICATIONS).

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

Blockers of α-adrenergic receptors. Sildenafil is recommended to be used with caution in patients who are concomitantly taking α-adrenergic receptor blockers, since in some cases this can lead to symptomatic hypotension in some predisposed patients. Symptomatic hypotension usually occurs within 4 hours after using sildenafil. In order to minimize the risk of postural hypotension, stabilization of blood pressure should be achieved with the help of α-adrenergic receptor blockers before using sildenafil. You should also consider using an initial dose of 25 mg (see APPLICATION). In addition, patients should be informed how to act in the event of symptoms of orthostatic hypotension.

Effect on bleeding. In vitro studies of human platelets indicate that sildenafil enhances the antiaggregatory effect of sodium nitroprusside. There is no information on the safety of prescribing sildenafil to patients with bleeding tendencies or acute gastric ulcers; therefore, sildenafil should be prescribed to this group of patients only after a careful assessment of the benefits and risks.

After taking 100 mg in healthy volunteers, there was no effect on the morphology or motility of spermatozoa (see Pharmacodynamics).

Loss of hearing. The patient should stop using PDE-5 inhibitors, including Vizarsin Q-Tab, and immediately seek medical attention in case of sudden hearing loss or loss. These phenomena, which can also be accompanied by tinnitus and dizziness, have been reported with an association over time with the use of PDE5 inhibitors, including Vizarsin Q-Tab. It is impossible to determine whether these phenomena are directly related to the use of PDE-5 inhibitors or to other factors.

Simultaneous use with antihypertensive preparations. Vizarsin Q-Tab has a systemic vasodilator effect and can further lower blood pressure in patients using antihypertensive preparations. In a separate study of preparation interactions, the simultaneous use of amlodipine (5 mg or 10 mg) and the preparation Vizarsin Q-Tab (100 mg) orally noted an additional average decrease in systolic blood pressure by 8 mm Hg. Art. and diastolic blood pressure - by 7 mm Hg. Art.

Sexually transmitted diseases. The use of the preparation Vizarsin Q-Tab does not protect against sexually transmitted diseases. Consideration should be given to instructing patients on the necessary precautions to be taken to protect against sexually transmitted diseases, including HIV.

Vizarsin Q-Tab contains aspartame (E951), which is a source of phenylalanine. The preparation may be harmful to men with phenylketonuria.

Vizarsin Q-Tab contains sorbitol (E420). Men with rare hereditary diseases of fructose intolerance should not use the preparation .

Use during pregnancy and lactation. Vizarsin Q-Tab is not intended for use in women.

Children. The preparation is indicated for use in persons under the age of 18.

The ability to influence the reaction rate when driving or working with other mechanisms. Studies of the effect of the preparation on the ability to drive a car and work with mechanisms have not been conducted. Since in the course of clinical studies of the use of sildenafil, cases of dizziness and visual disturbances have been reported, before driving or working with other mechanisms, patients need to find out what their individual reaction to the use of Vizarsin Q-Tab is.

Interactions

Effect of other medicines on sildenafil

In vitro studies. Sildenafil metabolism is mediated mainly by the cytochrome P450 isoform (CYP) 3A4 (major pathway) and 2C9 (minor pathway). Thus, inhibitors of these isoenzymes can reduce the excretion of sildenafil.

In vivo studies. Research data showed a decrease in sildenafil clearance while taking CYP 3A4 inhibitors (ketoconazole, erythromycin, cimetidine).

Although there has been no increase in the frequency of side effects with the concomitant use of sildenafil and CYP 3A4 inhibitors, an initial dose of 25 mg of sildenafil should be considered.

The simultaneous use of an HIV protease inhibitor, which is a highly specific inhibitor of P450, in equilibrium (500 mg 2 times a day) with sildenafil (100 mg once) leads to a 300% (4 times) increase in the Cmax of sildenafil and a 1000% increase (11 times ) AUC of sildenafil in blood plasma. After 24 hours, the concentration of sildenafil in the blood plasma is approximately 200 ng / ml, while when using sildenafil, its concentration reached 5 ng / ml. This is due to the effects of ritonavir on P450 isoenzymes. Sildenafil had no effect on the pharmacokinetics of ritonavir. Based on these pharmacokinetic results, concomitant administration of sildenafil with ritonavir is not recommended, however, the maximum dose of sildenafil should under no circumstances exceed 25 mg in 48 hours.

Concomitant use of the HIV protease inhibitor saquinavir, an inhibitor of CYP 3A4, at an equilibrium (1200 mg 3 times daily) concentration with sildenafil (100 mg once) leads to a 140% increase in the Cmax of sildenafil and an increase of 210% in the AUC of sildenafil. No effect of sildenafil on saquinavir pharmacokinetics has been identified (see APPLICATION). More potent CYP 3A4 inhibitors such as ketoconazole and itraconazole are expected to have a more pronounced effect.

With the introduction of a single dose of 100 mg of sildenafil with erythromycin, a specific inhibitor of CYP 3A4, in a stable state (500 mg 2 times a day daily for 5 days), there was an 182% increase in the systemic exposure of sildenafil (AUC). In healthy male volunteers, there was no effect of azithromycin (500 mg / day for 3 days) on AUC, Cmax, Tmax, elimination rate constant and subsequent T½ of sildenafil or its main metabolite in the circulation. Cimetidine (an inhibitor of cytochrome P450 and a nonspecific inhibitor of CYP 3A4) at a dose of 800 mg, when used simultaneously with 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 inhibitor of CYP 3A4 in the intestinal wall and may cause a moderate increase in plasma levels of sildenafil.

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

Although studies of specific interaction with all preparations have not been conducted, according to population pharmacokinetic analysis, the pharmacokinetics of sildenafil did not change when used simultaneously with preparations belonging to the group of CYP 2C9 inhibitors (tolbutamide, warfarin, phenytoin), the group of CYP 2D6 inhibitors (selective reverse inhibitors seizure of serotonin, tricyclic antidepressants), a group of thiazide and thiazide-like diuretics, loop and potassium-sparing diuretics, ACE inhibitors, calcium antagonists, β-adrenergic receptor antagonists or inducers of CYP 450 metabolism (rifampicin, barbiturates).

In a study with healthy male volunteers, the concomitant use of endothelin antagonist bosentan (a moderate inducer of CYP 3A4, CYP 2C9 and possibly CYP 2C19) in an equilibrium state (125 mg 2 times a day) and sildenafil in an equilibrium state (80 mg 3 times per day) led to a decrease in AUC and Cmax of sildenafil by 62.6 and 55.4%, respectively. Therefore, the simultaneous use of such powerful inducers of CYP 3A4 as rifampicin can lead to a more pronounced decrease in the concentration of sildenafil in blood plasma.

Nicorandil is a hybrid of a calcium channel activator and nitrate. Due to its nitrate component, it has the potential for serious interactions with sildenafil.

Effect of sildenafil on other medicines

In vitro studies. Sildenafil is a weak inhibitor of cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 150 μM). Considering that the Cmax of sildenafil in blood plasma is approximately 1 μM, it is unlikely that the preparation can affect the clearance of substrates of these isoenzymes.

There is no data on the interaction of sildenafil and nonspecific PDE inhibitors, such as theophylline or dipyridamole.

In vivo studies. Since it is known that sildenafil affects the metabolism of NO / cGMP, it has been established that sildenafil potentiates the hypotensive effect of nitrates, therefore, its simultaneous use with NO donors or nitrates in any form is contraindicated (see CONTRAINDICATIONS).

The simultaneous use of sildenafil and blockers of α-adrenergic receptors can lead to the development of symptomatic hypotension in some predisposed patients. This reaction often occurred within 4 hours after the use of sildenafil (see APPLICATION and SPECIAL INSTRUCTIONS). In 3 studies of specific preparation interactions, the α-adrenergic receptor blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) were used simultaneously in patients with benign prostatic hyperplasia, stabilization of which was achieved with the use of doxazosin ... In these populations, there was an average additional decrease in blood pressure in the supine position by 7/7; 9/5 and 8/4 mm Hg. Art. and an average decrease in blood pressure in the standing position by 6/6; 11/4 and 4/5 mm Hg. Art. respectively. With the simultaneous use of sildenafil and doxazosin in patients whose condition stabilization was achieved with the use of doxazosin, the development of symptomatic orthostatic hypotension was sometimes reported. These reports reported cases of dizziness and lightheadedness, but no syncope.

There were no significant interactions with the simultaneous use of sildenafil (50 mg), tolbutamide (250 mg) and warfarin (40 mg), which are metabolized by CYP 2C9.

Sildenafil (50 mg) does not increase the duration of bleeding caused by acetylsalicylic acid (150 mg).

Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers at an average maximum blood ethanol level of 80 mg / dL.

In patients receiving sildenafil, there were no differences in the profile of side effects compared to placebo with the simultaneous use of such classes of antihypertensive preparations as diuretics, β-adrenoreceptor blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive preparations(vasodilator and central action), blockers of adrenergic neurons, blockers of calcium channels and blockers of α-adrenergic receptors. In a special study of the interaction with the simultaneous use of sildenafil (100 mg) and amlodipine in patients with arterial hypertension, an additional decrease in systolic blood pressure in the supine position by 8 mm Hg was noted. Art. The decrease in diastolic blood pressure was 7 mm Hg. Art. In terms of magnitude, this additional decrease in blood pressure was comparable to that observed when using only sildenafil in healthy volunteers (see PHARMACOLOGICAL PROPERTIES).

Sildenafil at a dose of 100 mg did not affect the pharmacokinetic parameters of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of CYP 3A4.

In healthy male volunteers, the use of sildenafil in an equilibrium state (80 mg 3 times a day) led to an increase in AUC and Cmax of bosentan (125 mg 2 times a day) by 49.8 and 42%, respectively.

Overdose

In clinical studies involving volunteers, when using a single dose of sildenafil up to 800 mg, adverse reactions were similar to those noted when using sildenafil at lower doses, but they occurred more often and were more severe. the use of sildenafil at a dose of 200 mg led to an increase in the effectiveness, but caused an increase in the number of cases of the development of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).

In case of overdose, if necessary, resort to the usual supportive measures. An acceleration of the clearance of sildenafil during hemodialysis is unlikely due to the high degree of binding of the preparation to blood plasma proteins and the lack of elimination of sildenafil in the urine.

Storage conditions

At a temperature not exceeding 30 ° C in the original packaging to protect against moisture.

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