Viagra pills 100mg, 12pcs

Composition

1 tab. sildenafil (in the form of citrate) 100 mg Auxiliary substances: microcrystalline cellulose, calcium hydrophosphate, croscarmellose sodium, magnesium stearate. Composition of the film shell: Opadry blue OY-LS-20921 (hypromellose, lactose, triacetin, titanium dioxide (E171), indigo carmine-based aluminum varnish (E132)) and Opadry transparent YS-2-19114-A (hypromellose, triacetin).

Pharmacological action

Sildenafil is a potent selective inhibitor of cyclo-guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE-5). Mechanism of action The realization of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous bodies during sexual stimulation. This, in turn, leads to an increase in cGMP levels, subsequent relaxation of the smooth muscle tissue of the cavernous bodies, and increased blood flow. Sildenafil does not have a direct relaxing effect on the isolated human cavernous body, but it enhances the effect of nitric oxide (NO) by inhibiting PDE-5, which is responsible for the breakdown of cGMP. Sildenafil is selective for PDE-5 in vitro, its activity against PDE-5 exceeds the activity against other known phosphodiesterase isoenzymes: PDE-6-by 10 times; PDE-1-by more than 80 times; PDE-2, PDE-4, PDE-7–PDE-11-by more than 700 times. Sildenafil is 4000 times more selective for PDE-5 compared to PDE-3, which is of crucial importance, since PDE-3 is one of the key enzymes in the regulation of myocardial contractility. A prerequisite for the effectiveness of sildenafil is sexual stimulation. Clinical data Cardiological studies The use of sildenafil in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in sBP in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg, and dBP-5.3 mm Hg. A more pronounced, but also transient effect on blood pressure was observed in patients taking nitrates (see the sections “Contraindications” and “Interaction”). In a study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe CHD (more than 70% of patients had stenosis of at least one coronary artery), sBP and dBP at rest decreased by 7 and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not disrupt blood flow in stenosed coronary arteries, and also led to an increase (by approximately 13%) in adenosine-induced coronary flow in both stenosed and intact coronary arteries. In a double-blind, placebo-controlled study,144 patients with erectile dysfunction and stable angina who were taking antianginal medications (other than nitrates) performed physical exercises until the severity of angina symptoms decreased. The duration of exercise was significantly longer (19.9 seconds; 0.9-38.9 seconds) in patients taking sildenafil in a single dose of 100 mg compared to patients receiving placebo. A randomized, double-blind, placebo-controlled study examined the effect of varying the dose of sildenafil (up to 100 mg) in men (n = 568) with erectile dysfunction and hypertension taking more than two antihypertensive medications. Sildenafil improved erections in 71% of men compared to 18% in the placebo group. The incidence of adverse events was comparable to that in other patient groups, as well as in individuals taking more than three antihypertensive medications. Visual impairment studies In some patients,1 h after taking sildenafil at a dose of 100 mg, the Farnsworth-Munsel 100 test revealed a slight and transient impairment of the ability to distinguish shades of color (blue/green).2 hours after taking the drug, these changes were absent. It is believed that color vision disorders are caused by inhibition of PDE-6, which is involved in the process of light transmission in the retina of the eye. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure, or pupil diameter. In a placebo-controlled cross-sectional study of patients with proven early-age macular degeneration (n = 9), sildenafil at a single dose of 100 mg was well tolerated. There were no clinically significant visual changes assessed by special visual tests (visual acuity, Amsler grating, color perception, color transmission modeling, Humphrey perimeter, and photostress). Efficacy and safety of sildenafil were evaluated in 21 randomized, double-blind, placebo-controlled trials lasting up to 6 months in 3,000 patients aged 19 to 87 years with erectile dysfunction of various etiologies (organic, psychogenic, or mixed). The effectiveness of the drug was evaluated globally using the erectile diary, the international index of erectile function (validated sexual function questionnaire), and a partner survey. The efficacy of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all studies conducted and has been confirmed in long-term studies lasting 1 year. In fixed-dose studies, the ratio of patients who reported that therapy improved their erections was 62% (25 mg sildenafil dose),74% (50 mg sildenafil dose), and 82% (100 mg sildenafil dose), compared to 25% in the placebo group. Analysis of the international index of erectile function showed that in addition to improving erections, treatment with sildenafil also increased the quality of orgasm, allowed achieving satisfaction from sexual intercourse and overall satisfaction. Overall,59% of patients with diabetes,43% of patients who underwent radical prostatectomy, and 83% of patients with spinal cord injuries reported improved erections during treatment with sildenafil (compared to 16%,15%, and 12% in the placebo group, respectively). Pharmacokineticspharmacokinetics of sildenafil in the recommended dose range is linear. Suction. After oral use, sildenafil is rapidly absorbed. Absolute bioavailability is on average about 40% (from 25 to 63%). In vitro, sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) suppresses the activity of human phosphodiesterase type 5 (PDE-5) by 50%. After a single 100 mg dose of sildenafil, the average Cmax of free sildenafil in the blood plasma of men is about 18 ng / ml (38 nM). Cmax when taking sildenafil orally on an empty stomach is reached on average within 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not change significantly (AUC decreases by 11%). Distribution. The average VSS of sildenafil is 105 liters. The association of sildenafil and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the sildenafil dose (average 188 ng) was detected in semen 90 minutes after taking the drug. Metabolism. Sildenafil is mainly metabolized in the liver by the cytochrome CYP3A4 isoenzyme (major pathway) and the cytochrome CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite formed as a result of N-demethylation of sildenafil undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of sildenafil, and its activity against PDE-5 in vitro is about 50% of that of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism; T1 / 2 is about 4 hours. Output. The total clearance of sildenafil is 41 l / h, and the final T1/2 is 3-5 hours. After oral use, as well as after intravenous use, sildenafil is excreted as metabolites mainly by the intestines (about 80% of the oral dose) and to a lesser extent by the kidneys (about 13% of the oral dose). Pharmacokinetics in special patient groupslong-lived patients. In healthy elderly patients (older than 65 years), the clearance of sildenafil is reduced, and the concentration of free sildenafil in blood plasma is approximately 40% higher than in young (18-45 years). Age does not have a clinically significant effect on the incidence of side effects. Impaired renal function. In mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-49 ml/min) renal insufficiency, the pharmacokinetics of sildenafil do not change after a single oral dose of 50 mg. In severe renal insufficiency (creatinine clearance < 30 ml/min), sildenafil clearance decreases, resulting in approximately a twofold increase in AUC (100%) and Cmax (88%) compared to those with normal renal function in patients of the same age group. Impaired liver function. In patients with cirrhosis of the liver (stages A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared to those with normal liver function in patients of the same age group. The pharmacokinetics of sildenafil in patients with severe hepatic impairment (Child-Pugh stage C) have not been studied.

Indications

Treatment of erectile dysfunction characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse. Sildenafil is only effective with sexual stimulation.

Use during pregnancy and lactation

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

Recommendations for use

Inside, approximately 1 hour before sexual activity.The recommended dose for most adult patients is 50 mg. Depending on 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 application is 1 time per day. Impaired renal function. In mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), no dose adjustment is required, in severe renal insufficiency (creatinine clearance Liver function disorders. Since the elimination of sildenafil is impaired in patients with liver damage (in particular cirrhosis), the dose of Viagra® should be reduced to 25 mg. Co-use with other drugs When co-administered with ritonavir, the maximum single dose of Viagra® should not exceed 25 mg, and the frequency of use-1 time in 48 hours (see the section “Interaction”). When co-administered with inhibitors of the cytochrome CYP3A4 isoenzyme (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Viagra® should be 25 mg (see the section “Interaction”). To minimize the risk of postural hypotension in patients taking alpha-blockers, Viagra® should be started only after hemodynamic stabilization has been achieved in these patients. Consideration should also be given to reducing the initial dose of sildenafil (see sections “Special instructions” and “Interaction”). Elderly patients. No dose adjustment of Viagra® is required.

Contraindications

hypersensitivity to sildenafil or any other component of the drug; application in patients receiving constantly or intermittently donators of nitric oxide, organic nitrates or nitrites in any form, as sildenafil enhances the hypotensive effect of nitrates (see “Interaction”); concomitant use with other agents for the treatment of erectile dysfunction (safety and efficacy of the drug Viagra® when used together has not been studied, see section “Special instructions”), so the use of such combinations is not recommended; it is not intended for use on the registered indication in children under 18 years of age; not intended for use on the registered indication in women. With caution: anatomical deformity of the penis (angulation, cavernous fibrosis or Peyronie’s disease) (see section “Special instructions”); diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocytemia) (see section “Special instructions”); diseases accompanied by bleeding; exacerbation of peptic ulcer disease; hereditary retinitis pigmentosa (see section “Special instructions”); heart failure, unstable angina, myocardial infarction, stroke or life-threatening arrhythmias in the last 6 months, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP >

Side effects

General disorders: hypersensitivity reactions (including skin rash). Changes in the central nervous system and peripheral nervous system: seizures. Changes in the cardiovascular system: tachycardia, decreased blood pressure, syncope, nosebleeds. Gastrointestinal disorders: vomiting. Changes in the visual organ: pain in the eyes, redness of the eyes/injections of sclera. Reproductive system disorders: prolonged erections and / or priapism.

Interaction

The effect of other drugs on the pharmacokinetics of sildenafil The metabolism of sildenafil occurs mainly under the action of cytochrome CYP3A4 (main pathway) and CYP2C9 isoenzymes, so inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, respectively, increase the clearance of sildenafil. A decrease in the clearance of sildenafil was observed with the simultaneous use of inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the cytochrome CYP3A4 isoenzyme, when co-administered with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma by 56%. A single dose of 100 mg of sildenafil together with erythromycin (500 mg / day 2 times a day for 5 days), a specific inhibitor of the cytochrome CYP3A4 isoenzyme, against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%. When co-administered with sildenafil (100 mg once) and saquinavir (1200 mg / day in 3 doses), an HIV protease inhibitor and cytochrome CYP3A4 isoenzyme, while achieving a constant concentration of saquinavir in the blood, the Cmax of sildenafil increased by 140%, and the AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir. Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, can also cause stronger changes in the pharmacokinetics of sildenafil. Simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg twice daily), an HIV protease inhibitor and a strong cytochrome P450 inhibitor, while achieving a constant concentration of ritonavir in the blood leads to an increase in sildenafil Cmax by 300% (4 times), and AUC-by 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng / ml (after a single application of sildenafil alone-5 ng/ml). If sildenafil is taken at the recommended doses in patients receiving simultaneously strong inhibitors of the cytochrome CYP3A4 isoenzyme, the Cmax of free sildenafil does not exceed 200 nM, and the drug is well tolerated. A single antacid dose (magnesium hydroxide/aluminum hydroxide) does not affect the bioavailability of sildenafil. Inhibitors of the cytochrome CYP2C9 isoenzyme (tolbutamide, warfarin), cytochrome CYP2D6 isoenzyme (SSRIs, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACE inhibitors and calcium antagonists do not affect the pharmacokinetics of sildenafil. Azithromycin (500 mg / day for 3 days) does not affect the AUC, Cmax, Tmax, elimination rate constant and T1/2 of sildenafil or its main circulating metabolite. Effect of sildenafil on other DRUGS Sildenafil is a weak inhibitor of cytochrome P 450 isoenzymes-1A2,2C9,2C19,2D6,2E1 and 3A4 (IR 50 >150 mmol). When taking sildenafil at the recommended doses, its Cmax is about 1 micromol, so it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes. Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter, and when they are prescribed for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated. When the alpha-blocker doxazosin (4 or 8 mg) and sildenafil (25,50, or 100 mg) were co-administered in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional reduction in sBP/dBP in the supine position was 7/7,9/5, and 8/4 mm Hg, respectively, and in the standing position-6/6,11/4, and 4/5 mm Hg, respectively. Rare cases of symptomatic postural hypotension, which manifested itself in the form of dizziness (without fainting), have been reported in such patients. In some sensitive patients receiving alpha-blockers, concomitant use of sildenafil may lead to symptomatic hypotension. There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the cytochrome CYP2C9 isoenzyme. Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome CYP3A4 isoenzyme, at a constant level in the blood. Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg). Sildenafil (50 mg) did not enhance the antihypertensive effect of alcohol in healthy volunteers with an average blood alcohol Cmax of 0.08% (80 mg/dl). In patients with arterial hypertension, there were no signs of interaction between sildenafil (100 mg) and amlodipine. The average additional reduction in blood pressure in the supine position is 8 mm Hg (sBP) and 7 mm Hg (dBP). The use of sildenafil in combination with antihypertensive agents does not lead to additional side effects.

Overdose

Symptoms: with a single dose of Viagra® up to 800 mg, adverse events were comparable to those with lower doses, but were more common. Treatment: symptomatic. Hemodialysis does not accelerate the clearance of sildenafil, since the latter is actively bound to plasma proteins and is not excreted by the kidneys.

Special instructions

To diagnose erectile dysfunction, determine their possible causes, and choose appropriate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination. Sexual activity poses a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient for a CVS examination. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP >Clinical studies have shown no differences in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular mortality (0.3 per 100 people per year) in patients treated with Viagra® compared to patients treated with placebo. Drugs intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.The drug Viagra ® has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. However, before prescribing Viagra®, the doctor should carefully assess the risk of possible undesirable manifestations of vasodilating effects in patients with the corresponding diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular exit tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with a rare syndrome of multiple systemic atrophy, manifested by a severe violation of blood pressure regulation by the autonomic nervous system. Rare cases of non-arterial anterior ischemic optic neuropathy have been reported as a cause of visual impairment or loss with all PDE-5 inhibitors, including sildenafil. Most of these patients had risk factors such as excavation of the optic nerve head, age over 50 years, diabetes mellitus, hypertension, CHD, hyperlipidemia, and smoking. No causal relationship was found between the use of PDE5 inhibitors and the development of anterior ischemic optic neuropathy of non-arterial origin. The doctor should inform the patient about the increased risk of developing anterior ischemic optic neuropathy of non-arterial origin, if this condition has already been noted in the past. Since the combined use of sildenafil and alpha-blockers can lead to symptomatic hypotension in some sensitive patients, Viagra® should be prescribed with caution to patients taking alpha-blockers (see the section “Interaction”). To minimize the risk of postural hypotension in patients taking alpha-blockers, Viagra® should be started only after hemodynamic stabilization has been achieved in these patients. Consideration should also be given to reducing the initial dose of Viagra® (see section “Dosage and use”). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of retinal phosphodiesterase functions. There is no information on the safety of using Viagra® in patients with retinitis pigmentosa, so sildenafil should be used with caution (see section “Contraindications”, subsection “With caution”). Sildenafil enhances the antiplatelet effect of sodium nitroprusside (a nitric oxide donor) on human platelets in vitro. There is no information on the safety of using Viagra® in patients with internal bleeding or active peptic ulcer of the stomach, so it should be used with caution (see the section “Contraindications”, subsection “With caution”). Treatment of erectile dysfunction should be used with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, Peyronie’s disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia) (see section “Contraindications”, subsection “With caution”). The safety and efficacy of Viagra ® in combination with other drugs for the treatment of erectile dysfunction has not been studied, so the use of such combinations is not recommended (see “Contraindications”). Some post-marketing and clinical studies using all PDE-5 inhibitors, including sildenafil, have reported sudden hearing loss or loss in patients. However, most of these patients had risk factors for the development of this pathology, and no correlation was found between the use of PDE5 inhibitors and sudden hearing loss or loss. In case of sudden hearing loss or loss, sildenafil therapy should be discontinued and your doctor should be consulted immediately. Influence on the ability to drive a car or perform work that requires an increased rate of physical and mental reactions. While taking sildenafil, no negative effects on the ability to drive a car or other technical means were observed. However, since taking sildenafil may reduce blood pressure, develop chromatopsia, blurred vision, etc. side effects, you should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Storage conditions

In a dry place, at a temperature not exceeding 30 °C. Keep out of reach of children.

Shelf life

5 years

Active ingredient

Sildenafil

Conditions of release from pharmacies

By prescription

Purpose

For adults as prescribed by a doctor, For men

Indications

Erectile Dysfunction