1 tablet film coating contains:
Active Ingredient:
Sildenafil citrate (equivalent to 25 mg, 50 mg or 100 mg of sildenafil)
Excipients:
microcrystalline cellulose, calcium hydrogen phosphate, croscarmellose sodium, stearate .magniya; film coating: Opadry Blue OY-LS-20921 (contains hypromellose, lactose, triacetin, titanium dioxide (E171) aluminum lake and indigo on the basis of (E132)) and Opadry clear YS-2-19114-A (contains hypromellose and triacetin)

For blue coating film may be added to 30 ug / g of vanillin and / or biotin; the content of one or both of the components in the film coating is up to 0.75 mg, 1.5 mg and 3.0 mg doses of 25 mg, 50 mg and 100 mg, respectively.

Description

Blue pills, film-coated, diamond-shaped, slightly anadrol 50 for sale biconcave, with cut and rounded edges, engraved with «Pfizer» on one side and «VGR 25», «VGR 50″ or «VGR 100″ on the other side, respectively.

 

Pharmacotherapeutic group:

a treatment for erectile dysfunction – PDE5 inhibitor

pharmacological properties

pharmacodynamics

Sildenafil – a powerful selective inhibitor tsikloguanozinmonofosfat (cGMP) -specific phosphodiesterase type 5 (PDE5).

Mechanism of action

Implementation of the physiological mechanism of erection involves the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This in turn leads to an increase in cGMP level, the subsequent relaxation of the corpus cavernosum smooth muscle tissue and increased blood flow.

Sildenafil has no direct relaxing effect on isolated human corpus cavernosum body, but enhances the effect of nitric oxide (NO) by inhibiting PDE5, which is responsible for the breakdown of cGMP.

Sildenafil against PDE5 selective in vitro, its activity against PDE5 superior activity against other known phosphodiesterase isoenzymes: PDE6 – 10 times; FDE1 – more than 80 times; PDE2, PDE4, FDE7-FDE11 – more than 700 times. Sildenafil is 4000 times more selective for PDE5 compared with PDE3, which is essential because PDE3 is one of the key enzymes in the regulation of myocardial contractility.

A mandatory condition for the effectiveness of sildenafil is sexual stimulation.

Clinical data

cardiac assessment

Sildenafil at doses up to 100 mg did not lead to clinically meaningful changes in the ECG in healthy volunteers. The maximum reduction of systolic pressure in the supine position after sildenafil 100 mg was 8.3 mmHg. Art and diastolic blood pressure -. 5.3 mm Hg. Art. More pronounced, but also a transient effect on blood pressure (BP) was seen in patients taking nitrates anadrol 50 for sale (see. Sections “Contraindications” and “Interaction with other medicinal products”).

The study hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (CAD) (more than 70% of patients had stenosis of at least one coronary artery), systolic and diastolic pressure at rest decreased by 7 % and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil had no effect on cardiac output, and did not violate the blood flow in stenotic coronary arteries, but also led to an increase (about 13%), adenosine-induced coronary flow in stenotic and in the intact coronary arteries.

In a double-blind, placebo-controlled study of 144 patients with erectile dysfunction and stable angina receiving antianginal medications (except nitrates) performed exercise to the point, when the severity of angina 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 with patients receiving placebo.

In a randomized, double-blind, placebo-controlled study examined the effect of the change of the dose of sildenafil (100 mg) in men (n = 568) with erectile dysfunction and hypertension, taking more than two antihypertensive drugs. Sildenafil improved erections in 71% of men compared with 18% in the placebo group. The frequency of adverse events was comparable to that in other groups of patients, as well as in patients taking more than three antihypertensive drugs.

Studies of visual impairment
in some patients within 1 hour after administration of sildenafil 100 mg using the Farnsworth-Munselya 100 test revealed mild and transient impaired ability to distinguish between shades of color (blue / green). After 2 hours after ingestion, these changes were absent. It is believed that a violation of color vision caused by the anadrol 50 for sale inhibition of PDE6, which is involved in the transmission of light in the retina.Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure and pupil diameter.
In placebo-controlled crossover study of patients with proven rannevozrastnoy-related macular degeneration (n = 9), sildenafil single dose of 100 mg was well tolerated. There were no clinically significant changes in vision, measured at a special visual tests (visual acuity, Amsler grille, color perception, color modeling passing, Humphrey perimeter and fotostress).

Efficacy
The efficacy and safety of sildenafil were evaluated in 21 randomized, double-blind, placebo-controlled study lasting up to 6 months in 3000 patients aged 19 to 87, with erectile dysfunction of various etiologies (organic, psychogenic or mixed). Efficacy was evaluated using the global diary erections, International Index of Erectile Function (validated questionnaire on the status of sexual function), and survey partner. The effectiveness of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all the studies, and has been confirmed in long-term studies lasting 1 year. In using a fixed dose studies proportion of patients who reported that the treatment improved their erection was 62% (the dose Sildenafil 25 mg), 74% (Sildenafil 50 mg dose) and 82% (sildenafil 100 mg dose) compared to 25% in the placebo group. Analysis of the international index of erectile function showed that in addition to improving erectile sildenafil treatment also improves the quality of orgasm, can achieve satisfaction from sexual intercourse and overall satisfaction.

According to the summarized data, among patients reported improved erections in the treatment of sildenafil were 59% of patients with diabetes, 43% of patients who underwent radical prostatectomy and 83% of patients with spinal cord injuries (vs. 16%, 15% and 12% in the placebo group, respectively ).

Pharmacokinetics

The pharmacokinetics of sildenafil in the recommended dose range is linear.

Suction

After oral administration, sildenafil is rapidly absorbed. Average absolute bioavailability is about 40% (from 25% to 63%). In vitro sildenafil at a concentration of about 1.7 ng / ml (3.5 nM) of human PDE5 inhibits 50%. After a single dose of sildenafil 100 mg average maximum concentration of sildenafil free in plasma (Cmax) is about 18 men ng / ml (38 nM). Cmax while anadrol 50 for sale taking sildenafil inside fasting achieved on average for 60 min (from 30 min to 120 min). When taken in combination with fatty food intake rate decreases: Cmax decreased by an average of 29% and the time to maximum concentration (Tmax) is increased by 60 minutes, but the absorption level was not significantly changed (area under the concentration-time curve (the AUC) decreases 11%).

Distribution

Sildenafil volume of distribution at steady state an average of 105 liters.
Communication sildenafil and its main circulating metabolite N-demetilnogo plasma proteins is approximately 96% and is independent of the total concentration of the drug. Less than 0.0002% of the dose of sildenafil (mean 188 ng) was found in semen at 90 min after dosing. Metabolism Sildenafil metabolized mainly in the liver by the action of the isoenzyme cytochrome CYP3A4 (major route) and isoenzyme cytochrome CYP2C9 (minor route). The main circulating active metabolite resulting from demethylation .N-sildenafil undergoes further metabolism. Selectivity of action against PDE metabolite comparable with that of sildenafil and its activity against PDE5 in vitro is approximately 50% activity sildenafil. The concentration of metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. N-demetilny metabolite undergoes further metabolism; its half-life period (T1 / 2) is about 4 hours.

 

breeding

Total clearance of sildenafil is 41 l / h, and the terminal T1 / 2 – 3.5 h. After oral administration as well as after intravenous administration of sildenafil appears as metabolites, mainly intestine (about 80% of the oral dose) and to a lesser extent, the kidneys (approximately 13% of the oral dose).

Pharmacokinetics in special patient groups

Elderly patients
Healthy elderly patients (65 years) sildenafil reduced clearance and plasma concentration of free sildenafil is about 40% higher than in young (18-45 years). Age has no clinically significant anadrol 50 for sale effect on the incidence of side effects.

Impaired Renal Function
In mild (creatinine clearance (CC) of 50-80 mL / min) or moderate (creatinine clearance 30-49 ml / min) renal impairment the pharmacokinetics of sildenafil following a single oral dose of 50 mg is not changed.In severe renal failure (creatinine clearance (30 ml / min) sildenafil clearance is reduced, which results in approximately doubling the value AUC (100%) and Cmax (88%) compared with those parameters in normal renal function in patients of the same age group.

Hepatic dysfunction
in patients with cirrhosis (stage A and B according to the classification of Child-Pugh) sildenafil clearance is reduced, leading to an increase in the value AUC (84%) and Cmax (47%) compared with those indices in normal liver function in patients the same age group. The pharmacokinetics of sildenafil in patients with severely impaired hepatic function (stage C by Child-Pugh classification) has not been studied.

Indications

Treatment of erectile dysfunction characterized by the inability to achieve or retain an erection of the penis sufficient for satisfactory sexual intercourse. Sildenafil is effective only during sexual stimulation.

Contraindications

Hypersensitivity to sildenafil or any other component of the product.
Use in patients treated continuously or intermittently donator of nitric oxide, organic nitrates or nitrites in any form as sildenafil enhances the hypotensive nitrates action (see. “Interaction with other medicinal products” section)
The safety and efficacy of the drug Viagra® when combined with other means of treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended (see. “Special instructions” section)
at the registered indication the drug Viagra® is not intended for use in children under 18 years
at the registered Viagra® indication preparation is not intended for use in women

Carefully

– Anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie’s disease) (see “Special Instructions” section.)
– Disease, predisposing to the development of priapism (sickle-cell anemia, multiple myeloma, leukemia, thrombocythemia) (see section “Special instructions. “)
– a disease accompanied by bleeding
– Aggravation of peptic ulcer disease
– Hereditary retinitis pigmentosa (see” Special instructions “).
– heart failure, unstable angina, transferred in the last 6 months anadrol 50 for sale of myocardial infarction, stroke, or life-threatening arrhythmia, hypertension (blood pressure> 170 / 100 mm Hg. Art.) or hypotension (blood pressure <90/50 mm Hg. Art.) (see. “Special instructions” section)

Pregnancy and lactation

As a registered indication the drug is not intended for use in women

Dosing and Administration
Inside.

The recommended adult dose for most patients is 50 mg in about 1 hour prior to sexual activity. Given the efficacy and tolerability of the dose can be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. Multiplicity maximum recommended application – once a day.

Impaired renal function
Mild to moderate degrees of renal insufficiency (creatinine clearance 30-80 ml / min) dose adjustment is not required, in severe renal insufficiency (creatinine clearance <30 ml / min) – sildenafil dose should be reduced to 25 mg.

Liver dysfunction
Since sildenafil excretion in patients with impaired liver damage (particularly in cirrhosis) Viagra® drug dose should be reduced to 25 mg.

The combined use with other medicinal products
When used together with ritonavir, the maximum single dose of the drug Viagra® should not exceed 25 mg, and the multiplicity of application – 1 time in 48 hours (see section “Interaction with other medicinal products.”).
When combined with inhibitors of CYP3A4 isoenzyme of cytochrome (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of the drug Viagra® should be 25 mg (see. section “Interaction with other medicinal products”).
to minimize the risk of postural hypotension in patients taking? adrenoblokatorom Viagra® receiving the drug should be started only after the stabilization of hemodynamics in these patients. It should also consider reducing the starting dose of sildenafil (see. Sections “Special Instructions” and “Interaction with other medicinal products”).

Elderly patients
Adjustment of dose of the drug Viagra® is not required.

Side effect

Usually, the side effects of the drug Viagra® weakly or moderately expressed and are transient in nature.
As with the use of fixed-dose studies have shown that the incidence of some adverse events increased with anadrol 50 for sale increasing dose.

The organs and organ systems Side effects Sildenafil% Placebo%
The most common side effects (> 1/10)
Nervous system Headache 10.8 2.8
The cardiovascular system Vasodilation ( “tides” of blood
to the skin of the face)
10.9 1.4
Common adverse events (> 1/100 and <1/10)
Nervous system Dizziness 2.9 1.0
organ of vision Changing the view (blurred vision, changes in sensitivity
to light)
2.5 0.4
Hromatopsiya (mild and transient, mostly change the perception of shades) 1.1 0.03
The cardiovascular system Cardiopalmus 1.0 0.2
Respiratory system Rhinitis (stuffy nose) 2.1 0.3
Digestive system Dyspepsia 3.0 0.4

When using Viagra® drug in doses greater than recommended, adverse events were similar to those noted above, but it is usually more common. Violations of the general condition: hypersensitivity reactions (including rash). Changes in the central and peripheral nervous system: convulsions. Changes in the cardiovascular system : tachycardia, decreased blood pressure, fainting, nose bleeding. Gastrointestinal disorders : vomiting. Changes on the part of the organ of vision: eye pain, eye redness / scleral injection.

 

Violations of the reproductive system: prolonged erection and / or priapism.

Overdose

In single dose of the drug Viagra® at a dose of 800 mg of adverse events were comparable to those of taking the drug at lower doses, but were more common. Treatment is symptomatic. Hemodialysis does not accelerate clearance of sildenafil, as the latter is actively bound to plasma proteins and excreted by the kidneys. Interaction with other drugs The influence of other drugs on the pharmacokinetics of sildenafil

 

Metabolism Sildenafil is mainly under the influence of isoenzyme cytochrome CYP3A4 (major route) and CYP2C9, therefore inhibitors of these isoenzymes may reduce sildenafil clearance and inducers, respectively, to increase the clearance of sildenafil. Decreased clearance of sildenafil, while the use of isoenzyme cytochrome CYP3A4 inhibitors (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), nonspecific inhibitor isoenzyme cytochrome CYP3A4, when co-administered with sildenafil (50 mg) sildenafil causes an increase in the plasma concentration of 56%. A single dose of 100 mg sildenafil together with erythromycin (500 mg / day, 2 times a day for 5 days), a specific inhibitor of the isoenzyme cytochrome CYP3A4, against the backdrop of the constant blood concentration of erythromycin, AUC increases by 182% sildenafil. When co-administered sildenafil (single dose 100 mg) and saquinavir (1200 mg / day, 3 times a day), an inhibitor of HIV protease and isoenzyme cytochrome CYP3A4, against the backdrop of constant saquinavir concentration Cmax blood sildenafil increased by 140%, and the AUC was increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir. More potent inhibitors isoenzyme cytochrome CYP3A4, such as ketoconazole and itraconazole, may cause more severe changes in the pharmacokinetics of sildenafil.
Simultaneous use of sildenafil (single dose 100 mg) and RTV (500 mg, 2 times a day), HIV protease inhibitor and a potent inhibitor of cytochrome P450, against the backdrop of a constant concentration in the blood of ritonavir increases the Cmax of sildenafil 300% (4 times) and AUC 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng / ml (after one use of sildenafil – 5 ng / ml).
If sildenafil is taken at the recommended doses, patients receiving both potent inhibitors isoenzyme cytochrome CYP3A4, the Cmax free sildenafil does anadrol 50 for sale not exceed 200 nM, and the drug is well tolerated.
A single dose of antacid (hydroxide / aluminum hydroxide magnesium) does not affect the bioavailability of sildenafil.
isoenzyme inhibitors of cytochrome of CYP2C9 (tolbutamide, warfarin), isoenzyme cytochrome of CYP2D6 (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide diuretics, ACE inhibitors and calcium antagonists do not affect the pharmacokinetics of sildenafil.
Azithromycin (500 mg / day for 3 days) did not affect the AUC, Cmax, Tmax, elimination rate constant and T1 / 2 of sildenafil or its main circulating metabolite. Effect of sildenafil on other medicinal productssildenafil is a weak inhibitor of cytochrome P450 isoenzymes – 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (IC50> 150 umol). When taken in recommended doses of sildenafil its max of about 1 micromolar, it is unlikely that sildenafil may affect the clearance of substrates of these isoenzymes.

 

Sildenafil increases hypotensive effects of nitrates as a long-term use of the latter, and at their assignment for acute indications. In this regard, the use of sildenafil in combination with nitrates or donators contraindicated nitrogen oxide.
When concomitantly? -adrenoblocker Doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) in patients with benign prostatic hyperplasia patients with hemodynamically stable average additional reduction in systolic / diastolic blood pressure in the supine position was 7.7 mmHg. st., 9/5 mm Hg. Art. and 8/4 mm Hg. Art., respectively, and in the standing position – 6.6 mm Hg. st., 11/4 mm Hg. Art. and 4/5 mm Hg. Art., respectively. Reported rare cases of such patients symptomatic postural hypotension, manifested in the form of dizziness (without fainting). In certain sensitive patients receiving -.? Blockers, simultaneous use of sildenafil may result in symptomatic hypotension.
No evidence of significant interaction with tolbutamide (250 mg) or warfarin (40 mg) are metabolized by cytochrome CYP2C9, is not revealed.
Sildenafil (100 mg) has no effect on the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir are substrates isoenzyme cytochrome CYP3A4, when a constant level in the blood.
Sildenafil (50 mg) does not cause an additional increase in bleeding time at the reception of acetylsalicylic acid (150 mg).
Sildenafil (50 mg) does not potentiate the hypotensive effect of alcohol in healthy volunteers at the maximum blood alcohol concentration by an average of 0.08% (80 mg / dl).
in patients with arterial hypertension signs of interaction between sildenafil (100 mg) with amlodipine has not been identified. The average additional reduction in blood pressure in the supine position is 8 mm Hg. Art. (systolic) and 7 mm Hg. Art. (diastolic).
The use of sildenafil in combination with antihypertensive agents is not causing additional side effects.

special instructions

For the diagnosis of erectile dysfunction, determine their possible causes and select appropriate treatment is necessary to collect a complete medical history and conduct a thorough physical examination.

Sexual activity is a risk in the presence of heart disease, so before beginning any therapy for erectile dysfunction your doctor should refer the patient to the examination of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina, transferred in the last 6 months of myocardial infarction or stroke, life-threatening arrhythmias, hypertension (blood pressure> 170/100 mm Hg. Art.) Or hypotension (blood pressure <90/50 mm Hg. Art.) (see. “Precautions” section). In clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 person-years) and mortality rate from cardiovascular diseases (0.3 per 100 person-years) in patients receiving the drug Viagra®, compared with patients receiving placebo.

Preparations for the treatment of erectile dysfunction, should not be given to men for whom sexual activity is undesirable.

The drug Viagra® has systemic vasodilatory effect resulting in a transient decrease in blood pressure that is not clinically significant phenomenon and does not lead to any consequences in most patients.However, before prescribing the drug Viagra® doctor should carefully evaluate the risk of potential adverse events vasodilating action in patients with relevant diseases, especially against sexual activity.Increased susceptibility to vasodilators observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), and is rarely encountered with multiple system atrophy syndrome, manifesting severe dysregulation of blood pressure by the autonomic nervous system.

Rare cases of anterior ischemic optic neuropathy nearterialnogo genesis as the reasons for the deterioration or loss of vision have been reported during treatment with all PDE5 inhibitors, including sildenafil.Most of these patients had risk factors, such as the excavation of (deepening) the optic nerve head, age over 50 years, diabetes mellitus, hypertension, coronary heart disease (CHD), hyperlipidemia and smoking. Cause-and-effect relationship between PDE-5 inhibitors intake and the development of anterior ischemic optic neuropathy nearterialnogo origin was not revealed. The physician should inform the patient about the increased risk of anterior ischemic optic neuropathy nearterialnogo genesis, if previously this state had already noted. Since the combined use of sildenafil and -.? Blockers may lead to symptomatic hypotension in certain sensitive patients, Viagra® drug should be used with caution in patients receiving adrenoblokatory (see “Interaction with other medicinal products” section.)?. To minimize the risk of postural hypotension in patients taking beta-blockers, taking Viagra® drug should be started only after anadrol 50 for sale the stabilization of hemodynamics in these patients. It should also consider reducing the initial dose of the drug Viagra® (see. “Dosage and Administration” section). The physician should inform the patient about what actions to take in case of the onset of symptoms of postural hypotension.

A small number of patients with hereditary retinitis pigmentosa are genetically determined disorders of retinal phosphodiesterases functions of the eye. Information on the safety of the Viagra® drug in patients with retinitis pigmentosa no, so Sildenafil should be used with caution (see. “With ostorozh.nostyu” section).

Sildenafil enhances the antiplatelet effect of sodium nitroprusside (nitric oxide donator) on human platelets in vitro. Information on the safety of the Viagra® drug in patients with internal bleeding, or active peptic ulcer of the stomach are not available, so it should be used with caution (see. “With ostorozh.nostyu” section).

Means of treatment of erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie’s disease), or in patients with risk factors for the development of priapism (sickle-cell anemia, multiple myeloma, leukemia) (see. Section “With careful. of “).

The safety and efficacy of the drug Viagra®, together with other facilities for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended (see. “Contraindications”).

In some post-marketing and clinical trials with the use of all PDE5 inhibitors, including sildenafil, reported a sudden decrease or loss of hearing patients. However, most of these patients had risk factors for this disease, and it was not found any correlation between the use of PDE5 inhibitors and sudden decrease or loss of hearing. In the event of sudden decrease or loss anadrol 50 for sale of hearing should discontinue therapy with sildenafil and consult a doctor immediately.

Effects on ability to drive and management mechanisms

While taking sildenafil any negative impact on the ability to drive a motor vehicle or other technical means were observed. However, since when taking sildenafil may decrease blood pressure, hromatopsii development, blurred vision, etc. side effects, should be attentive to the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dose regimen.

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