Expiration date: 04/2026
The composition and form of issue:
Tablets, film-coated. 1 tablet contains:
sildenafil citrate 25, 50 or 100 mg
other ingredients: microcrystalline calcium hydrogen phosphate croscarmellose sodium magnesium stearate
film shell: Opadry blue OY-LS-20921 (contains hypromellose, lactose, triatsetin, titanium dioxide (E171) and an aluminum lacquer based Indigo (E132) and Opadry YS transparent-2-19114-A (contains hypromellose and triatsetin)
the blue film can be added to 30 µg/g of vanillin and/or Biotin the content of one or both components in film coating will be up to 0.75, 1.5 and 3.0 mcg for doses of 25, 50 and 100 mg, respectively
in blister packs of 1, 2, 4, 8 or 12 PCs in a box 1, 2 or 3 blisters.
Description pharmaceutical form:
Blue tablets, film-coated, diamond-shaped, slightly biconvex with cut and rounded edges, engraved with "Pfizer" on one side and "VGR 25", "VGR 50" or "VGR 100" on the other side, respectively.
Pharmacological action:
A treatment for erectile dysfunction phosphodiesterase-5 inhibitor.
Pharmacokinetics:
The pharmacokinetics of sildenafil in a recommended dose range is linear.
Suction. After intake of sildenafil is rapidly absorbed. Absolute bioavailability averages about 40% (from 25 to 63%). In vitro sildenafil at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of phosphodiesterase 5-th type (PDE-5) a person 50%. After a single dose of sildenafil in a dose 100 mg average free sildenafil Cmax in blood plasma men is about 18 ng/ml (38 nm). Cmax when taking sildenafil inside fasting achieved on average over 60 min (from 30 to 120 min). When taken in combination with fatty food the rate of absorption is reduced: Cmax is decreased on average by 29% and Tmax increased by 60 min, however, the extent of absorption was not significantly altered (AUC reduced by 11%).
Distribution. VSS for sildenafil is 105 L. the average
The connection of sildenafil and its main circulating N-demethylase metabolite with blood plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose sildenafil (average 188 ng) were detected in semen after 90 min after administration of the drug.
Metabolism. Sildenafil is metabolized primarily in the liver under the action of the isoenzyme cytochrome CYP3A4 (major route) and cytochrome isozyme CYP2C9 (minor route). The main circulating active metabolite resulting from N-demethylation of sildenafil undergoes further metabolism. Selectivity of action of this metabolite in relation to the PDE is comparable to sildenafil, and its activity against PDE5 in vitro is about 50% of the activity of sildenafil. The concentration of metabolite in plasma of healthy volunteers was about 40% of the concentration of sildenafil. N-dimethly metabolite undergoes further metabolism T1/2 is about 4 h.
Excretion. Total clearance of sildenafil is 41 l/h, and the final T1/2 — 3-5 hours After ingestion, as well as after I/V administration sildenafil is excreted as metabolites mainly the intestines (about 80% of oral dose) and to a lesser extent by the kidneys (about 13% of oral dose).
Pharmacokinetics in special patient groups
Elderly patients. In healthy elderly patients (over 65 years) the clearance of sildenafil is reduced, and the free concentration of sildenafil in plasma is about 40% higher than in young (18-45 years). Age has no clinically significant effect on the incidence of adverse effects.
The impairment of renal function. If (Cl — creatinine 50-80 ml/min) and moderate (Cl — creatinine 30-49 ml/min) renal insufficiency the pharmacokinetics of sildenafil after a single oral dose of 50 mg not changed. In severe renal failure (Cl creatinine &le30 ml/min) sildenafil clearance is reduced, leading to approximately twofold increase in AUC values (100%) and Cmax (88%) compared with those with normal indices of renal function in patients in the same age group.
The liver dysfunction. In patients with liver cirrhosis (stages A and b according to the classification of child-Pugh) sildenafil clearance is reduced, which leads to increased values of AUC (84%) and Cmax (47%) compared with those with normal indices of liver function in patients of the same age group. The pharmacokinetics of sildenafil in patients with severe liver dysfunction (stage C classification child-Pugh) has not been studied.
Description pharmacological action:
Sildenafil — a powerful selective inhibitor of tsikloguanozinmonofosfat (cGMP)-specific phosphodiesterase 5-th type (PDE-5).
Mechanism of action
Realization of physiological mechanism of erection is associated with release of nitric oxide (NO) in cavernous bodies during sexual stimulation. This, in turn, leads to increased levels of cGMP, the subsequent relaxation of smooth muscle of the corpora cavernosa and increase blood flow.
Sildenafil has no direct relaxing effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting PDE-5, which are responsible for the breakdown of cGMP.
Selective sildenafil against PDE5 in vitro, its activity against PDE5 superior activity against other known phosphodiesterase isoenzymes: PDE-6 — 10 times PDE-1 more than 80 times, PDE-2, PDE-4, PDE-7 PDE–11 more than 700 times. Sildenafil 4000 times more selective against PDE-5 compared to PDE-3, which is essential because PDE-3 is a key enzyme regulating myocardial contractility.
Mandatory condition for the effectiveness of sildenafil is sexual stimulation.
Clinical data
Cardiology research
The use of sildenafil at doses up to 100 mg did not lead to clinically meaningful ECG changes in healthy volunteers. The maximum reduction in the garden in the supine position after taking sildenafil in a dose of 100 mg was 8.3 mm Hg. art., DBP — 5.3 mm Hg. article More pronounced, but also a transient effect on BP was noted in patients taking nitrates (see sections "Contraindications" and "Interaction").
In a study of hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis at least one coronary artery), SBP and DBP at rest decreased by 7 and 6% respectively and pulmonary systolic pressure decreased by 9%. Sildenafil does not affect cardiac output and didn't break the 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 in 144 patients with erectile dysfunction and stable angina receiving antianginal medications (except nitrates) do physical exercises until when expression of symptoms of angina decreased. Duration of exercise was significantly higher (with a 19,9 0,9–38,9 C) in patients taking sildenafil in a single dose of 100 mg compared with patients receiving placebo.
In a randomized double-blind placebo-controlled study studied the effect of variable doses of sildenafil (100 mg) in men (n = 568) with erectile dysfunction and arterial hypertension taking more than two antihypertensive drugs. Sildenafil improved erections in 71% of men compared to 18% in the placebo group. The frequency of adverse effects was comparable to that in other patient groups, as well as for persons taking more than three antihypertensive drugs.
The study of visual disorders
In some patients, after 1 h after taking sildenafil in a dose of 100 mg using the test of Farnsworth-Muntele 100 revealed a slight and transient impaired ability to distinguish shades of color (blue/green). After 2 h after ingestion, these changes were absent. It is believed that the breach of color vision is caused by inhibition of PDE-6, which is involved in the transmission of light in the retina of the eye. Sildenafil does not affect visual acuity, contrast perception, electroretinogram, intraocular pressure or pupil diameter.
In a placebo-controlled cross-over study of patients with proven rannemvozraste-related macular degeneration (n = 9) sildenafil in a single dose of 100 mg were well tolerated. There were no clinically meaningful changes in vision measured by special visual tests (visual acuity, Amsler grille, color perception, simulation of color passing, perimeter Humphrey and photostress).
Efficiency
The efficacy and safety of sildenafil was evaluated in 21 randomized, double blind, placebo-controlled study lasting up to 6 months, in 3000 patients aged 19 to 87 years with erectile dysfunction of various etiologies (organic, psychogenic, or mixed). Efficacy of the drug was assessed globally using diary erections, international index of erectile function (validierung questionnaire on the state of sexual function) and polling 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 studies and was confirmed in long-term studies lasting 1 year. In studies with the use of fixed-dose proportion of patients reporting that treatment improved their erections were 62% (dose of sildenafil 25 mg), 74% (dose sildenafil — 50 mg) and 82% (dose sildenafil — 100 mg) compared to 25% in the placebo group. The analysis of the international index of erectile function showed that in addition to the improvement in erection treatment sildenafilom also increased the quality of the orgasm, allowed to achieve satisfaction from sexual intercourse and overall satisfaction.
According to the generalized data, among the patients reporting improvement of erections in the treatment sildenafilom was 59% of patients with diabetes, 43% of patients who undergo radical prostatectomy, and 83% of patients with spinal cord injury (versus 16, 15 and 12% in the placebo group, respectively).
Indications:
- Treatment of erectile dysfunction characterized by the inability to achieve or sustain a penile erection sufficient for satisfactory sexual intercourse.
- Sildenafil is effective only during sexual stimulation.
Contraindications:
- hypersensitivity to sildenafil or any component of the drug
- use in patients receiving continuously or intermittently the donators of nitrogen oxide, organic nitrates or nitrites in any form, as sildenafil enhances the hypotensive effect of nitrates (see section "Interactions")
- the combined use with other drugs for the treatment of erectile dysfunction (the safety and efficacy of the drug Viagra in a joint application was not investigated, see "Special indications"), so the use of such combinations is not recommended
- not intended for use in the registered indications in children under 18 years
- not intended for use in the registered indications in women.
With caution:
anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease) (see "Special instructions")
diseases predisposing to the development of priapism (sickle-cell anemia, multiple myeloma, leukemia, thrombocythemia) (see "Special instructions")
diseases accompanied by bleeding
exacerbation of peptic ulcer disease
hereditary retinitis pigmentosa (see "Special instructions")
heart failure, unstable angina, migrated in the last 6 months myocardial infarction, stroke, or life-threatening arrhythmia, arterial hypertension (AD>170/100 mm Hg. Hg), or hypotension (AD<90/50 mm Hg. calendar) (see "Special instructions").
Application of pregnancy and breast-feeding:
The registered indication the drug is not intended for use in women.
Side effects:
Usually the side effects of the drug Viagra slightly or moderately expressed and are transient in nature.
In studies with the use of a fixed dose shown that the frequency of some adverse events increased with increasing dose.
Table
| Organs and organ systems | Side effects | Sildenafil, % | Placebo, % |
| The most common side effects (>1/10) | |||
| Nervous system | Headache | 10,8 | 2,8 |
| CCC | Vasodilation (flushing to the face) | 10,9 | 1,4 |
| Common side effects (>1/100 ? <1/10) | |||
| Nervous system | Dizziness | 2,9 | 1,0 |
| The organ of vision | Vision changes (blurred vision, sensitivity to light) | 2,5 | 0,4 |
| Chromatopsia (mild and transient, mostly change the perception of shades of color) | 1,1 | 0,03 | |
| CCC | Palpitations | 1,0 | 0,2 |
| Respiratory system | Rhinitis (nasal congestion) | 2,1 | 0,3 |
| Digestive system | Dyspepsia | 3,0 | 0,4 |
When using the drug Viagra in doses exceeding recommended, adverse events were similar to that noted above, but usually met more often.
Violation of General condition: hypersensitivity reactions (including skin rash).
Changes in the Central nervous system and peripheral nervous system: convulsions.
Changes in the CVS: tachycardia, decreased blood pressure, fainting, epistaxis.
Gastrointestinal disorders: vomiting.
Changes in the organ: eye pain, eye redness/injection sclera.
Violations of the reproductive system: prolonged erection and/or priapism.
Drug interactions:
The influence of other drugs on the pharmacokinetics of sildenafil
Sildenafil metabolism is mainly under the influence of isoenzymes of cytochrome CYP3A4 (major route) and CYP2C9, therefore inhibitors of these isoenzymes may reduce sildenafil clearance and inducers, respectively, increase sildenafil clearance. Marked decrease in clearance of sildenafil with simultaneous use of inhibitors of cytochrome isoenzyme CYP3A4 (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a nonspecific inhibitor of the isoenzyme cytochrome CYP3A4, with a joint appointment with sildenafilom (50 mg) causes an increase in the concentration of sildenafil in plasma by 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, on the background to achieve a constant concentration of erythromycin in the blood leads to the increase in sildenafil AUC by 182%. When co-administered sildenafil (once 100 mg) and saquinavir (1200 mg/day in 3 divided doses), an inhibitor of HIV protease, and cytochrome isoenzyme CYP3A4, on the background to achieve a constant concentration of saquinavir in the blood, Cmax of sildenafil was increased by 140% and AUC increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir. Stronger inhibitors of isoenzyme cytochrome CYP3A4, such as ketoconazole and Itraconazole, can cause more dramatic changes in pharmacokinetics of sildenafil.
The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P450, on the background to achieve a constant concentration of ritonavir in the blood leads to an increase in Cmax of sildenafil by 300% (4 times), and AUC of 1000% (11-fold). After 24 hours the concentration of sildenafil in plasma is about 200 ng/ml (after a single application of one sildenafil — 5 ng/ml).
If sildenafil is taken in recommended doses, patients receiving both strong inhibitors of cytochrome isoenzyme CYP3A4, free sildenafil Cmax does not exceed 200 nm, and the drug is well tolerated.
A single dose of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.
Inhibitors of cytochrome isozyme CYP2C9 (tolbutamide, warfarin), CYP2D6 isoenzyme of cytochrome (SSRIs, tricyclic antidepressants), thiazide and tiazidopodobnye diuretics, ACE inhibitors and calcium antagonists have no effect on the pharmacokinetics of sildenafil.
Azithromycin (500 mg/day for 3 days) has no effect on the AUC, Cmax, Tmax, rate constant of elimination and T1/2 sildenafil or its primary circulating metabolite.
The effect of sildenafil on other drugs
Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes — 1A2, 2S9, 2S19, 2D6, 2E1 and 3A4 (IK50 >150 µmol). When receiving sildenafil at recommended doses, its Cmax is about 1 mol, it is unlikely that sildenafil may affect the clearance of substrates of these isoenzymes.
Sildenafil enhances the hypotensive effect of nitrates as long-term use, and in their nomination for acute indications. In this regard, the use of sildenafil in combination with nitrates or donors of nitrogen oxide is contraindicated.
While admission &alpha-blocker doxazosin (4 or 8 mg) and sildenafil (25, 50 or 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional decline in garden/dad in the supine position was 7/7, 9/5 mmHg, and 8/4. article, respectively, while in the standing position — 6/6, 11/4 mmHg, and 4/5. article respectively. Reported rare cases of such patients symptomatic postural hypotension, manifested in the form of dizziness (no syncope). Certain sensitive patients receiving &alpha-blockers, simultaneous use of sildenafil can cause symptomatic hypotension.
Signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the CYP2C9 isoenzyme of the cytochrome could be detected.
Sildenafil (100 mg) has no effect on the pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir are substrates of the isoenzyme cytochrome CYP3A4, with their constant level in the blood.
Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking aspirin (150 mg).
Sildenafil (50 mg) enhances the hypotensive effect of alcohol in healthy volunteers Cmax in blood alcohol on average of 0.08% (80 mg/DL).
In patients with arterial hypertension signs of interaction of sildenafil (100 mg), amlodipine was not revealed. The average additional reduction in blood pressure in the supine position is 8 mm Hg. article (SBP) and 7 mm Hg. article (DBP).
The use of sildenafil in combination with antihypertensive drugs does not lead to additional side effects.
Method of application and dose:
Inside, approximately 1 hour before sexual activity.
The recommended dose for most adult patients is 50 mg given efficacy and tolerability the dose may be increased to 100 mg or reduced to 25 mg. the Maximum recommended dose is 100 mg. the Maximum recommended multiplicity of application 1 time per day.
Violations of kidney function. In mild to moderate renal insufficiency (Cl creatinine clearance 30-80 ml/min) dose adjustment is not required, when severe kidney failure (Cl creatinine <30 ml/min) — dose of sildenafil should be reduced to 25 mg.
Violations liver function. Since the elimination of sildenafil is disrupted in patients with liver damage (particularly cirrhosis), the dose of the drug Viagra should be reduced to 25 mg.
The combined use with other drugs
When used together with ritonavir maximum single dose of Viagra should not exceed 25 mg, and the multiplicity of application 1 times in 48 hours (see section "Interactions").
When used together with inhibitors of cytochrome isoenzyme CYP3A4 (erythromycin, saquinavir, ketoconazole, Itraconazole) initial dose of Viagra should be 25 mg (see section "Interactions").
To minimize the risk of developing postural hypotension in patients receiving &alpha-blockers, the drug Viagra should be started only after achieving stabilization of hemodynamics in these patients. You should also consider lower starting doses of sildenafil (see "Special instructions" and "Interaction").
Elderly patients. Dose adjustment of the drug Viagra is not required.
Overdose:
Symptoms: when a single dose of the drug Viagra the dose to 800 mg adverse events were comparable to those when taking drug at lower doses, but met often.
Treatment: symptomatic. Hemodialysis does not accelerate clearance of sildenafil, as last activity binds to plasma proteins and is not excreted by the kidneys.
Special instructions:
For diagnostics of violations of erection, determination of them possible reasons and choice of adequate treatment it is necessary to collect a complete medical history and conduct a thorough physical examination.
Sexual activity represents a certain risk at presence of diseases of the heart, therefore, before any therapy at the violations of erection the physician should refer the patient to the survey of CCC. Sexual activity undesirable in patients with heart failure, unstable angina, migrated in the last 6 months myocardial infarction or stroke, life-threatening arrhythmias, arterial hypertension (AD>170/100 mm Hg. Hg), or hypotension (AD<90/50 mm Hg. calendar) (see "Contraindications" subsection "With caution"). Clinical studies have shown no differences in the incidence of myocardial infarction (1.1 per 100 persons per year) or frequency of mortality from cardiovascular disease (0.3 per 100 people per year) patients treated with the drug Viagra, compared with patients receiving 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 systemic vasodilating action, resulting in transient reduction in blood pressure that is not clinically significant phenomenon and does not lead to any consequences in most patients. However, before prescribing Viagra physician should carefully assess the risk of possible undesirable manifestations vasodilating effect in patients with relevant diseases, especially against sexual activity. Increased susceptibility to vasodilators observed in patients with obstruction of the output tract of the left ventricle (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as the rarely occurring syndrome of multiple system atrophy, manifested severe violation of the regulating blood pressure the autonomic nervous system.
Were marked by rare cases of anterior ischemic optic neuropathy parcelling Genesis as the cause of deterioration or loss of vision in the background of the application of all inhibitors of PDE5, including sildenafil. Most of these patients had risk factors, such as excavation (deepening) of the head of the optic nerve, age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and Smoking. The causal connection between the inhibitors PDE-5 and development of anterior ischemic optic neuropathy parcelling Genesis is not revealed. The physician should inform the patient about the increased risk of developing anterior ischemic optic neuropathy parcelling Genesis, if you previously this state he noted. Since the combined use of sildenafil and alpha-blockers may lead to symptomatic hypotension in individual sensitive patients, the drug Viagra should be used with caution in patients receiving &alpha-adrenergic blocking agents (see "Interactions"). To minimize the risk of developing postural hypotension in patients receiving &alpha-blockers, the drug Viagra should be started only after achieving stabilization of hemodynamics in these patients. You should also consider reducing the initial dose Viagra (see "Method of application and dosage"). The physician should inform patients about what action should be taken in the event of the onset of symptoms of postural hypotension.
A small number of patients with hereditary pigmented retinitis are genetically determined disorders of phosphodiesterase of the retina. Information about the safety of the drug Viagra in patients with pigmented retinitis absent, so sildenafil should be used with caution (see section "Contraindications", subsection "With caution").
Sildenafil enhances antiaggregatory effect of sodium nitroprusside (donor of nitric oxide) on human platelets in vitro. Information about the safety of the drug Viagra in patients with internal bleeding or active peptic ulcer of the stomach do not exist, so it should be used with caution (see section "Contraindications", subsection "With caution").
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 priapism (sickle cell anemia, multiple myeloma, leukemia) (see section "Contraindications", subsection "With caution").
The safety and efficacy of the drug Viagra together with other drugs for the treatment of erectile dysfunction has not been studied, so the use of such combinations is not recommended (see section "Contraindications").
In some post-marketing and clinical studies with the use of all inhibitors of PDE5, including sildenafil, reported a sudden decrease or loss of hearing patients. However, most of these patients had risk factors development of this disease, and it was not found any correlation between the use of inhibitors PDE-5 and sudden decrease or loss of hearing. In case of sudden decrease or loss of hearing should discontinue therapy sildenafilom and immediately consult a doctor.
Effects on ability to drive and other mechanisms. In patients receiving sildenafil any negative effect on the ability to drive a car or other means was not observed. However, because while taking sildenafil may reduce blood pressure, development of chromatopsia, blurred vision etc side effects one should be attentive to the individual action of the drug in these situations, especially in the beginning of treatment and when changing the dosing regimen.
