1. Name of medicine
Viagra
2. Quantitative and qualitative
Active ingredient: sildenafil citrate
Viagra 25 mg: tablet contains sildenafil citrate at a dose equivalent to 25 mg sildenafil.
Viagra 50 mg: tablet contains sildenafil citrate at doses equivalent to 50 mg sildenafil.
Viagra 100 mg: tablet contains sildenafil citrate in a dosage of 100 mg sildenafil.
The list of inactive ingredients
Microcrystalline cellulose, calcium gidrofosfat (anhydrous), kroskarmelloza sodium, magnesium stearate, gipromelloza, titanium dioxide (E171), lactose, triatsetin, lacquer aluminum indigo carmine (E132).
3. Pharmacological properties
Sildenafil; ATC code G04V E
3.1. Pharmacodynamic properties
Viagra is a new oral medication designed to treat erectile dysfunction. A violation is restored erectile function and provides a natural response to sexual arousal.
Physiological mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide activates the enzyme guanilattsiklazu, leading to increased levels of cyclic guanozinmonofosfata (tsGMF), relaxation of smooth muscles of cavernous bodies and increasing the blood flow to the penis.
Sildenafil is a potent and selective inhibitor specific tsGMF-fosfodiesterazy type 5 (FDE5), which is responsible for the collapse of the tsGMF in the corpus cavernosum. Viagra has an effect on peripheral arousal. Sildenafil has no direct relaxant effect on corpus cavernosum but also actively improving the relaxing effect of NO in this tissue. When the road Navarre / tsGMF observed in sexual initiation, inhibition FDE5 influenced sildenafil leads to increased levels of tsGMF in the corpus cavernosum. Thus, for the demonstration of a favorable pharmacological effect of Viagra requires sexual stimulation.
When receiving a single dose of Viagra in the 100 mg in healthy volunteers, the drug produced no clinically significant changes in ECG. The maximum decrease in systolic blood pressure in the prone position in the application of the drug into a dose of 100 mg was on average 8.4 mm Hg. Section A decrease in diastolic blood pressure in the prone position was 5.5 mm Hg. Art Reducing blood pressure is vazodilatiruyuschimi sildenafil effects, possibly through raising tsGMF in vascular smooth muscle.
Viagra has no effect on visual acuity and contrast perception. Some patients in 1 hours after taking the drug in a dose of 100 mg showed mild and transient violation distinguish colors (blue / green) using the Farnsworth-Munsell test 100, at 2 h after taking medication, these changes were absent. The mechanism provided for violations of oppression felt FDE6 color, which is involved in the transfer of light in the retina. In vitro studies have shown that the effect of sildenafil FDE6 10 times lower than its activity against FDE5.
In vitro studies indicate that the activity against sildenafil FDE5 10 -10 000 times larger than its activity against other isoforms fosfodiesterazy (FDE 1, 2, 3, 4 and 6). In particular, activity against FDE5 4 sildenafil 000 times larger than its activity against FDE3 - tsAMF specific fosfodiesterazy involved in the reduction of the heart.
3.1.1. For more information on clinical trials
Efficacy and safety of Viagra has been studied in 21 randomized, double-blind study platsebokontroliruemom for 6 months. Viagra used by more than 3,000 patients with erectile dysfunction of various etiologies (organic, psychogenic, mixed), aged 19 to 87 years. Effectiveness is determined by the overall assessment, the newspapers, the assembly of registration, evaluation of the International Index of Erectile Function (IIEF, a questionnaire to assess sexual function), and the survey of partners.
Effectiveness of Viagra, which is estimated by the drug’s ability to attack, and the preservation of an erection sufficient for sexual intercourse, has been demonstrated in 21 studies, and persisted over the long term (one year). If you use drugs in fixed doses, the proportion of patients reported improvement in erectile function was 62% (25 mg), 74% (50 mg) and 82% (100 mg), and to receive a placebo - 25% . In addition to improving erectile function, IIEF results showed that the treatment of Viagra also improved orgasm, satisfaction from sexual intercourse and overall satisfaction.
In all studies, the proportion of diabetic patients, improvements in the treatment of Viagra amounted to 59% of patients experienced a radical prostatektomiyu - 43% of patients with spinal cord injury - 83% (vs. 16%, 15 % and 12% of patients receiving placebo, respectively).
3.2. Pharmacokinetic properties
Intake
Viagra readily absorbed. The concentration of drug in plasma after administration in the stomach reaches its peak within 30-120 minutes (mean 60 min). The absolute bioavailability of oral, with an average of 41% (25-63%). The pharmacokinetics of the ingestion of Viagra in the range of doses (25-100 mg) is linear.
When you receive Viagra in combination with fatty food intake rate decreases; Tmax is increased by 60 minutes, and Cmax were reduced by half from 29%.
Distribution
The volume of distribution (Vss) sildenafil at steady state is an average of 105 liters, indicating that its tissue distribution. Sildenafil and its major circulating metabolite N-desmetilovy by approximately 96% binds to plasma proteins. Protein binding does not depend on the total concentration of the drug.
In healthy volunteers who received Viagra (100 mg once), less than 0.0002% (average 188 ng) dose was found in semen after 90 minutes after administration.
Metabolism
Sildenafil is primarily metabolized by the action of CYP3A4 (major route) and CYP2C9 (optional pathname) of the liver microsomal isozyme. The main circulating metabolite formed by the N-desmetilirovaniya sildenafil. According to the selectivity of action comparable to sildenafilom FDE metabolite and its activity against FDE5 is approximately 50% activity of the drug. Concentrations of metabolites in plasma is about 40% of the sildenafil. N-desmetilmetabolit continue under its metabolism, during his terminal half is approximately 4 h.
Derivation
Total body clearance of sildenafil equal to 41 l / h, terminal elimination half - 3-5 h. After ingestion or intravenous sildenafil is in the form of metabolites mainly in the faeces (approximately 80% tax-dose) and to a lesser extent in the urine (approximately 13% imposed dose).
Pharmacokinetics in special patient groups:
Older people
In healthy elderly volunteers (65 years and over) reduced sildenafil clearance and the concentration of free drug in plasma by approximately 40% higher than in young healthy volunteers (18-45 years). However, an analysis of safety data showed that age does not influence the frequency of undesirable events.
Renal
In volunteers with mild (creatinine clearance 50-80 ml / min) and moderate (creatinine clearance 30-49 ml / min) the pharmacokinetics of renal Viagra after a single oral (50 mg) did not change. In volunteers with severe (creatinine clearance <30>
4. Clinical part.
4.1. Indications for Use
Viagra is used to treat erectile dysfunction.
Contraindications
Viagra is contraindicated in patients with hypersensitivity to any component of the tablets.
Thanks to the well-known effects on the exchange of nitric oxide / tsGMF (see Pharmacodynamic properties). Viagra amplified hypotensive effect of nitrates, so its use contraindicated in patients receiving nitric oxide donors or nitrates in any form.
4.3 Dosage and Administration
Viagra tablets are inside.
The use of adult
Recommended dose is 50 mg taken, if necessary, about an hour before anticipated sexual activity. Given the efficiency and portability of the dose may be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of application - once a day.
* Request for elderly and patients with renal or hepatic
The elderly and patients with renal or hepatic impairment is recommended applying the same scheme.
The use in children
Viagra should not be for children.
4.4. Special warnings and precautions
To diagnose erectile dysfunction, to determine possible causes of their choice and adequate treatment is necessary to compile a complete medical history and perform a thorough physical exam.
Sexual activity poses a risk in the presence of heart disease. In this respect, before any therapy in the erection of violations doctor considers it necessary to study the cardiovascular system.
Drugs used to treat erectile dysfunction, you should use with caution in patients with anatomical deformation of the penis (eg angulyatsiya, cavernosal fibrosis or Peyronie’s disease) and those suffering from diseases that predispose to the development priapizma (such as anemia cell anemia, multiple myeloma or leukemia).
Drugs used to treat erectile dysfunction should not designate the men for whom sexual activity is undesirable.
The safety and effectiveness of Viagra in combination with other funds intended for the treatment of erectile dysfunction, has not been studied. In this sense, the use of such combinations is not recommended.
Viagra does not affect bleeding time, even in the appointment, in combination with aspirin. In vitro studies of human platelets indicate that sildenafil increases antiagregatsionny effect of sodium nitroprusside (nitric oxide donor). Information about the safety of Viagra in patients with diseases accompanying bleeding, ulcer or exacerbation of the disease is not. In this sense, these patients must use Viagra with caution.
A small number of patients with hereditary pigmentary retinitom there are violations of hereditary retinal fosfodiesteraz activity. Information about the safety of Viagra in patients with pigment retinitom no. In this sense, these patients must use Viagra with caution.
4.5. Interaction with other medicaments and other forms of interaction
Effect of other drugs on Viagra
In vitro studies:
Sildenafil metabolism is principally under the influence of the isoforms 3A4 (major route) and 2S9 (less meaningfully), cytochrome P450. Therefore, inhibitors of this isoenzyme may decrease the clearance of sildenafil.
In vivo studies:
Tsimetidin (800 mg), a non-inhibitor of CYP3A4, while admission to the Viagra Sildenafil causes increased plasma concentrations by 56% in healthy volunteers.
Population pharmacokinetic analysis of clinical studies showed a reduction in sildenafil clearance while the application of inhibitors of CYP3A4 (such as ketokonazol, erythromycin, tsimetidin). However, the frequency of undesirable phenomena in these patients is not increased.
Only receive an antacid (magnesium hydroxide / aluminum hydroxide) did not influence the bioavailability of Viagra.
According to a population pharmacokinetic analysis of the CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 (such as selective serotonin inhibitors reverse the seizure, tricyclic antidepressants) and tiazidopodobnye thiazide diuretics, loop diuretics and kaliysberegayuschie, inhibitors of APF , calcium antagonists, beta-and adrenoblokatory inducers of CYP450 metabolism (such as rifampicin, barbiturates) have no influence on the pharmacokinetics of sildenafil.
Viagra’s effects on other drugs
In vitro studies:
Sildenafil is a weak inhibitor of cytochrome P450 isoenzyme - 1A2, 2S9, 2S19, 2D6, 2E1 and 3A4 (IK50> 150 mol). Andalusia sildenafil implement the recommended dose of its maximum concentration in plasma is about 1 mol, therefore, unlikely that Viagra can affect the clearance of isoenzyme substrates.
In vivo studies:
Signs of significant interaction with tolbutamidom (250 mg) or warfarin (40 mg), metabolized by CYP2C9, is not revealed.
Viagra (50 mg) did not produce an additional increase in bleeding time to receive aspirin (150 mg).
Viagra (50 mg) was amplified hypotensive effect of alcohol in healthy volunteers at the maximum level of alcohol in the blood of an average of 80 mg / dL.
In patients with signs of hypertension interaction Viagra (100 mg) with amlodipinom not detected. The average reduction in blood pressure in the prone position (systolic - 8 mm Hg. Art, Diastolic - a 7 mm Hg. Art) was comparable to that on receipt of a Viagra in healthy volunteers (see Pharmacodynamic properties).
Analysis of information security has demonstrated the lack of differences in the nature of side effects in patients taking Viagra in combination with antihypertensives in without them.
Viagra amplified hypotensive effect of nitrates in the sample of acute and long-term use in the past. In this sense, the use of Viagra in combination with nitrates or nitric oxide donors contraindicated (see Contraindications).
4.6. Application of pregnancy and lactation
Viagra is not designed for use in women.
In reproductive studies in rats and rabbits sildenafil oral application is not teratogenic action does not affect the reproductive function and does not cause a violation of peri / postnatal development of the fetus and newborn.
Unique in receiving a dose of Viagra 100 mg in healthy volunteers has not been accompanied by changes in sperm motility or morphology.
4.7. Impact on ability to drive and use machines
When driving, or require special precautions.
4.8. Adverse Reactions
In clinical studies conducted in several countries around the world have used Viagra, more than 3700 patients (aged 19 to 87 years). Over 550 patients were treated for more than a year.
Portability Viagra was good. Platsebokontroliruemyh In clinical studies the frequency of discontinuation of treatment due to unwanted effects was low and comparable to that when receiving placebo. Unwanted effects were generally transient and light or moderately expressed.
In studies with all models of undesirable phenomena in patients who received Viagra, was similar. In fixed dose studies of the frequency of undesirable events increased with increasing dose. In studies with the selection of doses chosen (such as research to better reflect the implementation of the recommended regimen), the nature of unwanted effects was comparable to that in studies with fixed doses.
In clinical studies, with a selection of individual doses, the majority of the following reactions phenomenon, linking the dose reduction was possible, probable or unknown:
Cardiovascular: headache, flushing, dizziness.
Digestion: dyspepsia.
Breathing: Nose mortgaged.
Senses a change in vision (light and transient, especially changing the color of objects, as well as an increased perception of light and clarity of the violation).
If you are using the drug in doses that exceed recommended, adverse reactions were similar to those mentioned above, but usually meet more often.
Priapizma cases not marked.
4.9. Overdosage
In studies in healthy volunteers who received the drug in single doses of 800 mg of adverse events were comparable with those of Viagra intake in lower doses, but have met more often.
In cases of overdose should take the standard symptoms. Dialysis should not accelerate the payment sildenafil, as the last activity is associated with plasma proteins and does not appear in the urine.
5. Part of the pharmaceutical industry
5.1. Composition
Viagra 25 mg tablets: blister packs of aklar / aluminum containers of 1,2, 4, 8 and 12 tablets. Bottles of high density polyethylene and 4, 8 and 12 tablets.
Viagra 50 mg tablets: blister packs of aklar / aluminum containers of 1, 2, 4, 8 and 12 tablets. Bottles of high density polyethylene and 4, 8 and 12 tablets.
Viagra pills 100 mg: aklar ampoules / aluminum containers of 1, 2, 4, 8 and 12 tablets. Bottles of high density polyethylene and 4, 8 and 12 tablets.