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Many men in our time often face a depressing problem, the name of which is erectile dysfunction. Provided timely measures are taken to combat this violation, sexual activity is successfully resumed. The main thing is to correctly draw up a course of therapy. If doctors detect physiological factors that indicate impotence and prescribe Viagra, the instructions for use will tell you how to use it correctly. The drug has repeatedly proven its effectiveness in practice, so you can rely on it.
What is Viagra
The drug is intended for the treatment of impotence. Viagra is a powerful inhibitor that normalizes sexual functions in a natural way. By following the instructions in the instructions for use, with the help of this medicine, the patient will be able to resume sexual activity with minimal risk of harm to the body. Reviews of men about the effectiveness of Viagra confirm this fact.
Composition of Viagra
The active ingredient of the drug is sildenafil citrate. It restores the sexual function of a man and provides a long-lasting erection sufficient for a full-fledged sexual intercourse. To improve the absorption of the active substance by the body, the product is supplemented with a number of auxiliary components. The full composition of the drug is described in detail in the table below:
Release form
Blue biconvex film-coated tablets. In pharmacies, there are several variations of the drug, which differ in the dosage of the active ingredient. In addition, the manufacturer provides the opportunity to choose the number of tablets in the package - 1, 2, 4 and 12 pcs. For each specific case of decreased erection, doctors prescribe the necessary dosage and duration of treatment.
Pharmacodynamics and pharmacokinetics
Sildenafil is a selective inhibitor of cyclic guanosine monophosphate specific phosphodiesterase type 5. This component has been widely used for erectile dysfunction for several decades. Pharmacists call it a PDE-5 inhibitor for short. The physiological mechanism is realized due to the release of nitric oxide in the cavernous body during sexual stimulation. This effect leads to an increase in the level of cGMP, blood flow and subsequent relaxation of the smooth muscle tissues of the corpora cavernosa.
Sildenafil enhances the effect of nitric oxide by inhibiting PDE-5, which ensures the breakdown of cGMP. The full effect of the drug is possible only with sexual arousal. To evaluate the safety and efficacy of sildenafil, 21 studies were conducted on 3,000 patients aged 19 to 87 years with diagnosed erectile dysfunction of various etiologies. The effectiveness of the drug was fully confirmed.
In the recommended dosage range, the pharmacokinetics of sildenafil is linear. When administered orally, the agent is rapidly absorbed and immediately begins to act. The absolute bioavailability index varies from 25 to 63%. The average value is 40%. After a single dose of Viagra at a dose of 100 mg, the maximum plasma concentration of sildenafil is about 18 ng / ml. When taken orally on an empty stomach, this figure is reached in 60-90 minutes. Combining the drug with fatty foods reduces the rate of absorption.
Indications for use
Doctors prescribe Viagra to men to combat disorders in the genital area, characterized by the inability to achieve or maintain an erection of the penis, sufficient for a full-fledged sexual intercourse. Treatment is required if the frequency of such cases exceeds 25%. Achieving and maintaining a normal erection can be hampered by many physiological factors that are not related to the pathology that requires the use of Viagra.
How to take Viagra
According to the instructions for use, for the successful occurrence of an erection, it is necessary to use the drug 45-60 minutes before sexual contact. In most cases, the recommended dose is 50 mg. Taking into account tolerability and effectiveness, the required volume of the active substance can be increased to 100 mg or reduced to 25 mg. The maximum recommended frequency of use is 1 time per day.
special instructions
To obtain an accurate diagnosis regarding erectile dysfunction, determine the possible causes of their occurrence and choose the optimal method of treatment, it is necessary to collect a detailed medical history, as well as conduct a physical examination. Unauthorized use of Viagra before receiving the appropriate instructions from a doctor can be dangerous to a man's health.
An analysis of the practice of using Viagra made it possible to fix a number of important nuances that should be taken into account by doctors prescribing this drug and patients taking it:
- men with anatomical deformity of the penis and/or risk factors for priapism should use Viagra with caution;
- if the erection persists for more than 4 hours, the patient must urgently seek medical help (if priapism is not immediately treated, this can lead to serious damage to the tissues of the penis and irreversible loss of potency);
- it is not recommended to prescribe Viagra to men for whom sexual activity is undesirable;
- for men suffering from hypotension, the drug is prescribed only after a thorough diagnosis (the task of the doctor in this case is to exclude the risk of developing undesirable manifestations against the background of sexual activity).
With violations of the functions of the kidneys and liver
In patients with liver damage, the excretion of sildenafil is impaired (for example, with cirrhosis), so a dose adjustment is required for them. In such cases, the maximum allowable volume of the drug is 25 mg. Men suffering from mild to moderate renal insufficiency are allowed to take the drug in the required dosage. Care must be taken to avoid the occurrence of unwanted reactions of the body. For men with severe renal insufficiency, the dose of sildenafil is reduced to 25 mg.
drug interaction
Medically recorded cases of the entry of sildenafil into a chemical reaction with the active ingredients of other drugs:
- The metabolism of sildenafil is carried out under the influence of liver isoenzymes. The main components involved in this process are CYP2C9 and CYP3A4. Isoenzyme inhibitors are able to reduce the clearance of sildenafil, and inducers, on the contrary, increase it.
- Joint use with CYP3A4 inhibitors is accompanied by a decrease in the clearance of sildenafil.
- The minimum concentration of erythromycin can be dangerous, since this drug increases the AUC of sildenafil by almost 200%.
- The combination of Viagra and drugs such as Itraconazole and Ketoconazole is very harmful to the body. Their interaction leads to a mutual change in the pharmacokinetics of inhibitors and sildenafil.
- The active component of Viagra is an isoenzyme of cytochrome, so it is unlikely that it can affect the clearance of the substrates of this substance.
- In patients suffering from benign prostatic hyperplasia with stable hemodynamics, while using Viagra with doxazosin alpha-blockers, diastolic blood pressure decreases.
- The combination of sildenafil with antihypertensive drugs does not entail the appearance of additional side effects.
Interaction of Viagra with alcohol
Instructions for use says: drinking alcohol after taking the drug is highly undesirable. According to doctors, a small amount of alcohol is still allowed. The maximum allowable amount of pure alcohol is 40 g. You should not drink alcohol in excess of this measure, otherwise the effect of a Viagra tablet may completely dissipate.
Contraindications
Cases in which the use of Viagra is prohibited:
- continuous or intermittent use of oxide donors or organic nitrates (sildenafil enhances the hypotensive effect);
- simultaneous use with other drugs aimed at the treatment of erectile dysfunction;
- age up to 18 years;
- hypersensitivity to sildenafil or other components that make up the tablets;
- patients suffering from arterial hypertension and having had a myocardial infarction less than 6 months ago should take the drug with extreme caution.
Side effects of Viagra
Men taking Viagra may experience the following side effects:
- On the part of the organs of vision: cyanopsia, photophobia, chromatopsia, ischemic optic neuropathy, retinal dysfunction (in patients suffering from retinitis with pigment distortion).
- On the part of the hearing organs: deterioration or loss of hearing (in patients with appropriate risk factors).
- From the hemopoietic system: leukopenia, anemia.
- On the part of nutrition and metabolism: edema, gout, thirst, hyperglycemia.
- From the musculoskeletal system: back pain, myalgia, arthritis, arthrosis, muscle and bone pain, synovitis, myasthenia gravis.
- From the genitourinary system: nocturia, urinary incontinence, ejaculation disorder, genital edema, hematospermia.
- From the side of the central nervous system: headaches, dizziness, migraine, drowsiness, neuropathy, neuralgia, vertigo, tremor, fainting, convulsions.
Overdose
With a single use of the drug in a volume of 700-800 mg, adverse events were noted that were comparable to side effects that develop after taking sildenafil in low doses, but they were much more common. Viagra overdose requires urgent symptomatic treatment. Hemodialysis is not suitable in such cases as it does not accelerate the clearance of sildenafil.
Terms of sale and storage
In pharmacies of the Russian Federation, Viagra is available without a prescription. It is necessary to store the medicine in a dry place, protected from direct sunlight. The optimum temperature is not more than 30 °C. The shelf life of the drug is 5 years.
Analogues
Patients who have been prescribed sildenafil can use alternative drugs with a similar principle of action instead of Viagra. The modern pharmaceutical market offers many products with a similar principle of action. The most common analogues of the drug are listed in the list below:
- Levitra;
- Cialis;
- Vizarsin;
- Impaza;
- Tribestan;
- Sealex;
- Kamagra;
- Maxigra;
- erectile;
- Dynamico.
Viagra price
The cost of the drug is considered acceptable for the budget of the average Russian. At the same time, pharmacies offer many analogues, which differ markedly in price. Like Viagra, these drugs provide the desired effect during sexual arousal and require adherence to a certain regimen. As a rule, there is nothing complicated in this. After reading the instructions for use, any patient will be able to get the desired effect without causing damage to the body. The table below will help you navigate the cost of such drugs:
Video
INN: Sildenafil
Manufacturer: Fareva Amboise
Anatomical-therapeutic-chemical classification: Sildenafil
Registration number in the Republic of Kazakhstan: No. RK-LS-5 No. 012217
Registration period: 02.05.2018 - 02.05.2023
Instruction
Tradename
Viagra ®
International non-proprietary name
Sildenafil
Dosage form
Film-coated tablets 50 mg, 100 mg
Compound
One tablet contains
active substance - sildenafil citrate 70.225 mg and 140.450 mg (equivalent to sildenafil 50 mg and 100 mg),
auxiliary substances: microcrystalline cellulose, anhydrous calcium hydrogen phosphate, croscarmellose sodium, magnesium stearate,
Shell composition: Opadry blue OY-LS-20921 (hypromellose, lactose, triacetin, titanium dioxide (E 171) and indigo carmine aluminum varnish (E132)), Opadry transparent YS-2-19114 A (hypromellose and triacetin).
Description
Film-coated tablets, blue, biconvex, in the form of a rounded diamond marked "Pfizer" on one side and "VGR 50" (for a dosage of 50 mg) or "VGR 100" (for a dosage of 100 mg) on the other side.
Pharmacotherapeutic group
Preparations for the treatment of urological diseases. Other drugs for the treatment of urological diseases, including antispasmodics. Preparations for the treatment of erectile dysfunction. Sildenafil.
ATX code G04BE03
Pharmacological properties
Pharmacokinetics
Suction
Sildenafil is rapidly absorbed after oral administration. Peak plasma concentrations (Cmax) of sildenafil are reached within 30 to 120 minutes (median 60 minutes) after oral administration on an empty stomach. The mean absolute oral bioavailability is 41% (with a range of 25-63%). After oral administration of sildenafil in the recommended dose range (25-100 mg), the area under the pharmacokinetic curve (AUC) and Cmax increase in direct proportion to the dose taken.
When taking sildenafil with food, the absorption rate decreases with an average delay in the time to reach maximum plasma concentrations (tmax) of 60 minutes and an average decrease in Cmax by 29%.
Distribution
The mean equilibrium volume of distribution (Vd) for sildenafil is 105 L, indicating its distribution in body tissues.
After oral administration of sildenafil at a single dose of 100 mg, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/ml (with a coefficient of variation of 40%). Due to the fact that sildenafil (and its main circulating metabolite, N-desmethyl metabolite) is 96% bound to plasma proteins, the average maximum concentration of free sildenafil in plasma is 18 ng / ml (38 nM). Protein binding is independent of total drug concentrations.
In healthy volunteers who received sildenafil once at a dose of 100 mg, less than 0.0002% (average 188 ng) of the dose of the drug was determined in the ejaculate 90 minutes after taking the dose.
Metabolism
Research in vitro
The metabolism of sildenafil is carried out mainly with the participation of microsomal isoenzymes of the liver CYP3A4 (main pathway) and CYP2C9 (secondary pathway) of cytochrome P450. For this reason, inhibitors of these isoenzymes can reduce, and inducers of these isoenzymes - increase the clearance of sildenafil.
By N-demethylation, the main circulating metabolite of sildenafil is formed, which undergoes further metabolism with a final elimination half-life of approximately 4 hours. The metabolite is characterized by a phosphodiesterase selectivity profile comparable to that of sildenafil, and the activity of the metabolite in vitro in relation to phosphodiesterase type 5 (PDE-5) is approximately 50% of the activity of the original substance of the drug.
Plasma concentrations of this metabolite are approximately 40% of sildenafil concentrations.
Sildenafil is a weak inhibitor of cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC > 150 µM). Provided that the maximum concentration of sildenafil in blood plasma after taking the recommended doses of the drug is approximately 1 μm, it is unlikely that sildenafil will change the clearance of substrates of these isoenzymes.
breeding
The total clearance of sildenafil is 41 l / h, and the final half-life is from 3 to 5 hours. After oral administration, sildenafil is excreted as metabolites mainly in the faeces (about 80% of the oral dose) and to a lesser extent in the urine (about 13% of the oral dose).
Pharmacokinetics in special groups of patients
Elderly patients
In healthy elderly volunteers (aged 65 years or older), there was a decrease in the clearance of sildenafil, causing an increase in plasma concentrations of sildenafil and its active N-demethylated metabolite by approximately 90% compared with those in healthy younger volunteers (18-45 years old) . Due to age-related differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration is approximately 40%.
In patients with mild or moderate renal dysfunction (creatinine clearance 30-80 ml / min), the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. The increase in the average AUC and Cmax of the N-demethylated metabolite was up to 126% and up to 73%, respectively, compared with such indicators in people of the same age without impaired renal function. However, due to the high inter-patient variability, these differences were not statistically significant. In patients with severely impaired renal function (creatinine clearance< 30 мл/мин) клиренс силденафила снижался, что приводило к средним повышениям показателей AUC и Cmax, соответственно на 100 % и 88 % по сравнению с пациентами аналогичного возраста без нарушений функции почек. Кроме того, значения AUC и Cmax для N-деметилированного метаболита также значительно повышались - на 200 % и 79 %, соответственно.
In patients with mild to moderate liver cirrhosis (Child-Pugh stages A and B), sildenafil clearance was reduced, resulting in an increase in AUC (by 84%) and Cmax (by 47%) compared with volunteers of the same age without liver dysfunction.
The pharmacokinetics of sildenafil in patients with severe hepatic impairment has not been studied.
Pharmacodynamics
Mechanism of action
Viagra®, an oral drug for the treatment of erectile dysfunction, that is, during sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis.
The physiological mechanism of penile erection involves the release of nitric oxide (NO) in the cavernous bodies upon sexual stimulation. Nitric oxide activates the enzyme guanylate cyclase, which leads to increased levels of cyclic guanosine monophosphate (cGMP), followed by relaxation of smooth muscle in the corpus cavernosum and increased blood flow.
Sildenafil is a strong and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE-5), which is responsible for the breakdown of cGMP in the cavernous bodies. Sildenafil has a peripheral effect 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 metabolic pathway is activated, as occurs during sexual stimulation, PDE-5 inhibition by sildenafil results in an increase in cGMP levels in the cavernous bodies. Therefore, for sildenafil to provide the desired productive pharmacological action, sexual stimulation is necessary.
Pharmacodynamic effects
In vitro studies
Sildenafil selectively acts on PDE-5, which is involved in the regulation of the erection process. The action of Viagra® on PDE-5 is stronger than on other known phosphodiesterases. This effect of Viagra® action is 10 times stronger than the effect on PDE-6, which takes part in phototransformation processes in the retina. When used in the maximum recommended doses, the selectivity of sildenafil to PDE-5 is 80 times higher than its selectivity to PDE-1, more than 700 times - selectivity to PDE-2, PDE-3, PDE-4, PDE-7, PDE-8 , PDE-9, PDE-10 and PDE-11. In particular, the selectivity of sildenafil to PDE-5 is 4000 times higher than its selectivity to PDE-3, a cAMP-specific isoform of phosphodiesterase involved in the regulation of heart contractions.
Clinical efficacy and safety
The safety and efficacy of sildenafil have been confirmed by data from long-term studies.
Indications for use
Erectile dysfunction, characterized by the inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.
Viagra® is effective only with sexual stimulation.
Dosage and administration
For oral use.
Viagra ® may be taken with or without food. However, for the start of action of Viagra ® may take longer if taken with food.
Dosing regimen
Use in adults
Recommended dose of Viagra ® is 50 mg orally approximately 1 hour before sexual intercourse. Based on efficacy and tolerability, the dose may be increased to 100 mg. The maximum recommended dose is 100 mg.
The tablet should be swallowed whole with a glass of water.
Special patient groups
Elderly patients
In elderly patients (≥ 65 years), dose adjustment is not required.
Patients with impaired renal function
With mild to moderate renal dysfunction (creatinine clearance 30-80 ml / min), dose adjustment is not required. Due to a decrease in the clearance of sildenafil in patients with severe renal impairment (creatinine clearance< 30 мл/мин), следует рассмотреть возможность применения Виагры® в дозе 25 мг. Исходя из эффективности и переносимости препарата при необходимости, его дозу можно увеличивать поэтапно до 50 мг и до 100 мг.
Patients with impaired liver function
Due to the fact that the clearance of sildenafil is reduced in patients with impaired liver function (for example, cirrhosis), the possibility of using the drug at a dose of 25 mg should be considered. Based on the effectiveness and tolerability of the drug, if necessary, its dose can be increased in stages up to 50 mg and up to 100 mg.
Patients of childhood and adolescence
Sildenafil is not indicated for use in children (< 18 лет).
Use in patients taking other medicinal products
In order to reduce the risk of developing postural arterial hypotension in patients treated with alpha-blockers, the condition of patients receiving alpha-blockers should / stabilize the condition of patients receiving alpha-blockers before starting treatment with sildenafil. In addition, the possibility of using sildenafil should be considered, starting with a dose of 25 mg.
Side effects
When using Viagra®, undesirable effects were registered, which were classified according to the frequency of their manifestation as follows: very often (≥ 1/10), often (from ≥ 1/100 to< 1/10) , infrequently (from ≥ 1/1000 to< 1/100) and rare (≥ 1/10,000 and< 1/1000) .
Often
- headache
Often
Dizziness
Color distortions of vision (chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia), visual disturbance, blurred vision
Hyperemia, hot flashes
- nasal congestion
Dyspepsia, nausea
Infrequently
Hypersensitivity
Drowsiness, hypoesthesia
Lacrimation disorders (dry eyes, lacrimal gland dysfunction, increased lacrimation), eye pain, photophobia, photopsia, ocular hyperemia, visual brightness, conjunctivitis
Spatial disorientation (vertigo), tinnitus
Tachycardia, palpitations
Arterial hypertension, arterial hypotension
Epistaxis, sinus congestion
Pain in the upper abdomen, gastroesophageal reflux disease, vomiting, dry mouth
Myalgia, pain in the extremities
Hematuria
Chest pain, fatigue, feeling hot
Elevated heart rate
Rarely
- acute cerebrovascular accident, transient ischemic attack, seizure*, seizure recurrence*, syncope
Anterior non-arteritic ischemic optic neuropathy*, retinal vascular occlusion*, retinal hemorrhage, arteriosclerotic retinopathy, retinal disease, glaucoma, visual field defect, diplopia, decreased visual acuity, myopia, asthenopia, vitreous floaters, iris disease, mydriasis, presence of iridescent circles in the field of vision, swelling of the eye, swelling of the eye, visual disturbance, conjunctival hyperemia, eye irritation, unusual sensation in the eye, swelling of the eyelids, discoloration of the sclera
Deafness
- sudden cardiac death*, myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina
Feeling of tightness in the throat, swelling of the nose, dryness of the nasal mucosa
Oral hypoesthesia
Stevens-Johnson syndrome*, toxic epidermal necrolysis*
Bleeding from the penis, priapism*, hematospermia, increased erection - irritability
*adverse events recorded only during post-marketing surveillance.
Reporting Suspected Adverse Reactions
Communication of information about suspected adverse reactions identified after registration of the medicinal product is of great importance. This allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals and patients are asked to report any adverse reactions to the address provided at the end of this package leaflet.
Contraindications
Hypersensitivity to the active substance or to any of the excipients
Simultaneous administration of drugs that are donors of nitric oxide (amyl nitrite) or nitrates in any form
Simultaneous administration with guanylate cyclase stimulants (riociguat)
severe liver failure
Hereditary degenerative diseases of the retina (eg, hereditary retinitis pigmentosa (a small number of these patients have hereditary disorders of retinal phosphodiesterases))
Loss of vision in one eye due to anterior non-arteritic ischemic optic neuropathy, regardless of whether this episode was associated with previous use of a PDE-5 inhibitor or not
Arterial hypotension (BP< 90/50 мм рт. ст.)
Severe cardiovascular disease (eg, severe heart failure, unstable angina)
Myocardial infarction in the last 6 months
Stroke in the last 6 months
Concomitant use with CYP3A4 isoenzyme inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin, saquinavir, clarithromycin)
Concomitant use of drugs for the treatment of pulmonary arterial hypertension (bosentan, iloprost) and drugs containing sildenafil or any other PDE-5 inhibitor
Men with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption syndrome
Concomitant use with other oral or topical agents for the treatment of erectile dysfunction
Carefully:
anatomical deformity of the penis (including angulation, cavernous fibrosis, or Peyronie's disease)
conditions that predispose to priapism (such as sickle cell anemia (an abnormality of red blood cells), multiple myeloma (cancer of the bone marrow), or leukemia (cancer of the blood cells))
blood clotting problems (hemophilia)
bleeding disorders
exacerbation of peptic ulcer of the stomach or duodenum
simultaneous administration with drugs of the alpha-adrenergic blocking group
According to the registered indication, the drug is not intended for use in children and adolescents under the age of 18 years and in women.
Drug Interactions
Effect of other medicinal products on sildenafil
Research in vivo
With the simultaneous administration of sildenafil with CYP3A4 inhibitors (such as ketoconazole, erythromycin and cimetidine), a decrease in the clearance of sildenafil is observed. In this group of patients, there is no increased frequency of side effects, however, it is necessary to start treatment with Viagra® at an initial dose of 25 mg.
Simultaneous administration of the HIV protease inhibitor ritonavir, which is a strong inhibitor of cytochrome P450, in an equilibrium state (500 mg twice a day) with sildenafil (100 mg single dose) leads to an increase in the maximum concentration (Cmax) of sildenafil by 300% (4-fold), as well as an increase in plasma AUC of sildenafil by 1000% (11-fold). After 24 hours, plasma levels of sildenafil are approximately 200 ng/mL compared to approximately 5 ng/mL after sildenafil alone. These data are consistent with the pronounced effects of ritonavir on a wide range of cytochrome P450 substrates. Based on the above data, the concomitant use of sildenafil with ritonavir is not recommended.
Viagra does not affect the pharmacokinetics of ritonavir.
The maximum dose of sildenafil should not, under any circumstances, exceed 25 mg in 48 hours.
Simultaneous administration of the HIV protease inhibitor saquinavir, which is an inhibitor of CYP3A4, in an equilibrium state (1200 mg three times a day) with sildenafil (100 mg single dose) leads to an increase in Cmax of sildenafil by 140%, as well as an increase in AUC of sildenafil by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir. Stronger CYP3A4 inhibitors, such as ketoconazole and itraconazole, have a more pronounced effect.
With a single dose of sildenafil at a dose of 100 mg together with erythromycin, a moderate inhibitor of CYP3A4, at steady state (500 mg twice a day for 5 days), there is an increase in systemic exposure of sildenafil by 182% (determined by the AUC value).
Azithromycin (at a dose of 500 mg per day for 3 days) does not affect the AUC, Cmax, Tmax, elimination rate constant or subsequent half-life of sildenafil or its main circulating metabolite.
The simultaneous use of cimetidine (800 mg), which is an inhibitor of cytochrome P450 and a non-specific inhibitor of CYP3A4 with sildenafil (at a dose of 50 mg) in healthy volunteers, causes an increase in plasma concentrations of sildenafil by 56%.
Grapefruit juice is a weak inhibitor of CYP3A4-mediated metabolism in the intestinal wall and may cause a moderate increase in plasma levels of sildenafil.
A single dose of an antacid (magnesium hydroxide / aluminum hydroxide) does not affect the bioavailability of sildenafil.
CYP2C9 inhibitors (tolbutamide, warfarin and phenytoin) receptors and inducers of P450 metabolic activity (rifampicin, barbiturates) do not affect the pharmacokinetics of sildenafil.
Co-administration of the endothelin antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and probably CYP2C19) at steady state (125 mg twice daily) with sildenafil at steady state (80 mg three times daily) resulted in a decrease in AUC and Cmax for sildenafil by 62.6% and 55.4% respectively. Thus, it is believed that simultaneous use with strong CYP3A4 inducers, such as rifampin, causes a more pronounced decrease in plasma concentrations of sildenafil.
Simultaneous use with other PDE-5 inhibitors or other treatments for erectile dysfunction
The safety and efficacy of sildenafil in combination with other PDE5 inhibitors or other medicinal products containing sildenafil for the treatment of pulmonary arterial hypertension (PAH) or other drugs for the treatment of erectile dysfunction have not been studied. In this regard, the use of such combinations of drugs is not recommended.
Nicorandil is a hybrid of a potassium channel activator and nitrate. Due to the nitrate component, it is potentially capable of entering into serious interactions with sildenafil.
Effect of sildenafil on other medicinal products
Research in vitro
Data on the interaction of sildenafil with non-specific phosphodiesterase inhibitors, such as theophylline or dipyridamole, are not available.
In vivo studies
Consistent with the known action of sildenafil on the NO/cGMP signaling pathway, sildenafil is capable of enhancing the hypotensive effect of nitrates, namely a significant reduction in blood pressure. Therefore, its simultaneous use with nitric oxide donors (amyl nitrite) or nitrates in any form is contraindicated.
Riociguat
In clinical studies, riociguat enhanced the hypotensive effect of PDE-5 inhibitors. Data on a favorable clinical effect with the use of this combination in the studied population were absent. The simultaneous use of riociguat with PDE-5 inhibitors, including sildenafil, is contraindicated.
Simultaneous reception with alpha-blockers
It is recommended to use sildenafil with caution in patients taking a drug of the alpha-blocker group, since their simultaneous use can lead to symptomatic arterial hypotension in some sensitive patients. Most likely, this can be observed within 4 hours after taking a dose of sildenafil. To reduce the risk of developing postural arterial hypotension, a state of hemodynamic stability should be achieved in patients receiving treatment with alpha-blockers before starting treatment with sildenafil. The possibility of using sildenafil should be considered, starting with a dose of 25 mg. In addition, clinicians should instruct patients on what to do if symptoms of postural hypotension occur.
With the simultaneous use of sildenafil and doxazosin in patients stabilized with doxazosin therapy, rare cases of symptomatic arterial hypotension, dizziness and presyncope, but not syncope, have been reported.
With the simultaneous use of sildenafil (at a dose of 50 mg) with tolbutamide (at a dose of 250 mg) or warfarin (at a dose of 40 mg), both of which are metabolized by CYP2C9, no significant interactions were found.
Sildenafil (at a dose of 50 mg) does not contribute to an increase in bleeding time caused by taking acetylsalicylic acid (at a dose of 150 mg).
Sildenafil (at a dose of 50 mg) does not increase the hypotensive effect of alcohol in healthy volunteers at an average maximum blood alcohol level of 80 mg / dL.
Combining the following classes of antihypertensive drugs: diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilators and centrally acting), adrenergic neuroblockers, calcium channel blockers and alpha-adrenergic blockers - did not reveal a difference in the side effect profile in patients taking sildenafil compared with patients receiving placebo. In special drug interaction studies in which sildenafil (at a dose of 100 mg) was used simultaneously with amlodipine in patients with arterial hypertension, an additional decrease in systolic blood pressure in the supine position was 8 mm. rt. Art. The corresponding additional reduction in diastolic blood pressure in the supine position was 7 mm. rt. Art. These additional blood pressure reductions were similar in magnitude to those observed when sildenafil was used in healthy volunteers as monotherapy.
Sildenafil (at a dose of 100 mg) does not affect the pharmacokinetics at steady state of the HIV protease inhibitors saquinavir and ritonavir, both of which are CYP3A4 substrates.
When used simultaneously with bosentan, sildenafil at steady state (80 mg three times a day) causes an increase in the AUC and Cmax of bosentan (125 mg twice a day) by 49.8% and 42%, respectively, in healthy male volunteers.
special instructions
To diagnose erectile dysfunction and determine its possible underlying causes, a medical history and physical examination should be performed before pharmacological treatment is considered.
Risk factors for cardiovascular disease
Before starting treatment for erectile dysfunction, the attending physician should assess the cardiovascular status of their patients, since there is a certain degree of risk of cardiac complications associated with sexual activity.
Before prescribing sildenafil, physicians should carefully consider the possibility of adverse effects of the vasodilating effect of this drug on the condition of patients with certain underlying diseases, especially in combination with sexual activity. The group of hypersensitivity to vasodilators includes patients with left ventricular outflow tract narrowing (for example, aortic valve stenosis, hypertrophic obstructive cardiomyopathy), as well as patients with a rare multiple system atrophy syndrome, manifested as a severe degree of impaired autonomic control of blood pressure.
Sildenafil leads to a slight and short-term decrease in blood pressure, which in most cases has no clinical manifestations. The average maximum decrease in systolic blood pressure in the supine position after oral administration of sildenafil at a dose of 100 mg was 8.4 mm Hg. Art. The corresponding change in diastolic blood pressure in the supine position was 5.5 mm. rt. Art. These reductions in blood pressure are consistent with the vasodilating effects of sildenafil, possibly due to increased levels of cGMP in vascular smooth muscle. A single oral dose of sildenafil up to 100 mg in healthy volunteers did not cause any clinically significant ECG changes.
In patients with severe ischemic heart disease (CHD), sildenafil at a dose of 100 mg did not affect cardiac output and did not reduce blood flow through stenotic coronary arteries.
Viagra® enhances the hypotensive effect of nitrates.
According to the action of Viagra ® on the metabolic pathway "nitric oxide / cyclic guanosine monophosphate (cGMP)", sildenafil is capable of enhancing the hypotensive effect of nitrates, therefore its simultaneous use with nitric oxide donators (such as amyl nitrite) or nitrates is contraindicated in any form.
During the post-registration period, cases of serious cardiovascular complications have been reported, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular bleeding, transient ischemic attack, arterial hypertension and arterial hypotension during the use of sildenafil. Most, but not all, of these patients had prior cardiovascular risk factors. Many of these events have been reported during or shortly after sexual intercourse, and several have been reported shortly after taking sildenafil without sexual activity. It is not possible to determine whether these events were directly related to the use of sildenafil, to sexual activity, to existing cardiovascular disease, to a combination of these factors, or to other factors.
Priapism
Medicinal products for the treatment of erectile dysfunction, including sildenafil, should be used with caution in patients with anatomical deformity of the penis (such as angulation, cavernous fibrosis, or Peyronie's disease), as well as in patients with diseases predisposing to the development of priapism (such as falciform cell anemia, multiple myeloma, or leukemia).
During the post-registration use of sildenafil, cases of prolonged erection and priapism have been reported. In the event of an erection lasting more than 4 hours, the patient should seek urgent medical attention. If left untreated, priapism can lead to damage to the tissues of the penis and irreversible loss of potency.
Impact on vision
There have been cases of visual impairment in connection with the intake of sildenafil and other PDE-5 inhibitors, namely a rare disease - anterior non-arteritic ischemic optic neuropathy. In case of any defects in visual acuity, you must stop taking Viagra® and consult a doctor.
Effect on blood clotting
Research in vitro using human platelets indicate that sildenafil enhances the antiaggregatory effect of sodium nitroprusside. There are no data on the safety of sildenafil in patients with bleeding disorders or active peptic ulcer, so sildenafil should be used after a careful assessment of the benefit/risk ratio.
Viagra should not be used in men with rare hereditary galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome, due to the lactose content in the drug shell.
Pregnancy and lactation
Viagra® is not indicated for use by women.
Appropriate and strictly controlled studies of the use of Viagra® in pregnant and lactating women have not been conducted.
reproductive function
The effect of the drug on sperm motility or morphology after a single oral dose of sildenafil at a dose of 100 mg was not found.
Features of the effect of the drug on the ability to drive a motor vehicle or potentially dangerous mechanisms
The effect of sildenafil on the ability to drive vehicles or operate potentially dangerous machinery has not been studied.
Before driving vehicles or working with mechanisms, patients should find out how their body reacts to taking Viagra®, due to side effects of the drug, such as dizziness and impaired visual perception.
Overdose
Adverse reactions reported in studies with a single dose of the drug at a dose of up to 800 mg with the participation of volunteers were comparable to those observed with lower doses of the drug, but their frequency and severity were higher. Taking higher doses of Viagra® (200 mg) does not lead to an increase in the effectiveness of the drug, but only to an increase in the frequency of adverse reactions (headache, hyperemia, dizziness, dyspepsia, nasal congestion and impaired visual perception).
In case of overdose, standard symptomatic measures should be taken.
Viagra is one of the popular drugs for restoring a healthy erection and treating premature ejaculation. The drug has a high-quality and fast action, is suitable for men of all age categories, has a minimal risk of side effects in the absence of contraindications. You can use Viagra every day. The medicine is not addictive when taken regularly.
It accumulates in a small amount in the blood, however, in the absence of severe liver pathologies, it does not harm health and does not cause complications of existing chronic ailments. Taking Viagra is recommended for men who are not able to independently achieve a strong erection and hold it for a full-fledged sexual intercourse. Erectile dysfunction is the most common disease, which is expressed by sluggish and short-lived erections, premature release of seminal fluid and low sexual energy.
Viagra can be drunk as an auxiliary product in the complex therapy of prostatitis or infertility. The drug is suitable for healthy men who want not only to increase the duration of their intimacy, but also to enhance the sensations received from orgasm. To achieve a temporary effect, it is recommended to take Viagra occasionally.
How to take Viagra for the first time?
How to choose the right dose of the drug?
The drug is available in three standard dosages: 25, 50 and 100 mg. It is not at all obvious that the larger the dose, the more effective the drug will be. Everyone is different. For example, a high dose of Viagra in women can cause the clitoris to become too sensitive and instead of pleasure, lovemaking will turn into monstrous torment. On the other hand, too low a dosage of the drug may not be enough for a full erection in a man.
There are several approaches to the selection of the dosage of the drug. Usually, the drug is prescribed in an average dosage of 50 mg, and then, depending on the onset (or not onset) effect, the dosage is adjusted or, in case of a good effect, does not change. Another approach is to start treatment with a minimum dosage, increasing it until a good therapeutic effect occurs.
The maximum daily dose is 100 milligrams. This amount of the component is safe for middle-aged men who do not have chronic kidney or liver pathologies. The effect of the drug persists for four hours.
The selection of the dose should be done by a doctor who will do it more professionally and with less risk to your health.
Dosage and age
Older men and those who suffer from chronic pathologies of the liver or kidneys should reduce the daily dose to 25-50 milligrams (depending on their health). With regular use of the product (more than twice a week), the daily dose of the active substance should also be reduced.
With frequent use, it is recommended to use 25 milligrams every 24 hours. When using medicines containing vasodilators, you must use the minimum dose of Viagra(up to 25 milligrams per day), after consulting a doctor. Before starting the treatment of sexual dysfunction with Viagra, a number of contraindications must be excluded.
Peculiarities
Viagra should be taken 55-60 minutes before sexual intercourse. The drug should be washed down with warm water or other non-alcoholic liquid. Viagra can be taken with or without food. During treatment, it is recommended to refuse to take food, the fat content of which is above 30%. Fatty food interferes with the high-quality absorption of medicinal substances into the blood and slows down the action of this product.
Give preference to cereals, fruits and vegetables. Viagra should not be taken at the same time as medications containing nitrates, alpha-blockers, nitric oxide donators, and other types of inhibitors. These substances reduce the effect of Sildenafil by increasing its plasma concentration. The break between taking these substances and Viagra should be three weeks. The terms of release and storage of Viagra tablets are indicated on the packaging. Do not accept the product after its expiration date. Before treatment, read the instructions. Make sure that the air temperature in the room does not exceed 25 degrees Celsius.
In addition, do not lose hope for those men whom Viagra did not help the first time. The drug can be taken daily without worrying about health. In addition, it is recommended to make several attempts, and the drug will definitely help next time. In this case, you must comply with the dose prescribed by the doctor.
Popular questions
Can Viagra be taken with alcohol and food?
It is possible, but everything should be only in moderation. A small amount of alcohol will help you relax and tune in to a sexual wave. At the same time, you should not abuse strong alcoholic beverages, which can slow down the effect of the drug.
What to do if Viagra does not work?
Of course, each person has his own characteristics of the body, and the drug can affect them in different ways. In this case, do not despair if the drug did not work the first time. In some cases, several doses of Viagra are required for it to start working. It all depends on the individual parameters and characteristics of the person.
How often can you take Viagra?
The question of how often you can take Viagra is still debatable. After all, such a question really worries men, since we are talking about their health. Men have specific phobias - firstly, they are afraid that this sexual stimulant will definitely harm their health, and, secondly, the body will “get used to it” and, perhaps, will forget how to maintain an erection on its own. In fact, such fears are in vain, because for more than fifteen years of its existence, the drug has been repeatedly subjected to research and tests on a large number of patients with erectile dysfunction. Clinically validated trials have shown that long-term use of Viagra does not pose a great danger to the body. It has been proven that it does not affect either the nervous system or the genitourinary system, and in particular the erection. In addition, the use of Viagra as a drug to improve erection for a regular period of more than three years qualitatively changes the potency. That is, Viagra treats not only symptomatic impotence, but is engaged in its therapeutic treatment. To some extent, this sexual stimulant also acts as a sedative. Many representatives of the stronger sex know the situation when one bad experience provokes the appearance of fear of the next possible failures, and they are not motivated by anything. Very quickly, a man is overcome by fears, a feeling of insecurity in his strengths and capabilities. And regular use of the drug helps the patient to be successful in the intimate sphere.
Viagra contraindications are:
- Individual intolerance to the main drug component (Sildenafil);
- minor age;
- severe diseases of the cardiovascular system (unstable angina pectoris, mitral or aortic valve insufficiency, myocarditis, hypertension, coronary diseases, atherosclerosis);
- serious disorders in the liver or kidneys (acute liver or kidney failure);
- peptic ulcer of the stomach or duodenum;
- chronic pathologies of the nervous system;
- tendency to bleed;
- injury or deformity of the penis;
- diseases of the retina, inherited;
- epilepsy.
The drug is contraindicated in men who have suffered a heart attack or stroke (during the first six months), as well as other major surgical interventions.
Preparation: VIAGRA ®
Active ingredient: sildenafil
ATX code: G04BE03
KFG: Drug for the treatment of erectile dysfunction. PDE-5 inhibitor
ICD-10 codes (indications): F52.2, N48.4
KFU code: 28.08.01.01.01
Reg. number: P No. 015875/01
Date of registration: 12.08.09
The owner of the reg. Award: PFIZER PGM (France)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Coated tablets light blue, diamond-shaped, slightly biconvex, with cut and rounded edges, with the inscription "Pfizer" on one side and "VGR 25" on the other.
Excipients:
Coated tablets light blue, diamond-shaped, slightly biconvex, with cut and rounded edges, with the inscription "Pfizer" on one side and "VGR 50" on the other.
Excipients: microcrystalline cellulose, anhydrous calcium hydrogen phosphate, croscarmellose sodium, magnesium stearate, film coating Opadry blue and Opadry transparent.
1 PC. - blisters (1) - packs of cardboard.
Coated tablets light blue, diamond-shaped, slightly biconvex, with cut and rounded edges, with the inscription "Pfizer" on one side and "VGR 100" on the other.
Excipients: microcrystalline cellulose, anhydrous calcium hydrogen phosphate, croscarmellose sodium, magnesium stearate, film coating Opadry blue and Opadry transparent.
1 PC. - blisters (1) - packs of cardboard.
2 pcs. - blisters (1) - packs of cardboard.
4 things. - blisters (1) - packs of cardboard.
* non-proprietary international name recommended by WHO - sildenafil.
VIAGRA INSTRUCTION FOR A SPECIALIST.
Description of the drug VIAGRA approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
Drug for the treatment of erectile dysfunction. Sildenafil is a potent selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5).
The implementation of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, subsequent relaxation of the smooth muscle tissue of the cavernous body and an increase in blood flow.
Sildenafil does not have a direct relaxing effect on the isolated human corpus cavernosum, but enhances the effect of NO through inhibition of PDE5, which is responsible for the breakdown of cGMP.
Sildenafil is selective for PDE5 in vitro , its activity against PDE5 exceeds activity against other known phosphodiesterase isoenzymes: PDE6 - 10 times; PDE1 - more than 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. Sildenafil is 4,000 times more selective for PDE5 than PDE3, which is of paramount importance, since PDE3 is one of the key enzymes in the regulation of myocardial contractility.
A prerequisite for the effectiveness of sildenafil is sexual stimulation.
Clinical Data
Cardiac research
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 systolic blood pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg. Art., and diastolic blood pressure - 5.3 mm Hg. Art. A more pronounced, but also transient effect on blood pressure was noted in patients taking nitrates.
In a study of the hemodynamic effect of sildenafil at a single dose of 100 mg in 14 patients with severe CAD (more than 70% of patients had stenosis of at least one coronary artery), resting systolic and diastolic BP decreased by 7% and 6%, respectively. , and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not impair blood flow in stenotic coronary arteries, and also led to an increase (by approximately 13%) of adenosine-induced coronary blood flow in both stenotic and intact coronary arteries.
In a double-blind, placebo-controlled study, 144 patients with erectile dysfunction and stable angina who were taking antianginal drugs (except nitrates) performed physical exercise until the severity of angina symptoms improved. The duration of the exercise was significantly longer (19.9 sec; 0.9-38.9 sec) in patients taking sildenafil at a single dose of 100 mg compared with patients receiving placebo.
In a randomized, double-blind, placebo-controlled study, the effect of changing the dose of sildenafil (up to 100 mg) was studied 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 groups of patients, as well as in individuals taking more than three antihypertensive drugs.
Research on visual impairment
In some patients, 1 hour after taking sildenafil at a dose of 100 mg using the Farnsworth-Munsel 100 test, a mild and transient impairment in the ability to distinguish shades of color (blue / green) was detected. 2 hours after taking the drug, these changes were absent. It is believed that the violation of color vision is caused by inhibition of PDE6, which is involved in the process of light transmission in the retina. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure, or pupil diameter.
In a placebo-controlled crossover study of patients with proven early age-related macular degeneration (n = 9), sildenafil at a single dose of 100 mg was well tolerated. There were no clinically significant visual changes assessed by specific visual tests (visual acuity, Amsler grating, color perception, color flow simulation, Humphrey perimeter, and photostress).
Efficiency
The efficacy and safety of sildenafil was evaluated in 21 randomized, double-blind, placebo-controlled trials lasting up to 6 months in 3000 patients aged 19 to 87 with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The effectiveness of the drug was assessed globally using an erection diary, an international index of erectile function (a validated questionnaire on the state of sexual function) and a partner survey. The effectiveness of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory 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 reporting that the therapy improved their erections was: 62% (sildenafil 25 mg dose), 74% (sildenafil 50 mg dose) and 82% (sildenafil 100 mg dose), compared with 25 % in the placebo group. An analysis of the international index of erectile function showed that, in addition to improving erection, treatment with sildenafil also increased the quality of orgasm, made it possible to achieve satisfaction from sexual intercourse and overall satisfaction.
According to the pooled data, 59% of patients with diabetes, 43% of patients who underwent radical prostatectomy and 83% of patients with spinal cord injuries (compared with 16%, 15% and 12% in the placebo group) were among patients who reported improvement in erection with sildenafil treatment. respectively).
PHARMACOKINETICS
Suction
Sildenafil is rapidly absorbed after oral administration. Absolute bioavailability averages 40% (25-63%). In vitro, sildenafil at a concentration of approximately 1.7 ng / ml (3.5 nM) inhibits human PDE5 by 50%. After a single dose of 100 mg of the drug inside, Cmax is 18 ng / ml (38nM) and is achieved when taken on an empty stomach for an average of 60 minutes (30-120 minutes).
When taken in combination with fatty foods, the rate of absorption is reduced; T max increases by 60 minutes, and C max decreases by an average of 29%. However, the degree of absorption does not change significantly (AUC decreases by 11%).
Distribution
V d of sildenafil in the equilibrium state averages 105 liters.
Sildenafil and its major circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is independent of the total concentration of sildenafil. Less than 0.0002% of the dose (mean 188 ng) was found in semen 90 minutes after taking sildenafil.
Metabolism
Sildenafil is metabolized mainly in the liver by the action of CYP3A4 isoenzymes (the main route) and CYP2C9 (the secondary route).
The main circulating metabolite, which is formed as a result of N-demethylation of sildenafil, undergoes further metabolism.
In terms of selectivity of action on PDE, the metabolite is comparable to sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil.
The plasma concentration of the metabolite is approximately 40% of that of sildenafil.
The N-demethyl metabolite undergoes further metabolism; its T 1/2 is about 4 hours.
breeding
The total clearance of sildenafil from the body is 41 l / h, and the final T 1/2 is 3-5 hours. After oral administration, sildenafil is excreted as metabolites, mainly with feces (approximately 80% of the dose) and, to a lesser extent, with urine (approximately 13% of the dose).
Pharmacokinetics in special clinical situations
In elderly (65 years and older) patients, the clearance of sildenafil is reduced, and the concentration of free active substance in plasma is approximately 40% higher than its concentration in young (18-45 years) patients.
With mild renal failure (CC 50-80 ml / min) and moderate (CC 30-49 ml / min) severity, the pharmacokinetic parameters of sildenafil after oral administration once (50 mg) do not change.
In severe renal failure (CC? 30 ml / min), the clearance of sildenafil is reduced, which leads to an approximately two-fold increase in AUC (100%) and C max (88%) compared with those with normal renal function in patients of the same age group .
In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil is reduced, which leads to an increase in AUC (84%) and C max (47%) compared with those with normal liver function in patients of the same age. groups.
The pharmacokinetics of sildenafil in patients with severe hepatic impairment (Child-Pugh class C) has not been studied.
INDICATIONS
Erectile dysfunction, characterized by the inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.
Sildenafil is effective only in the presence of sexual stimulation.
DOSING MODE
The drug is taken orally.
At elderly patients dose adjustment is not required.
At renal failure of mild to moderate severity (CC 30-80 ml / min) dose adjustment is not required, with severe renal failure (CC<30 мл/мин) the dose is reduced to 25 mg.
At liver dysfunction the dose of the drug can be reduced to 25 mg.
When combined with ritonavir, the maximum single dose of Viagra ® should be 25 mg, the frequency of use should be 1 time in 48 hours.
When combined with inhibitors of the CYP3A4 isoenzyme (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Viagra ® should be 25 mg.
To minimize the risk of postural hypotension in patients taking alpha-blockers, sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. Should consider the feasibility of reducing the initial dose of the drug Viagra ® .
SIDE EFFECT
Side effects are usually transient and mild to moderate.
The frequency of adverse events increases with increasing dose and is practically independent of age.
| Organs and organ systems | Side effects | Sildenafil (%) | Placebo (%) |
| Most common (>1/10) | |||
| Nervous system | headache | 10.8 | 2.8 |
| The cardiovascular system | vasodilation (flushing of the face) | 10.9 | 1.4 |
| Often (>1/100 and< 1/10) | |||
| Nervous system | dizziness | 2.9 | 1.0 |
| Organ of vision | vision changes (blurred vision, change in sensitivity to light) | 2.5 | 0.4 |
| chromatopsia (mild and transient, mainly change in the perception of shades of color) | 1.1 | 0.03 | |
| The cardiovascular system | increase in heart rate | 1.0 | 0.2 |
| Respiratory system | rhinitis (nasal congestion) | 2.1 | 0.3 |
| Digestive system | dyspepsia | 3.0 | 0.4 |
When using the drug in doses exceeding the recommended, side effects were similar to those noted above, but usually occurred more often.
Allergic reactions: hypersensitivity reactions (including skin rash).
From the side of the central nervous system: convulsions.
From the side of the cardiovascular system: tachycardia, decreased blood pressure, fainting, epistaxis.
From the digestive system: vomit.
From the side of the organ of vision: eye pain, eye redness/scleral injections.
From the reproductive system: prolonged erection and/or priapism.
CONTRAINDICATIONS
Hypersensitivity to the components of the drug;
Use in patients receiving permanently or intermittently nitric oxide donators, organic nitrates or nitrates in any form (since sildenafil enhances the hypotensive effect of nitrates).
The drug is not intended for use in children and adolescents aged 18 years, in women.
With caution the drug should be used for anatomical deformation of the penis (including with angulation, cavernous fibrosis or Peyronie's disease); in diseases predisposing to the development of priapism (such as sickle cell anemia, multiple myeloma, leukemia, thrombocytopenia); in diseases accompanied by bleeding; with exacerbation of peptic ulcer of the stomach and duodenum; hereditary retinitis pigmentosa; heart failure, unstable angina, past 6 months of myocardial infarction, stroke, severe, life-threatening arrhythmias, hypertension (BP over 170/100 mm Hg) or hypotension (BP less than 90/50 mm Hg) .
PREGNANCY AND LACTATION
According to the registered indication, the drug is not intended for use in women.
SPECIAL INSTRUCTIONS
To diagnose erectile dysfunction, determine their possible causes and select adequate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination.
Sexual activity poses a certain risk in heart disease; in this regard, before starting any therapy for erectile dysfunction, the doctor may consider it necessary to examine the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, hypertension (BP>170/100 mmHg), or hypotension (BP<90/50 мм рт.ст.). В клинических исследованиях показано отсутствие различий в частоте развития инфаркта миокарда (1.1 на 100 человек в год) или частоте смертности от сердечно-сосудистых заболеваний (0.3 на 100 человек в год) у пациентов, получавших препарат Виагра ® , по сравнению с пациентами, получавшими плацебо.
Viagra ® has a systemic vasodilating effect, which leads to a transient decrease in blood pressure. This effect is not clinically significant and does not lead to any consequences in most patients. However, before prescribing Viagra ®, the physician must carefully weigh the risk of adverse manifestations of the vasodilating effect in patients with certain concomitant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators has been observed in patients with left ventricular outflow tract obstruction (eg, aortic stenosis, hypertrophic obstructive cardiomyopathy) and the rare multiple system atrophy syndrome, manifested by severe autonomic dysregulation of blood pressure.
Rare cases of anterior ischemic optic neuropathy of non-arterial origin have been noted as a cause of deterioration or loss of vision, against the background of the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as excavation (deepening) of the optic nerve head, age over 50 years, diabetes mellitus, arterial hypertension, coronary artery disease, hyperlipidemia, and smoking. A causal relationship between the use of PDE5 inhibitors and non-arterial anterior ischemic optic neuropathy has not been identified. The physician 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 him before.
Since the combined use of sildenafil and alpha-blockers can lead to symptomatic hypotension in some susceptible patients, sildenafil should be used with caution in patients taking alpha-blockers. To minimize the risk of postural hypotension in patients taking alpha-blockers, sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. The feasibility of reducing the initial dose of sildenafil should be considered. In addition, the physician should inform patients about what actions to take if symptoms of postural hypotension appear.
Sildenafil enhances the antiplatelet effect of sodium nitroprusside (nitric oxide donor) on human platelets in vitro. There are no data on the safety of using Viagra in patients with internal bleeding or active peptic ulcer of the stomach, therefore, in such cases, the drug should be used with caution.
A small number of patients with hereditary retinitis pigmentosa have hereditary disorders of retinal phosphodiesterases. There is no information on the safety of sildenafil in patients with retinitis pigmentosa; in this regard, in such patients, the drug Viagra ® should be used with caution.
Drugs intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.
The safety and efficacy of sildenafil when used in combination with other drugs intended for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended.
In some post-marketing and clinical studies using all PDE5 inhibitors, including sildenafil, a sudden decrease or loss of hearing in patients has been reported. However, in most cases, these patients had risk factors for the development of this pathology, and no correlation was found between the use of PDE5 inhibitors and sudden decrease or loss of hearing. The patient should be warned that in the event of a sudden decrease or loss of hearing, it is necessary to stop therapy with sildenafil, and immediately consult a doctor.
Influence on the ability to drive vehicles and control mechanisms
While taking the drug Viagra ®, no negative effect on the ability to drive a car or other technical means was observed. However, since when taking the drug, a decrease in blood pressure, the development of chromatopsia, blurred vision, one should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosing regimen.
OVERDOSE
With a single dose of the drug at a dose of up to 800 mg, adverse events were comparable to those when taking sildenafil at lower doses, but were more common.
Treatment: if necessary, carry out symptomatic therapy. Hemodialysis does not accelerate the clearance of sildenafil, because the latter actively binds to plasma proteins and is not excreted in the urine.
DRUG INTERACTIONS
Effect of other drugs on the metabolism of sildenafil
The metabolism of sildenafil occurs mainly in the liver under the action of CYP3A4 (the main route) and CYP2C9 isoenzymes, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, respectively, increase the clearance of sildenafil.
With the simultaneous use of CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine), a decrease in the clearance of sildenafil was noted.
Cimetidine (800 mg), which is a non-specific inhibitor of CYP3A4, when taken simultaneously with sildenafil (50 mg), causes an increase in plasma concentrations of sildenafil by 56%.
A single dose of sildenafil at a dose of 100 mg simultaneously with erythromycin, a specific inhibitor of CYP3A4 (when taking erythromycin 2 times / day, 500 mg for 5 days), against the background of achieving a constant level of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%.
With the simultaneous use of sildenafil (once at a dose of 100 mg) and saquinavir, which is both an inhibitor of HIV protease and an inhibitor of CYP3A4 (when taking saquinavir 3 times / day at a dose of 1200 mg), against the background of achieving a constant level of saquinavir in the blood, C max sildenafil in the blood increased by 140%, and AUC increased by 210%. Sildenafil did not affect the pharmacokinetic parameters of saquinavir.
Stronger inhibitors of the CYP3A4 isoenzyme, such as ketoconazole or itraconazole, can cause more pronounced changes in the pharmacokinetics of sildenafil.
Simultaneous use of sildenafil (once at a dose of 100 mg) and ritonavir, which is an inhibitor of HIV protease and a strong inhibitor of the isoenzymes of the cytochrome P450 system (when taking ritonavir 500 mg 2 times / day), while achieving a constant level of ritonavir in the blood, C max sildenafil increased by 300% (4 times), and AUC by 1000% (11 times). After 24 hours, the concentration of sildenafil in plasma was approximately 200 ng / ml (with a single application of one sildenafil - 5 ng / ml).
A single dose of an antacid (magnesium hydroxide / aluminum hydroxide) does not affect the bioavailability of sildenafil.
CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide-like diuretics, ACE inhibitors and calcium antagonists do not affect the pharmacokinetic parameters of sildenafil.
Simultaneous administration of azithromycin (500 mg / day for 3 days) does not affect AUC, C max , T max , excretion rate constant and T 1/2 of sildenafil or its main circulating metabolite.
Effect of sildenafil on other medicinal products
Sildenafil is a weak inhibitor of isoenzymes of the cytochrome P450 system - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IK 50 > 150 μmol). It is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.
Sildenafil enhances the hypotensive effect of nitrates both with long-term use and with acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donators is contraindicated.
With the simultaneous administration of the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional reduction in systolic / diastolic blood pressure in the supine position was 7 /7 mm Hg, 9/5 mm Hg and 8/4 mm Hg. respectively, and in the standing position - 6/6 mm Hg, 11/4 mm Hg. and 4/5 mm Hg. respectively. Rare cases have been reported in these patients of symptomatic postural hypotension, manifested in the form of dizziness (without syncope). In selected sensitive patients receiving alpha-blockers, the simultaneous use of sildenafil may lead to symptomatic hypotension.
Signs of a significant interaction of sildenafil with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9, have not been identified.
Sildenafil at a dose of 100 mg does not affect the pharmacokinetic parameters of HIV protease inhibitors at their constant concentration in the blood, such as saquinavir and ritonavir, which are both CYP3A4 substrates.
Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).
Sildenafil (50 mg) does not enhance the hypotensive effect of ethanol in healthy volunteers with a maximum blood ethanol level of 80 mg/dL on average.
In patients with arterial hypertension, there were no signs of the interaction of sildenafil (100 mg) with amlodipine. The average additional decrease in blood pressure in the supine position is: systolic - by 8 mm Hg, diastolic - by 7 mm Hg.
The use of sildenafil in combination with antihypertensive agents does not lead to additional side effects.
TERMS AND CONDITIONS OF DISCOUNT FROM PHARMACIES
The drug is dispensed by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 30°C. Shelf life - 5 years.
