Product name: 100 Ereksil
Active substance (INN): Sildenafil citrate
Dosage form: Tablets film-coated 50 mg and 100 mg
Pharmacotherapeutic group: Means for potency correction
Storage conditions: In a dry, dark place at a temperature no higher than 25 ° C.
Shelf life: 2 years.
Conditions of supply of pharmacies: With recipe
Sildenafil citrate is a potent and selective inhibitor of specific phosphodiesterase type 5 (PDE5).
The physiological mechanism of erection of the penis involves the release of nitric oxide (NO) in the cavernous body during sexual stimulation. Nitric oxide activates guanylate cyclase enzyme, which results in increased levels of cyclic guanosine monophosphate (cGMP) and, respectively, relax smooth muscle of the corpus cavernosum, resulting in increased blood flow to the penis.
Sildenafil has no direct relaxing effect on isolated human corpus cavernosum body, but actively enhances the relaxing effect of NO on this tissue by inhibiting PDE-5, responsible for the breakdown of cGMP in the cavernous body.
This leads to increased levels of cGMP, resulting in smooth muscle relaxation and increased blood flow to the cavernous body.
Therefore, the use of sildenafil in the recommended dose is ineffective in the absence of sexual stimulation.
Effect of sildenafil on erectile dysfunction: a double-blind, placebo-controlled crossover study of patients with erectile dysfunction of various etiologies (organic, psychogenic, mixed) were the result of sexual stimulation offensive prolonged erection sufficient for sexual intercourse, after administration of sildenafil compared to placebo.
Effect of Sildenafil on blood pressure: when using the drug orally at a dose of 100 mg maximum decrease in systolic blood pressure (BP) in the supine position was on average 8.4 mm Hg and diastolic blood pressure in the supine position was 5.5 mmHg. Art. More pronounced, but similarly transient effect on blood pressure was observed in patients concurrently treated with nitrates.
Effect of sildenafil on hemodynamics: single dose of sildenafil 100 mg did not cause clinically significant changes in ECG in healthy volunteers.
Effect of Sildenafil on vision: in some patients after 1 hour after dosing at a dose of 100 mg and 200 showed mild and transient violation color discrimination (blue / green), 2 hours after receiving these changes were absent. Established mechanism of color vision disturbances considered the inhibition of PDE 6, which is involved in the transmission of light in the retina.
Sildenafil has no effect on visual acuity, contrast sensitivity, intraocular pressure or the diameter of the pupil.
The pharmacokinetics of sildenafil depends on the dosage ranges used inside. Metabolism preparation is mainly in the liver (mainly cytochrome P450 isoenzyme 3A4) to form the active metabolite by properties similar sildenafil.
The drug is quickly absorbed through the gastrointestinal tract. After receiving its fasting inside the maximum concentration (Cmax) is achieved within 30-120 minutes (median 60 minutes). The absolute bioavailability of an average of 41% (25-63%). When receiving sildenafil in combination with fatty food absorption rate decreases; time to reach maximum concentration (Tmax) is increased by 60 minutes, and the average Cmax is reduced by 29%.
The volume of distribution (Vd) of sildenafil at steady state is the average of 105 liters, which indicates that its distribution into the tissues. Sildenafil and its major circulating N-desmetilovy metabolite by approximately 96% bound to plasma proteins. Protein binding is independent of total concentration of sildenafil. In healthy volunteers receiving sildenafil, less than 0.0002% (average 188 ng) dose was found in semen at 90 min after administration.
Sildenafil is metabolized primarily by the action of P450 3A4 (major route) and P450 2C9 (optional path) of the liver microsomal isoenzymes. The main circulating metabolite which is formed by the N-desmetilirovaniya sildenafil undergoes further metabolism. By selective action on PDE metabolite comparable with sildenafil and its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil. The concentration of metabolite in plasma is approximately 40% of those of sildenafil. The total body clearance of sildenafil is 41 l / h, and the half-life (T1 / 2) in the terminal phase of 3-5 h. Deduced as metabolites in feces mainly (approximately 80% of the dose administered orally) and to a lesser extent in the urine (approximately 13% of the administered orally).
Pharmacokinetics in special clinical situations: an increase of sildenafil in the blood plasma area under the curve “concentration-time» (AUC) is influenced by the following factors:
– Age of 65 years (increased AUC by 40%);
– Lack of liver function (e.g., liver cirrhosis, 84%);
– Severe renal insufficiency (creatinine clearance (CC) <30 ml / min, 100%); - Concomitant medications - inhibitors of cytochrome P450 3A4 (eg, erythromycin, 182%, saquinavir, 210%).
Treatment of erectile dysfunction characterized by the inability to achieve or retain penile erection sufficient for sexual intercourse satisfaction.
Sildenafil is effective only in the presence of sexual arousal!
Dosing and Administration
The drug is taken orally. For most patients, the recommended dose is 50 mg, the drug is taken when needed for approximately 1 hour prior to sexual activity, and after a fatty meal – 1.5-2 hours prior to sexual activity. Given the efficacy and tolerability of the dose can be increased to 100 mg or decreased to 25 mg. The maximum recommended multiplicity of application – 1 time / day.
Adverse effects are usually transient in nature and are mild or moderate. The nature of adverse events in studies related to the selection of doses was comparable to those in studies with fixed doses, as these studies to better reflect the recommended application circuit.
Cardio-vascular system: vasodilation symptoms.
From the gastrointestinal tract: diarrhea, abdominal pain, nausea.
From the musculoskeletal system: back pain, arthralgia, myalgia.
From the nervous system: dizziness, increased muscle tone, insomnia.
The respiratory system: nasal congestion, pharyngitis, rhinitis, sinusitis, respiratory tract infection, respiratory failure.
Dermatological reactions: rash.
From the senses: vision changes (mild and transient, mostly change the color of objects, as well as increased perception of light and blurred vision), conjunctivitis.
With the genitourinary system: urinary tract infection, a violation of the prostate gland.
In postmarketing observations met reports of prolonged erection and / or priapism.
Effect of Sildenafil on other drugs: cimetidine (800 mg), a nonspecific inhibitor of cytochrome P450 3A4, in in vivo studies, while taking sildenafil caused an increase in the plasma concentration of the latter by 56% in healthy volunteers.
A single dose of sildenafil 100 mg simultaneously with erythromycin, a specific inhibitor of cytochrome P450 3A4 (with erythromycin 2 times / day. 500 mg over 5 days) during achieved a constant level of erythromycin Blood contributed to increase AUC sildenafil 182%. Also, while taking sildenafil 100 mg and saquinavir, which is a HIV protease inhibitor and an inhibitor of cytochrome P450 3A4 (when taking saquinavir 3 times / day. At a dose of 1200 mg) on a background until a constant level of saquinavir in the blood, the maximum sildenafil concentration in blood was increased by 140%, and the AUC was increased by 210%. Sildenafil had no effect on the pharmacokinetic parameters of saquinavir.
The simultaneous use of sildenafil (single dose 100 mg) and ritonavir is an inhibitor of HIV protease and sufficiently potent inhibitor of cytochrome P450 (in a dose of 500 mg 2 times / day) due to obtain a constant level of ritonavir in blood, Cmax increased by 300% ( 4-fold) and AUC 1000% (11 times). After 24 hours of sildenafil plasma level was 200 ng / ml (comparative concentration after a single application of sildenafil after 24 hours was 5 ng / ml). This is consistent with the effect of ritonavir on a number of drugs that are substrates of cytochrome P450. Sildenafil had no effect on the pharmacokinetic parameters of ritonavir.
Population pharmacokinetic analysis of clinical studies has demonstrated a decrease in clearance of sildenafil, while the use of cytochrome P450 3A4 inhibitors (such as ketoconazole, itrakonozol, erythromycin).
A single dose of antacid (hydroxide / magnesium aluminum hydroxide) did not affect the bioavailability of sildenafil.
The results of pharmacokinetic studies in patients taking part in a clinical trial of sildenafil showed that inhibitors of cytochrome P450 2C9 (such as tolbutamide, warfarin), cytochrome P450 2D6 (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide diuretics, loop and Potassium-sparing diuretics, ACE inhibitors and calcium antagonists had no effect on the pharmacokinetic parameters of sildenafil.
Effect of sildenafil on other drugs: patients with arterial hypertension signs of interaction between sildenafil (100 mg) with amlodipine has not been identified.
Sildenafil (50 mg) did not cause an additional increase in bleeding time at the reception of acetylsalicylic acid (150 mg).
Sildenafil (50 mg) did not enhance the hypotensive effect of ethanol was in healthy volunteers at the maximum level in the blood ethanol in average 80 mg / ml.
Sexual activity is a risk for heart disease; therefore sildenafil before treatment should be conducted examination of the cardiovascular system.
In clinical studies, sildenafil have systemic vasodilatory effects, which leads to a transient decrease in blood pressure. Prior to the appointment of the drug the doctor should carefully weigh the risk of adverse events vasodilating action in patients with various comorbidities, especially against sexual activity. Increased susceptibility to vasodilators observed in patients with left ventricular obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy), as well as a rare multi-system atrophy different, manifesting severe violation of autonomic control of blood pressure.
Due to lack of information on the safety of sildenafil, the drug should be used with caution in the following patient groups:
– Myocardial infarction, cerebrovascular sufferers, as well as life threatening arrhythmia within the last 6 months;
– Suffering from orthostatic hypotension (blood pressure of 90/50) or hypertension (BP 170/110);
, are suffering heart failure or coronary heart disease due to unstable angina;
– With hereditary retinitis retininom with inherited disorders associated with the synthesis of retinal phosphodiesterase;
– In patients with anatomical deformation of the penis (such as angulation, cavernous fibrosis or Peyronie’s disease) and in patients with diseases that predispose to the development of priapism (such as sickle cell anemia, multiple myeloma or leukemia).
Preparations for the treatment of erectile dysfunction, should not be given to men for whom sexual activity is undesirable. In addition, the safety and efficacy of sildenafil when used in combination with other agents intended for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended.
In applying the drug in patients aged over 65 years, patients with impaired hepatic function, patients with severe renal insufficiency and in patients receiving concomitant medications – inhibitors of cytochrome P450 3A4 (eg, erythromycin, saquinavir) is an increase in levels of sildenafil in plasma. This can help increase the effectiveness of the drug and may cause side effects. Similarly, groups of patients it is advisable use of the drug at a dose of 25 mg / day.
The drug may cause dizziness and blurred vision, so patients need to assess their response to the drug before you get behind the wheel of a car or using machinery.
Keep out of the reach of children, and it should not be used after the expiration date.
In studies in healthy volunteers in single dose of the drug in doses up to 800 mg of adverse events were comparable to those when taking sildenafil at lower doses, but were more common.
Treatment: symptomatic therapy if necessary. Dialysis does not accelerate clearance of sildenafil, as the latter is actively bound to plasma proteins and is excreted in the urine.
Hypersensitivity to the drug.
The drug is contraindicated in patients receiving either permanently or intermittently donator of nitric oxide, organic nitrates or nitrates in any form as sildenafil enhances the hypotensive effect of nitrates taken continuously or in an emergency.
The preparation is not intended for use in children and women. There are no adequate and well-controlled trials in pregnancy and lactation in women was conducted.