Erexesil
Erexesil: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Use in childhood
- 10. In case of impaired renal function
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Erexesil
ATX code: G04BE03
Active ingredient: sildenafil (Sildenafil)
Manufacturer: West Pharma Produce de Especialidadesh Pharmaseuticash S. A. (West Pharma Producoes de Especialidades Farmaceuticas) (Portugal)
Description and photo updated: 30.11.2018
Erexesil is a drug designed to treat erectile dysfunction.
Release form and composition
Dosage form - film-coated tablets: blue, oval; at a dosage of 25 mg on one side engraved "-", at a dosage of 50 mg - without engraving, at a dosage of 100 mg - engraved "+" (in a cardboard box 1 blister containing 1 or 4 tablets, or 2 blisters containing 4 tablets, and instructions for the use of Ereksezil).
Composition of 1 tablet (25/50/100 mg):
- active substance: sildenafil - 25, 50 or 100 mg (sildenafil citrate - 35.12; 70.24 or 140.48 mg);
- auxiliary components: magnesium stearate - 2.25 / 4.5 / 9 mg; calcium hydrogen phosphate - 22.5 / 45/90 mg; microcrystalline cellulose - 81.13 / 162.26 / 324.52 mg; croscarmellose sodium - 9/18/36 mg;
- film shell: Opadry II 85F20464 blue (macrogol 3350 - 0.606 / 1.212 / 2.424 mg; polyvinyl alcohol - 1.2 / 2.4 / 4.8 mg; talc - 0.444 / 0.888 / 1.776 mg; titanium dioxide - 0.54 / 1.08 / 2.16 mg; indigo carmine aluminum varnish - 0.21 / 0.42 / 0.84 mg) - 3/6/12 mg.
Pharmacological properties
Pharmacodynamics
The active substance of Erexesil - sildenafil, is a potent selective inhibitor of cGMP (cycloguanosine monophosphate), related to PDE5 (specific type 5 phosphodiesterase).
Erexesil is indicated for the treatment of erectile dysfunction. The implementation of the physiological mechanism of erection is associated with the release of NO (nitric oxide), which occurs during sexual stimulation in the corpus cavernosum. This causes an increase in the level of cGMP, further relaxation of the smooth muscle tissue of the corpus cavernosum and, as a result, increased blood flow.
Sildenafil does not have a direct relaxing effect on the isolated corpus cavernosum, but against the background of its use, the effect of NO is enhanced by inhibiting PDE5, which is responsible for the breakdown of cGMP.
The substance is selective for PDE5, the activity for which is higher than that for other known phosphodiesterase isozymes: PDE2, PDE4, PDE7 – PDE11 - more than 700 times; PDE1 - more than 80 times; PDE6 - 10 times.
Sildenafil is 4000 times more selective for PDE5 than for PDE3. This is extremely important, since PDE3 is one of the key enzymes in the regulation of myocardial contractility.
Sexual stimulation is a prerequisite for the effective action of Erexezil.
Sildenafil therapy in a dose of up to 100 mg in healthy volunteers did not lead to clinically significant changes in the electrocardiogram (ECG). After taking the indicated dose, the maximum decrease in systolic and diastolic pressure in the supine position is 8.3 and 5.3 mm Hg. Art. respectively. The development of a more pronounced, but also transient effect on blood pressure (blood pressure) was observed in patients who took nitrates.
When conducting studies of the hemodynamic effect, it was found that after taking a single dose of 100 mg of sildenafil in 14 patients with severe coronary heart disease, the systolic and diastolic pressure at rest decreased by 7 and 6%, respectively, and the pulmonary systolic pressure by 9%. Sildenafil does not affect cardiac output, the process of blood flow in the stenotic coronary arteries does not disturb, and also leads to an increase (by approximately 13%) in adenosine-induced coronary flow in stenotic and intact coronary arteries.
In some patients, 60 minutes after taking 100 mg of sildenafil using the 100-shade Farnsworth-Munsell test, a transient and mild disorder associated with the ability to distinguish shades of color (green and blue) was detected. These changes were absent 2 hours after the application of sildenafil. There is an assumption that this violation is associated with inhibition of PDE6, which is involved in the process of light transmission in the retina. The substance does not affect the perception of contrast, visual acuity, electroretinogram, pupil diameter or intraocular pressure.
In a placebo-controlled crossover study in patients with proven early age macular degeneration (n = 9), sildenafil was well tolerated at a dose of 100 mg once. No clinically significant changes in vision assessed by special visual tests (including visual acuity, Amsler grating, modeling of color passage, color perception, photostress and Humphrey perimeter) were identified.
The safety / efficacy profile of sildenafil has been evaluated in more than 20 randomized, double-blind, placebo-controlled studies up to 6 months in duration in patients aged 19–87 years with erectile dysfunction of various etiologies (organic, psychogenic, mixed). Efficacy was assessed globally using a partner survey, the International Erectile Function Index (a validated sexual function questionnaire), and an erection diary.
The effectiveness of sildenafil, which is defined as the ability to achieve and maintain an erection sufficient for satisfactory intercourse, has been documented in all studies and confirmed in studies conducted over 12 months. When analyzing the international index of erectile function, it was found that against the background of the use of sildenafil, an increase in the quality of orgasm, achievement of satisfaction from intercourse and general satisfaction were also noted.
According to generalized information, among the patients who reported improved erection: patients with diabetes mellitus - 59%; patients who underwent radical prostatectomy - 43%; patients with spinal cord injuries - 83% (data are significantly higher than in the placebo group - 15, 15 and 12%, respectively).
Pharmacokinetics
Sildenafil is rapidly absorbed from the gastrointestinal tract after oral administration. The absolute bioavailability averages 40% (25 to 63%). At a concentration of approximately 1.7 ng / ml (3.5 nM), sildenafil inhibits human PDE5 activity by 50%. The average C max (maximum concentration) of the free substance in the blood plasma of men after taking 100 mg of sildenafil as a single dose is approximately 18 ng / ml (38 nM). C max when applying fasting usually achieved in 60 minutes (range: 30-120 minutes). The intake of fatty foods leads to a slowdown in the absorption rate, a decrease in C max by an average of 29%, while T max(time to reach maximum concentration) increases by 60 minutes. However, the degree of absorption does not change significantly [AUC (area under the concentration-time curve) decreases by 11%].
The pharmacokinetics of the substance when used in the recommended dose range is linear. V d (volume of distribution) of sildenafil at equilibrium is ~ 105 liters. Sildenafil and its main circulating N-demethyl metabolite bind to plasma proteins at a level of approximately 96% and does not depend on the total concentration of the drug. 90 minutes after taking Erexesil, less than 0.000 2% of the dose of sildenafil (~ 188 ng) is found in the semen.
Sildenafil metabolism occurs mainly in the liver, the isoenzymes CYP3A4 and CYP2C9 are involved in the process (main and secondary pathways, respectively). The formation of the main circulating active metabolite is due to the N-demethylation of sildenafil and further metabolism. The metabolite in terms of selectivity for PDE is comparable to sildenafil, and its effect with respect to PDE5 is approximately 50% of the activity of the parent substance. The plasma concentration of the metabolite in the blood of healthy volunteers is approximately 40% of the concentration of sildenafil.
The total clearance of sildenafil is 41 l / h. The final T 1/2 (half-life) of the substance is from 3 to 5 hours, the N-demethyl metabolite is about 4 hours. The excretion of sildenafil is carried out mainly in the form of metabolites (both with oral and intravenous administration) through the intestine (about 80% of the dose) and by the kidneys (about 13% of the dose).
In healthy elderly patients (over 65 years old), the clearance of sildenafil is reduced, and the plasma concentration of free substances in the blood is approximately 40% higher than in young patients (18–45 years old). Age does not have a clinically significant effect on the incidence of adverse reactions.
In severe renal failure [in patients with CC (creatinine clearance) <30 ml / min], the clearance of sildenafil decreases, which leads to a significant increase in the AUC and C max values (approximately 100 and 88%, respectively), in comparison with similar indicators in patients that same age group without renal dysfunction.
The clearance of sildenafil in patients with cirrhosis of the liver (according to the Child-Pugh classification of severity classes A and B) decreases, which causes an increase in the AUC and C max values (by about 84 and 47%, respectively), in comparison with similar indicators in patients of the same age group without liver dysfunction. The pharmacokinetics of Erexesil in patients with severely impaired liver function (according to the Child-Pugh classification of severity class C) has not been studied.
Indications for use
Erexesil is prescribed for the treatment of erectile dysfunction, which is characterized by an inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.
Erexesil is effective only for sexual stimulation.
Contraindications
Absolute:
- diseases / conditions that require constant or intermittent intake of donors of nitric oxide, organic nitrates or nitrites in any form;
- combination therapy with other drugs used to treat erectile dysfunction (safety profile has not been studied);
- combination therapy with ritonavir;
- children / adolescence up to 18 years old;
- female;
- individual intolerance to the components of the drug.
Relative (Erexesil tablets are used under medical supervision):
- anatomical deformity of the penis (cavernous fibrosis, angulation, Peyronie's disease);
- arterial hypertension (blood pressure above 170/110 mm Hg);
- arterial hypotension (blood pressure below 90/50 mm Hg. Art.);
- increased tendency to bleeding;
- heart failure;
- a stroke, myocardial infarction, or life-threatening arrhythmias in the past six months;
- unstable angina;
- hereditary retinitis pigmentosa;
- burdened history of episodes of anterior non-arteritis ischemic neuropathy of the optic nerve;
- diseases that predispose to the occurrence of priapism (sickle cell anemia, myeloma, leukemia, thrombocytopenia);
- exacerbation of gastric ulcer and duodenal ulcer.
Erexesil, instructions for use: method and dosage
Erexesil tablets are taken orally.
The recommended single dose is 50 mg, taken about 1 hour before sexual activity. Given the effectiveness and tolerability of the drug, the dose can be changed to a lower (25 mg) or higher (maximum - 100 mg) side.
The drug should not be taken more often than once a day.
For patients with severe renal failure (CC <30 ml / min) and liver damage (including cirrhosis) Erexesil is prescribed at a dose of 25 mg.
Recommendations for combined use with certain medicinal products:
- ritonavir: the maximum single dose of Erexesil is 25 mg, the frequency of administration is once every 48 hours;
- inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, saquinavir, itraconazole): the initial dose of Erexesil is 25 mg;
- α-blockers: to reduce the likelihood of postural hypotension, the drug is recommended to be used only after hemodynamic stabilization has been achieved; the feasibility of reducing the starting dose of sildenafil should also be considered.
Side effects
Side effects in most cases are transient, mild or moderate. During the research it was found that the frequency of some violations increases with increasing dose.
Possible side reactions of Erexesil, depending on the frequency of their development [> 10% - very often; (> 1% and 0.1% and 0.01% and <0.1%) - rarely; <0.01% - very rare]:
- cardiovascular system: very often - vasodilation; often - rapid heartbeat (tachycardia);
- nervous system: very often - headache; often - dizziness;
- digestive system: often - dyspepsia;
- respiratory system: often - rhinitis;
- organ of vision: often - visual impairment (change in sensitivity to light, blurred visual perception), chromatopsia (transient and mild, refers mainly to the perception of shades of color).
When using Erexesil in excess of the recommended doses, adverse reactions were similar to those indicated above, but usually occurred more often:
- reproductive system: priapism / prolonged erection;
- digestive system: vomiting;
- nervous system: convulsions;
- cardiovascular system: epistaxis, decreased blood pressure, tachycardia, fainting;
- organ of vision: eye pain, scleral vascular injection / eye redness;
- immune system: hypersensitivity reactions (including skin rash).
Overdose
With a single dose of 800 mg of Erexesil, adverse reactions were comparable to those with the use of the drug in lower doses, but developed more often.
The main symptoms: increased severity of undesirable effects.
Therapy: symptomatic, hemodialysis does not accelerate the clearance of sildenafil, since the substance actively binds to plasma proteins and is not excreted by the kidneys.
special instructions
In order to diagnose erectile dysfunction, identify possible causes of their appearance and select adequate therapy, it is required to collect a complete medical history and conduct a thorough physical examination of the patient.
In the presence of heart disease, sexual activity is a certain risk, therefore, before starting any treatment for erectile dysfunction, the patient must be sent for examination in order to identify pathologies from the cardiovascular system. Sexual activity in patients with the following diseases / conditions is considered undesirable:
- arterial hypertension (blood pressure above 170/110 mm Hg);
- arterial hypotension (blood pressure below 90/50 mm Hg. Art.);
- heart failure;
- unstable angina;
- a stroke, myocardial infarction, or life-threatening arrhythmias in the past six months.
Sildenafil has a systemic vasodilator effect, leading 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 Erexesil, the physician must carefully balance the benefits of therapy with the risk of possible undesirable manifestations of vasodilating action in patients with corresponding diseases, especially against the background of sexual activity.
In patients with obstruction of the left ventricular outflow tract (hypertrophic obstructive cardiomyopathy, aortic stenosis), as well as with the rare syndrome of multiple systemic atrophy, which is manifested by severe violations of blood pressure regulation by the autonomic nervous system, there is an increased sensitivity to vasodilators.
There is evidence of rare cases of anterior ischemic neuropathy of the optic nerve of non-arterial etiology, which is the cause of deterioration / loss of vision during the use of sildenafil (as well as other PDE5 inhibitors). Most of these patients had risk factors, including deepening (excavation) of the optic nerve head, diabetes mellitus, age 50 years, arterial hypertension, coronary heart disease, smoking, and hyperlipidemia. A causal relationship between the use of Erexesil and the occurrence of anterior ischemic neuropathy of the optic nerve of non-arterial genesis has not been identified. If this condition has already been noted in the patient, he should be informed of the existing risk.
Combination therapy of Erexesil and α-blockers in some sensitive patients can lead to the development of symptomatic hypotension, therefore, sildenafil should be prescribed with caution to patients taking α-blockers. To reduce the likelihood of this disorder, Erexesil therapy is started only after hemodynamic stabilization has been achieved. You also need to consider the feasibility of reducing the initial dose of the drug. The patient needs to be aware of the actions that are indicated when symptoms of postural hypotension appear.
In some clinical and post-marketing studies using Erexesil, as well as other PDE5 inhibitors, sudden hearing loss / loss has been reported. However, in most cases, the patients had risk factors for the development of this pathology, no correlation was found between the use of Erexesil and sudden hearing impairment. In case of sudden hearing loss / loss, therapy should be discontinued and a doctor should be consulted immediately.
Influence on the ability to drive vehicles and complex mechanisms
During therapy with Erexesil, patients should take into account the likelihood of a decrease in blood pressure, the development of chromatopsia, blurred vision and other adverse reactions. It is very important to pay close attention to the individual effect of the drug on the reaction rate and ability to concentrate, especially at the beginning of treatment and in cases of changes in the dosage regimen.
Pediatric use
Erexesil is not prescribed for patients under 18 years of age.
With impaired renal function
For patients with severe renal impairment (CC <30 ml / min), Erexesil is prescribed at a dose of 25 mg.
For violations of liver function
For patients with liver damage (including cirrhosis), Erexesil is prescribed at a dose of 25 mg.
Drug interactions
Sildenafil metabolism occurs mainly under the action of isoenzymes CYP3A4 and CYP2C9, therefore, against the background of combined use with inhibitors of these isoenzymes, a decrease in the clearance of sildenafil is possible, and with inductors, accordingly, its increase. A decrease in the clearance of a substance is observed when combined with inhibitors of the isoenzyme of cytochrome CYP3A4 (ketoconazole, erythromycin, cimetidine).
Possible interactions:
- cimetidine (800 mg, with the use of 50 mg of sildenafil): the plasma concentration of sildenafil increases by 56%;
- erythromycin (500 mg per day for a course of 5 days, when 100 mg of sildenafil is used once): against the background of reaching C ss (equilibrium concentration) of erythromycin in the blood, an increase in the AUC of sildenafil by 182% occurs;
- saquinavir (1200 mg per day, when using 100 mg of sildenafil once): C max of sildenafil, against the background of reaching C ss of saquinavir in the blood, increases by 140%, and AUC increases by 210%; sildenafil has no effect on the pharmacokinetics of saquinavir;
- ketoconazole and itraconazole (stronger inhibitors of the cytochrome CYP3A4 isoenzyme): can lead to stronger changes in the pharmacokinetics of sildenafil;
- ritonavir (1000 mg per day, with the use of 100 mg of sildenafil once): against the background of reaching the C ss of ritonavir in the blood, there is an increase in C max and AUC of sildenafil 4 and 11 times, respectively. The plasma concentration of sildenafil in the blood after 24 hours is approximately 200 ng / ml (after a single dose of sildenafil alone - 5 ng / ml).
If, against the background of combined use with strong inhibitors of the cytochrome CYP3A4 isoenzyme, the dosage regimen of sildenafil is not violated, then the C max value of the free substance does not exceed 200 nM, and Erexesil is well tolerated.
Sildenafil is one of the weak inhibitors of cytochrome P 450 isoenzymes - 1A2, 2C9, 2D6, 2C19, 3A4 and 2E1 (inhibitory concentration of IC 50 > 150 μmol). If the recommended dosage regimen is observed, the C max of sildenafil is approximately 1 μmol, therefore, the effect of the substance on the clearance of substrates of these isoenzymes is unlikely.
Sildenafil against the background of the use of nitrates (long-term therapy or prescription for acute indications) enhances their hypotensive effect. Combined treatment with nitric oxide donors or nitrates is contraindicated.
With the simultaneous use of 25, 50 or 100 mg of sildenafil with the α-blocker doxazosin (4 or 8 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional decrease in systolic and diastolic pressure in the supine and standing position is 7/7, 9/5/8/4 and 6/6, 11/4/4/5 mm Hg. Art. respectively. There are reports of rare cases of symptomatic postural hypotension in such patients, which manifests itself as dizziness (without fainting). In some sensitive patients receiving α-blockers, combination therapy with sildenafil may lead to symptomatic hypotension.
Analogs
The analogues of Erexesil are Ridjamp, Silden, Dynamico, Viatail, Kamastil, VIVAIRA, Juvena, Maxigra, Sildenafil, Viagra, Tornetis, Silafil, Vildegra, Vizarsin.
Terms and conditions of storage
Store at temperatures up to 25 ° C. Keep out of the reach of children.
Shelf life is 4 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Erexesil
In numerous reviews of Erexesil on specialized sites and forums, patients characterize it as an effective drug. At the same time, some men point to the development of side effects, especially against the background of disorders of the cardiovascular system.
Price for Erexesil in pharmacies
Approximate price for Erexesil, film-coated tablets:
- dosage 50 mg: 1 pc. in the package - 620 rubles., 4 pcs. - 721 rubles;
- dosage 100 mg: 1 pc. in the package - 355 rubles., 4 pcs. - 889 rubles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
