Trade name: CEKLON
Active ingredient (INN): Sildenafil citrate
Dosage form: film-coated tablets
Each coated tablet contains:
Active ingredient: Sildenafil citrate equivalent to Sildenafil 50 mg or 100 mg.
Excipients: microcrystalline cellulose, starch, starch (for paste), methylparaben, propylparaben, magnesium stearate, purified water, purified talc, sodium glycollate starch, paint film coating, methylene chloride, isopropyl alcohol.
Cyclone 50 mg: from light blue to dark blue, film-coated, diamond-shaped, embossed “50” on one side and smooth on the other side tablets.
Cyclone 100 mg: from light blue to dark blue, film-coated, diamond-shaped, embossed “100” on one side and smooth on the other side tablets.
Pharmacotherapeutic group: Means for potency corrections
ATX code: G04BE03
Sildenafil citrate is a potent and selective inhibitor of specific phosphodiesterase type 5 (PDE 5).
The physiological mechanism of penile erection involves the release of nitric oxide (NO) in the corpora cavernosa upon sexual stimulation. NO activates the enzyme guanylate cyclase, which leads to an increase in the level of cyclic guanosine manophosphate (cGMP) and, accordingly, relaxed smooth muscles of the corpus cavernosum, as a result of which blood flow in the penis increases.
Sildenafil does not have a direct relaxing effect on the isolated corpus cavernosum, but actively enhances the relaxing effect of NO on this tissue by inhibiting PDE 5, which is responsible for the breakdown of cGMP in the corpus cavernosum. This leads to an increased level of cGMP, resulting in relaxation of smooth muscles and increased blood flow in the corpus cavernosum.
Therefore, the use of sildenafil in the recommended doses is ineffective in the absence of sexual stimulation.
Effect of Sildenafil on erectile dysfunction:
In a double-blind, placebo-controlled, crossover study of patients with erectile dysfunction of various etiologies (organic, psychogenic, mixed), the result of sexual stimulation was the onset of a prolonged erection, sufficient for intercourse, after the appointment of sildenafil compared with placebo.
Effect of sildenafil on blood pressure :
When using the drug orally at a dose of 100, the 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 mm Hg. Art. A more pronounced, but similarly transient, blood pressure was observed in patients simultaneously receiving nitrates.
The effect of Sildenafil on hemodynamics:
A single dose of Sildenafil 100 mg did not cause clinically significant changes in the ECG in healthy volunteers.
Effect of Sildenafil on vision:
In some patients, 1 hour after taking the drug at a dose of 100 and 200 mg, a mild and transient violation of various colors (blue / green) was revealed, after 2 hours after administration, these changes were absent. The established mechanism of color disturbance is inhibition of PDE 6, which is involved in the process of light transmission in the retina. Sildenafil has no effect on visual acuity, contrast sensitivity, intraocular pressure, or pupil diameter.
The pharmacokinetics of Sildenafil depends on the dose ranges used internally.
The metabolism of the drug is carried out mainly in the liver (mainly with the help of the isoenzyme cytochrome P450 3A4) with the formation of an active metabolite, similar in properties to sildenafil.
Absorption and distribution.
The drug is rapidly absorbed through the gastrointestinal tract. After taking it inside on an empty stomach, Sildenafilmax is achieved within 30-120 minutes (an average of 60 minutes). The absolute bioavailability averages 41% (25% -63%). When taking sildenafil in combination with fatty foods, the absorption rate decreases; T max increases by 60 minutes, and Sildenafilmax decreases by 29%.
The volume of distribution (Vd) of sildenafil in the equilibrium state averages 105 liters, which indicates its distribution in the tissue. Sildenafil and its main circulating N-desmethyl is approximately 96% bound to plasma proteins. Protein binding is independent of the total concentration of sildenafil. In healthy volunteers receiving sildenafil, less than 0.002% (mean 188 ng) of the dose
were detected in semen 90 minutes after ingestion.
Metabolism and excretion.
Sildenafil is metabolized mainly by cytochrome P450 3A4 (main pathway) and cytochrome P450 2C9 (additional pathway) of liver microsomal isoenzymes. The main circulating metabolite, which is formed by N-demethylation of sildenafil, is metabolized. In terms of the selectivity of action on PDE, the metabolite is comparable to sildenafil, and its activity against PDE 5 in vitro is approximately 50% of the activity of sildenafil itself.
The plasma concentration of the metabolite is approximately 40% of that of sildenafil.
The total clearance of sildenafil from the body is 41 l / h, and the half-life (T 1/2) in the terminal phase is 3-5 hours. urine (approximately 13% of the dose administered orally).
Pharmacokinetics in special cases.
The following factors affect the increase in the level of sildenafil in blood plasma (AUC):
– age over 65 years (increase in AUC by 40%);
– Lack of liver function (for example, liver cirrhosis, 84%);
– severe renal failure (CC <30 ml / min, 100%);
– concomitant use of drugs – inhibitors of cytochrome P450 3A4 (for example, erythromycin, 182%, Saquinavir, 210%).
Indications for use:
Treatment of erectile dysfunction, characterized by an inability to achieve or maintain an erection of the penis sufficient to obtain satisfaction from intercourse.
Sildenafil is only effective when sexually aroused!
Method of administration and dosage:
The drug is taken orally.
For most patients, the recommended dose is 50 mg, the drug is taken about 1 hour before sexual activity, and after eating fatty foods – 1.5-2 hours before sexual activity. Taking into account the effectiveness and tolerability, the dose can be increased to 100 mg or reduced to 25 mg.
The maximum recommended frequency of use is 1 time per day.
Adverse events are usually transient and are mild or moderate. Adverse events in dose selection studies were comparable to those in fixed dose studies, as such studies better reflect the recommended regimen.
On the part of the body as a whole: asthenia, pain, abdominal pain, back pain, infection, flu-like syndrome.
On the part of the cardiovascular system: symptoms of vasodilation.
From the gastric – intestinal tract: diarrhea, abdominal pain, nausea.
From the side of the musculoskeletal system: back pain, arthralgia, myalgia.
From the nervous system: dizziness, increased muscle tone, insomnia.
Respiratory system: nasal congestion, pharyngitis, rhinitis, sinusitis, respiratory tract infections, respiratory failure.
Dermatological reactions: rash.
On the part of the senses: changes in vision (mild and transient; mainly a change in the color of objects, as well as increased perception of light and impaired clarity of vision), conjunctivitis.
From the genitourinary system: urinary tract infections, dysfunction of the prostate gland.
In post-marketing observations, there have been reports of cases of prolonged erection and / or priapism.
Hypersensitivity to the components of the drug.
The drug is contraindicated for use in patients receiving or intermittently donors of nitric oxide, organic nitrates or nitrates in any form, since sildenafil enhances the hypotensive effect of nitrates used constantly or in emergency cases.
Pregnancy and lactation
The drug is not intended for use in women and children. There have been no adequate and well-controlled trials in pregnancy and lactation in women.
The effect of other drugs on sildenafil.
Cimetidine (800 mg), which is a nonspecific inhibitor of cytochrome P450 3A4, in vitro studies, when taken simultaneously with sildenafil, caused an increase in plasma concentration of the latter by 56% in healthy volunteers.
A single dose of Sildenafil at a dose of 100 mg simultaneously with erythromycin, a specific inhibitor of cytochrome P450 3A4 (when taking erythromycin 2 times / day, 500 mg for 5 days) against the background of reaching a constant level of erythromycin in the blood, contributed to an increase in the AUC of Sildenafil by 182%. Also, with the simultaneous administration of Sildenafil at a dose of 100 mg and saquinavir, which is both an HIV protease inhibitor and an inhibitor of cytochrome P450 3A4 (when taking saquinavir 3 times / day at a dose of 1200 mg) against the background of reaching a constant level of saquinavir in the blood, the maximum concentration of Sildenafil in the blood increased by 140%, and the AUC increased by 120%. Sildenafil had no effect
on the pharmacokinetic parameters of saquinavir.
Simultaneous use of Sildenafil (single dose of 100 mg) and ritonavir, which is an inhibitor of HIV protease and a rather strong inhibitor of cytochrome P450 (at a dose of 500 mg 2 times / day) against the background of reaching a constant level of ritonavir in the blood, C max increased by 300% (4-fold), and AUC by 1000% (11-fold). After 24 hours, the blood plasma level of Sildenafil was 200 ng / ml (the comparative concentration with a single use of Sildenafil alone after 24 hours was 5 ng / ml). This is consistent with the effects of ritonavir on a range of drug substrates.
Cytochrome P450. Sildenafil had no effect on pharmacokinetic parameters
A population pharmacokinetic analysis of the results of a clinical study showed a decrease in the clearance of sildinafil with the simultaneous use of inhibitors of cytochrome P450 3A4 (such as ketoconazole, itraconazole, erythromycin).
A single dose of an antacid (magnesium hydroxide / aluminum hydroxide) did not affect the bioavailability of sildinafil.
The results of pharmacokinetic studies of patients who took part in clinical trials of sildinafil showed that inhibitors of cytochrome P450 2C9 (such as tolbutamide, warfarin), cytochrome P 450 2D6 (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiopodiazides and potassium-sparing diuretics, ACE inhibitors and calcium antagonists do not affect the pharmacokinetic parameters of sildinafil.
The effect of sildinafil on other drugs.
In patients with arterial hypertension, there were no signs of interaction of sildinafil (100mg) with amlodipine.
Sildenafil (50mg) did not cause an additional increase in bleeding time with acetylsalicylic acid (150mg).
Sildenafil (50 mg) did not enhance the hypotensive effect of ethanol in healthy volunteers with a maximum blood ethanol level of 80 mg / ml on average.
Sexual activity poses a certain risk in heart disease;
In this regard, before starting therapy with sildenafil, an examination of the cardiovascular system should be performed.
In clinical studies, sildinafil exerted a systemic vasodilating effect, which leads to a transient decrease in blood pressure. Before prescribing the drug, the doctor should carefully weigh the risk of undesirable manifestations of vasodilating action in patients with various concomitant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with left ventricular obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy), as well as rare multiple atrophy of various systems, manifested by severe impairment of autonomic blood pressure control.
Due to the lack of information about the safety of the use of sildinafil, the drug should be used with caution in the following groups of patients:
– suffered myocardial infarction, suffering from cerebrovascular accident, as well as life-threatening arrhythmia during the last 6 months;
– suffering from orthostatic hypotension (BP 90/50) or hypertension (AD170 / 110);
– suffering from heart failure or ischemic heart disease due to unstable angina pectoris.
– with hereditary retinitis pigmentosa, with hereditary disorders associated with the synthesis of retinal phosphodiesterases.
– in patients with anatomical deformity of the penis (for example, 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).
Drugs intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable. In addition, the safety and efficacy of sildinafil 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.
When using the drug in patients over the age of 65, patients with liver fusion disorders, patients with severe renal failure, as well as in patients receiving concomitantly drugs – inhibitors of cytochrome P450 3A4 (for example, erythromycin, saquinavir), an increase in the plasma level of Sildenafil occurs. This can contribute to both an increase in the effectiveness of the drug and the possibility of the appearance of side affects. For such groups of patients, it is advisable to prescribe the drug at a dose of 25 mg / day.
Influence on the ability to drive vehicles and control mechanisms.
The drug can cause dizziness and visual impairment, therefore patients should evaluate their reaction to the drug before driving a car or using equipment.
In studies in healthy volunteers with a single dose of the drug in doses up to 800 mg, adverse events were comparable to those when taking Sildenafil in lower doses, but they were more common.
Treatment: if necessary, symptomatic therapy is performed. Hemodialysis accelerates the clearance of Sildenafil creatinine, since the latter actively binds to plasma proteins and is not excreted in the urine.
Do not use after expiration date
Store in a dark place at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
1 or 4 tablets of 50/100 mg in a blister, one blister in a cardboard box with instructions for use.
Terms of dispensing from pharmacies:
Prescribed by a doctor