Sildenafil 100 mg 20 coated tablets

Treatment of erectile dysfunction characterized by the inability to achieve or maintain an erection of the penis sufficient for satisfactory sexual intercourse in adult men.
Sildenafil is effective only with sexual stimulation!

Orally.
The recommended dose for most patients is 50 mg approximately 1 hour before sexual activity. Depending on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of use is once daily. The onset of action of Sildenafil may be delayed when taken with food compared to fasting (see the "Pharmacokinetics" section).
Renal function impairment
In cases of mild to moderate renal insufficiency (CrCl 30-80 mL/min), dose adjustment is not required; in severe renal insufficiency (CrCl

Composition per tablet:
active ingredient: sildenafil citrate - 140.45 mg (equivalent to sildenafil - 100 mg);
excipients: microcrystalline cellulose type 102, calcium hydrogen phosphate dihydrate, colloidal silicon dioxide, povidone K-30, sodium croscarmellose, magnesium stearate;
coating composition: Opadry II 85F30695 blue [polyvinyl alcohol, titanium dioxide, talc, macrogol, aluminum lake based on indigo carmine, iron oxide yellow dye].

Round biconvex tablets coated with a blue film, with a score line.
The core of the tablets is white or almost white in cross-section.

Hypersensitivity to sildenafil or any of the excipients
Due to its known effect on nitric oxide/cyclic guanosine monophosphate (cGMP) metabolism (see "Pharmacodynamics" section), sildenafil enhances the hypotensive effect of nitrates; therefore, its use is contraindicated in patients receiving nitric oxide donors (such as amyl nitrite) or nitrates in any form.
Simultaneous use of PDE-5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic arterial hypotension (see "Interactions with Other Medicinal Products" section).
Erectile dysfunction medications, including sildenafil, are contraindicated in patients for whom sexual activity is not recommended (e.g., patients with severe cardiovascular conditions such as unstable angina, severe heart failure).
Sildenafil is contraindicated in patients with vision loss in one eye due to non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this condition is related to previous use of PDE-5 inhibitors (see "Special Precautions" section).
The use of sildenafil is contraindicated in patients with: severe liver failure, arterial hypotension (blood pressure less than 90/50 mmHg), recent stroke or myocardial infarction, and known hereditary degenerative retinal diseases, such as retinitis pigmentosa (a small number of such patients have genetic disorders of retinal phosphodiesterase), as the safety of sildenafil has not been studied in these subgroups.
According to the registered indication, sildenafil is not intended for use in children and adolescents under 18 years of age.
According to the registered indication, sildenafil is not intended for use in women.

With caution
Anatomical deformity of the penis (angulation, cavernosal fibrosis, or Peyronie's disease) (see "Special Precautions" section).
Conditions predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia) (see "Special Precautions" section).
Patients with a history of anterior non-arteritic ischemic optic neuropathy (see "Special Precautions" section).
Simultaneous use of alpha-adrenergic receptor blockers.
Conditions associated with bleeding.
Peptic ulcer disease of the stomach and duodenum.

For the diagnosis of erectile dysfunction, determining its possible causes, and selecting appropriate treatment, a complete medical history must be collected, and a thorough physical examination must be conducted.
Risk factors for cardiovascular diseases
Sexual activity poses a certain risk in the presence of heart diseases; therefore, before starting any therapy for erectile dysfunction, the doctor may find it necessary to examine the patient's cardiovascular system.
Sildenafil has a vasodilatory effect, leading to a slight transient decrease in blood pressure (see the "Pharmacodynamics" section). Before prescribing sildenafil, the doctor should carefully assess the risk of possible adverse effects of the vasodilatory action in patients with relevant conditions, especially in the context of sexual activity. Increased sensitivity to vasodilators is observed in patients with left ventricular outflow obstruction (e.g., aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with the rare syndrome of multiple system atrophy, which manifests as severe dysregulation of blood pressure by the autonomic nervous system.
The drug Sildenafil enhances the hypotensive effect of nitrates (see the "Contraindications" section).
During post-marketing surveillance, cases of serious cardiovascular complications (including myocardial infarction, unstable angina, sudden coronary death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, arterial hypertension, and hypotension) have been reported, which had a temporal association with the use of sildenafil. Most of these patients, but not all, had risk factors for cardiovascular complications. Many of the mentioned adverse events occurred shortly after sexual activity, and some were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct link between these events and the mentioned or other factors.
Priapism
Drugs for the treatment of erectile dysfunction, including sildenafil, should be used with caution in patients with anatomical deformities of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease) or in patients with conditions predisposing to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
During post-marketing use of sildenafil, reports of prolonged erection and priapism have been received. If an erection lasts longer than 4 hours, the patient should seek emergency medical assistance. If priapism is not treated promptly, it may lead to tissue damage of the penis and irreversible loss of potency.
Co-administration with other PDE-5 inhibitors or other treatments for erectile dysfunction
The safety and efficacy of sildenafil when used in combination with other PDE-5 inhibitors or other medications for the treatment of pulmonary arterial hypertension containing sildenafil (e.g., Revatio), as well as other means for treating erectile dysfunction, have not been studied; therefore, the use of such combinations is not recommended.
Effects on vision
Spontaneous reports of visual disturbances have been received with the use of sildenafil and other PDE-5 inhibitors (see the "Side Effects" section). In spontaneous reports and observational studies, cases of a rare condition - non-arteritic anterior ischemic optic neuropathy (NAION) - have been noted, which were associated with the use of sildenafil and other PDE-5 inhibitors (see the "Side Effects" section). Patients should be warned that in the event of sudden vision loss, they should discontinue the use of Sildenafil and seek medical attention immediately (see the "Contraindications" section).
Co-administration with ritonavir
The co-administration of sildenafil and ritonavir is not recommended (see the "Interactions with Other Medications" section).
Co-administration with alpha-adrenergic blockers
Since the co-administration of sildenafil and alpha-adrenergic blockers may lead to symptomatic hypotension in certain sensitive patients, sildenafil should be prescribed with caution to patients taking alpha-adrenergic blockers (see the "Interactions with Other Medications" section). The development of this condition is most likely to occur within 4 hours after taking a dose of sildenafil. To minimize the risk of developing orthostatic hypotension, sildenafil therapy should only be initiated in hemodynamically stable patients taking alpha-adrenergic receptor blockers. It is also advisable to consider starting sildenafil at an initial dose of 25 mg (see the "Dosage and Administration" section). Additionally, doctors should inform patients about the actions to take in case of symptoms of orthostatic hypotension.
Effects on blood coagulation
In vitro studies on human platelets have shown that sildenafil potentiates the anti-aggregatory effect of sodium nitroprusside. There is no information on the safety of sildenafil use in patients with bleeding disorders or acute peptic ulcers; therefore, the use of sildenafil in these patients is only possible after careful assessment of the benefit/risk ratio.
Women
The drug Sildenafil is not intended for use in women.

Summary of Safety Profile
The safety profile of sildenafil is based on data obtained from 9,570 patients who received the drug during 74 double-blind placebo-controlled clinical trials. The most commonly reported adverse reactions among patients taking sildenafil in clinical trials included headache, skin flushing, dyspepsia, nasal congestion, dizziness, nausea, hot flashes, visual disturbances, cyanopsia, and color perception disorders.
Information on adverse reactions reported during post-marketing surveillance was collected over a period of >10 years. Since not all adverse reactions were reported to the marketing authorization holder, and consequently, not all adverse reactions were included in the safety database, the frequency of these reactions cannot be reliably determined.
Table Summary of Adverse Reactions
The table presents adverse reactions by system-organ classes (SOC) and frequency. Within each frequency group, adverse reactions are listed in order of decreasing severity. The frequency of occurrence is defined as: very common (≥ 1/10), common (from ≥ 1/100 to

Symptoms
In studies involving healthy volunteers, adverse events that developed after a single dose of sildenafil up to 800 mg were comparable to those observed with lower doses, but the frequency and severity of these events increased. The use of sildenafil at a dose of 200 mg did not lead to increased efficacy but resulted in a higher incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).
Treatment
In case of overdose, standard supportive measures should be taken as necessary. Acceleration of sildenafil clearance during hemodialysis is unlikely due to the high degree of binding of sildenafil to plasma proteins and the absence of drug elimination through urine.

Influence of Other Medicinal Products on the Pharmacokinetics of Sildenafil
In Vitro Studies
The metabolism of sildenafil primarily occurs through the action of cytochrome P450 isoenzymes CYP3A4 (the main pathway) and CYP2C9; therefore, inhibitors of these isoenzymes may reduce the clearance of sildenafil, while inducers may increase the clearance of sildenafil.
In Vivo Studies
Population pharmacokinetic analysis of clinical trial data demonstrated a decrease in sildenafil clearance when used concurrently with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although no increase in the frequency of adverse events was observed with the concurrent use of sildenafil and CYP3A4 inhibitors, it is advisable to consider starting the medication at a dose of 25 mg.
Concurrent administration of sildenafil (at a dose of 100 mg as a single dose) and ritonavir (500 mg twice daily), an HIV protease inhibitor and a strong inhibitor of cytochrome P450, at steady-state concentrations of ritonavir in the blood, resulted in a 300% (4-fold) increase in Cmax of sildenafil and a 1000% (11-fold) increase in AUC. After 24 hours, the concentration of sildenafil in plasma remained at 200 ng/ml compared to 5 ng/ml after a single dose of sildenafil alone. This is consistent with the pronounced effect of ritonavir on a number of drugs that are substrates of cytochrome P450. Sildenafil did not affect the pharmacokinetics of ritonavir. Based on the results of pharmacokinetic studies, the concurrent use of sildenafil and ritonavir is not recommended (see the "Dosage and Administration" section), and under no circumstances should the maximum dose of sildenafil exceed 25 mg within 48 hours.
Concurrent administration of sildenafil (at a dose of 100 mg as a single dose) and saquinavir (at a dose of 1200 mg three times daily), an HIV protease inhibitor and an inhibitor of CYP3A4 isoenzyme, at steady-state concentrations of saquinavir in the blood, resulted in a 140% increase in Cmax of sildenafil and a 210% increase in AUC. Sildenafil did not affect the pharmacokinetics of saquinavir (see the "Dosage and Administration" section). Stronger CYP3A4 inhibitors, such as ketoconazole and itraconazole, may cause more pronounced changes.
A single dose of sildenafil at 100 mg in combination with erythromycin (500 mg twice daily for 5 days), a moderate CYP3A4 isoenzyme inhibitor, at steady-state concentrations of erythromycin in the blood, led to an increase in AUC of sildenafil by 182%. Administration of azithromycin (500 mg daily for 3 days) by healthy male volunteers did not affect the AUC, Cmax, Tmax, elimination rate constant, or half-life of sildenafil or its main circulating metabolite. Cimetidine (at a dose of 800 mg), an inhibitor of cytochrome P450 and a non-specific CYP3A4 inhibitor, when taken concurrently with sildenafil (at a dose of 50 mg), increased the concentration of sildenafil in plasma by 56% in healthy volunteers.
Grapefruit juice is a weak inhibitor of CYP3A4 metabolism in the intestinal wall and may cause a moderate increase in the level of sildenafil in plasma.
A single dose of an antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.
Although specific studies on the interaction of sildenafil with all medicinal products have not been conducted, population pharmacokinetic analysis indicates that the pharmacokinetics of sildenafil did not change when used concurrently with drugs belonging to the group of CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, β-adrenoceptor antagonists, or CYP450 metabolism inducers (such as rifampicin, barbiturates). In a study involving healthy male volunteers, the concurrent use of the endothelin antagonist bosentan (which is a moderate inducer of CYP3A4, CYP2C9, and possibly CYP2C19) at steady-state (125 mg twice daily) and sildenafil at steady-state (80 mg three times daily) resulted in a decrease in AUC and Cmax of sildenafil by 62.6% and 55.4%, respectively. It can be expected that the concurrent use of strong CYP3A4 inducers, such as rifampicin, will cause a more pronounced decrease in the concentration of sildenafil in plasma.
Nicorandil has potassium channel activating properties and nitrate-like effects. Due to its nitrate component, this drug has the potential to interact clinically significantly with sildenafil.
Influence of Sildenafil on Other Medicinal Products
In Vitro Studies
Sildenafil is a weak inhibitor of isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (IC50 > 150 µM) of cytochrome P450. At recommended doses, its Cmax is about 1 µmol, making it unlikely that sildenafil will affect the clearance of substrates of these isoenzymes.
Data on the interaction of sildenafil with non-specific phosphodiesterase inhibitors, such as theophylline and dipyridamole, are lacking.
In Vivo Studies
In line with the known effect on the NO/cGMP signaling cascade (see the "Pharmacodynamics" section), it has been demonstrated that sildenafil potentiates the hypotensive effect of nitrates; therefore, the use of nitric oxide donors or nitrates in any form in conjunction with sildenafil is contraindicated (see the "Contraindications" section).
Riociguat: Preclinical studies have shown an additional effect of lowering systemic arterial pressure when PDE-5 inhibitors and riociguat are used concurrently. In clinical studies, riociguat has shown an enhancement of the hypotensive effect of PDE-5 inhibitors. There is no data on the favorable clinical effect of this combination in population studies. The concurrent use of riociguat and PDE-5 inhibitors, including sildenafil, is contraindicated (see the "Contraindications" section).
Concurrent use of sildenafil and alpha-adrenoceptor blockers may lead to symptomatic hypotension in certain predisposed patients. This condition is most likely to occur within 4 hours after taking a dose of sildenafil (see the "Dosage and Administration" and "Special Precautions" sections). In three studies of specific drug interactions, patients with stable benign prostatic hyperplasia (BPH) receiving doxazosin were concurrently administered the alpha-adrenoceptor blocker doxazosin (at doses of 4 mg and 8 mg) and sildenafil (at doses of 25, 50, and 100 mg). In these studies, patients experienced an average additional decrease in blood pressure while lying down of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, and an average decrease in blood pressure while standing of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively. Reports of symptomatic orthostatic hypotension were infrequent in patients receiving sildenafil and doxazosin in a stable state while on doxazosin. These reports included cases of dizziness and pre-syncope without syncope.
No significant interaction of sildenafil (at a dose of 50 mg) with tolbutamide (at a dose of 250 mg) or warfarin (at a dose of 40 mg) - drugs metabolized by CYP2C9 - was found.
Sildenafil (at a dose of 50 mg) did not potentiate the increase in bleeding time caused by acetylsalicylic acid (at a dose of 150 mg).
Sildenafil (at a dose of 50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers at a maximum blood ethanol level averaging 80 mg/dl.
In patients taking sildenafil, no differences in safety profiles compared to placebo were noted when used concurrently with classes of antihypertensive drugs such as diuretics, β-adrenoceptor blockers, ACE inhibitors, angiotensin II receptor antagonists, antihypertensive agents (vasodilators and centrally acting agents), adrenergic receptor blockers, calcium channel blockers, and α-adrenoceptor blockers. In a special clinical study aimed at investigating drug interactions, concurrent use of sildenafil (100 mg) and amlodipine in patients with hypertension resulted in an additional decrease in systolic blood pressure while the patient was lying down by 8 mmHg. The corresponding decrease in diastolic blood pressure was 7 mmHg. In magnitude, these additional decreases in blood pressure were comparable to those observed in the group of healthy volunteers receiving sildenafil alone (see the "Pharmacodynamics" section).
Sildenafil (at a dose of 100 mg) did not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of CYP3A4, at steady-state.
Sildenafil at steady-state (80 mg three times daily) caused an increase in AUC of bosentan (125 mg twice daily) by 49.8% and Cmax by 42% in healthy male volunteers.
The addition of a single dose of sildenafil to sacubitril/valsartan at steady-state in patients with hypertension was associated with a significantly greater reduction in blood pressure compared to the use of sacubitril/valsartan alone. Therefore, caution should be exercised when prescribing sildenafil to patients receiving sacubitril/valsartan.

Sildenafil is a potent selective inhibitor of cyclic guanosine monophosphate (cGMP) - specific phosphodiesterase type 5 (PDE5).
Mechanism of Action
Sildenafil is intended for the oral treatment of erectile dysfunction. Under natural conditions, i.e., in the presence of sexual stimulation, it restores impaired erectile function by enhancing blood flow to the penis. The physiological mechanism underlying penile erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. The resulting nitric oxide activates the enzyme guanylate cyclase, leading to an increase in cyclic guanosine monophosphate (cGMP) levels, which causes relaxation of smooth muscles in the corpus cavernosum and increased blood flow.
Sildenafil is a potent selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE-5), which is responsible for the breakdown of cGMP in the corpus cavernosum. Sildenafil exerts a peripheral effect on erection. Sildenafil does not have a direct relaxing effect on isolated human corpus cavernosum but actively enhances the relaxing effect of NO on this tissue. When the NO/cGMP cascade is activated during sexual stimulation, the inhibition of PDE-5 by sildenafil leads to an increase in cGMP levels in the corpus cavernosum. Thus, sexual stimulation is necessary for the desired pharmacological effect of sildenafil to occur.
In vitro studies have demonstrated that sildenafil is selective for PDE-5, which is involved in the process of erection. Its activity against PDE-5 exceeds its activity against other known phosphodiesterases. It is 10 times less active against PDE-6, which is involved in the phototransduction process in the retina. At the maximum recommended doses, sildenafil is 80 times less selective for PDE-1 and 700 times less selective for PDE-2, 3, 4, 7, 8, 9, 10, and 11. Furthermore, sildenafil's selectivity for PDE-5 is approximately 4000 times greater than its selectivity for PDE-3, the cAMP-specific phosphodiesterase involved in regulating heart contractions.
Clinical Data
Clinical Efficacy and Safety
To assess the time after taking the drug during which sildenafil leads to the onset of erection in response to sexual stimulation, two clinical studies were developed. In a clinical study involving patients taking sildenafil on an empty stomach, during the performance of penile plethysmography (using the RigiScan device), the median time to the onset of erection in patients who achieved an erection with 60% rigidity (sufficient for sexual intercourse) was 25 minutes (ranging from 12 to 37 minutes). In a separate study using the RigiScan device, sildenafil was still able to induce an erection in response to sexual stimulation 4-5 hours after administration.
Sildenafil causes a mild and transient decrease in blood pressure, which in most cases has no clinical manifestations. The average maximum decrease in systolic blood pressure, measured in the supine position, after oral administration of sildenafil at a dose of 100 mg was 8.4 mm Hg. The corresponding change in diastolic blood pressure was 5.5 mm Hg. These decreases in blood pressure are consistent with the vasodilatory effect of sildenafil, likely due to increased cGMP levels in the smooth muscles of blood vessels. A single oral administration of sildenafil at doses up to 100 mg did not lead to clinically significant changes in ECG in healthy volunteers.
In a study of the hemodynamic effects of a single oral dose of sildenafil at 100 mg in 14 patients with severe ischemic heart disease (IHD) (with stenosis of at least one coronary artery greater than 70%), the mean systolic and diastolic blood pressure at rest decreased by 7% and 6% from baseline, respectively. The mean pulmonary artery systolic pressure decreased by 9%. Sildenafil had no effect on cardiac output and did not disrupt blood flow in stenosed coronary arteries.
In a double-blind placebo-controlled clinical study using a physical exercise test involving 144 patients with erectile dysfunction and chronic stable angina who were continuously taking antianginal medications (excluding nitrates), no clinically significant differences in the time to the onset of limiting angina with sildenafil compared to placebo were demonstrated.
Mild and transient disturbances in color discrimination (blue/green) were observed in some patients during the 100-hue Farnsworth-Munsell test one hour after taking sildenafil at a dose of 100 mg. These changes completely disappeared two hours after administration of the drug. The possible mechanism for this change in color recognition is related to the inhibition of PDE-6, which is involved in the phototransduction cascade in the retina. Sildenafil does not affect visual acuity or contrast sensitivity. In a small placebo-controlled clinical study involving patients with documented age-related macular degeneration (n=9), the administration of sildenafil (single dose of 100 mg) did not cause significant changes in the results of vision tests (visual acuity, Amsler grid, modeling of traffic light color recognition, Humphrey perimeter, and photostress).
A single oral dose of sildenafil at 100 mg in healthy volunteers did not affect sperm motility or morphology.
Additional Clinical Study Data
In clinical studies, sildenafil was administered to more than 8000 patients aged 19 to 87 years. The studies included the following patient groups: elderly individuals (19.9%), patients with hypertension (30.9%), patients with diabetes (20.3%), ischemic heart disease (5.8%), hyperlipidemia (19.8%), spinal cord injuries (0.6%), depression (5.2%), transurethral resection of the prostate (3.7%), and radical prostatectomy (3.3%). The following patient groups were not adequately represented or were excluded from clinical studies: patients after pelvic organ surgery, patients after radiation therapy, patients with severe renal or hepatic insufficiency, and patients with certain cardiovascular diseases (see the "Contraindications" section). In studies using a fixed dose, the proportion of patients reporting improvement in erectile function with the drug was 62% (25 mg), 74% (50 mg), and 82% (100 mg) compared to 25% in the placebo group. In controlled clinical studies, the number of cases of sildenafil discontinuation was small and comparable to the placebo group. The number of patients reporting improvement with sildenafil in all these studies was as follows: psychogenic erectile dysfunction (84%), mixed erectile dysfunction (77%), organic erectile dysfunction (68%), elderly patients (67%), diabetes (59%), ischemic heart disease (69%), hypertension (68%), transurethral resection of the prostate (61%), radical prostatectomy (43%), spinal cord injuries (83%), depression (75%). The safety and efficacy of sildenafil are confirmed by data from long-term studies.

Absorption
Sildenafil is rapidly absorbed. Maximum observed plasma concentrations after oral administration of sildenafil on an empty stomach are reached within 30 - 120 minutes (median 60 minutes). The absolute bioavailability averages about 41% (25-63%). After oral administration of the drug within the recommended dose range (25-100 mg), the AUC and Cmax of sildenafil increase proportionally to the dose. When sildenafil is taken with food, the rate of absorption decreases, with the time to reach maximum concentration (tmax) increasing by an average of 60 minutes, and Cmax decreasing by an average of 29%.
Distribution
The volume of distribution of sildenafil at steady state (Vd) averages 105 L, indicating its distribution in tissues. The maximum total concentration of sildenafil in plasma after a single oral dose of 100 mg averages about 440 ng/mL (coefficient of variation -40%). Since the binding of sildenafil (and its main circulating N-desmethyl metabolite) to plasma proteins reaches 96%, the average maximum concentration of the free fraction of sildenafil in plasma is 18 ng/mL (38 nM). Binding to plasma proteins is independent of the total concentration of the drug.
In healthy volunteers, 90 minutes after a single oral dose of 100 mg of sildenafil, less than 0.0002% of the administered dose was detected in the ejaculate (on average - 188 ng).
Biotransformation
Sildenafil is primarily metabolized by CYP3A4 (main pathway) and CYP2C9 (additional pathway) microsomal liver isoenzymes. The main circulating metabolite is formed as a result of N-demethylation of sildenafil. This metabolite has a phosphodiesterase selectivity profile similar to that of sildenafil, and its activity against PDE-5 in vitro is approximately 50% of the activity of the parent compound. Concentrations of this metabolite in plasma are about 40% of the concentrations of sildenafil. The N-demethylated metabolite undergoes further metabolism; its terminal half-life is about 4 hours.
Elimination
The total clearance of sildenafil from the body is 41 L/hour, and the terminal half-life is 3-5 hours. After oral or intravenous administration, sildenafil is eliminated mainly as metabolites, primarily in feces (about 80% of the orally administered dose) and to a lesser extent in urine (about 13% of the orally administered dose).
Special patient groups
Renal insufficiency
In volunteers with mild to moderate renal insufficiency (creatinine clearance 30-80 mL/min), the pharmacokinetic parameters of sildenafil after a single oral dose (50 mg) did not change. The mean AUC and Cmax values of the N-desmethyl metabolite increased by 126% and 73%, respectively, compared to volunteers of the same age without renal impairment. However, due to significant interindividual variability, these differences were not statistically significant. In volunteers with severe renal insufficiency (creatinine clearance