Sildenafil (Viagra)

• active substance: sildenafil citrate in terms of sildenafil - 100 mg;
• excipients (core): microcrystalline cellulose - 83.5 mg; lactose monohydrate (milk sugar) - 83.5 mg; croscarmellose sodium (primellose) - 15.0 mg; povidone (medium molecular weight polyvinylpyrrolidone) - 15.0 mg; magnesium stearate - 3.0 mg;
• excipients (shell): Opadray II (polyvinyl alcohol, partially hydrolyzed - 3.6 mg; titanium dioxide E 171 - 2.061 mg; macrogol (polyethylene glycol 3350) - 1.818 mg; talc - 1.332 mg; aluminum varnish based on brilliant blue - 0.1728 mg; iron oxide (II) yellow E 172 - 0.0153 mg; iron oxide (II) black E 172 - 0.0009 mg).

Film-coated tablets, 25 mg, 50 mg and 100 mg.

On 1, 2, 4 or 10 tablets in a blister strip packaging.

20 tablets in polymer jars or polymer bottles.

Each jar, bottle, 1 blister strip of 1, 2, 4 or 10 tablets, together with instructions for use, are placed in a cardboard box.

Description of the dosage form

Film-coated tablets of blue color, round, biconvex. The tablets on a break are white or almost white.

pharmachologic effect

Erectile dysfunction treatment agent - PDE-5 inhibitor.

Pharmacokinetics

The pharmacokinetics of sildenafil in the recommended dose range is linear.

Suction

After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages about 40% (from 25% to 63%). Invitro sildenafil at a concentration of about 1.7 ng / ml (3.5 nM) inhibits human PDE5 activity by 50%. After a single dose of sildenafil in a dose of 100 mg, the average maximum concentration of free sildenafil in blood plasma (Cmax) in men is about 18 ng / ml (38 nM). Cmax when taking sildenafil inside on an empty stomach is achieved on average within 60 minutes (from 30 minutes to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: Cmax decreases by an average of 29%, and the time to reach the maximum concentration (Tmax) increases by 60 minutes, but the degree of absorption does not change significantly (the area under the concentration-time pharmacokinetic curve (AUC) decreases by 11%).

Distribution

The volume of distribution of sildenafil at steady state averages 105 liters.

The connection of sildenafil and its main circulating N-demethyl metabolite with blood plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the sildenafil dose (average 188 ng) was found in semen 90 minutes after taking the drug.

Metabolism

Sildenafil is metabolized mainly in the liver by the action of the cytochrome CYPZA4 isoenzyme (main pathway) and the cytochrome CYP2C9 isoenzyme (minor pathway).

The main circulating active metabolite resulting from N-demethylation of sildenafil is further metabolized. The selectivity of this metabolite against PDE is comparable to that of sildenafil, and its in vitro activity against PDE5 is about 50% of the activity of sildenafil.

The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism; its half-life (T1 / 2) is about 4 hours.

Withdrawal

The total clearance of sildenafil is 41 l / h, and the final T1 / 2 is 3-5 hours. After oral administration, as well as after intravenous administration, sildenafil is excreted as metabolites, mainly by the intestines (about 80% of the oral dose) and, to a lesser extent, by the kidneys (about 13% of the oral dose).

Pharmacokinetics in special patient groups

Elderly patients

In healthy elderly patients (over 65 years old), the clearance of sildenafil is reduced, and the concentration of free sildenafil in the blood plasma is about 40% higher than in young people (18-45 years old). Age does not have a clinically significant effect on the incidence of side effects.

Renal dysfunction

With mild (creatinine clearance (CC) 50-80 ml / min) and moderate (CC 30-49 ml / min) degree of renal failure, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal failure (CC ≤ 30 ml / min), the clearance of sildenafil decreases, which leads to an approximately twofold increase in the AUC (100%) and Cmax (88%) values ​​compared with those with normal renal function in patients of the same age group.

Liver dysfunction

In patients with cirrhosis of the liver (stages A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase in the AUC (84%) and Cmax (47%) values ​​compared with those with normal liver function in patients of the same age. groups. The pharmacokinetics of sildenafil in patients with severely impaired liver function (stage C according to the Child-Pugh classification) has not been studied.

Pharmacodynamics

Sildenafil is a potent selective inhibitor of cycloguanosine monophosphate (cGMP), a specific phosphodiesterase type 5 (PDE5).

Mechanism of action

The implementation of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. This, in turn, leads to an increase in cGMP levels, subsequent relaxation of the smooth muscle tissue of the corpus cavernosum 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 nitric oxide (NO) by inhibiting PDE5, which is responsible for the breakdown of cGMP.

Sildenafil is selective for PDE5 in vitro, its activity against PDE5 is superior to that against other known phosphodiesterase isoenzymes: PDE6 - 10 times; PDE1 - more than 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. Sildenafil is 4000 times more selective for PDE5 compared to PDE3, which is of great importance, since PDE3 is one of the key enzymes in the regulation of myocardial contractility.

Sexual stimulation is a prerequisite for the effectiveness of sildenafil.

Clinical data

Cardiological examinations

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 pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg. Art., and diastolic pressure - 5.3 mm Hg. Art. A more pronounced, but also transient effect on blood pressure (BP) was observed in patients taking nitrates.

In a study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (CHD) (more than 70% of patients had stenosis of at least one coronary artery), the systolic and diastolic pressure at rest decreased by 7 % and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not interfere with blood flow in stenotic coronary arteries, and also led to an increase (by about 13%) in adenosine-induced coronary flow in both stenotic and intact coronary arteries.

In a double-blind, placebo-controlled study, 144 patients with erectile dysfunction and stable angina pectoris taking antianginal drugs (other than nitrates) did physical exercise until the angina symptoms subsided. The duration of the exercise was significantly longer (19.9 seconds; 0.9 - 38.9 seconds) in patients taking sildenafil in a single dose of 100 mg compared with patients receiving placebo.

A randomized, double-blind, placebo-controlled study investigated the effect of varying the dose of sildenafil (up to 100 mg) in men (n = 568) with erectile dysfunction and arterial hypertension, taking more than two antihypertensive drugs. Sildenafil improved erection in 71% of men compared with 18% in the placebo group. The incidence of adverse effects was comparable to that in other patient groups, as well as in those 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 of the ability to distinguish shades of color (blue / green) was revealed. These changes were absent 2 hours after taking the drug. It is believed that the impairment 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 macular degeneration (n = 9), sildenafil at a single dose of 100 mg was well tolerated. There were no clinically significant changes in vision, assessed by special visual tests (visual acuity, Amsler grating, color perception, modeling of color transmission, Humphrey perimeter and photostress).

Efficiency

The efficacy and safety of sildenafil was evaluated in 21 randomized, double-blind, placebo-controlled studies lasting up to 6 months in 3000 patients aged 19 to 87, with erectile dysfunction of various etiologies (organic, psychogenic or mixed). The efficacy of the drug was assessed globally using an erection diary, an international erectile function index (a validated questionnaire on the state of sexual function) and a partner survey.

The efficacy of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory intercourse, has been demonstrated in all studies and has been confirmed in long-term studies of 1 year duration. In studies using a fixed dose, the ratio of patients reporting that therapy improved their erections was 62% (25 mg sildenafil dose), 74% (50 mg sildenafil dose) and 82% (100 mg sildenafil dose) versus 25% in the placebo group. Analysis of the international index of erectile function showed that, in addition to improving erection, treatment with sildenafil also increased the quality of orgasm, allowed to achieve satisfaction from intercourse and overall satisfaction.

According to pooled data, 59% of diabetic patients, 43% of patients with radical prostatectomy, and 83% of patients with spinal cord injury among patients reporting improved erections with sildenafil treatment were 59% of patients with diabetes (versus 16%, 15% and 12% in the placebo group, respectively). ).

Indications for use

Treatment of erectile dysfunction characterized by the inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.

Sildenafil is only effective for sexual stimulation.

Contraindications for use

Hypersensitivity to sildenafil or any other component of the drug Use in patients receiving continuous or intermittent nitric oxide donors, organic nitrates or nitrites in any form, since sildenafil enhances the hypotensive effect of nitrates.

The safety and effectiveness of the drug Sildenafil when used together with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended.

According to a registered indication, Sildenafil is not intended for use in children under 18 years of age.

According to the registered indication, Sildenafil is not intended for use in women.

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Concomitant use of sildenafil with ritonavir is not recommended.

Carefully

Anatomical deformity of the penis (angulation, cavernous fibrosis, or Peyronie's disease).

Diseases that predispose to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia).

Diseases accompanied by bleeding.

Exacerbation of gastric ulcer and 12 duodenal ulcer.

Hereditary retinitis pigmentosa.

Heart failure, unstable angina pectoris, myocardial infarction, stroke or life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg) or hypotension (BP

In patients with episodes of development of anterior non-arteritic ischemic neuropathy of the optic nerve (in history).

Use during pregnancy and children

According to the registered indication, the drug is not intended for use in women.

Side effects

When using the drug Sildenafil in doses higher than recommended, the adverse events were similar to those noted above, but usually more common.

General disorders: facial edema, photosensitivity reactions, shock, asthenia, pain, chills, abdominal pain, chest pain.

Allergic reactions: hypersensitivity reactions (including skin rash), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Disturbances from the central and peripheral nervous system: drowsiness, insomnia, hypesthesia, paresthesia, ataxia, neuralgia, neuropathy, tremor, depression, unusual dreams, decreased reflexes, stroke, transient ischemic attack, convulsions, incl. recurrent.

Violations of the cardiovascular system: tachycardia, increase or decrease in blood pressure, myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina pectoris, AV block, cerebral thrombosis, heart failure, ECG disorders, cardiomyopathy, sudden death, fainting.

Respiratory disorders: epistaxis, asthma, shortness of breath, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum production, increased cough.

Gastrointestinal disorders: vomiting, nausea, dryness of the oral mucosa, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, rectal bleeding, gingivitis.

Disturbances from the organ of vision: eye pain, redness of the eyes / scleral injections, conjunctival lesions, impaired lacrimation, anterior ischemic optic neuropathy, retinal vascular occlusion, visual field defects, mydriasis, cataracts, eye pain.

Hearing disorders: vertigo, tinnitus, ear pain, deafness.

Blood and lymphatic system disorders: anemia, leukopenia.

Metabolic and nutritional disorders: thirst, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.

Musculoskeletal disorders: arthritis, arthrosis, myalgia, tendon rupture, tendovaginitis, bone pain, myasthenia gravis, synovitis.

Disorders of the skin and subcutaneous tissues: urticaria, herpes simplex, itching, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

Disorders from the genitourinary system: cystitis, nocturia, frequent urination, gynecomastia, urinary incontinence, ejaculation disorders, genital edema, anorgasmia.

Reproductive system disorders: prolonged erection and / or priapism.

Drug interactions

The effect of other drugs on the pharmacokinetics of sildenafil

Sildenafil metabolism occurs mainly under the action of cytochrome isoenzymes CYPZA4 (main pathway) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, respectively, increase the clearance of sildenafil. A decrease in the clearance of sildenafil was noted with the simultaneous use of inhibitors of the cytochrome CYPZA4 isoenzyme (ketoconazole, erythromycin, cimetidine).

Cimetidine (800 mg), a nonspecific inhibitor of the cytochrome CYPZA4 isoenzyme, when taken together with sildenafil (50 mg), causes an increase in plasma concentration of sildenafil by 56%. A single dose of 100 mg of sildenafil together with erythromycin (500 mg / day 2 times a day for 5 days), a specific inhibitor of the cytochrome CYPZA4 isoenzyme, against the background of reaching a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%.

With the combined administration of sildenafil (100 mg once) and saquinavir (1200 mg / day 3 times a day), an inhibitor of HIV protease and cytochrome CYP3A4 isoenzyme, against the background of reaching a constant concentration of saquinavir in the blood, the Cmax of sildenafil increased by 140%, and AUC increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir.

Stronger inhibitors of the cytochrome CYPZA4 isoenzyme, such as ketoconazole and itraconazole, can also cause stronger changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg twice a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P450, against the background of reaching a constant concentration of ritonavir in the blood leads to an increase in the Cmax of sildenafil by 300% (4 times ), and AUC by 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng / ml (after a single use of one sildenafil - 5 ng / ml), which is consistent with the information on the pronounced effect of ritonavir on the pharmacokinetics of various substrates of cytochrome P450. Sildenafil has no effect on the pharmacokinetics of ritonavir. The combination of sildenafil with ritonavir is not recommended.

If sildenafil is taken in the recommended doses by patients receiving simultaneously strong inhibitors of the cytochrome CYPZA4 isoenzyme, then the Cmax of free sildenafil does not exceed 200 nM, and the drug is well tolerated.

A single dose of an antacid (magnesium hydroxide / aluminum hydroxide) does not affect the bioavailability of sildenafil.

Inhibitors of the cytochrome CYP2C9 isoenzyme (tolbutamide, warfarin), the cytochrome CYP2D6 isoenzyme (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACP inhibitors, and do not exert calcium antagonists on calcium inhibitors.

Azithromycin (500 mg / day for 3 days) has no effect on AUC, Cmax, Tmax, elimination rate constant and T1 / 2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other medicinal products

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50> 150 μmol). When sildenafil is taken at recommended doses, its Cmax is about 1 μmol, so it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter and with their appointment for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

With the simultaneous administration of the α-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 decrease in systolic / diastolic blood pressure in the supine position was 7 / 7 mmHg Art., 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. Reported rare cases of the development of symptomatic postural hypotension in such patients, manifested in the form of dizziness (without fainting). In some sensitive patients receiving α-blockers, the simultaneous use of sildenafil may lead to symptomatic hypotension.

Signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the cytochrome CYP2C9 isoenzyme, have not been identified.

Sildenafil (100 mg) has no effect on the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome CYPZA4 isoenzyme, at a constant level in the blood.

Sildenafil (50 mg) does not cause an additional increase in bleeding time when acetylsalicylic acid (150 mg) is taken.

Sildenafil (50 mg) does not enhance the hypotensive effect of alcohol in healthy volunteers with a maximum blood alcohol concentration of an average of 0.08% (80 mg / dL). In patients with arterial hypertension, no signs of interaction of sildenafil (100 mg) with amlodipine were found. The average additional decrease in blood pressure in the supine position is 8 mm Hg. (systolic) and 7 mm Hg. (diastolic).

The use of sildenafil in combination with antihypertensive drugs does not lead to additional side effects.

Dosage

Inside.

The recommended dose for most adult patients is 50 mg approximately 1 hour 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 dose is 100 mg. The maximum recommended frequency of use is once a day.

Renal dysfunction

With mild to moderate renal failure (CC 30-80 ml / min), dose adjustment is not required, with severe renal failure (CC

Liver dysfunction

Since the elimination of sildenafil is impaired in patients with liver damage (in particular, with cirrhosis), the dose of Sildenafil should be reduced to 25 mg.

Concomitant use with other drugs

When used together with ritonavir, the maximum single dose of Sildenafil should not exceed 25 mg, and the frequency of use should be 1 time per 48 hours.

When used together with inhibitors of the cytochrome CYPZA4 isoenzyme (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Sildenafil should be 25 mg.

To minimize the risk of postural hypotension in patients taking α-blockers, Sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. Consideration should also be given to reducing the starting dose of sildenafil.

Elderly patients

No dose adjustment is required for Sildenafil.

Overdose

With a single dose of Sildenafil in a dose of up to 800 mg, adverse events were comparable to those when taking the drug at lower doses, but they were more common.

Treatment is symptomatic. Hemodialysis does not accelerate the clearance of sildenafil, since the latter actively binds to plasma proteins and is not excreted by the kidneys.

Precautionary measures

To diagnose erectile dysfunction, determine their possible causes and choose an adequate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination. Erectile dysfunction drugs should be used with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, Peyronie's disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia).

Drugs intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.

Sexual activity poses a certain risk in the presence of heart disease, therefore, before starting any therapy for erectile dysfunction, the doctor should refer the patient to an examination of the state of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina pectoris, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP> 170/100 mm Hg) or hypotension (BP

Cardiovascular complications

During the post-marketing use of sildenafil for the treatment of erectile dysfunction, adverse events have been reported such as serious cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension ) who had a temporary connection with the use of sildenafil.

Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some of them were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct connection between the observed undesirable phenomena and the indicated or other factors.

Hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not clinically significant and does not lead to any consequences in most patients. However, before prescribing the drug Sildenafil, the doctor should carefully assess the risk of possible undesirable manifestations of vasodilating action in patients with relevant diseases, especially against the background of sexual activity. An increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple systemic atrophy, manifested by severe impairment of blood pressure regulation by the autonomic nervous system.

Since the combined use of sildenafil and α-blockers can lead to symptomatic hypotension in some sensitive patients, the drug Sildenafil should be used with caution in patients taking α-blockers

To minimize the risk of postural hypotension in patients taking α-blockers, Sildenafil should be started only after stabilization of hemodynamic parameters in these patients. You should also consider the feasibility of reducing the initial dose of Sildenafil. The physician should inform patients about what to do if symptoms of postural hypotension occur.

Visual impairment

Rare cases of the development of anterior non-arteritic ischemic neuropathy of the optic nerve as a cause of deterioration or loss of vision were noted 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 disc, age over 50 years, diabetes mellitus, arterial hypertension, coronary heart disease, hyperlipidemia, and smoking. A causal relationship between the intake of PDE5 inhibitors and the development of anterior non-arteritis ischemic neuropathy of the optic nerve was not revealed. The physician should inform the patient about the increased risk of developing anterior non-arteritic ischemic neuropathy of the optic nerve, if this condition has already been noted. In the event of a sudden loss of vision, patients should immediately receive the necessary medical attention. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of the functions of retinal phosphodiesterases. There is no information on the safety of using the drug Sildenafil in patients with retinitis pigmentosa, therefore, sildenafil should be used with caution.

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden hearing impairment or loss associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden hearing impairment or loss. A causal relationship between the use of PDE5 inhibitors and sudden hearing impairment or hearing loss has not been established. In case of sudden hearing loss or hearing loss while taking sildenafil, you should immediately consult your doctor.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro. There are no data on the safety of using sildenafil in patients with a tendency to bleeding or exacerbation of gastric ulcer and duodenal ulcer, so Sildenafil should be used with caution in these patients. The incidence of nosebleeds in patients with PH associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%). In patients who received sildenafil in combination with a vitamin K antagonist, the incidence of nosebleeds was higher (8.8%) than in patients who did not take a vitamin K antagonist (1.7%).

Use in conjunction with other treatments for erectile dysfunction.

The safety and efficacy of Sildenafil in conjunction with other drugs for the treatment of erectile dysfunction have not been studied, so the use of such combinations is not recommended.

Influence on the ability to drive vehicles and use mechanisms

While taking sildenafil, there was no negative effect on the ability to drive a car or other technical means.

However, since taking sildenafil may decrease blood pressure, develop chromatopsia, blurred vision, etc. side effects, you should be attentive to the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.