Sildenafil-SZ, pills 50mg, 10pcs

Composition

of 1 tab. sildenafil (in citrate form) 50 mg

Auxiliary substances:

microcrystalline cellulose – 54 mg,

lactose monohydrate (milk sugar) – 74 mg,

croscarmellose sodium (primellose) – 10 mg,

povidone (polyvinylpyrrolidone medium molecular weight) – 10 mg,

magnesium stearate-2 mg.

Shell composition:

Opadray II (polyvinyl alcohol, partially hydrolyzed-2.4 mg, titanium dioxide (E171) – 1.374 mg, macrogol (polyethylene glycol 3350) – 1.212 mg, talc-0.888 mg, aluminum varnish based on diamond blue-0.1152 mg, iron oxide (II) yellow (E172) – 0.0102 mg, iron oxide (II) black (E172) – 0.0006 mg).

Pharmacological action

Sildenafil is a potent selective inhibitor of cyclo-guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

Indications

Treatment of erectile dysfunction characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse.

Sildenafil is only effective with sexual stimulation.

Use during pregnancy and lactation

The drug is not intended for use in women.

Contraindications

• hypersensitivity to sildenafil or any other component of the drug;
• application in patients receiving constantly or intermittently donators of nitric oxide, organic nitrates or nitrites in any form, as sildenafil enhances the hypotensive effect of nitrates (see “Interaction”);
• the safety and efficacy of sildenafil when used together with other means for the treatment of erectile dysfunction has not been studied, so the use of such combinations is not recommended (see “Special instructions”);
• it is not recommended simultaneous use of sildenafil with ritonavir;
• according to the registered indication, the drug sildenafil is not intended for use in women;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• according to the registered indication, the drug sildenafil is not intended for use in children under 18 years of age.

With caution:  anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie’s disease) (see “Special instructions”); diseases of, predisposing to the development of priapism (sickle-cell anemia, multiple myeloma, leukemia, thrombocythemia — see “Special instructions”); diseases accompanied by haemorrhage; exacerbation of gastric ulcer and duodenal ulcer; hereditary retinitis pigmentosa (see “Special instructions”); heart failure, unstable angina, moved in last 6 months, myocardial infarction, stroke or life-threatening arrhythmias, hypertension (BP >170/100 mm Hg. St. ) or hypotension (blood pressure

Side effects

Usually, the side effects of Sildenafil are mild to moderate and transient.

In fixed-dose studies, it has been shown that the frequency of

Organs and organ systems Side effects of Sildenafil,% Placebo,%Most common side effects (> 1/10)Nervous system Headache 164 Cardiovascular systemvasodilation (“hot flashes” of blood to the skin of the face)101 Common side effects (> 1/100 and >Nervous system Vertigo 21 Organs of vision Visual disturbances (blurred vision, color vision disorders)2,50,4 Chromatopsia (mild and transient, mainly changes in the perception of color shades)1,10,03 Cardiovascular systemaccording to palpitations 1,00,2 Respiratory Systemarinitis (nasal congestion)42 Digestive systemdispepsia 72 Diarrhea 31 Urinary systeminfections of the urinary tract 32 Skin and subcutaneous tissue rash 21

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

General health disorders:  facial swelling, 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).

Central and peripheral nervous system disorders:  drowsiness, insomnia, hypesthesia, paresthesia, ataxia, neuralgia, neuropathy, tremor, depression, unusual dreams, decreased reflexes, stroke, transient ischemic attack, convulsions, including recurrent ones.

Disorders of the cardiovascular system:  tachycardia, increased or decreased blood pressure, myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina, AV block, cerebral thrombosis, heart failure, ECG disorders, cardiomyopathy, sudden death, syncope.

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

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

Visual disturbances:  eye pain, redness of the eyes/sclera injections, conjunctival damage, lacrimation disorder, anterior ischemic optic neuropathy, retinal vascular occlusion, visual field defects, mydriasis, cataracts, eye pain.

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

Disorders of the blood and lymphatic system:  anemia, leukopenia.

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

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

Skin and subcutaneous tissue disorders:  urticaria, herpes simplex, pruritus, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

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

Reproductive system disorders:  prolonged erections and / or priapism.

Interaction

Effect of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of cytochrome CYP3A4 (main pathway) and CYP2C9 isoenzymes, so 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 observed with the simultaneous use of inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the cytochrome CYP3A4 isoenzyme, when co-administered with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma 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 CYP3A4 isoenzyme, against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%.

When co-administered with sildenafil (100 mg once) and saquinavir (1200 mg / day 3 times a day), an HIV protease inhibitor and cytochrome CYP3A4 isoenzyme, while achieving a constant concentration of saquinavir in the blood, the Cmax of sildenafil increased by 140%, and the AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir.

Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, can also cause stronger changes in the pharmacokinetics of sildenafil.

Simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg twice daily), an HIV protease inhibitor and a strong cytochrome P450 inhibitor, while achieving a constant concentration of ritonavir in the blood leads to an increase in sildenafil Cmax by 300% (4 times), and AUC by 1000% (11 times). After 24 hours, the concentration of sildenafil in blood plasma is about 200 ng / ml (after a single application of sildenafil alone-5 ng / ml), which is consistent with the information about the pronounced effect of ritonavir on the pharmacokinetics of various cytochrome P 450 substrates. Sildenafil has no effect on the pharmacokinetics of ritonavir. Concomitant use of sildenafil with ritonavir is not recommended. If sildenafil is taken at the recommended doses in patients receiving simultaneously strong inhibitors of the cytochrome CYP3A4 isoenzyme, the Cmax of free sildenafil does not exceed 200 nM, and the drug is well tolerated.

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

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

Azithromycin (500 mg / day for 3 days) has no effect on the AUC, Cmax Tmax, elimination rate constant and T 1/2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other medications

Sildenafil is a weak inhibitor of cytochrome P450-1A2,2C9,2C19,2D6,2E1AND ZA4 isoenzymes (IR 50>150 mmol). When taking sildenafil at the recommended doses, its Cmax is about 1 mmol, 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 when they are prescribed for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

When the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg,50 mg and 100 mg) were co – administered in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional reduction in systolic/diastolic blood pressure in the supine position was 7/7 mm Hg,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 mmHg, respectively. Rare cases of symptomatic postural hypotension, which manifested itself in the form of dizziness (without fainting), have been reported in such patients. In some sensitive patients receiving alpha-blockers, concomitant use of sildenafil may lead to symptomatic hypotension.

There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the cytochrome CYP2C9 isoenzyme.

Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome CYP3A4 isoenzyme, at constant blood levels. Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg). Sildenafil (50 mg) does not enhance the hypotensive effect of alcohol in healthy volunteers with a maximum blood alcohol concentration of 0.08% (80 mg/dl) on average.

In patients with arterial hypertension, there were no signs of interaction between sildenafil (100 mg) and amlodipine. 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 agents does not lead to additional side effects.

How to take, course of use and dosage

Sildenafil is taken orally. The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Depending on the efficacy 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 application is 1 time per day.

Impaired renal function. In mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), no dose adjustment is required, in severe renal insufficiency (creatinine clearance

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

Joint use with other drugs. When co-administered with ritonavir, the maximum single dose of Sildenafil should not exceed 25 mg, and the frequency of use should be 1 time in 48 hours (see “Interaction”). When co-administered with inhibitors of the cytochrome CYP3A4 isoenzyme (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Sildenafil should be 25 mg (see “Interaction”). To minimize the risk of postural hypotension in patients taking alpha-blockers, Sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. Consideration should also be given to reducing the initial dose of sildenafil (see “Special Instructions” and “Interactions”).

Elderly patients. No dose adjustment of Sildenafil is required.

Overdose

With a single dose of Sildenafil up to 800 mg, adverse events were comparable to those with lower doses, but 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.

Special instructions

To diagnose erectile dysfunction, determine their possible causes, and choose appropriate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination. Treatment of erectile dysfunction 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, so before starting any therapy for erectile dysfunction, the doctor should refer the patient for a cardiovascular examination. Sexual activity is undesirable in patients with heart failure, unstable angina, a history of myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP > Clinical studies have shown no differences in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular mortality (0.3 per 100 people per year) in patients treated with Sildenafil compared to patients treated with placebo.

Cardiovascular complications

Adverse events such as serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension, and hypotension) that were temporarily associated with the use of sildenafil have been reported during post-marketing use of sildenafil for the treatment of erectile dysfunction. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events were observed shortly after sexual activity, and some of them were observed after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct link between the observed adverse events and the above or other factors.

Hypotension

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

Since the combined use of sildenafil and alpha-blockers can lead to symptomatic hypotension in some sensitive patients, Sildenafil should be prescribed with caution to patients taking alpha-blockers. To minimize the risk of postural hypotension in patients taking a-blockers, Sildenafil should be started only after the hemodynamic parameters have stabilized in these patients. Consideration should also be given to reducing the initial dose of Sildenafil. The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Visual impairments

Rare cases of anterior non-arteritic ischemic optic neuropathy have been reported as a cause of visual impairment or loss with all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as an excavated optic disc, age over 50 years, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia, and smoking. No causal relationship was found between the use of PDE5 inhibitors and the development of anterior non-arteritic ischemic optic neuropathy. The doctor 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 case of sudden loss of vision, patients should immediately receive the necessary medical care. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of retinal phosphodiesterase functions. There is no information on the safety of Sildenafil in patients with retinitis pigmentosa, so sildenafil should be used with caution.

Hearing disorders

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 deterioration or loss of hearing. No causal relationship has been established between the use of PDE5 inhibitors and sudden hearing impairment or hearing loss. In case of sudden hearing loss or loss of hearing while taking sildenafil, you should immediately consult your doctor.

Bleeding issues

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 sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, 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 treated with 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 means of treating erectile dysfunction.

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

Influence on the ability to drive motor vehicles and manage mechanisms

While taking sildenafil, no negative effects on the ability to drive a car or other technical means were observed.

However, since taking sildenafil may reduce blood pressure, develop chromatopsia, blurred vision, etc. side effects, you should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Form of production

Film-coated tablets of blue color, round, biconvex; on the break – white or almost white color.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Sildenafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets