Sildenafil-SZ, 25 mg 20 pcs

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

Sildenafil is effective only with sexual stimulation.

Indications

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

Sildenafil is effective only during sexual stimulation.

Special instructions

To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination. Treatments for erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie’s disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia) (see section “Caution”).

Medicines intended to treat 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 an examination of the condition of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP < 90/50 mm Hg) (see section "Precautions"). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of death from cardiovascular diseases (0.3 per 100 people per year) in patients receiving Sildenafil compared with patients receiving placebo.

Cardiovascular complications

During post-marketing use of sildenafil for the treatment of erectile dysfunction, 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) were reported, which were temporarily associated 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 occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors.

Hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. However, before prescribing Sildenafil, the physician should carefully assess the risk of possible undesirable manifestations of the vasodilating effect in patients with relevant diseases, especially against the background of sexual activity. 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 system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.
Since the combined use of sildenafil and α-blockers can lead to symptomatic hypotension in some sensitive patients, Sildenafil should be administered with caution to patients taking α-blockers (see section “Interaction with other drugs”). To minimize the risk of developing postural hypotension in patients taking α-blockers, Sildenafil should be started only after hemodynamic stability has been achieved in these patients. You should also consider the advisability of reducing the initial dose of Sildenafil (see section “Dosage and Administration”). The physician should inform patients about what actions to take if symptoms of postural hypotension occur.

Visual impairment

Rare cases of anterior non-arteritic ischemic optic neuropathy as a cause of deterioration or loss of vision have been reported with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as optic disc excavation, age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. A cause-and-effect relationship between the use of PDE5 inhibitors and the development of anterior non-arteritic ischemic optic neuropathy has not been identified. The physician should inform the patient about the increased risk of developing anterior non-arteritic ischemic optic neuropathy if this condition has already been noted. In case of sudden loss of vision, patients should receive the necessary medical attention immediately. A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of retinal phosphodiesterases. There is no information on the safety of using Sildenafil in patients with retinitis pigmentosa, so sildenafil should be used with caution (see section “With caution”).

Hearing impairment

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

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 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 (see section “With caution”). The incidence of epistaxis 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%). Patients receiving sildenafil in combination with a vitamin K antagonist had a higher incidence of epistaxis (8.8%) than patients not taking a vitamin K antagonist (1.7%).

Use in conjunction with other means of treating erectile dysfunction.

The safety and effectiveness of Sildenafil in combination with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see section “Contraindications”).

Impact on the ability to drive vehicles and operate machinery

While taking sildenafil, no negative effects on the ability to drive a car or use other technical equipment 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.

Active ingredient

Sildenafil

Composition

active substance:
sildenafil citrate in terms of sildenafil – 25 mg;
excipients (core):
microcrystalline cellulose –
50.0 mg;
lactose monohydrate (milk sugar) – 61.5 mg;
croscarmellose sodium (primellose) – 7.5 mg;
povidone (medium molecular weight polyvinylpyrrolidone) – 4.5 mg;
magnesium stearate – 1.5 mg;
excipients (shell):
Opadry II (polyvinyl alcohol, partially hydrolyzed – 2.0 mg; titanium dioxide E 171 – 1.145 mg; macrogol (polyethylene glycol 3350) – 1.01 mg; talc – 0.74 mg; aluminum varnish based on brilliant blue – 0.096 mg; iron oxide (II) yellow E 172 – 0.0085 mg; iron oxide (II) black E 172 – 0.0005 mg).

Contraindications

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 (see section “Interaction with other drugs”)
The safety and effectiveness of Sildenafil when used in combination with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see section “Special instructions”)
According to its registered indication, Sildenafil is not intended for use in children under 18 years of age.
According to its 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.

With caution:

Anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie’s disease) (see section “Special instructions”).
Diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia)
(see section “Special instructions”).
Diseases accompanied by bleeding.
Exacerbation of peptic ulcer of the stomach and duodenum.
Hereditary retinitis pigmentosa (see section “Special instructions”).
Heart failure, unstable angina, myocardial infarction, stroke or life-threatening arrhythmias in the last 6 months, arterial hypertension (BP > 170/100 mm Hg) or hypotension (BP < 90/50 mm Hg) (see section "Special instructions"). In patients with episodes of anterior non-arteritic ischemic optic neuropathy (history).

Side Effects

Typically, the side effects of Sildenafil are mild or moderate and transient.

Fixed-dose studies have shown that the incidence of some adverse events increases with increasing dose.

When using the drug Sildenafil in doses exceeding the recommended ones, adverse events were similar to those noted above, but usually occurred more often.

General condition 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).

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

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

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

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

Visual disorders: eye pain, eye redness/scleral injections, conjunctival damage, lacrimation disorders, 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.

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

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

Reproductive system disorders: prolonged erection and/or priapism.

Interaction

The influence of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the influence of the cytochrome CYP3A4 (main pathway) and CYP2C9 isoenzymes, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, accordingly, increase the clearance of sildenafil. A decrease in the clearance of sildenafil was noted with the simultaneous use of inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a nonspecific inhibitor of the cytochrome CYP3A4 isoenzyme, when taken together with sildenafil (50 mg), causes an increase in plasma sildenafil concentrations 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 inhibitor of HIV protease 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 has no effect on the pharmacokinetics of saquinavir.

Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, may cause more severe changes in the pharmacokinetics of sildenafil.

The simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg 2 times a day), 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 the blood plasma is about 200 ng/ml (after a single dose of sildenafil alone – 5 ng/ml), which is consistent with information about the pronounced effect of ritonavir on the pharmacokinetics of various cytochrome P450 substrates. Sildenafil has no effect on the pharmacokinetics of ritonavir. The combined use of sildenafil with ritonavir is not recommended.

If sildenafil is taken in recommended doses by patients simultaneously receiving strong inhibitors of the cytochrome CYP3A4 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, 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 T1/2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other drugs

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 approximately 1 µmol, so it is unlikely that sildenafil could affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with long-term 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 taking the α-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) simultaneously 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 mm Hg. art., 9/5 mm Hg. and 8/4 mm Hg, respectively, and in a standing position – 6/6 mm Hg, 11/4 mm Hg. and 4/5 mmHg, respectively. Rare cases of symptomatic postural hypotension, manifested in the form of dizziness (without fainting), have been reported in such patients. In selected sensitive patients receiving α-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 their 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, no signs of interaction between sildenafil (100 mg) and amlodipine were detected. 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.

Overdose

With a single dose of Sildenafil in doses up to 800 mg, adverse events were comparable to those when taking the drug in 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.

Manufacturer

North Star NAO, Russia