Sildenafil-SZ, 50 mg 4 pc

How to take, the dosage

Ingestion.

The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Depending on efficacy and tolerability, the dose may 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 daily.

Renal dysfunction

In mild to moderate renal failure (CKR 30-80 ml/min), no dose adjustment is necessary; in severe renal failure (CKR < 30 ml/min), the sildenafil dose should be reduced to 25 mg.

Hepatic disorders

Because sildenafil excretion is impaired in patients with liver damage (particularly in cirrhosis), the dose of sildenafil should be reduced to 25 mg.

Combined use with other medicinal products

In co-administration with ritonavir, the maximum single dose of Sildenafil should not exceed 25 mg, and the frequency of use should be once every 48 hours (see section “Interaction with other medicinal products”). When concomitant use with cytochrome CYPCA4 isoenzyme inhibitors (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Sildenafil should be 25 mg (see section “Interaction with other medicinal products”). To minimize the risk of postural hypotension in patients taking α-adrenoblockers, Sildenafil should be started only after hemodynamic stabilization is achieved in these patients. It should also be considered to reduce the starting dose of sildenafil (see sections “Special Precautions” and “Interaction with other medicinal products”).

Elderly patients

There is no need to adjust the dose of sildenafil.

Interaction

Influence of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of cytochrome CYP3A4 isoenzymes (main pathway) and CYP2C9, therefore inhibitors of these isoenzymes may decrease sildenafil clearance, and inducers, respectively, increase sildenafil clearance. There was noted a decrease in sildenafil clearance when concomitant use of inhibitors of CYP3A4 cytochrome isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of cytochrome CYP3A4 isoenzyme, when taken together with sildenafil (50 mg) increases sildenafil concentration in plasma by 56%. A single use of sildenafil at a dose of 100 mg in combination with erythromycin (500 mg 2 times per day for 5 days), a specific inhibitor of cytochrome CYP3A4 enzyme, on the background of achieving a constant concentration of erythromycin in blood, leads to an increase in sildenafil AUC by 182%.

When taking sildenafil (100 mg single dose) and saquinavir (1200 mg/day 3 times/day), an HIV protease inhibitor and CYP3A4 cytochrome isoenzyme, together, against achieving a steady concentration of saquinavir in the blood Cmax of sildenafil was increased by 140% and AUC was increased by 210%. Sildenafil has no effect on the pharmacokinetics of saquinavir.

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

If sildenafil is taken in recommended doses in patients receiving concomitant strong CYP3A4 cytochrome isoenzyme inhibitors, the Cmax of sildenafil free is less than 200 nM and the drug is well tolerated.

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

CYP2C9 cytochrome isoenzyme inhibitors (tolbutamide, warfarin), CYP2D6 cytochrome isoenzyme inhibitors (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACE inhibitors and calcium antagonists, have no effect on sildenafil pharmacokinetics.

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

The effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes -1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IK50>150 μmol). When sildenafil is taken at the 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 long-term use of the latter and when prescribed for acute indications. Therefore, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

The concomitant administration of the alpha-adrenoblocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics produced an average additional decrease of systolic/diastolic BP in supine position of 7/7 mm Hg, 9/5 mmHg and 8/4 mmHg, respectively, and 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg in the standing position, respectively. Rare cases of symptomatic postural hypotension, manifested as dizziness (without fainting), have been reported in these patients. In some sensitive patients receiving alpha-adrenoblockers, concomitant use of sildenafil may lead to symptomatic hypotension.

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

Sildenafil (100 mg) has no effect on the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome CYP3A4 isoenzyme, when their blood levels are constant.

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

Sildenafil (50 mg) does not increase the hypotensive effects of ethanol in healthy volunteers at a maximum blood ethanol concentration of 0.08% (80 mg/dL) on average.

In patients with arterial hypertension, there is no evidence of interaction between sildenafil (100 mg) and amlodipine. The mean additional reduction of BP in the supine position is 8 mmHg (systolic) and 7 mmHg (diastolic).

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

.

Special Instructions

To diagnose erectile dysfunction, determine its possible causes, and choose an adequate treatment, a complete medical history and a thorough physical examination must be taken. Erectile dysfunction treatments should be used with caution in patients with anatomic penile deformities (angulation, cavernous fibrosis, Peyronie’s disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia) (see section “Caution”).

The drugs intended to treat erectile dysfunction should not be prescribed for men for whom sexual activity is undesirable.

Sexual activity poses some risk if you have heart disease, so your doctor should refer you for a cardiovascular exam before starting any erectile dysfunction therapy. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke within the last 6 months, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg), or hypotension (BP < 90/50 mm Hg) (see “Caution”). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or cardiovascular mortality (0.3 per 100 people per year) in patients treated with Sildenafil compared to patients treated with placebo.

Cardiovascular Complications

In the postmarketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as serious cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, and hypertension and hypotension) that were temporarily associated with sildenafil use.

The majority, but not all, of these patients had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some occurred after sildenafil without subsequent sexual activity. A direct relationship between these adverse events and these or other factors cannot be established.

Hypotension

Sildenafil has a systemic vasodilatory effect resulting in a transient decrease in BP, which is not clinically significant and has no effect in most patients. However, before prescribing sildenafil, the physician should carefully evaluate the risk of possible adverse vasodilatory effects in patients with related conditions, especially during sexual activity. Increased susceptibility to vasodilators is seen in patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), and with the rare syndrome of multiple systemic atrophy manifested by severe disruption of BP regulation by the autonomic nervous system.

Because co-administration of sildenafil and α-adrenoblockers may lead to symptomatic hypotension in some sensitive patients, sildenafil should be used with caution in patients taking α-adrenoblockers (see section “Interaction with other drugs”).

In order to minimize the risk of postural hypotension in patients taking α-adrenoblockers, Sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. It should also be considered to reduce the starting dose of Sildenafil (see section “Dosage and administration”). The physician should inform patients about what actions should be taken if symptoms of postural hypotension occur.

Visual impairment

Rare cases of development of anterior nonarteritic ischemic optic neuropathy as a cause of visual impairment or loss have been reported with all FDE5 inhibitors, including sildenafil. Most of these patients had risk factors such as optic disc excavation (deepening), age over 50 years, diabetes mellitus, arterial hypertension, coronary heart disease, hyperlipidemia, and smoking. No causal relationship between the intake of FDE5 inhibitors and the development of anterior nonarteritic ischemic optic neuropathy has been identified. The physician should inform the patient about the increased risk of anterior nonarteritic ischemic optic neuropathy if this condition has already been reported. In case of sudden loss of vision, patients should be treated immediately. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of retinal phosphodiesterase functions. There is no information about the safety of Sildenafil in patients with retinitis pigmentosa, so Sildenafil should be used with caution (see section “Caution”).

Hearing impairment

Some postmarketing and clinical studies have reported cases of sudden hearing impairment or loss associated with use of all FDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden deterioration or hearing loss. A causal relationship between the use of FDE5 inhibitors and sudden hearing impairment or hearing loss has not been established. If there is sudden hearing loss or hearing loss while taking sildenafil, consult a physician 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 peptic ulcer disease, so sildenafil should be used with caution in these patients (see “Caution” section). The incidence of nasal bleeding in patients with LH associated with diffuse connective tissue disease was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%). Patients who received sildenafil in combination with a vitamin K antagonist had a higher rate of nasal bleeding (8.8%) than patients who did not take a vitamin K antagonist (1.7%).

Performance with other treatments for erectile dysfunction.

The safety and effectiveness of Sildenafil with other erectile dysfunction drugs have not been studied, so this combination is not recommended (see section “Contraindications”).

Influence on driving and operating ability

There have been no adverse effects on the ability to drive or operate machinery while taking sildenafil.

However, since taking sildenafil may result in decreased blood pressure, chromatopsia, blurred vision, and other adverse events, careful consideration should be given to the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosing regimen.

.

Contraindications

– use in patients receiving nitric oxide donators, organic nitrates or nitrites in any form continuously or intermittently, since sildenafil increases the hypotensive effect of nitrates;

Sildenafil-SZ is not indicated for use in children and adolescents under the age of 18 years;

– Sildenafil-SZ is not indicated for use in women;

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

– Simultaneous use of sildenafil with ritonavir is not recommended;

– Hypersensitivity to sildenafil or any other component of the drug.

The safety and effectiveness of sildenafil-SZ when used together with other treatments for erectile dysfunction has not been studied, so these combinations are not recommended.

With caution:

– anatomical deformity of the penis (angulation, cavernous fibrosis or Peyronie’s disease);

– Diseases predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia).

Diseases that cause bleeding.p> – exacerbation of gastric and duodenal ulcer disease;

– hereditary retinitis pigmentosa;

– Heart failure, unstable angina, myocardial infarction, stroke, or life-threatening arrhythmias within the past 6 months, arterial hypertension (BP >170/100 mmHgStd) or hypotension (BP <90/50 mm Hg);

– in patients with episodes of anterior nonarteritic ischemic optic neuropathy (history).

.

Side effects

In the body in general: asthenia, pain, abdominal pain, back pain, infection, flu-like syndrome.

Cardiovascular system: vasodilation (side effect reported in clinical trials).
Digestive system: diarrhea, nausea.

Muscular system: joint pain, muscle pain.

CNS and peripheral nervous system disorders: dizziness (side effect reported in clinical trials), increased muscle tone, insomnia.

Respiratory system disorders: nasal congestion, pharyngitis, rhinitis (side effect reported in clinical studies), sinusitis, respiratory tract infections, respiratory disorders.

Dermatological reactions: rash.

Sensory organs: changes in vision: mild and transient, mainly changes in the color of objects, as well as increased perception of light and blurred vision (side effect reported in clinical studies), conjunctivitis.

Urinary system disorders: urinary tract infections.

Perior genital system disorders: disorders of prostate function.

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

The following are the adverse events reported during post-marketing use.

Cardiovascular disorders: arterial hypotension, syncope, tachycardia, palpitations.

Digestive system disorders: vomiting (side effect reported in clinical trials).

Anxiety of the sexual system: prolonged erection and/or priapism.

Sensory system disorders: pain in the eyes, redness of the eyes.

Others: allergic reactions.

The side effects were usually transient and mild to moderate.

In fixed-dose studies, the incidence of side effects increased with increasing doses.

The nature of side effects in studies in which the dose was adjusted, because such studies better reflect the recommended regimen, was comparable to that in fixed-dose studies.

Overdose

Symptoms: When taking Sildenafil-SZ in a single dose up to 800 mg, adverse events were comparable to those with lower doses, but were more frequent.

Treatment: symptomatic therapy. Hemodialysis does not accelerate clearance of sildenafil, as the latter is actively bound to plasma proteins and is not excreted by the kidneys.

.

Pregnancy use

The drug is not intended for use in women according to its registered indication.

Similarities

Viagra, Dynamico, Sildenafil NW, Effex, Visarsin, Visarsin Ku-tab, Effex Sildenafil, Sildenafil, Wildegra, Gent