Cardiovascular complications

During the post-marketing use of Vega Coin for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) were reported, which had a temporary connection with the use of Vega Extra 120. 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 were observed after taking Vega Coin without subsequent sexual activity. It is not possible to establish a direct link between the reported adverse events and those or other factors.

Hypotension

Vega Coin 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 Vega Coin, 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. Increased susceptibility to vasodilators is observed in patients with obstruction of the output tract of the left ventricle (aortic stenosis, GOCMP), as well as with the rare syndrome of multiple systemic atrophy, manifested by a severe violation of the regulation of blood PRESSURE from the autonomic nervous system.

Since the combined use of Vega Extra 120 Mg and α-blockers can lead to symptomatic hypotension in some sensitive patients, Vega Coin should be used with caution in patients taking α-blockers (see "Interaction"). To minimize the risk of postural hypotension in patients taking α-blockers, the drug Cobra Vega Extra should be started only after achieving stabilization of hemodynamic parameters in these patients. It should also consider reducing the initial dose of Vega Coin (see. "Dosage and administration"). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

The pharmacokinetics of Extra Vega in the recommended dose range is linear.

Suction. After intake of Vega Extra Cobra 130 Mg is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vega Coin at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Vegab Extra 100 mg average Cmax free Vega Coin in plasma men is about 18 ng/ml (38 nm). Cmax when taking Vega Coin inside fasting is achieved for an average of 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the rate of absorption decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not change significantly (AUC decreases by 11%).

Distribution. The average Vss of Vega Pills is 105 l. the Association of Sildenafil Vega Extra 130 Mg Cobra and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of Vega 120 Mg (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

Metabolism. Cobra Vega 120 Mg is metabolized mainly in the liver by the action of CYP3A4 isoenzyme (main pathway) and CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite, formed as a result of N-demethylation of Cobra 120 Vega Extra, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vegal Extra, and its activity against PDE-5 in vitro is about 50% of the activity of Vegah Cobra. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of Vegah Extra 120 Mg. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.

Breeding. The total clearance of Vega Extra Cobra 130 Mg is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Vega Coin is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).

Contraindications

hypersensitivity to Vega Coin or any other component of the drug;

application in patients receiving constantly or intermittently nitric oxide donators, organic nitrates or nitrites in any form, as Vegah Extra 120 Indication enhances the hypotensive effect of nitrates (see "Interaction»);

the combined use of inhibitors of PDE5, including Vega Coin, called guanylate cyclase stimulants such as riociguat, because it can lead to symptomatic hypotension;

concomitant use with other agents for the treatment of erectile dysfunction (safety and efficacy of Vega Coin when used together has not been studied (see. "Special instructions»);

lactose intolerance, lactase deficiency, glucose-papacosma malabsorption;

severe liver failure (class C classification for child-Pugh);

simultaneous administration of ritonavir;

severe cardiovascular diseases (severe heart failure, unstable angina, stroke or myocardial infarction during the last 6 months, life-threatening arrhythmias, hypertension (BP >170/100 mm Hg). art.) or hypotension (blood PRESSURE <90/50 mm Hg.art.) (see "Special instructions»);

patients with episodes of development partizanai anterior ischemic optic neuropathies (NESN) with loss of vision in one eye;

hereditary retinitis pigmentosa (see special instructions»);

according to the registered indication is not intended for use in women;

according to the registered indication is not intended for use in children under 18 years.

With caution: anatomic deformity 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; ulcer disease of stomach and duodenum in the acute phase; liver dysfunction; severe renal insufficiency (Cl creatinine <30 ml/min); patients with an episode of partizanai development of the anterior ischemic optic neuropathies in history (see "Special instructions); simultaneous reception of blockers α-adrenergic receptors.

Use during pregnancy and breast-feeding

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

Clinical data

In a placebo-controlled cross-examination of patients with proven early age macular degeneration (n=9), Vega Coin was well tolerated at a single dose of 100 mg. There were no clinically significant changes in vision evaluated by special visual tests (visual acuity, Amsler lattice, color perception, color simulation, Humphrey perimeter and photostress).

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

The effectiveness of Vega Coin, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all studies and confirmed in long-term studies lasting 1 year. In studies with the use of fixed-dose proportion of patients reporting that treatment improved their erections were 62% (dose of Vegal Extra 25 mg), 74% (dose Vega Coin 50 mg) and 82% (dose Vega Visa 100 mg) compared to 25% in the placebo group. Analysis of the international index of erectile function showed that in addition to improving erection treatment Vega Extra Cobra 130 Mg also increased the quality of orgasm, allowing to achieve satisfaction from sexual intercourse and overall satisfaction.

According to the generalized data, 59% of patients with diabetes, 43% of patients who underwent radical prostatectomy and 83% of patients with spinal cord injuries (against 16, 15 and 12% in the placebo group, respectively) were reported to have improved erection in the treatment of Sildenafil Vega Extra 130.

Pharmacokinetics

Vegah Extra 120 Indication