Cardiovascular complications

During the post-marketing use of Extra Vega 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 Vegah Extra 120 Mg. 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 Extra 120 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 Extra 120 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 Visa, 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 Cobra 120 and α-blockers can lead to symptomatic hypotension in some sensitive patients, Vega Cobra 120 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 120 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 Cobra 120 Mg (see. "Dosage and administration"). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Contraindications

hypersensitivity to Vega Extra 120 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 Vega Extra 120 enhances the hypotensive effect of nitrates (see "Interaction»);

the combined use of inhibitors of PDE5, including Vegal Extra, 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 Extra 120 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.

Cardiovascular complications

During the post-marketing use of Vega Pills 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 Extra 120 without subsequent sexual activity. It is not possible to establish a direct link between the reported adverse events and those or other factors.

Visual impairment

In rare cases, during post-approval use of all of the inhibitors of PDE5, including Vega Cobra 120 Mg, reported NESN is a rare disease and the cause of the decrease or loss of vision. Most of these patients had risk factors, such as decreased ratios of excavation diameter to optic disc (stagnant disc), age over 50, diabetes, hypertension, CHD, hyperlipidemia, and Smoking. In an observational study evaluated whether recent use of drugs class of inhibitors PDE-5 with an acute onset NESN. The results indicate approximately a 2-fold increase in risk of developing NESN within 5T1/2 after application of the PDE-5 inhibitor. According to published literature, the annual incidence of npins IS 2.5–11.8 cases per 100,000 men aged ≥50 years in the General population. Patients should be advised to stop Vega Cobra 120 Mg therapy in case of sudden loss of vision and consult a doctor immediately. Persons who have already had a case NESN have an increased risk of relapse NESN. Therefore, the doctor should discuss this risk with such patients, as well as the potential chance of adverse effects of PDE-5 inhibitors. PDE-5 inhibitors, including Vega Extra 120, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.

When using the drug Vega Extra 120 in doses exceeding the recommended, adverse events were similar to those noted above, but usually more common.

*Side effects identified during post-marketing studies.

Interaction

Effect of other drugs on the pharmacokinetics of Vega Extra 120

The metabolism of Sildenafil Tablets Vegah Extra Cobra occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Vega Extra 120, and inducers, respectively, increase the clearance of Vega Extra 120. A decrease in the clearance of Vegab Extra with simultaneous use of inhibitors of CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine).

Cimetidine (800 mg), a nonspecific inhibitor of CYP3A4 isoenzyme, when taken together with Vega Visa (50 mg) causes an increase in the concentration of Vega Extra 120 in plasma by 56%.

A single dose of 100 mg of Sildenafil Vega Extra 120 together with erythromycin (500 mg/day 2 times a day for 5 days), a moderate inhibitor of CYP3A4 isoenzyme, while achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of Vega Extra 120 by 182%.

When co-administered Vega Visa (once 100 mg) and saquinavir (1200 mg/day 3 times daily), an inhibitor of HIV protease and of CYP3A4, on the background to achieve a constant concentration of saquinavir in the blood, Cmax of Cobra Vega 120 Mg was increased by 140% and the AUC increased by 210%.

Stronger inhibitors of CYP3A4 isoenzyme, such as ketoconazole and Itraconazole, can cause more pronounced changes in the pharmacokinetics of Vegah Extra 120 Indication.

The simultaneous use of Vega Extra 120 (100 mg once) and ritonavir (500 mg 2 times a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P450, on the background to achieve a constant concentration of ritonavir in the blood leads to an increase in Cmax of Vega Extra 120 by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Vega Extra 120 in blood plasma is about 200 ng/ml (after a single application of one Vega Extra 120 — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Vegah Extra 120 Indication does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Vega Extra 120 is not recommended. In any case, the maximum dose of Vega Cobra 120 under any circumstances should not exceed 25 mg for 48 hours. If Vega Extra 120 is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Vega Visa does not exceed 200 nm, and the drug is well tolerated.

Single administration of antacid (magnesium hydroxide/aluminum hydroxide) does not affect the bioavailability of Vega Extra 120.

Studies involving healthy volunteers with simultaneous use of endothelin receptor antagonist, bosentan (CYP3A4 isoenzyme inducer (moderate), CYP2C9, and possibly CYP2C19) in Css (125 mg 2 times a day) and Vegah Extra 120 Mg in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Vega Extra 120 by 62.6 and 52.4%, respectively. Vega Extra 120 increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.

It is assumed that the simultaneous use of Vega Extra 120 Mg with powerful inducers of CYP3A4 isoenzyme, such as rifampicin, can lead to a greater decrease in the concentration of Vega Extra 120 Mg in blood plasma.

CYP2D6 isoenzyme inhibitors (SSRIs, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACE inhibitors and calcium antagonists have no effect on the pharmacokinetics of Vega Extra 120.

Azithromycin (500 mg/day for 3 days) has no effect on AUC, Cmax, Tmax, excretion rate constant and T1/2 Vega Extra 120 or its main circulating metabolite.

The pharmacokinetics of Vega Extra 120 in the recommended dose range is linear.

Suction. After intake of Vega Extra 120 is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vega Extra 120 at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Vega Extra 120 100 mg average Cmax free Cobra Vega Extra in plasma men is about 18 ng/ml (38 nm). Cmax when taking Vega Extra 120 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 Vegal Extra is 105 l. the Association of Vega Extra 120 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 Extra 120 (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

Metabolism. Vega Extra 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 Vega Extra 120, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vega Extra 120, and its activity against PDE-5 in vitro is about 50% of the activity of Vegal Extra. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of Vega Extra 120. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.

Breeding. The total clearance of Vegah Extra 120 Mg is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Sildenafil Vega Extra 130 Mg is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).

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