Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden hearing loss or impairment associated with the use of all PDE-5 inhibitors, including Vegal Extra. Most of these patients had risk factors for sudden impairment or hearing loss. There is no causal relationship between the use of PDE-5 inhibitors and sudden hearing impairment or hearing loss. In case of sudden hearing impairment or hearing loss while taking Vegah Extra 120 Mg, consult a doctor immediately.

Bleedings

Vegah Extra 120 Mg enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donator, on human platelets in vitro. Data on the safety of Vegah Extra 120 Mg in patients with a tendency to bleeding or exacerbation of gastric ulcer and duodenal ulcer are not available, so the drug Vega Visa in these patients should be used with caution (see With caution).

The incidence of nosebleeds in patients with pulmonary hypertension associated with diffuse connective tissue diseases was higher (Vegah Extra 120 Mg — 12.9%, placebo — 0%) than in patients with primary pulmonary arterial hypertension (Vegal Extra — 3%, placebo — 2.4%). Patients receiving Vegah Extra 120 Mg in combination with an antagonist of vitamin K, the frequency of nasal bleeding was higher (8.8 percent) than patients who were not taking an antagonist of vitamin K (1.7 percent).

Use in conjunction with other means for the treatment of erectile dysfunction

The safety and efficacy of Vegah Cobra together with other PDE-5 inhibitors or other drugs for the treatment of pulmonary hypertension containing Vega Extra 120 Mg (eg, Revatsio®), or other means for the treatment of erection disorders have not been studied, so the use of such combinations is not recommended (see "Contraindications").

Influence on the ability to drive and mechanisms. In patients receiving Vegah Extra 120 Mg any negative effect on the ability to drive a car or other means was not observed. However, since when taking Vegah Extra 120 Mg may develop dizziness, lowering blood PRESSURE, the development of chromatopsia, blurred vision, etc. side effects, care should be taken when driving and doing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions. Also, you should be careful about the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Cardiovascular complications

During the post-marketing use of Vegah Extra 120 Mg 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 Vegah Extra 120 Mg 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 Vegab Extra, 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 Vegah Extra 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 Vegah Extra 120 Mg, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.

When using the drug Vegah Extra 120 Mg 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 Vegah Extra 120 Mg

The metabolism of Vegah Extra 120 Mg occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Vegah Extra 120 Mg, and inducers, respectively, increase the clearance of Vega Extra Strong 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 Vegah Extra 120 Mg in plasma by 56%.

A single dose of 100 mg of 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 Cobra 130 Mg by 182%.

When co-administered Vega Extra 120 (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 Vega Visa 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 Mg.

The simultaneous use of Vegah Extra 120 Indication (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 Vegah Extra 120 Mg by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Vegah Extra 120 Mg in blood plasma is about 200 ng/ml (after a single application of one Vegah Extra 120 Mg — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Vegal Extra does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Vega Cobra 120 Mg is not recommended. In any case, the maximum dose of Vegah Extra 120 Mg under any circumstances should not exceed 25 mg for 48 hours. If Sildenafil Tablets Vegah Extra Cobra is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Vegah Extra 120 Mg 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 Cobra 120 Vega Extra.

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 Signature Cobra Vega in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Vegah Extra 120 Mg by 62.6 and 52.4%, respectively. Vega Visa increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.

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

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

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

Suction. After intake of Vegah Extra 120 Mg is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vegah Extra 120 Mg at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Sildenafil Vega Extra 130 100 mg average Cmax free Cobra Vega Extra Strong 120mg in plasma men is about 18 ng/ml (38 nm). Cmax when taking Sildenafil Vega Extra 130 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 Vegah Extra 120 Mg is 105 l. the Association of Vegah Extra 120 Mg 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 Coin (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

Metabolism. Sildenafil Tablets Vega Extra Cobra 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 Vegah Extra 120 Mg, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vegah Extra 120 Mg, and its activity against PDE-5 in vitro is about 50% of the activity of Vegah Extra 120 Mg. 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 Sildenafil Tablets Vega Extra Cobra is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Vegah Extra 120 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).

Contraindications

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

the combined use of inhibitors of PDE5, including Vegah Extra 120 Mg, 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 Cobra 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.

Sildenafil Tablets Vegah Extra Cobra