Clinical data

Cardiac studies. The use of Signature Cobra Vega in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in systolic pressure in the supine position after taking Vega Extra Strong 120 at a dose of 100 mg was 8.3 mm Hg.art., and diastolic pressure — 5.3 mm Hg.a More pronounced, but also transient effect on blood PRESSURE was observed in patients taking nitrates (see "Contraindications" and "Interaction").

In a study of the hemodynamic effect of Vega Extra Strong 120 in a single dose of 100 mg in 14 patients with severe coronary artery disease (more than 70% of patients had stenosis of at least one coronary artery), systolic and diastolic resting pressure decreased by 7 and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil Vega Extra 130 did not affect cardiac output and did not interfere with blood flow in stenotic coronary arteries, and also led to an increase (by about 13%) of adenosine-induced coronary flow in both stenotic and intact coronary arteries. In a double-blind placebo-controlled study of 144 patients with erectile dysfunction and stable angina, taking antianginal drugs (except nitrates), exercise was performed until the severity of symptoms of angina increased. The duration of the exercise was significantly longer (19.9 seconds; 0.9–38.9 seconds) in patients taking Vegal Extra in a single dose of 100 mg, compared with patients receiving placebo.

In a randomized double-blind placebo-controlled study, the effect of changing the dose of Vega Extra Strong 120 (up to 100 mg) in men (n=568) with erectile dysfunction and hypertension, taking more than two antihypertensive drugs, was studied. Vega Extra Strong 120 improved erection in 71% of men compared to 18% in the placebo group. The frequency of adverse effects was comparable to that in other groups of patients, as well as in those taking more than three antihypertensive drugs.

Studies of visual impairment. In some patients, 1 h after taking Vegab Extra at a dose of 100 mg with the Farnsworth-Mansell test 100 revealed a slight and transient violation of the ability to distinguish shades of color (blue/green). After 2 hours after taking the drug, these changes were absent. It is believed that color vision impairment is caused by inhibition of PDE-6, which is involved in the process of color transmission in the retina. Vega Extra Strong 120 had no effect on visual acuity, contrast perception, electroretinogram, IOP or pupil diameter.

Visual impairment

In rare cases, during post-approval use of all of the inhibitors of PDE5, including Vega Extra 120, 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 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 Extra Strong 120 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 Vegab Extra, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk. In patients with episodes of development PINZN with loss of vision in one eye receiving Vega Extra Strong 120 is contraindicated (see "Contraindications").

A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of the PDE of the retina. Information about the safety of the drug Vega Visa in patients with retinitis pigmentosa absent, so these patients should not be used Sildenafil Vega Extra 130 Mg (see "Contraindications").

Clinical data

In a placebo-controlled cross-examination of patients with proven early age macular degeneration (n=9), Vega Extra Strong 120 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 Sildenafil Vega Extra 120, 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 Vega Cobra 120 Mg 25 mg), 74% (dose Vega Extra Strong 120 50 mg) and 82% (dose Vega Extra Cobra 130 Mg 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 Strong 120 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 Vega Extra Strong 120.

Pharmacokinetics

Cardiovascular complications

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

When using the drug Vega Cobra 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 Strong 120

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

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

A single dose of 100 mg of Vega Extra Strong 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 Strong 120 by 182%.

When co-administered Vega Extra Strong 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 Coin 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 Vega Visa.

The simultaneous use of Vega Extra Strong 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 Strong 120 by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Vega Extra Strong 120 in blood plasma is about 200 ng/ml (after a single application of one Vega Extra Strong 120 — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Signature Cobra Vega does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Sildenafil Vega Extra 130 Mg is not recommended. In any case, the maximum dose of Vega Extra Strong 120 under any circumstances should not exceed 25 mg for 48 hours. If Vegal Extra is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Cobra Vega 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 Vega Extra Strong 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 Vega Extra Strong 120 in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Vega Extra Strong 120 by 62.6 and 52.4%, respectively. Vegal Extra increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.

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

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

Extra Vega