Signature Cobra Vega is a potent selective inhibitor of cGMP-specific PDE-5.

Mechanism of action

The implementation of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, the subsequent relaxation of smooth muscle tissue of the cavernous body and an increase in blood flow.

Vega Pills does not have a direct relaxing effect on the isolated cavernous human body, but enhances the effect of nitric oxide by inhibiting PDE-5, which is responsible for the disintegration of cGMP.

Selective Vegab Extra against PDE5 in vitro, its activity against PDE5 superior activity against other known PDE isoenzymes: PDE-6 — 10 times; PDE-1 more than 80 times; PDE-2, PDE-4, PDE-7 PDE–11 more than 700 times. Vega Extra 120 is 4000 times more selective for PDE-5 than PDE-3, which is crucial because PDE-3 is one of the key enzymes in the regulation of myocardial contractility.

A prerequisite for the effectiveness of Sildenafil Vega Extra 130 Mg Cobra is sexual stimulation.

Signature Cobra Vega restores impaired erectile function in conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.

Clinical data

Cardiac studies. The use of Sildenafil Tablets Vega Extra Cobra 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 Vegab Extra 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 Cobra Vega Extra Strong 120mg 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%. Signature Cobra Vega 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 Sildenafil Tablets Vegah Extra Cobra 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 Signature Cobra Vega (up to 100 mg) in men (n=568) with erectile dysfunction and hypertension, taking more than two antihypertensive drugs, was studied. Signature Cobra Vega 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 Vega Extra Cobra 130 Mg 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 Cobra 120 had no effect on visual acuity, contrast perception, electroretinogram, IOP or pupil diameter.

Contraindications

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

the combined use of inhibitors of PDE5, including Signature Cobra Vega, 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 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 Signature Cobra 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 Vega Visa. 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 Cobra 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 Cobra 120 Vega 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 Cobra Vega 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 Indication, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.

When using the drug Signature Cobra Vega 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 Cobra 130 Mg

The metabolism of Vega Visa occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Vega Coin, and inducers, respectively, increase the clearance of Vega Pills. A decrease in the clearance of Cobra Vega 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 Signature Cobra Vega in plasma by 56%.

A single dose of 100 mg of Signature Cobra Vega 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 Cobra Vega by 182%.

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

The simultaneous use of Extra Vega (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 Sildenafil Tablets Vegah Extra Cobra by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Vega Pills in blood plasma is about 200 ng/ml (after a single application of one Sildenafil Vega Extra 130 Mg — 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 Signature Cobra Vega is not recommended. In any case, the maximum dose of Signature Cobra Vega under any circumstances should not exceed 25 mg for 48 hours. If Signature Cobra Vega is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Cobra Vega 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 Signature Cobra Vega.

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 Cobra in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Sildenafil Vega Extra 120 by 62.6 and 52.4%, respectively. Sildenafil Vega Extra 130 increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.

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

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

Vega Coin