Clinical data

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

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

Suction. After intake of Vega Pills is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vega 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 Vega Pills in plasma men is about 18 ng/ml (38 nm). Cmax when taking Vega Extra Strong 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 Vega Pills is 105 l. the Association of Extra Vega 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 Pills (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

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

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

Influence of Vega Pills on other drugs

Vega Pills is a weak inhibitor of cytochrome P450 — 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 ISOENZYMES (IC50 >150 µmol). When taking Sildenafil Tablets Vegah Extra Cobra in recommended doses, its Cmax is about 1 µmol, so it is unlikely that Vega Extra 120 can affect the clearance of the substrates of these isoenzymes.

Vega Pills increases the hypotensive effect of nitrates both with long-term use of the latter, and with their appointment for urgent indications. In this regard, the use of Vega Pills in combination with nitrates or nitric oxide donators is contraindicated. While taking α-adrenoblocker doxazosin (4 and 8 mg) and Vega Pills (25, 50 and 100 mg) in patients with benign prostate hyperplasia with stable hemodynamics, the average additional decrease in sad/dad in the supine position was 7/7, 9/5 and 8/4 mm Hg.article, respectively, while in the standing position — 6/6, 11/4 mmHg, and 4/5.art. respectively. Reported rare cases of symptomatic postural hypotension in such patients, manifested in the form of dizziness (without fainting). In some sensitive patients receiving α-blockers, simultaneous use of Sildenafil Vega Extra 130 Mg Cobra can lead to symptomatic hypotension.

There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9 isoenzyme.

Vega Pills (100 mg) has no effect on the pharmacokinetics of the HIV protease inhibitor, saquinavir, which is a substrate of CYP3A4 isoenzyme, at its constant level in the blood.

The simultaneous use of Vega Pills at equilibrium (80 mg 3 times a day) leads to an increase in the AUC and Cmax of bosentan (125 mg 2 times a day) by 49.8 and 42%, respectively.

Vega Pills (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).

Vega Extra 120 Mg (50 mg) does not increase the hypotensive effect of alcohol in healthy volunteers with Cmax of alcohol in the blood on average 0.08‰ (80 mg/DL).

In patients with hypertension, no signs of interaction of Vega Pills (100 mg) with amlodipine were found. The average additional reduction in blood PRESSURE in the supine position is 8 mm Hg.V. (systolic) and 7 mm Hg.V. (diastolic).

The use of Vega Pills in combination with antihypertensive agents does not lead to additional side effects.

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 Pills. 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 Pills 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 Pills 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 Cobra 120 Vega Extra, 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 Pills and α-blockers can lead to symptomatic hypotension in some sensitive patients, Cobra Vega Extra Strong 120 Mg 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 Vega Pills should be started only after achieving stabilization of hemodynamic parameters in these patients. It should also consider reducing the initial dose of Vega Pills (see. "Dosage and administration"). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Vegah Cobra