Clinical data
In a placebo-controlled cross-examination of patients with proven early age macular degeneration (n=9), Vegal Extra 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 Cobra 120 Mg 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 Vegal Extra, 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 Vegal Extra 25 mg), 74% (dose Cobra Vega Extra 50 mg) and 82% (dose Vega Extra 120 100 mg) compared to 25% in the placebo group. Analysis of the international index of erectile function showed that in addition to improving erection treatment Vegal Extra 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 Vegal Extra.
Pharmacokinetics
Vegal Extra 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.
Sildenafil Tablets Vegah Extra Cobra 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 Vegah Extra 120 Indication 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. Vegah Cobra 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 Vega Cobra 120 Mg is sexual stimulation.
Vegal Extra restores impaired erectile function in conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.
Influence of Vegal Extra on other drugs
Vega Extra 120 is a weak inhibitor of cytochrome P450 — 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 ISOENZYMES (IC50 >150 µmol). When taking Vegal Extra in recommended doses, its Cmax is about 1 µmol, so it is unlikely that Extra Vega can affect the clearance of the substrates of these isoenzymes.
Vegal Extra 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 Vegal Extra in combination with nitrates or nitric oxide donators is contraindicated. While taking α-adrenoblocker doxazosin (4 and 8 mg) and Vegal Extra (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 Signature Cobra Vega 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.
Cobra Vega Extra Strong 120 Mg (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 Extra Vega 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 Cobra 120 Mg (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).
Vega Cobra 120 (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 Cobra Vega 120 Mg (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 Vegal Extra in combination with antihypertensive agents does not lead to additional side effects.
The pharmacokinetics of Vegal Extra in the recommended dose range is linear.
Suction. After intake of Sildenafil Tablets Vega Extra Cobra is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vegal Extra at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Vegal Extra 100 mg average Cmax free Vegal Extra in plasma men is about 18 ng/ml (38 nm). Cmax when taking Vegal Extra 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 Coin is 105 l. the Association of Cobra Vega 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 Vegab Extra (an average of 188 ng) was found in sperm 90 minutes after taking the drug.
Metabolism. Sildenafil Vega Extra 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 Sildenafil Vega Extra 130 Mg Cobra, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vega 120 Mg, 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 Cobra Vega Extra Strong 120 Mg. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.
Breeding. The total clearance of Cobra Vega Extra is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Vega Visa is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).
Sildenafil Tablets Vegah Extra Cobra