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 Coin. 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 120 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 Coin, 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 Coin 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 Vega Coin, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.
When using the drug Vega Coin 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
The metabolism of Cobra Vega 120 occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Vega Extra, and inducers, respectively, increase the clearance of Vega Coin. A decrease in the clearance of Vega Coin with simultaneous use of inhibitors of CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine).
Cimetidine (800 mg), a nonspecific inhibitor of CYP3A4 isoenzyme, when taken together with Vegab Extra (50 mg) causes an increase in the concentration of Vega Coin in plasma by 56%.
A single dose of 100 mg of Vega Coin 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 Coin by 182%.
When co-administered Cobra 120 Vega Extra (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 Cobra 120.
The simultaneous use of Vegal Extra (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 Coin by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Sildenafil Vega Extra 130 in blood plasma is about 200 ng/ml (after a single application of one Vega Extra — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Vega Extra 120 does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Vegah Extra 120 Indication is not recommended. In any case, the maximum dose of Vega Coin under any circumstances should not exceed 25 mg for 48 hours. If Cobra Vega Extra is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Signature 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 Vega Coin.
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 Coin in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Vega Coin by 62.6 and 52.4%, respectively. Vega Coin increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.
It is assumed that the simultaneous use of Vega Coin with powerful inducers of CYP3A4 isoenzyme, such as rifampicin, can lead to a greater decrease in the concentration of Cobra Vega Extra Strong 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 Vega Extra 120 Mg.
Azithromycin (500 mg/day for 3 days) has no effect on AUC, Cmax, Tmax, excretion rate constant and T1/2 Vega Pills or its main circulating metabolite.
Contraindications
hypersensitivity to Vega Extra 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 Vega Extra Cobra 120 enhances the hypotensive effect of nitrates (see "Interaction»);
the combined use of inhibitors of PDE5, including Vega Coin, 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 Sildenafil Vega Extra 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.
The pharmacokinetics of Cobra Vega Extra Strong 120 Mg in the recommended dose range is linear.
Suction. After intake of Signature Cobra Vega is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Sildenafil Vega Extra 130 Mg Cobra at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Vegah Cobra 100 mg average Cmax free Vega Extra Cobra 130 Mg in plasma men is about 18 ng/ml (38 nm). Cmax when taking Signature Cobra Vega 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 Cobra Vega Extra is 105 l. the Association of Vega Cobra 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. Vega Coin 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 Cobra Vega, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vega Coin, and its activity against PDE-5 in vitro is about 50% of the activity of Vega Coin. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of Vega Coin. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.
Breeding. The total clearance of Vega Coin is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Vega Coin is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).
Clinical data
In a placebo-controlled cross-examination of patients with proven early age macular degeneration (n=9), Vega Coin 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 Cobra Vega 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 Vega Coin, 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 Coin 25 mg), 74% (dose Vega Coin 50 mg) and 82% (dose Vega Coin 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 Cobra Vega 120 Mg 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 Coin.
Pharmacokinetics
Vega Extra
