Cardiovascular complications

During the post-marketing use of Cobra Vega Extra 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 Cobra. 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 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 Cobra, 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 Cobra 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 Cobra, 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 Cobra

The metabolism of Vega Cobra occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Vega Cobra, and inducers, respectively, increase the clearance of Vega Visa. 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 Cobra (50 mg) causes an increase in the concentration of Sildenafil Vega Extra 120 in plasma by 56%.

A single dose of 100 mg of Vegah Extra 120 Indication 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 Cobra by 182%.

When co-administered Sildenafil Vega Extra 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 Vegah 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 Vega Cobra.

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

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

It is assumed that the simultaneous use of Sildenafil Vega Extra 130 with powerful inducers of CYP3A4 isoenzyme, such as rifampicin, can lead to a greater decrease in the concentration of Vega Cobra 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 Cobra 130 Mg.

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

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

Suction. After intake of Vega Cobra is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vega 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 Vega Cobra 100 mg average Cmax free Vega Cobra in plasma men is about 18 ng/ml (38 nm). Cmax when taking Vega Cobra 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 Sildenafil Vega Extra 130 Mg 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 Cobra (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

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

Breeding. The total clearance of Vega Cobra 120 is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Sildenafil Vega Extra 130 Mg Cobra is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).

Visual impairment

In rare cases, during post-approval use of all of the inhibitors of PDE5, including Vega Extra Cobra 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 Cobra 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 Cobra Vega Extra Strong 120 Mg, 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 Vegah Cobra 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 Cobra Vega 120 Mg in patients with retinitis pigmentosa absent, so these patients should not be used Vega Cobra (see "Contraindications").

Clinical data

Cardiac studies. The use of Cobra Vega 120 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 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 Cobra 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%. Vegal Extra 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 Vega 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 Extra Cobra 130 Mg (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 Sildenafil Tablets Vegah Extra Cobra 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. Vegah Cobra had no effect on visual acuity, contrast perception, electroretinogram, IOP or pupil diameter.

Sildenafil Vega Extra 130 Mg Cobra