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 Extra 120. 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 Sildenafil Vega Extra 130 Mg Cobra without subsequent sexual activity. It is not possible to establish a direct link between the reported adverse events and those or other factors.

Hypotension

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

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden hearing loss or impairment associated with the use of all PDE-5 inhibitors, including Cobra Vega Extra. Most of these patients had risk factors for sudden impairment or hearing loss. There is no causal relationship between the use of PDE-5 inhibitors and sudden hearing impairment or hearing loss. In case of sudden hearing impairment or hearing loss while taking Vega Extra, consult a doctor immediately.

Bleedings

Vega Extra 120 enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donator, on human platelets in vitro. Data on the safety of Vega Extra 120 in patients with a tendency to bleeding or exacerbation of gastric ulcer and duodenal ulcer are not available, so the drug Vega Extra 120 in these patients should be used with caution (see With caution).

The incidence of nosebleeds in patients with pulmonary hypertension associated with diffuse connective tissue diseases was higher (Vegal Extra — 12.9%, placebo — 0%) than in patients with primary pulmonary arterial hypertension (Vegab Extra — 3%, placebo — 2.4%). Patients receiving Vega Extra Cobra 120 in combination with an antagonist of vitamin K, the frequency of nasal bleeding was higher (8.8 percent) than patients who were not taking an antagonist of vitamin K (1.7 percent).

Use in conjunction with other means for the treatment of erectile dysfunction

The safety and efficacy of Vega Extra 120 together with other PDE-5 inhibitors or other drugs for the treatment of pulmonary hypertension containing Cobra Vega Extra Strong 120mg (eg, Revatsio®), or other means for the treatment of erection disorders have not been studied, so the use of such combinations is not recommended (see "Contraindications").

Influence on the ability to drive and mechanisms. In patients receiving Vegab Extra any negative effect on the ability to drive a car or other means was not observed. However, since when taking Vega Extra 120 may develop dizziness, lowering blood PRESSURE, the development of chromatopsia, blurred vision, etc. side effects, care should be taken when driving and doing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions. Also, you should be careful about the individual action of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Cardiovascular complications

During the post-marketing use of Vegah Extra 120 Mg 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 Vegah Extra 120 Mg. 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 Extra 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 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 Extra 120 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 Extra 120, 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 120 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 120

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

A single dose of 100 mg of Vega Extra 120 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 Extra by 182%.

When co-administered 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 Vega Extra 120 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 Cobra Vega Extra.

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 Cobra 120 Vega Extra by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Vega Extra 120 in blood plasma is about 200 ng/ml (after a single application of one Vega Extra 120 — 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 Vega Extra 120 is not recommended. In any case, the maximum dose of Vega Extra 120 under any circumstances should not exceed 25 mg for 48 hours. If Vegab Extra is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Vega Extra 120 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 Sildenafil Vega Extra 130 Mg 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 Vega Extra 120 in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Vega Pills by 62.6 and 52.4%, respectively. Cobra Vega 120 Mg increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.

It is assumed that the simultaneous use of Vega Extra 120 with powerful inducers of CYP3A4 isoenzyme, such as rifampicin, can lead to a greater decrease in the concentration of Vega Extra 120 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.

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

Clinical data

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

Sildenafil Vega Extra 130 Mg