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 Vegal 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 Sildenafil Vega Extra 130, consult a doctor immediately.
Bleedings
Sildenafil Vega Extra 130 enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donator, on human platelets in vitro. Data on the safety of Sildenafil Vega Extra 130 in patients with a tendency to bleeding or exacerbation of gastric ulcer and duodenal ulcer are not available, so the drug Vega Cobra 120 Mg 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 (Sildenafil Vega Extra 130 — 12.9%, placebo — 0%) than in patients with primary pulmonary arterial hypertension (Sildenafil Vega Extra 130 — 3%, placebo — 2.4%). Patients receiving Vegah Cobra 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 Sildenafil Vega Extra 130 together with other PDE-5 inhibitors or other drugs for the treatment of pulmonary hypertension containing Sildenafil Vega Extra 130 (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 Sildenafil Vega Extra 130 any negative effect on the ability to drive a car or other means was not observed. However, since when taking Vegah Extra 120 Indication 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.
Clinical data
Cardiac studies. The use of Sildenafil Vega Extra 130 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 Sildenafil Vega 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 Sildenafil Vega Extra 130 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%. Sildenafil Vega Extra 130 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 Cobra Vega 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 Cobra Vega Extra (up to 100 mg) in men (n=568) with erectile dysfunction and hypertension, taking more than two antihypertensive drugs, was studied. Sildenafil Vega Extra 130 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 Vega Extra 130 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. Sildenafil Vega Extra 130 had no effect on visual acuity, contrast perception, electroretinogram, IOP or pupil diameter.
Cardiovascular complications
During the post-marketing use of Sildenafil Vega Extra 130 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 Sildenafil Vega Extra 130. 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 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 Sildenafil Vega Extra 130, 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 Strong 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 Sildenafil Vega Extra 130, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.
When using the drug Sildenafil Vega Extra 130 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 Sildenafil Vega Extra 130 occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Sildenafil Vega Extra 130, and inducers, respectively, increase the clearance of Vega Extra Cobra 120. A decrease in the clearance of Sildenafil Vega Extra 130 with simultaneous use of inhibitors of CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine).
Cimetidine (800 mg), a nonspecific inhibitor of CYP3A4 isoenzyme, when taken together with Sildenafil Vega Extra 130 (50 mg) causes an increase in the concentration of Vega 120 Mg in plasma by 56%.
A single dose of 100 mg of Cobra Vega 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 Sildenafil Vega Extra 130 by 182%.
When co-administered Sildenafil Vega Extra 130 (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 Cobra Vega Extra Strong 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 Sildenafil Vega Extra 130.
The simultaneous use of Sildenafil Vega Extra 130 Mg (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 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 Sildenafil Vega Extra 130 — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Vega Cobra 120 does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Sildenafil Vega Extra 130 is not recommended. In any case, the maximum dose of Sildenafil Vega Extra 130 under any circumstances should not exceed 25 mg for 48 hours. If Sildenafil Vega Extra 130 is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Sildenafil Vega Extra 130 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 Vegah 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 Sildenafil Vega Extra 130 in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Sildenafil Vega Extra 130 by 62.6 and 52.4%, respectively. Sildenafil Vega Extra 130 increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.
It is assumed that the simultaneous use of Vega Extra 120 Mg with powerful inducers of CYP3A4 isoenzyme, such as rifampicin, can lead to a greater decrease in the concentration of Sildenafil Vega Extra 130 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 Sildenafil Vega Extra 130.
Azithromycin (500 mg/day for 3 days) has no effect on AUC, Cmax, Tmax, excretion rate constant and T1/2 Sildenafil Vega Extra 130 Mg Cobra or its main circulating metabolite.
The pharmacokinetics of Vegal Extra in the recommended dose range is linear.
Suction. After intake of Cobra Vega 120 is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Signature Cobra Vega 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 Sildenafil Vega Extra 130 in plasma men is about 18 ng/ml (38 nm). Cmax when taking Vega Cobra 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 Sildenafil Vega Extra 120 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 Sildenafil Vega Extra 130 Mg (an average of 188 ng) was found in sperm 90 minutes after taking the drug.
Metabolism. Vega Extra Strong 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, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vegah Extra 120 Indication, and its activity against PDE-5 in vitro is about 50% of the activity of Sildenafil Vega Extra 130 Mg. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of Sildenafil Vega Extra 130. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.
Breeding. The total clearance of Sildenafil Tablets Vegah Extra Cobra 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 is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).
Cobra Vega 120
