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 Sildenafil Vega Extra 130 Mg. 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 Cobra, consult a doctor immediately.
Bleedings
Vegal Extra enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donator, on human platelets in vitro. Data on the safety of Vegal Extra in patients with a tendency to bleeding or exacerbation of gastric ulcer and duodenal ulcer are not available, so the drug Vega 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 (Vega Extra — 12.9%, placebo — 0%) than in patients with primary pulmonary arterial hypertension (Vegal Extra — 3%, placebo — 2.4%). Patients receiving Vegal Extra 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 Cobra 120 Mg together with other PDE-5 inhibitors or other drugs for the treatment of pulmonary hypertension containing Vegal Extra (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 Signature Cobra Vega any negative effect on the ability to drive a car or other means was not observed. However, since when taking Cobra Vega 120 Mg 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 Cobra 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. 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 Vegah Cobra 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 Vegah 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 Vegal Extra 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 Extra Vega 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 Sildenafil Vega Extra 120
The metabolism of Vegal Extra occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Vegal Extra, and inducers, respectively, increase the clearance of Vegah Extra 130. A decrease in the clearance of Vegal 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 Vegal Extra (50 mg) causes an increase in the concentration of Sildenafil Vega Extra 130 Mg Cobra in plasma by 56%.
A single dose of 100 mg of Vega 120 Mg 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 Mg Cobra by 182%.
When co-administered Vegal 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 Sildenafil Tablets Vegah Extra Cobra 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 Vegal 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 Vega Extra Strong 120 Mg by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Vega Extra 120 Mg in blood plasma is about 200 ng/ml (after a single application of one Vegah Cobra — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Vegah Extra 120 Mg does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Vegal Extra is not recommended. In any case, the maximum dose of Vegal Extra under any circumstances should not exceed 25 mg for 48 hours. If Vega Extra Cobra 120 is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Vegal Extra 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 Vegal Extra.
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 Vegal Extra 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. Vegal Extra increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.
It is assumed that the simultaneous use of Cobra Vega Extra 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 Cobra Vega 120 Mg.
Azithromycin (500 mg/day for 3 days) has no effect on AUC, Cmax, Tmax, excretion rate constant and T1/2 Vegal Extra or its main circulating metabolite.
Suction. After intake of Vega Coin is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Extra 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 Vegal Extra 100 mg average Cmax free Vega Extra Cobra 130 Mg 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 Vegal Extra is 105 l. the Association of Sildenafil Tablets Vega Extra 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 Sildenafil Vega Extra 130 (an average of 188 ng) was found in sperm 90 minutes after taking the drug.
Metabolism. Vegal Extra 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 Vegal Extra, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vegah Extra 130, 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 Vegal Extra. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.
Breeding. The total clearance of Vegal Extra is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Vegal Extra is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).
Dosage and administration
Inside, can be taken with or without water. When taking the drug, you should put a tablet, dispersed in the oral cavity, on the tongue, after which it will quickly dissolve, and it can be swallowed. The tablet should be taken immediately after opening the blister. Patients who are recommended a dose of Sildenafil Tablets Vega Extra Cobra 100 mg, the second tablet of Vegal Extra 50 mg should be taken after complete dissolution of the first tablet.
The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Taking into account the effectiveness and tolerability of the dose can be increased to 100 mg or reduced to 25 mg (only tablets coated with a film, the appropriate dosage). The maximum recommended dose is 100 mg. Patients who are recommended a dose of Cobra 120 Vega Extra 100 mg, it is necessary to take 2 table., dispersible in the oral cavity, dosage 50 mg consecutively one after another. The maximum recommended frequency of use — 1 time per day. It should be borne in mind that the absorption of Vegal Extra significantly slows down when used in combination with fatty foods.
Special patient groups
Renal impairment. In mild to moderate renal failure dose adjustment is not required, in severe renal failure (Creatinine CL <30 ml/min) Vegal Extra dose should be reduced to 25 mg.
Hepatic impairment. Since the excretion of Vegal Extra is disturbed in patients with liver damage (in particular, cirrhosis), the dose of Signature Cobra Vega should be reduced to 25 mg.
Joint application with other drugs. Joint use with ritonavir is not recommended. In any case, the maximum dose of Vegal Extra under any circumstances should not exceed 25 mg, and the frequency of application — 1 time in 48 h (see "Interaction").
When combined with inhibitors of CYP3A4 isoenzyme (erythromycin, saquinavir, ketoconazole, Itraconazole), the initial dose of Cobra Vega 120 should be 25 mg (see "Interaction").
To minimize the risk of postural hypotension in patients taking α-blockers, Sildenafil Vega Extra 120 should be started only after achieving hemodynamic stabilization in these patients. Consideration should also be given to reducing the initial dose of Vegal Extra (see special instructions and Interactions).
Old age. Adjustment of the dose of Sildenafil Tablets Vega Extra Cobra is not required.
Cobra Vega Extra
